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Sample records for h1n1 infection imaging

  1. Imaging Findings in Patients With H1N1 Influenza A Infection

    International Nuclear Information System (INIS)

    Bakhshayeshkaram, Mehrdad; Saidi, Bahareh; Tabarsi, Payam; Zahirifard, Soheila; Ghofrani, Mishka

    2011-01-01

    Swine influenza (H1N1) is a very contagious respiratory infection and World Health Organization (WHO) has raised the alert level to phase 6 (pandemic). The study of clinical and laboratory manifestations as well as radiologic imaging findings helps in its early diagnosis. The aim of this study was to evaluate the imaging findings of patients with documented H1N1 infection referred to our center. Thirty-one patients (16 men) with documented H1N1 infection were included in our study. The initial radiography obtained from the patients was reviewed regarding pattern (consolidation, ground glass, nodules and reticulation), distribution (focal, multifocal, and diffuse) and the lung zones involved. Computed tomography (CT) scans were also reviewed for the same abnormalities. The patient files were studied for their possible underlying diseases. The mean age was 37.97 ± 13.9 years. Seventeen (54.8%) patients had co-existing condition (eight respiratory, five cardiovascular, two immunodeficiency, two cancer, four others). Twelve (38.7%) patients required intensive care unit (ICU) admission. Five (16.1%) patients died. (25.8%) had normal initial radiographs. The most common abnormality was consolidation (12/31; 38.7%) in the peripheral region (11/31; 35.5%) followed by peribronchovascular areas (10/31; 32.3%) which was most commonly observed in the lower zone. The patients admitted to the ICU were more likely to have two or more lung zones involved (P = 0.005). In patients with the novel swine flu infection, the most common radiographic abnormality observed was consolidation in the lower lung zones. Patients admitted to ICU were more likely to have two or more lung zones involved

  2. Imaging manifestation of A H1N1 influenza with pneumonia

    International Nuclear Information System (INIS)

    Yang Jun; Xu Yunliang; Lu Zhibin; Wang Xiaojie; Li Shuo; Du Lei; Guo Limin; Li Xingwang

    2010-01-01

    Objective: To evaluate the imaging features of pneumonia caused by A (H1N1) influenza virus. Methods: Imaging data of 51 patients with pneumonia caused by A H1N1 influenza were retrospectively reviewed. All patients underwent mobile chest radiographs and 44 patients underwent CT as well. On the basis of the lesion degree in the lung, the patients were classified into mild, moderate and serious types. Results: Mild type showed patchy consolidation at chest imaging in 4 patients. Moderate type demonstrated consolidation and (or) ground-glass opacities more than 2 lung fields in 33 patients, including 30 bilateral and 3 unilateral. Serious type displayed diffuse consolidation and ground-glass opacities, probably accompanying with interstitial lesions in the lungs in 14 patients, including 6 patients with ARDS, 2 with infection and 1 with cutaneous emphysema. Conclusion: The imaging features of pneumonia caused by A H1N1 influenza mainly manifest as consolidation and ground-glass opacities, probably accompanying with interstitial changes. The imaging findings show various in patients with infection. Some serious patients even develope to ARDS. (authors)

  3. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses.

    Science.gov (United States)

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-09-24

    The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.

  4. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

    Science.gov (United States)

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

    2010-01-01

    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains. © INRA, EDP Sciences, 2010.

  5. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    Science.gov (United States)

    Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

    2012-01-01

    There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  6. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    Directory of Open Access Journals (Sweden)

    Charles Nfon

    Full Text Available There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI. In addition, heterologous cell mediated immunity (CMI was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  7. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

  8. Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses

    OpenAIRE

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Jung, Kwonil; Kang, Bo-Kyu; Song, Daesub

    2014-01-01

    Background The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. Findings The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decrease...

  9. Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

    Science.gov (United States)

    Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

    2011-02-01

    The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

  10. Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection.

    Science.gov (United States)

    Ling, Man To; Tu, Wenwei; Han, Yan; Mao, Huawei; Chong, Wai Po; Guan, Jing; Liu, Ming; Lam, Kwok Tai; Law, Helen K W; Peiris, J S Malik; Takahashi, K; Lau, Yu Lung

    2012-01-01

    Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response.

  11. Pre-infection of pigs with Mycoplasma hyopneumoniae modifies outcomes of infection with European swine influenza virus of H1N1, but not H1N2, subtype.

    Science.gov (United States)

    Deblanc, C; Gorin, S; Quéguiner, S; Gautier-Bouchardon, A V; Ferré, S; Amenna, N; Cariolet, R; Simon, G

    2012-05-25

    Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Comparison of temporal and spatial dynamics of seasonal H3N2, pandemic H1N1 and highly pathogenic avian influenza H5N1 virus infections in ferrets.

    Directory of Open Access Journals (Sweden)

    Judith M A van den Brand

    Full Text Available Humans may be infected by different influenza A viruses--seasonal, pandemic, and zoonotic--which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1, and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi, as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues--including the central nervous system--for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.

  13. Narcolepsy: Association with H1N1 Infection and Vaccination

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    Ji Hyun Song

    2016-12-01

    Full Text Available Epidemiological studies have demonstrated an association between H1N1 influenza infection and vaccinations. This article reviews the various studies, and suggests the biological mechanisms explaining why and how H1N1 influenza infection or vaccine stimulates the autoimmune response, thereby resulting in narcolepsy. Among the vaccines, the effect of Pandemrix was scrutinized more than other vaccines, due to its higher association with an increase of narcolepsy onset. The consequences of using other vaccines which contain same or different adjuvants as Pandemrix, were also analyzed.

  14. Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets.

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    Stephen S H Huang

    Full Text Available Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 [H1N1pdm] and seasonal A/H1N1, A/H3N2, and B viruses. The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response. Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.

  15. Humans and ferrets with prior H1N1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic H1N1 influenza virus.

    Science.gov (United States)

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta

    2014-05-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.

  16. The Neurological Manifestations of H1N1 Influenza Infection; Diagnostic Challenges and Recommendations

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    Ali Akbar Asadi-Pooya

    2011-03-01

    Full Text Available Background: World Health Organization declared pandemic phase of human infection with novel influenza A (H1N1 in April 2009. There are very few reports about the neurological complications of H1N1 virus infection in the literature. Occasionally, these complications are severe and even fatal in some individuals. The aims of this study were to report neurological complaints and/or complications associated with H1N1 virus infection. Methods: The medical files of all patients with H1N1 influenza infection admitted to a specified hospital in the city of Shiraz, Iran from October through November 2009 were reviewed. More information about the patients were obtained by phone calls to the patients or their care givers. All patients had confirmed H1N1 virus infection with real-time PCR assay. Results: Fifty-five patients with H1N1 infection were studied. Twenty-three patients had neurological signs and/or symptoms. Mild neurological complaints may be reported in up to 42% of patients infected by H1N1 virus. Severe neurological complications occurred in 9% of the patients. The most common neurological manifestations were headache, numbness and paresthesia, drowsiness and coma. One patient had a Guillain-Barre syndrome-like illness, and died in a few days. Another patient had focal status epilepticus and encephalopathy. Conclusions: The H1N1 infection seems to have been quite mild with a self-limited course in much of the world, yet there appears to be a subset, which is severely affected. We recommend performing diagnostic tests for H1N1influenza virus in all patients with respiratory illness and neurological signs/symptoms. We also recommend initiating treatment with appropriate antiviral drugs as soon as possible in those with any significant neurological presentation accompanied with respiratory illness and flu-like symptoms

  17. Acute necrotizing encephalopathy in a child with H1N1 influenza infection

    International Nuclear Information System (INIS)

    Lyon, Jane B.; Remigio, Cheryl; Milligan, Thomas; Deline, Carol

    2010-01-01

    Since the World Health Organization declared a global pandemic of novel influenza A H1N1 in June 2009, there has been a sustained rise in the number of cases of this strain of influenza. Although most cases are mild with complete and uneventful recovery, multiple cases of severe infection with complications including death have been reported. To the best of our knowledge, the majority of fatal outcomes in the United States have been related to pulmonary complications. We report a 12-year-old girl infected with influenza A H1N1 whose clinical course was complicated by rapid progressive neurologic deterioration and striking CT and MRI findings consistent with acute necrotizing encephalopathy (ANE). To our knowledge this has not been reported in the pediatric radiology literature. We hope this case will alert radiologists to this complication and familiarize radiologists with imaging findings that herald ANE. (orig.)

  18. H1N1 infection in emergency surgery: A cautionary tale.

    LENUS (Irish Health Repository)

    Galbraith, J G

    2010-01-01

    Pandemic 2009 influenza A H1N1 has spread rapidly since its first report in Mexico in March 2009. This is the first influenza pandemic in over 40 years and it atypically affects previously healthy young adults, with higher rates of morbidity and mortality. The medical literature has been inundated with reports of H1N1 infection, the majority found in critical care and internal medicine journals with a relative paucity in the surgical literature. Despite this, it remains an important entity that can impact greatly on acute surgical emergencies. We present a case of previously healthy 31-year-old male who underwent open appendectomy. His post-operative recovery was complicated by acute respiratory distress syndrome secondary to H1N1 infection. This case report highlights the impact that H1N1 virus can have on acute surgical emergencies and how it can complicate the post-operative course.

  19. Bilateral Pulmonary Thromboembolism: An Unusual Presentation of Infection with Influenza A (H1N1 Virus

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    Parviz Saleh

    2010-06-01

    Full Text Available AbstractSwine flue is a highly contagious acute respiratory diseasecaused by a subtype of influenza A virus. Herein we presentthree patients with H1N1 infection complicated with pulmonarythromboembolism. The patients had chest pain and unexplaineddyspnea. Imaging studies showed bilateral hilar predominance.Computed tomographic angiography confirmed bilateral thromboembolism(an unusual presentation of H1N1 infection. We didnot find any predisposing factor including endothelial damage,stasis, or hypercoagulable state in these patients. They did notreceive any medication. After anticoagulation and treatment withoseltamivir, all the patients were discharged in good condition.To the best of our knowledge bilateral pulmonary thromboembolismhas not been reported in English language literature inpatients with swine flu infection. Appropriate diagnosis andtreatment will be life saving in this condition.Iran J Med Sci 2010; 35(2: 149-153.

  20. Pandemic (H1N1 2009 Influenza Virus Infection in A Survivor who has recovered from severe H7N9 Virus Infection, China

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    Shan-Hui Chen

    2016-10-01

    Full Text Available We firstly report a patient who presented with severe complications after infection with influenza A(H1N1 pdm2009, more than one year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination.

  1. Protection against H5N1 Highly Pathogenic Avian and Pandemic (H1N1) 2009 Influenza Virus Infection in Cynomolgus Monkeys by an Inactivated H5N1 Whole Particle Vaccine

    Science.gov (United States)

    Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2013-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3. PMID:24376571

  2. Protection against H5N1 highly pathogenic avian and pandemic (H1N1 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

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    Misako Nakayama

    Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

  3. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    Science.gov (United States)

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus.

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    Rith, Sareth; Chin, Savuth; Sar, Borann; Y, Phalla; Horm, Srey Viseth; Ly, Sovann; Buchy, Philippe; Dussart, Philippe; Horwood, Paul F

    2015-12-01

    Despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny. We document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09. Complete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID50 of 10(4)/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia. It is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan.

    Science.gov (United States)

    Hsieh, Ying-Hen; Tsai, Chen-An; Lin, Chien-Yu; Chen, Jin-Hua; King, Chwan-Chuen; Chao, Day-Yu; Cheng, Kuang-Fu

    2014-02-12

    Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms. Serum samples of 255 schoolchildren, who had not received vaccination and had pre-season HI Ab serotiters definition of Fever + (cough or sore throat or nose) + ( headache or pain or fatigue). Asymptomatic ratio for children is found to be substantially higher than that of the general population in literature. In providing reasonable quantification of the asymptomatic infected children spreading pathogens to others in a seasonal epidemic or a pandemic, our estimates of symptomatic ratio of infected children has important clinical and public health implications.

  6. Experimental infection of clade 1.1.2 (H5N1), clade 2.3.2.1c (H5N1) and clade 2.3.4.4 (H5N6) highly pathogenic avian influenza viruses in dogs.

    Science.gov (United States)

    Lyoo, K S; Na, W; Phan, L V; Yoon, S W; Yeom, M; Song, D; Jeong, D G

    2017-12-01

    Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in Asia, the haemagglutinin (HA) gene of this virus lineage has continued to evolve in avian populations, and H5N1 lineage viruses now circulate concurrently worldwide. Dogs may act as an intermediate host, increasing the potential for zoonotic transmission of influenza viruses. Virus transmission and pathologic changes in HPAI clade 1.1.2 (H5N1)-, 2.3.2.1c (H5N1)- and 2.3.4.4 (H5N6)-infected dogs were investigated. Mild respiratory signs and antibody response were shown in dogs intranasally infected with the viruses. Lung histopathology showed lesions that were associated with moderate interstitial pneumonia in the infected dogs. In this study, HPAI H5N6 virus replication in dogs was demonstrated for the first time. Dogs have been suspected as a "mixing vessel" for reassortments between avian and human influenza viruses to occur. The replication of these three subtypes of the H5 lineage of HPAI viruses in dogs suggests that dogs could serve as intermediate hosts for avian-human influenza virus reassortment if they are also co-infected with human influenza viruses. © 2017 Blackwell Verlag GmbH.

  7. Signal Immune Reactions of Macrophages Differentiated from THP-1 Monocytes to Infection with Pandemic H1N1PDM09 Virus and H5N2 and H9N2 Avian Influenza A Virus.

    Science.gov (United States)

    Sokolova, T M; Poloskov, V V; Shuvalov, A N; Rudneva, I A; Timofeeva, T A

    2018-03-01

    In culture of THP-1 cells differentiated into macrophages with PMA (THP-PMA macrophages) infected with influenza viruses of subtypes H1, H5 and H9, we measured the expression of TLR7 and RIG1 receptor genes, sensors of viral RNA and ribonucleoprotein, and the levels of production of inflammatory cytokines IL-1β, TNFα, IL-10, and IFNα. The sensitivity and inflammatory response of THP-PMA macrophages to pandemic influenza A virus H1N1pdm09 and avian influenza H5N2 and H9N2 viruses correlate with the intracellular level of their viral RNA and activation of the RIG1 gene. Abortive infection is accompanied by intensive macrophage secretion of TNFα, IL-1β, and toxic factors inducing cell death. Activity of endosomal TLR7 receptor gene changed insignificantly in 24 h after infection and significantly decreased in 48 and 72 h under the action of H5N2 and H9N2, which correlated with manifestation of the cytopathogenic effect of these viruses. H5N2 and H9N2 avian viruses in THP-PMA macrophages are strong activators of the expression of the gene of the cytoplasmic RIG1 receptor 24 and 48 h after infection, and the pandemic virus H1N1pdm09 is a weak stimulator of RIG1 gene. Avian influenza H5N2 and H9N2 viruses are released by rapid induction of the inflammatory response in macrophages. At the late stages of infection, we observed a minor increase in IL-10 secretion in macrophages and, probably, the polarization of a part of the population in type M2. The studied influenza A viruses are weak inductors of IFN in THP-PMA macrophages. In the culture medium of THP-PMA macrophages infected with H9N2 and H5N2 viruses, MTT test revealed high levels of toxic factors causing the death of Caco-2 cells. In contrast to avian viruses, pandemic virus H1N1pdm09 did not induce production of toxic factors.

  8. Outcomes of Oseltamivir Treatment for H1N1 Infection During Pregnancy: A Retrospective Study

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    Nermin Akdemir

    2011-04-01

    CONCLUSION: In this retrospective, study, we found that, H1N1 infection during pregnancy has a good prognosis and without complication for maternal health. Although oseltamivir therapy is safe in pregnant women, it can be associated with cardiac structural cardiac malformations in H1N1 infected pregnancy newborns

  9. Long term immune responses to pandemic influenza A/H1N1 infection in solid organ transplant recipients.

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    Aliyah Baluch

    Full Text Available In solid organ transplant (SOT recipients it is unknown if natural infection with influenza confers protection from re-infection with the same strain during the next influenza season. The purpose of this study was to determine if infection with pandemic influenza A/H1N1 (pH1N1 resulted in a long-term immunologic response. Transplant recipients with microbiologically proven pH1N1 infection in 2009/2010 underwent humoral and cell-mediated immunity (CMI testing for pH1N1 just prior to the next influenza season. Concurrent testing for A/Brisbane/59/2007 was done to rule-out cross-reacting antibody. We enrolled 22 adult transplant patients after pH1N1 infection. Follow up testing was done at a median of 7.4 months (range 5.8-15.4 after infection. After excluding those with cross-reactive antibody, 7/19 (36.8% patients were seroprotected. Detectable pH1N1-specific CD4+ and CD8+ interferon-γ producing T-cells were found in 11/22 (50% and 8/22 (36.4% patients respectively. Humoral immunity had a significant correlation with a CD4 response. This is the first study in transplant patients to evaluate long-term humoral and cellular response after natural influenza infection. We show that a substantial proportion of SOT recipients with previous pH1N1 infection lack long-term humoral and cellular immune responses to pH1N1. These patients most likely are at risk for re-infection.

  10. Pandemic influenza A H1N1 2009 infection versus vaccination: a cohort study comparing immune responses in pregnancy.

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    Barbra M Fisher

    Full Text Available BACKGROUND: With the emergence of H1N1 pandemic (pH1N1 influenza, the CDC recommended that pregnant women be one of five initial target groups to receive the 2009 monovalent H1N1 vaccine, regardless of prior infection with this influenza strain. We sought to compare the immune response of pregnant women to H1N1 infection versus vaccination and to determine the extent of passive immunity conferred to the newborn. METHODS/FINDINGS: During the 2009-2010 influenza season, we enrolled a cohort of women who either had confirmed pH1N1 infection during pregnancy, did not have pH1N1 during pregnancy but were vaccinated against pH1N1, or did not have illness or vaccination. Maternal and umbilical cord venous blood samples were collected at delivery. Hemagglutination inhibition assays (HAI for pH1N1 were performed. Data were analyzed using linear regression analyses. HAIs were performed for matched maternal/cord blood pairs for 16 women with confirmed pH1N1 infection, 14 women vaccinated against pH1N1, and 10 women without infection or vaccination. We found that pH1N1 vaccination and wild-type infection during pregnancy did not differ with respect to (1 HAI titers at delivery, (2 HAI antibody decay slopes over time, and (3 HAI titers in the cord blood. CONCLUSIONS: Vaccination against pH1N1 confers a similar HAI antibody response as compared to pH1N1 infection during pregnancy, both in quantity and quality. Illness or vaccination during pregnancy confers passive immunity to the newborn.

  11. Thoracic computerized tomographic (CT findings in 2009 influenza A (H1N1 virus infection in Isfahan, Iran

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    Mojtaba Rostami

    2011-01-01

    Full Text Available Background: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1 in an appropriate clinical setting. Methods: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23 rd 2009 to February 20 th 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1 virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. Results: Patchy infiltration (34.6%, lobar consolidation (30.8%, and interstitial infiltration (26.9% with airbronchogram (38.5% were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8% showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS. Conclusions: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1 in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific.

  12. Direct isolation of H1N2 recombinant virus from a throat swab of a patient simultaneously infected with H1N1 and H3N2 influenza A viruses.

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    Nishikawa, F; Sugiyama, T

    1983-01-01

    Two H1N2 recombinant viruses were isolated by a plaquing method from a throat swab of a patient who was simultaneously infected with H1N1 and H3N2 influenza viruses during the Tokyo epidemic of 1981. This is the first direct evidence that recombination of influenza viruses occurred in the human body.

  13. Pandemic (H1N1) 2009 virus infection during pregnancy in South India.

    Science.gov (United States)

    Pramanick, Angsumita; Rathore, Swati; Peter, John V; Moorthy, Mahesh; Lionel, Jessie

    2011-04-01

    To assess the clinical profile of pregnant/puerperal women from a semi-urban Indian population who were infected with pandemic (H1N1) 2009 virus (P[H1N1]2009v) and to evaluate their outcome. In a cross-sectional study, 566 women (79 pregnant/puerperal, 487 nonpregnant) who presented to a tertiary care hospital with influenza-like illness were tested for P(H1N1)2009v by real-time reverse transcriptase polymerase chain reaction. Outcomes measures were the maternal mortality and the perinatal mortality rate (PMR). Twenty (25%) pregnant/puerperal and 144 (30%) nonpregnant women tested positive for P(H1N1)2009v, with 5 pregnant and 3 postpartum women requiring admission to the intensive care unit (ICU). P(H1N1)2009v-related mortality was higher in pregnant than nonpregnant women (25% versus 8%; P=0.04). In the pregnant/puerperal cohort, factors associated with death included delayed presentation (median 6days versus 1.5days in survivors; P=0.007), need for ICU admission (P=0.004), need for ventilation (P=0.001), and renal failure (P=0.001). The PMR was 55.5/1000 births compared with 33.5/1000 births in the hospital overall during the study period. In a low-income country, P(H1N1)2009v infection in pregnancy is associated with considerable mortality. Delayed presentation to a tertiary care center, lack of awareness, and restricted access to treatment might have contributed to the high mortality. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  14. A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

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    Christopher W Woods

    Full Text Available There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1 or A/Wisconsin/67/2005 (H3N2, and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44% developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1 and 38 hours (p-value = 0.005, H3N2 before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009 infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent.

  15. Novel influenza A (H1N1) infection: chest CT findings from 21 cases in Seoul, Korea

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    Shim, S.S., E-mail: sinisim@ewha.ac.k [Department of Diagnostic Radiology and Center for Imaging Science, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of); Kim, Y. [Department of Diagnostic Radiology and Center for Imaging Science, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of); Ryu, Y.J. [Division of Pulmonary and Critical care medicine, Department of Internal Medicine, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2011-02-15

    Aim: To retrospectively evaluate the computed tomography (CT) appearances of novel influenza A (H1N1) infection. Materials and methods: Chest CT images obtained at clinical presentation in 21 patients (eight men, 13 women; mean age, 37 years; age range, 6-82 years) with confirmed novel influenza A (H1N1) infection were assessed. The radiological appearances of pulmonary parenchymal abnormalities, distribution, and extent of involvement on initial chest CT images were documented. The study group was divided on the basis of age [group 1, patients <18 years old (n = 8); group 2, patients {>=}18 years old (n = 13)]. Medical records were reviewed for underlying medical conditions and laboratory findings. The occurrence of recognizable CT patterns was compared for each group using the images from the initial CT examination. Results: The most common CT pattern observed in all patients was ground-glass attenuated (GGA) lesions (20/21, 95%). Bronchial wall thickening (9/21, 43%) was the second most common CT finding. Other common CT findings were consolidation (6/21, 29%), pleural effusion (6/21, 29%), pneumothorax or pneumomediastinum (5/21, 24%), and atelectasis (5/21, 24%). Among these, atelectasis and pneumomediastinum (pneumothorax) were only observed in group 1. The GGA lesions showed predilections for diffuse multifocal (10/20, 50%) or lower zone (8/20, 40%) distribution. Involvement of central lung parenchyma (12/20, 60%) was more common than a mixed peripheral and central pattern (6/20, 30%) or a subpleural pattern (2/20, 10%) at the time of presentation. Patchy GGA lesions were more frequent (18/20, 90%) than diffuse GGA lesions, and 75% (15/20) of these lesions had a bronchovascular distribution. Bilateral disease was present in all patients with GGA lesions. Bronchial wall thickening was predominantly centrally located and the distribution of the consolidation was non-specific. Conclusion: The predominantly centrally located GGA lesions, with common multifocal

  16. Novel influenza A (H1N1) infection: chest CT findings from 21 cases in Seoul, Korea

    International Nuclear Information System (INIS)

    Shim, S.S.; Kim, Y.; Ryu, Y.J.

    2011-01-01

    Aim: To retrospectively evaluate the computed tomography (CT) appearances of novel influenza A (H1N1) infection. Materials and methods: Chest CT images obtained at clinical presentation in 21 patients (eight men, 13 women; mean age, 37 years; age range, 6-82 years) with confirmed novel influenza A (H1N1) infection were assessed. The radiological appearances of pulmonary parenchymal abnormalities, distribution, and extent of involvement on initial chest CT images were documented. The study group was divided on the basis of age [group 1, patients <18 years old (n = 8); group 2, patients ≥18 years old (n = 13)]. Medical records were reviewed for underlying medical conditions and laboratory findings. The occurrence of recognizable CT patterns was compared for each group using the images from the initial CT examination. Results: The most common CT pattern observed in all patients was ground-glass attenuated (GGA) lesions (20/21, 95%). Bronchial wall thickening (9/21, 43%) was the second most common CT finding. Other common CT findings were consolidation (6/21, 29%), pleural effusion (6/21, 29%), pneumothorax or pneumomediastinum (5/21, 24%), and atelectasis (5/21, 24%). Among these, atelectasis and pneumomediastinum (pneumothorax) were only observed in group 1. The GGA lesions showed predilections for diffuse multifocal (10/20, 50%) or lower zone (8/20, 40%) distribution. Involvement of central lung parenchyma (12/20, 60%) was more common than a mixed peripheral and central pattern (6/20, 30%) or a subpleural pattern (2/20, 10%) at the time of presentation. Patchy GGA lesions were more frequent (18/20, 90%) than diffuse GGA lesions, and 75% (15/20) of these lesions had a bronchovascular distribution. Bilateral disease was present in all patients with GGA lesions. Bronchial wall thickening was predominantly centrally located and the distribution of the consolidation was non-specific. Conclusion: The predominantly centrally located GGA lesions, with common multifocal or

  17. Clinical characteristics and outcomes among pediatric patients hospitalized with pandemic influenza A/H1N1 2009 infection

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    Eun Lee

    2011-08-01

    Full Text Available Purpose : The purpose of this article is to describe the clinical and epidemiologic features and outcomes among children hospitalized with pandemic influenza A/H1N1 2009 infection. Methods : We retrospectively reviewed the charts of hospitalized pediatric patients (&lt;18 years diagnosed with pandemic influenza A/H1N1 2009 infection by reverse-transcriptase polymerase chain reaction at a tertiary hospital in Seoul, Korea, between September 2009 and February 2010. Results : A total of 72 children were hospitalized with pandemic influenza A/H1N1 2009 infection (median age, 6.0 years; range, 2 months to 18 years. A total of 40% had at least 1 underlying medical condition, including asthma (17%, malignancies (19%, and heart diseases (17%. Of the 72 patients, 54 (76% children admitted with H1N1 infection showed radiographic alterations compatible with pneumonia. There was no significant difference in pre-existing conditions between pandemic influenza A/H1N1 infected patients with or without pneumonia. Children with pandemic influenza A/ H1N1 pneumonia were more likely to have a lower lymphocyte ratio (P=0.02, higher platelet count (P=0.02, and higher level of serum glucose (P=0.003, and more commonly presented with dyspnea than did those without pneumonia (P=0.04. Conclusion : No significant differences in age, sex, or presence of preexisting conditions were found between children hospitalized with pandemic influenza A/H1N1 H1N1 influenza infection with pneumonia and those without pneumonia. Higher leukocyte count, higher glucose level, and a lower lymphocyte ratio were associated with the development of pandemic A/H1N1 2009 influenza pneumonia.

  18. New Onset Refractory Status Epilepticus in a Young Man with H1N1 Infection

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    Faisal Ibrahim

    2014-01-01

    Full Text Available Objective. To report a case of refractory status epilepticus (SE as an unusual early manifestation of H1N1 influenza infection. Introduction. H1N1 neurological complications have been reported and consist mainly of seizures or encephalopathy occurring in children. However, we only found a single report of an adult developing complex partial SE with H1N1 infection. Case Report. A 21-year-old previously healthy man was brought to the emergency room (ER after a witnessed generalized tonic clonic seizure (GTCS. He was fully alert and afebrile upon ER arrival, but a second GTCS prompted treatment with Lorazepam and Fosphenytoin. The initial EEG showed diffuse slowing, but a repeat one requested as the patient failed to regain consciousness revealed recurrent focal seizures of independent bihemispheric origin, fulfilling the criteria for nonconvulsive SE. Chest X-ray, followed by chest CT scan, showed a left upper lobe consolidation. H1N1 infection was confirmed with PCR on bronchoalveolar lavage material. Despite aggressive treatment with Midazolam, Propofol, and multiple high dose antiepileptic drugs, the electrographic seizures recurred at every attempt to reduce the intravenous sedative drugs. The patient died two weeks after his initial presentation. Conclusion. H1N1 should be added to the list of rare causes of refractory SE, regardless of the patient’s age.

  19. Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

    Science.gov (United States)

    Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

    2013-04-01

    The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

  20. How Does Influenza A (H1N1 Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

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    Sinem Civriz Bozdağ

    2012-03-01

    Full Text Available Clinical course of H1N1 infection in Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT patients is contraversial. We report three AHSCT patients who were infected with Influenza A/H1N1 infection. All of the patients were diagnosed with different hematological diagnosis and were at different stages of transplantation.All of them were treated with oseltamivir,zanamivir was switched with oseltamivir in one patient. All of the three patients were survived without any complication. Swine flu, can display with different courses and progress with bacterial or other viral infections in immunsupressed patients.

  1. Clinical and radiological features of pandemic H1N1 2009 influenza virus infection manifesting as acute febrile respiratory illness at their initial presentations: comparison with contemporaneous non-H1N1 patients

    International Nuclear Information System (INIS)

    Yun, Tae Jin; Park, Chang Min; Choi, Seung Hong; Lee, Hyun Ju; Goo, Jin Mo; Kwon, Gu Jin; Woo, Sung Koo; Park, Seung Hoon

    2011-01-01

    Background Since the first outbreak caused by the pandemic H1N1 2009 influenza in Mexico, the virus has spread widely across the world with meaningful morbidity and mortality. However, there are few data on the comparative investigations to assess the clinical and radiological features between the H1N1 patient and non-H1N1 patients. Purpose To assess the clinical and radiological features of patients infected by the pandemic H1N1 2009 flu virus at their initial presentation and to compare them with contemporaneous non-H1N1 patients with acute febrile respiratory illness. Material and Methods This retrospective study was approved by the ethics committee of the Armed Forces Medical Command, South Korea. From August to September 2009, 337 consecutive patients presented with an acute febrile respiratory illness in a tertiary military hospital. Reverse-transcriptase polymerase-chain-reaction tests were performed in 62 of these patients under the impression of H1N1 infection. Clinical and radiological features at their initial presentation were described for the H1N1 group (n = 35) and non-H1N1 group (n = 27) and compared between the two groups. Results Increased C-reactive protein level (97%) without leukocytosis (9%) or increased erythrocyte sedimentation rate (0%) was common in the H1N1 group at their initial presentation. On chest radiographs, 12 of 35 (34%) H1N1 patients had abnormal findings; nodules in 10 patients (83%) and consolidations in two (17%). Of the 28 H1N1 patients who underwent thin-section CT 16 patients (57%) showed abnormal findings; ground-glass opacities (GGOs) in 15 (94%), and nodules in 13 (81%). However, there were no significant differences between the H1N1 group and non-H1N1 group in terms of symptoms, laboratory results, or radiological findings (P > 0.05). Conclusion Patients with H1N1 infection show consistent clinical and radiological features at their initial presentation, however, clinical and radiological features of the H1N1 group are

  2. Clinical and radiological features of pandemic H1N1 2009 influenza virus infection manifesting as acute febrile respiratory illness at their initial presentations: comparison with contemporaneous non-H1N1 patients

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    Yun, Tae Jin (Dept. of Radiology, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of); Dept. of Radiology, Seoul National Univ. Hospital, Seoul (Korea, Republic of)); Park, Chang Min; Choi, Seung Hong; Lee, Hyun Ju; Goo, Jin Mo (Dept. of Radiology, Seoul National Univ. Hospital, Seoul (Korea, Republic of)), email: cmpark@radiol.snu.ac.kr; Kwon, Gu Jin (Dept. of Family Medicine, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of); Dept. of Family Medicine, Gangneung Asan Hospital, Gangneung (Korea, Republic of)); Woo, Sung Koo (Dept. of Radiology, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of)); Park, Seung Hoon (Dept. of Internal Medicine, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of))

    2011-05-15

    Background Since the first outbreak caused by the pandemic H1N1 2009 influenza in Mexico, the virus has spread widely across the world with meaningful morbidity and mortality. However, there are few data on the comparative investigations to assess the clinical and radiological features between the H1N1 patient and non-H1N1 patients. Purpose To assess the clinical and radiological features of patients infected by the pandemic H1N1 2009 flu virus at their initial presentation and to compare them with contemporaneous non-H1N1 patients with acute febrile respiratory illness. Material and Methods This retrospective study was approved by the ethics committee of the Armed Forces Medical Command, South Korea. From August to September 2009, 337 consecutive patients presented with an acute febrile respiratory illness in a tertiary military hospital. Reverse-transcriptase polymerase-chain-reaction tests were performed in 62 of these patients under the impression of H1N1 infection. Clinical and radiological features at their initial presentation were described for the H1N1 group (n = 35) and non-H1N1 group (n = 27) and compared between the two groups. Results Increased C-reactive protein level (97%) without leukocytosis (9%) or increased erythrocyte sedimentation rate (0%) was common in the H1N1 group at their initial presentation. On chest radiographs, 12 of 35 (34%) H1N1 patients had abnormal findings; nodules in 10 patients (83%) and consolidations in two (17%). Of the 28 H1N1 patients who underwent thin-section CT 16 patients (57%) showed abnormal findings; ground-glass opacities (GGOs) in 15 (94%), and nodules in 13 (81%). However, there were no significant differences between the H1N1 group and non-H1N1 group in terms of symptoms, laboratory results, or radiological findings (P > 0.05). Conclusion Patients with H1N1 infection show consistent clinical and radiological features at their initial presentation, however, clinical and radiological features of the H1N1 group are

  3. Novel Influenza A (H1N1) Virus Infection in Children: Chest Radiographic and CT Evaluation

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    Choi, Min Jeong; Lee, Young Seok; Lee, Jee Young; Lee, Kun Song [Dankook University College of Medicine, Dankook University Hospital, Cheonan (Korea, Republic of)

    2010-12-15

    The purpose of this study was to evaluate the chest radiographic and CT findings of novel influenza A (H1N1) virus infection in children, the population that is more vulnerable to respiratory infection than adults. The study population comprised 410 children who were diagnosed with an H1N1 infection from August 24, 2009 to November 11, 2009 and underwent chest radiography at Dankook University Hospital in Korea. Six of these patients also underwent chest CT. The initial chest radiographs were classified as normal or abnormal. The abnormal chest radiographs and high resolution CT scans were assessed for the pattern and distribution of parenchymal lesions, and the presence of complications such as atelectasis, pleural effusion, and pneumomediastinum. The initial chest radiograph was normal in 384 of 410 (94%) patients and abnormal in 26 of 410 (6%) patients. Parenchymal abnormalities seen on the initial chest radiographs included prominent peribronchial marking (25 of 26, 96%), consolidation (22 of 26, 85%), and ground-glass opacities without consolidation (2 of 26, 8%). The involvement was usually bilateral (19 of 26, 73%) with the lower lung zone predominance (22 of 26, 85%). Atelectasis was observed in 12 (46%) and pleural effusion in 11 (42%) patients. CT (n = 6) scans showed peribronchovascular interstitial thickening (n = 6), ground-glass opacities (n = 5), centrilobular nodules (n = 4), consolidation (n = 3), mediastinal lymph node enlargement (n = 5), pleural effusion (n = 3), and pneumomediastinum (n = 3). Abnormal chest radiographs were uncommon in children with a swine-origin influenza A (H1N1) virus (S-OIV) infection. In children, H1N1 virus infection can be included in the differential diagnosis, when chest radiographs and CT scans show prominent peribronchial markings and ill-defined patchy consolidation with mediastinal lymph node enlargement, pleural effusion and pneumomediastinum

  4. Novel Influenza A (H1N1) Virus Infection in Children: Chest Radiographic and CT Evaluation

    International Nuclear Information System (INIS)

    Choi, Min Jeong; Lee, Young Seok; Lee, Jee Young; Lee, Kun Song

    2010-01-01

    The purpose of this study was to evaluate the chest radiographic and CT findings of novel influenza A (H1N1) virus infection in children, the population that is more vulnerable to respiratory infection than adults. The study population comprised 410 children who were diagnosed with an H1N1 infection from August 24, 2009 to November 11, 2009 and underwent chest radiography at Dankook University Hospital in Korea. Six of these patients also underwent chest CT. The initial chest radiographs were classified as normal or abnormal. The abnormal chest radiographs and high resolution CT scans were assessed for the pattern and distribution of parenchymal lesions, and the presence of complications such as atelectasis, pleural effusion, and pneumomediastinum. The initial chest radiograph was normal in 384 of 410 (94%) patients and abnormal in 26 of 410 (6%) patients. Parenchymal abnormalities seen on the initial chest radiographs included prominent peribronchial marking (25 of 26, 96%), consolidation (22 of 26, 85%), and ground-glass opacities without consolidation (2 of 26, 8%). The involvement was usually bilateral (19 of 26, 73%) with the lower lung zone predominance (22 of 26, 85%). Atelectasis was observed in 12 (46%) and pleural effusion in 11 (42%) patients. CT (n = 6) scans showed peribronchovascular interstitial thickening (n = 6), ground-glass opacities (n = 5), centrilobular nodules (n = 4), consolidation (n = 3), mediastinal lymph node enlargement (n = 5), pleural effusion (n = 3), and pneumomediastinum (n = 3). Abnormal chest radiographs were uncommon in children with a swine-origin influenza A (H1N1) virus (S-OIV) infection. In children, H1N1 virus infection can be included in the differential diagnosis, when chest radiographs and CT scans show prominent peribronchial markings and ill-defined patchy consolidation with mediastinal lymph node enlargement, pleural effusion and pneumomediastinum

  5. Prevalence and risk factors for H1N1 and H3N2 influenza A virus infections in Minnesota turkey premises.

    Science.gov (United States)

    Corzo, Cesar A; Gramer, Marie; Lauer, Dale; Davies, Peter R

    2012-09-01

    Influenza virus infections can cause respiratory and systemic disease of variable severity and also result in economic losses for the turkey industry. Several subtypes of influenza can infect turkeys, causing diverse clinical signs. Influenza subtypes of swine origin have been diagnosed in turkey premises; however, it is not known how common these infections are nor the likely routes of transmission. We conducted a cross-sectional study to estimate the prevalence of influenza viruses and examine factors associated with infection on Minnesota turkey premises. Results from influenza diagnostic tests and turkey and pig premise location data were obtained from the Minnesota Poultry Testing Laboratory and the Minnesota Board of Animal Health, respectively, from January 2007 to September 2008. Diagnostic data from 356 premises were obtained, of which 17 premises tested positive for antibodies to influenza A virus by agar gel immunodiffusion assay and were confirmed as either H1N1 or H3N2 influenza viruses by hemagglutination and neuraminidase inhibition assays. Influenza infection status was associated with proximity to pig premises and flock size. The latter had a sparing effect on influenza status. This study suggests that H1N1 and H3N2 influenza virus infections of turkey premises in Minnesota are an uncommon event. The route of influenza virus transmission could not be determined; however, the findings suggest that airborne transmission should be considered in future studies.

  6. Prophylactic and therapeutic efficacy of avian antibodies against influenza virus H5N1 and H1N1 in mice.

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    Huan H Nguyen

    Full Text Available BACKGROUND: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1. METHODS AND FINDINGS: We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection. CONCLUSIONS: The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus

  7. Influenza A (H1N1) organising pneumonia.

    Science.gov (United States)

    Torrego, Alfons; Pajares, Virginia; Mola, Anna; Lerma, Enrique; Franquet, Tomás

    2010-04-27

    In November 2009, countries around the world reported confirmed cases of pandemic influenza H1N1, including over 6000 deaths. No peak in activity has been seen. The most common causes of death are pneumonia and acute respiratory distress syndrome. We report a case of a 55-year-old woman who presented with organising pneumonia associated with influenza A (H1N1) infection confirmed by transbronchial lung biopsy. Organising pneumonia should also be considered as a possible complication of influenza A (H1N1) infection, given that these patients can benefit from early diagnosis and appropriate specific management.

  8. Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

    Science.gov (United States)

    Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

    2009-08-06

    The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

  9. Chest X-ray findings in children with influenza A (H1N1) virus infection

    International Nuclear Information System (INIS)

    Zhou Min; Guo Wanliang; Wang Jian

    2011-01-01

    Objective: To assess the chest X-ray radiographic findings in children with influenza A (H1N1) virus infection. Methods: The chest X-ray radiographs in 67 children with influenza A (H1N1) virus infection were reviewed in this study. The chest radiographs were obtained 3-8 days after the onset of symptoms and for the follow-up. Results: The abnormalities were bilateral in 53 patients and unilateral in 7 patients. The predominant radiographic findings were bilateral patchy consolidation (n=42) with rapid confluence in 10 patients, lobular consolidation (n=7) with interstitial hyperplasia in 1 patient 3 month later, diffuse consolidation (n=11) with interstitial hyperplasia in all patients after 3 month. Conclusion: The predominant chest X-ray radiographic findings are bilateral patchy consolidation and diffuse consolidation with interstitial hyperplasia afterward. (authors)

  10. H1N1 influenza infection in children: Frequency, pattern, and outcome of chest radiographic abnormalities

    International Nuclear Information System (INIS)

    Yoo, S.-Y.; Kim, J.H.; Eo, H.; Jeon, T.Y.; Shin, K.E.; Shin, W.S.; Jung, H.N.; Kim, Y.-J.

    2011-01-01

    Aim: To describe the frequency, pattern, and outcome of chest radiographic abnormalities in children with H1N1 influenza infection. Materials and methods: Three hundred and fourteen paediatric patients with confirmed H1N1 influenza infection who underwent chest radiography at presentation at a single institution during the outbreak in 2009 were retrospectively reviewed. Abnormal chest radiographic findings related to acute infection were analysed in terms of frequency, pattern, and distribution. Medical records and follow-up radiographs were also reviewed to assess clinical features and outcomes. Results: Chest lesions suggesting acute infection were identified in 49 (16%) patients (mean age 8.2 years, range approximately 1.8-18.5 years). The most common finding was prominent peribronchial marking (71%), followed by air-space opacity (51%) with or without volume decrease, generalized hyperinflation (24%), and pleural effusion (20%). Other minor findings included pneumomediastinum (n = 2) and a nodule (n = 1). Distributions were bilateral (55%) or unilateral (45%) with frequent involvement of lower (78%), and middle (59%) lung zones. Thirty-nine patients (80%) were hospitalized and six (12%) required mechanical ventilation, followed by recovery. Thirty-one out of the 33 patients that underwent follow-up radiography showed marked resolution of all radiographic abnormalities. Conclusion: The frequency of a chest radiographic abnormality was found to be low in children with H1N1 influenza infection. Although typical radiographic findings of a viral lower respiratory infection were more common, unilateral involvement and air-space opacity were common, often with pleural effusion. Furthermore, pulmonary lesions showed near complete resolution on follow-up radiographs in the majority of patients.

  11. H1N1 influenza infection in children: Frequency, pattern, and outcome of chest radiographic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, S.-Y. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, J.H., E-mail: jhkate@skku.ed [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Eo, H.; Jeon, T.Y.; Shin, K.E.; Shin, W.S.; Jung, H.N. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Y.-J. [Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-04-15

    Aim: To describe the frequency, pattern, and outcome of chest radiographic abnormalities in children with H1N1 influenza infection. Materials and methods: Three hundred and fourteen paediatric patients with confirmed H1N1 influenza infection who underwent chest radiography at presentation at a single institution during the outbreak in 2009 were retrospectively reviewed. Abnormal chest radiographic findings related to acute infection were analysed in terms of frequency, pattern, and distribution. Medical records and follow-up radiographs were also reviewed to assess clinical features and outcomes. Results: Chest lesions suggesting acute infection were identified in 49 (16%) patients (mean age 8.2 years, range approximately 1.8-18.5 years). The most common finding was prominent peribronchial marking (71%), followed by air-space opacity (51%) with or without volume decrease, generalized hyperinflation (24%), and pleural effusion (20%). Other minor findings included pneumomediastinum (n = 2) and a nodule (n = 1). Distributions were bilateral (55%) or unilateral (45%) with frequent involvement of lower (78%), and middle (59%) lung zones. Thirty-nine patients (80%) were hospitalized and six (12%) required mechanical ventilation, followed by recovery. Thirty-one out of the 33 patients that underwent follow-up radiography showed marked resolution of all radiographic abnormalities. Conclusion: The frequency of a chest radiographic abnormality was found to be low in children with H1N1 influenza infection. Although typical radiographic findings of a viral lower respiratory infection were more common, unilateral involvement and air-space opacity were common, often with pleural effusion. Furthermore, pulmonary lesions showed near complete resolution on follow-up radiographs in the majority of patients.

  12. Predictors of H1N1 influenza in the emergency department: proposition for a modified H1N1 case definition.

    Science.gov (United States)

    Flick, H; Drescher, M; Prattes, J; Tovilo, K; Kessler, H H; Vander, K; Seeber, K; Palfner, M; Raggam, R B; Avian, A; Krause, R; Hoenigl, M

    2014-02-01

    Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate appropriate antiviral therapy and preventive measures. We analysed the differences in clinical presentation and laboratory parameters between emergency department patients with PCR-confirmed H1N1 influenza infection (n = 199) and those with PCR-negative influenza-like illness (ILI; n = 252). Cough, wheezing, leucopenia, eosinopenia and a lower C-reactive protein remained significant predictors of H1N1 influenza. Proposed combinations of clinical symptoms with simple laboratory parameters (e.g. reported or measured fever and either cough or leucocytes definitions that use clinical criteria alone. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  13. H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.

    Science.gov (United States)

    Khurana, Surender; Sasono, Pretty; Fox, Annette; Nguyen, Van Kinh; Le, Quynh Mai; Pham, Quang Thai; Nguyen, Tran Hien; Nguyen, Thanh Liem; Horby, Peter; Golding, Hana

    2011-12-01

    Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.

  14. Serosurveillance for pandemic influenza A (H1N1 2009 virus infection in domestic elephants, Thailand.

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    Weena Paungpin

    Full Text Available The present study conducted serosurveillance for the presence of antibody to pandemic influenza A (H1N1 2009 virus (H1N1pdm virus in archival serum samples collected between 2009 and 2013 from 317 domestic elephants living in 19 provinces situated in various parts of Thailand. To obtain the most accurate data, hemagglutination-inhibition (HI assay was employed as the screening test; and sera with HI antibody titers ≥20 were further confirmed by other methods, including cytopathic effect/hemagglutination based-microneutralization (microNT and Western blot (WB assays using H1N1pdm matrix 1 (M1 or hemagglutinin (HA recombinant protein as the test antigen. Conclusively, the appropriate assays using HI in conjunction with WB assays for HA antibody revealed an overall seropositive rate of 8.5% (27 of 317. The prevalence of antibody to H1N1pdm virus was 2% (4/172 in 2009, 32% (17/53 in 2010, 9% (2/22 in 2011, 12% (1/8 in 2012, and 5% (3/62 in 2013. Notably, these positive serum samples were collected from elephants living in 7 tourist provinces of Thailand. The highest seropositive rate was obtained from elephants in Phuket, a popular tourist beach city. Young elephants had higher seropositive rate than older elephants. The source of H1N1pdm viral infection in these elephants was not explored, but most likely came from close contact with the infected mahouts or from the infected tourists who engaged in activities such as elephant riding and feeding. Nevertheless, it could not be excluded that elephant-to-elephant transmission did occur.

  15. Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

    Science.gov (United States)

    Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

    2016-11-28

    H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

  16. Radiologic Review of an Outbreak of the Pandemic (H1N1) 2009 Virus Infection at a University Hospital in Seoul, Korea

    International Nuclear Information System (INIS)

    Choi, Seung Hee; Kang, Eun Young; Kim, Yoon Kyung; Woo, Ok Hee; Yong, Hwan Seok; Oh, Yu Whan; Kim, Jang Su

    2011-01-01

    To assess the frequency of radiologic abnormalities and investigate the radiologic findings of patients with a pandemic (H1N1) 2009 virus infection at a University hospital in Seoul, Korea. In November 2009, 9,427 patients were tested for pandemic (H1N1) 2009 virus and 3,849 (41%) were positive. Among them, only 338 (9%) underwent chest radiographs and 13 (0.3%) received chest CT. Two radiologists retrospectively reviewed all the radiologic images. Among the 338 patients, 287 (85%) were normal and 51 (15%) showed abnormalities. The frequency of abnormalities was significantly higher in children (41/212=19%) than in adults (10/126=8%) (p = 0.005). Of them, 42 (82%) patients had airspace pneumonia, whereas the remaining patients showed a bronchopneumonia pattern. Unilateral (82%) involvement was more common than bilateral (18%) involvement. Among patients who received chest CT, 12 (92%) showed abnormalities, with bilateral (67%) and random (75%) involvement being more common. Ground-glass opacity (67%) and centrilobular nodules (58%) were the more common CT findings. Only a small number of patients were critically ill enough to undergo further radiologic evaluation as a result of pandemic (H1N1) 2009 virus infection, and most patients had normal chest radiographs. Unilateral airspace pneumonia was the most common abnormality in patients infected with pandemic (H1N1) 2009 virus.

  17. Computed tomography findings in patients with H1N1 influenza A infection

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    Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Zanetti, Glaucia [Faculdade de Medicina de Petropolis (FMP), RJ (Brazil)

    2013-09-15

    The present study aimed to review high resolution computed tomography findings in patients with H1N1 influenza A infection. The most common tomographic findings include ground-glass opacities, areas of consolidation or a combination of both patterns. Some patients may also present bronchial wall thickening, airspace nodules, crazy-paving pattern, perilobular opacity, air trapping and findings related to organizing pneumonia. These abnormalities are frequently bilateral, with subpleural distribution. Despite their non specificity, it is important to recognize the main tomographic findings in patients affected by H1N1 virus in order to include this possibility in the differential diagnosis, characterize complications and contribute in the follow-up, particularly in cases of severe disease. (author)

  18. Computed tomography findings in patients with H1N1 influenza A infection

    International Nuclear Information System (INIS)

    Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson; Zanetti, Glaucia

    2013-01-01

    The present study aimed to review high resolution computed tomography findings in patients with H1N1 influenza A infection. The most common tomographic findings include ground-glass opacities, areas of consolidation or a combination of both patterns. Some patients may also present bronchial wall thickening, airspace nodules, crazy-paving pattern, perilobular opacity, air trapping and findings related to organizing pneumonia. These abnormalities are frequently bilateral, with subpleural distribution. Despite their non specificity, it is important to recognize the main tomographic findings in patients affected by H1N1 virus in order to include this possibility in the differential diagnosis, characterize complications and contribute in the follow-up, particularly in cases of severe disease. (author)

  19. Computer-aided assessment of pulmonary disease in novel swine-origin H1N1 influenza on CT

    Science.gov (United States)

    Yao, Jianhua; Dwyer, Andrew J.; Summers, Ronald M.; Mollura, Daniel J.

    2011-03-01

    The 2009 pandemic is a global outbreak of novel H1N1 influenza. Radiologic images can be used to assess the presence and severity of pulmonary infection. We develop a computer-aided assessment system to analyze the CT images from Swine-Origin Influenza A virus (S-OIV) novel H1N1 cases. The technique is based on the analysis of lung texture patterns and classification using a support vector machine (SVM). Pixel-wise tissue classification is computed from the SVM value. The method was validated on four H1N1 cases and ten normal cases. We demonstrated that the technique can detect regions of pulmonary abnormality in novel H1N1 patients and differentiate these regions from visually normal lung (area under the ROC curve is 0.993). This technique can also be applied to differentiate regions infected by different pulmonary diseases.

  20. Viremia associated with fatal outcomes in ferrets infected with avian H5N1 influenza virus.

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    Xue Wang

    Full Text Available Avian H5N1 influenza viruses cause severe disease and high mortality in infected humans. However, tissue tropism and underlying pathogenesis of H5N1 virus infection in humans needs further investigation. The objective of this work was to study viremia, tissue tropism and disease pathogenesis of H5N1 virus infection in the susceptible ferret animal model. To evaluate the relationship of morbidity and mortality with virus loads, we performed studies in ferrets infected with the H5N1 strain A/VN/1203/04 to assess clinical signs after infection and virus load in lung, brain, ileum, nasal turbinate, nasal wash, and blood. We observed that H5N1 infection in ferrets is characterized by high virus load in the brain and and low levels in the ileum using real-time PCR. In addition, viral RNA was frequently detected in blood one or two days before death and associated with symptoms of diarrhea. Our observations further substantiate pathogenicity of H5N1 and further indicate that viremia may be a bio-marker for fatal outcomes in H5N1 infection.

  1. Recognizing true H5N1 infections in humans during confirmed outbreaks.

    Science.gov (United States)

    Zaman, Mukhtiar; Gasimov, Viktor; Oner, Ahmet Faik; Dogan, Nazim; Adisasmito, Wiku; Coker, Richard; Bamgboye, Ebun L; Chan, Paul K S; Hanshaoworakul, Wanna; Lee, Nelson; Phommasack, Bounlay; Touch, Sok; Tsang, Owen; Swenson, Anna; Toovey, Stephen; Dreyer, Nancy Ann

    2014-02-13

    The goal of this study was to evaluate whether any characteristics that are evident at presentation for urgent medical attention could be used to differentiate cases of H5N1 in the absence of viral testing. Information about exposure to poultry, clinical signs and symptoms, treatments, and outcomes was abstracted from existing data in the global avian influenza registry (www.avianfluregistry.org) using standardized data collection tools for documented and possible cases of H5N1 infection who presented for medical attention between 2005-2011 during known H5N1 outbreaks in Azerbaijan, Indonesia, Pakistan and Turkey. Demography, exposure to poultry, and presenting symptoms were compared, with only the common symptoms of fever and headache presenting significantly more frequently in confirmed H5N1 cases than in possible cases. Reported exposure to  infected humans was also more common in confirmed cases. In contrast, unexplained respiratory illness, sore throat, excess sputum production, and rhinorrhea were more frequent in possible cases. Overall, oseltamivir treatment showed a survival benefit, with the greatest benefit shown in H5N1 cases who were treated within two days of symptom onset (51% reduction in case fatality). Since prompt treatment with antivirals conferred a strong survival benefit for H5N1 cases, presumptive antiviral treatment should be considered for all possible cases presenting during an outbreak of H5N1 as a potentially life-saving measure.

  2. Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus.

    Science.gov (United States)

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice N; Wei, Chih-Jen; Nabel, Gary J; Subbarao, Kanta

    2012-08-01

    Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic.

  3. Predicting Avian Influenza Co-Infection with H5N1 and H9N2 in Northern Egypt

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    Sean G. Young

    2016-09-01

    Full Text Available Human outbreaks with avian influenza have been, so far, constrained by poor viral adaptation to non-avian hosts. This could be overcome via co-infection, whereby two strains share genetic material, allowing new hybrid strains to emerge. Identifying areas where co-infection is most likely can help target spaces for increased surveillance. Ecological niche modeling using remotely-sensed data can be used for this purpose. H5N1 and H9N2 influenza subtypes are endemic in Egyptian poultry. From 2006 to 2015, over 20,000 poultry and wild birds were tested at farms and live bird markets. Using ecological niche modeling we identified environmental, behavioral, and population characteristics of H5N1 and H9N2 niches within Egypt. Niches differed markedly by subtype. The subtype niches were combined to model co-infection potential with known occurrences used for validation. The distance to live bird markets was a strong predictor of co-infection. Using only single-subtype influenza outbreaks and publicly available ecological data, we identified areas of co-infection potential with high accuracy (area under the receiver operating characteristic (ROC curve (AUC 0.991.

  4. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population

    Science.gov (United States)

    García-Ramírez, Román Alejandro; Ramírez-Venegas, Alejandra; Quintana-Carrillo, Roger; Camarena, Ángel Eduardo; Falfán-Valencia, Ramcés; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection. Methods 145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100. Results The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05–11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p  =  0.007) levels. Conclusions The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were

  5. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1 Virus Infection in the Mexican Population.

    Directory of Open Access Journals (Sweden)

    Román Alejandro García-Ramírez

    Full Text Available Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1 virus infections. Most patients infected with the influenza A (H1N1 pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α. We propose that single-nucleotide polymorphisms (SNPs in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1 pdm09 virus infection.145 patients with influenza A (H1N1 (pA/H1N1, 133 patients with influenza-like illness (ILI, and 360 asymptomatic healthy contacts (AHCs were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8 using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4 were measured on a Luminex 100.The IL6 rs1818879 (GA heterozygous genotype was associated with severe influenza A (H1N1 virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05-11.56, and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively. Genetic susceptibility was determined (pA/H1N1 vs. AHC: the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9, and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89. Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007. Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001 and IL-6 (p  =  0.007 levels.The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were associated with influenza A (H1N1 virus

  6. Avian Influenza A (H5N1)

    Centers for Disease Control (CDC) Podcasts

    In this podcast, CDC's Dr. Tim Uyeki discusses H5N1, a subtype of influenza A virus. This highly pathogenic H5N1 virus doesn't usually infect people, although some rare infections with H5N1 viruses have occurred in humans. We need to use a comprehensive strategy to prevent the spread of H5N1 virus among birds, including having human health and animal health work closely together.

  7. H1N1, H3N2 et B à Abidjan, Côte d'Ivoire

    African Journals Online (AJOL)

    English Title: Comparative analysis of the epidemiological and clinical profiles of influenza infection due to 2009 pH1N1, H1N1, H3N2 and B viruses in Abidjan, Cote d'Ivoire. English Abstract. Influenza can have various epidemiological and clinical characteristics. This study compares the epidemio-clinical profiles of ...

  8. Influenza A (H1N1) pneumonia: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Amorim, Viviane Brandao; Rodrigues, Rosana Souza; Barreto, Miriam Menna; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Zanetti, Glaucia [Escola de Medicina de Petropolis, RJ (Brazil); Hochhegger, Bruno [Santa Casa de Misericordia de Porto Alegre, RS (Brazil)

    2013-11-01

    Objective: to describe aspects found on HRCT scans of the chest in patients infected with the influenza A (H1N1) virus. Methods: we retrospectively analyzed the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection, confirmed through laboratory tests, between July and September of 2009. The HRCT scans were interpreted by two thoracic radiologists independently, and in case of disagreement, the decisions were made by consensus. Results: the most common HRCT findings were ground-glass opacities (85%), consolidation (64%), or a combination of ground-glass opacities and consolidation (58%). Other findings were airspace nodules (25%), bronchial wall thickening (25%), interlobular septal thickening (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping (3%). The findings were frequently bilateral (89%), with a random distribution (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy was identified. Conclusions: the most common findings were ground-glass opacities and consolidations, or a combination of both. Involvement was commonly bilateral with no axial or cranio caudal predominance in the distribution. Although the major tomographic findings in H1N1 infection are nonspecific, it is important to recognize such findings in order to include infection with the H1N1 virus in the differential diagnosis of respiratory symptoms. (author)

  9. Infection by rhinovirus: similarity of clinical signs included in the case definition of influenza IAn/H1N1.

    Science.gov (United States)

    de Oña Navarro, Maria; Melón García, Santiago; Alvarez-Argüelles, Marta; Fernández-Verdugo, Ana; Boga Riveiro, Jose Antonio

    2012-08-01

    Although new influenza virus (IAn/H1N1) infections are mild and indistinguishable from any other seasonal influenza virus infections, there are few data on comparisons of the clinical features of infection with (IAn/H1N1) and with other respiratory viruses. The incidence, clinical aspects and temporal distribution of those respiratory viruses circulating during flu pandemic period were studied. Respiratory samples from patients with acute influenza-like symptoms were collected from May 2009 to December 2009. Respiratory viruses were detected by conventional culture methods and genome amplification techniques. Although IAn/H1N1 was the virus most frequently detected, several other respiratory viruses co-circulated with IAn/H1N1 during the pandemic period, especially rhinovirus. The similarity between clinical signs included in the clinical case definition for influenza and those caused by other respiratory viruses, particularly rhinovirus, suggest that a high percentage of viral infections were clinically diagnosed as case of influenza. Our study offers useful information to face future pandemics caused by influenza virus, indicating that differential diagnoses are required in order to not overestimate the importance of the pandemic. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  10. A Meta-Analysis of the Prevalence of Influenza A H5N1 and H7N9 Infection in Birds.

    Science.gov (United States)

    Bui, C; Rahman, B; Heywood, A E; MacIntyre, C R

    2017-06-01

    Despite a much higher rate of human influenza A (H7N9) infection compared to influenza A (H5N1), and the assumption that birds are the source of human infection, detection rates of H7N9 in birds are lower than those of H5N1. This raises a question about the role of birds in the spread and transmission of H7N9 to humans. We conducted a meta-analysis of overall prevalence of H5N1 and H7N9 in different bird populations (domestic poultry, wild birds) and different environments (live bird markets, commercial poultry farms, wild habitats). The electronic database, Scopus, was searched for published papers, and Google was searched for country surveillance reports. A random effect meta-analysis model was used to produce pooled estimates of the prevalence of H5N1 and H7N9 for various subcategories. A random effects logistic regression model was used to compare prevalence rates between H5N1 and H7N9. Both viruses have low prevalence across all bird populations. Significant differences in prevalence rates were observed in domestic birds, farm settings, for pathogen and antibody testing, and during routine surveillance. Random effects logistic regression analyses show that among domestic birds, the prevalence of H5N1 is 47.48 (95% CI: 17.15-133.13, P bird outbreaks), the prevalence of H5N1 is still higher than H7N9 with an OR of 43.02 (95% CI: 16.60-111.53, P birds are postulated to be the source. Much lower rates of H7N9 in birds compared to H5N1 raise doubts about birds as the sole source of high rates of human H7N9 infection. Other sources of transmission of H7N9 need to be considered and explored. © 2016 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

  11. Characteristics and outcome of critically ill patients with 2009 H1N1 influenza infection in Syria

    Science.gov (United States)

    Alsadat, Reem; Dakak, Abdulrahman; Mazlooms, Mouna; Ghadhban, Ghasan; Fattoom, Shadi; Betelmal, Ibrahim; Abouchala, Nabil; Kherallah, Mazen

    2012-01-01

    Objectives: To describe the epidemiologic characteristics, clinical features, and outcome of severe cases of 2009 H1N1 influenza A infections who were admitted to the intensive care units (ICUs) in Damascus, Syria. Materials and Methods: Retrospectively, we collected clinical data on all patients who were admitted to the ICU with confirmed or suspected diagnosis of severe 2009 H1N1 influenza A with respiratory failure at 4 major tertiary care hospitals in Damascus, Syria. Acute Physiology and Chronic Health Evaluation (APACHE) II system was used to assess the severity of illness within the first 24 h after admission. The outcome was overall hospital mortality. Results: Eighty patients were admitted to the ICU with severe 2009 H1N1 infection. The mean age was 40.7 years; 69.8% of patients had ≥1 of the risk factors: asthmatics 20%, obesity 23.8%, and pregnancy 5%; and 72.5% had acute lung injury or adult respiratory distress syndrome, 12.5% had viral pneumonia, 42.5% had secondary bacterial pneumonia, and 15% had exacerbation of airflow disease. Mechanical ventilation was required in 73.7% of cases. The mean hospital length of stay was 11.7 days (median 8 days, range 0–77 days, IQR: 5–14 days). The overall mortality rate was 51% for a mean APACHE II score of 15.2 with a predicted mortality of 21% (standardized mortality ratio of 2.4, 95% confidence interval: 1.7–3.2, P value < 0.001). Conclusion: Critically ill patients with severe 2009 H1N1 infection in this limited resource country had a much higher mortality rate than the predicted APACHE II mortality rate or when compared with the reported mortality rates for severe cases in other countries during 2009 H1N1 pandemic. PMID:23210019

  12. The early days of pandemic (H1N1 2009 virus infection in the central region of Portugal

    Directory of Open Access Journals (Sweden)

    V. Duque

    2010-11-01

    Full Text Available Background: The first case of pandemic (H1N1 2009 virus infection was diagnosed in the central region of Portugal on June 16, 2009, in a woman infected in Canada. Methods: The aim of our study was, first to characterize the clinical and epidemiologic aspects of all the patients with clinical manifestations included in the definition of a case for investigation with samples submitted to diagnosis of the pandemic (H1N1 2009 virus infection, in the central region of Portugal; second, to assess the precision of the case definition of case for investigation considered in the study according to the presence or the absence of fever at the moment of clinical observation. We reviewed the medical records of all the patients presenting with Influenza like-illness classified as a case for investigation and the first cases of patients infected with the new pandemic (H1N1 2009 virus, diagnosed in the central region of Portugal during the pandemic period between June and August, 2009, were analyzed. Real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR testing was used to confirm the pandemic (H1N1 2009 virus infection. Data collection was performed using a standardized paper format in agreement with the General Health Directorate. Results and discussion: Pandemic (H1N1 2009 virus infection was confirmed in 255 patients. Overall, median age was 23 years and 42.7% were included in the category of 20 to 29 years. Confirmed infection in patients with less than 2 years or greater than 50 years was a rare event. The first cases were imported from Europe, namely France, Spain and England. In a second phase, pandemic (H1N1 2009 virus infection was acquired in the south of Portugal (Algarve. The incidence rate for pandemic (H1N1 2009 virus infection was 10.7 per 100,000 persons and was different according to the district. It was higher in the district of Coimbra and Guarda where the main roads are connecting to Europe. The median calculated incubation

  13. In vitro reassortment between endemic H1N2 and 2009 H1N1 pandemic swine influenza viruses generates attenuated viruses.

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    Ben M Hause

    Full Text Available The pandemic H1N1 (pH1N1 influenza virus was first reported in humans in the spring of 2009 and soon thereafter was identified in numerous species, including swine. Reassortant viruses, presumably arising from the co-infection of pH1N1 and endemic swine influenza virus (SIV, were subsequently identified from diagnostic samples collected from swine. In this study, co-infection of swine testicle (ST cells with swine-derived endemic H1N2 (MN745 and pH1N1 (MN432 yielded two reassortant H1N2 viruses (R1 and R2, both possessing a matrix gene derived from pH1N1. In ST cells, the reassortant viruses had growth kinetics similar to the parental H1N2 virus and reached titers approximately 2 log(10 TCID(50/mL higher than the pH1N1 virus, while in A549 cells these viruses had similar growth kinetics. Intranasal challenge of pigs with H1N2, pH1N1, R1 or R2 found that all viruses were capable of infecting and transmitting between direct contact pigs as measured by real time reverse transcription PCR of nasal swabs. Lung samples were also PCR-positive for all challenge groups and influenza-associated microscopic lesions were detected by histology. Interestingly, infectious virus was detected in lung samples for pigs challenged with the parental H1N2 and pH1N1 at levels significantly higher than either reassortant virus despite similar levels of viral RNA. Results of our experiment suggested that the reassortant viruses generated through in vitro cell culture system were attenuated without gaining any selective growth advantage in pigs over the parental lineages. Thus, reassortant influenza viruses described in this study may provide a good system to study genetic basis of the attenuation and its mechanism.

  14. Manifestations of infection by the novel influenza A (H1N1) virus at chest computed tomography

    International Nuclear Information System (INIS)

    Verrastro, Carlos Gustavo Yuji; D'Ippolito, Giuseppe

    2009-01-01

    Objective: the objective of this study was to describe chest computed tomography findings in confirmed cases of infection by the novel influenza A (H1N1) virus. Materials and methods: computed tomography studies of nine patients with laboratory-confirmed infection by the novel influenza A (H1N1) virus were consensually evaluated by three observers. The sample of the present study included five male and four female patients with ages ranging from 14 to 64 years (mean, 40 years). Four of the patients were previously healthy, four were kidney transplant recipients and one was pregnant at the time of diagnosis. Presence, extent and distribution of the following findings were evaluated: ground-glass opacities; centrilobular nodules; consolidation; interlobular septa thickening; pleural effusion; lymphadenopathy. Results: The most frequent findings were ground-glass opacities, centrilobular nodules and consolidations, present in nine (100%), five (55%) and four (44%) of cases, respectively. Pleural effusions and lymphadenopathy were less common findings, occurring in only two (22%) of the cases. Conclusion: ground-glass opacities, centrilobular nodules and consolidation were the most frequent findings in cases of infection by the novel influenza A (H1N1) virus. These changes are not typical or unique to this agent and may also occur in other viral or bacterial infections. (author)

  15. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

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    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  16. Exposure to a low pathogenic A/H7N2 virus in chickens protects against highly pathogenic A/H7N1 virus but not against subsequent infection with A/H5N1.

    Directory of Open Access Journals (Sweden)

    Júlia Vergara-Alert

    Full Text Available Recent evidences have demonstrated that the presence of low pathogenic avian influenza viruses (LPAIV may play an important role in host ecology and transmission of avian influenza viruses (AIV. While some authors have clearly demonstrated that LPAIV can mutate to render highly pathogenic avian influenza viruses (HPAIV, others have shown that their presence could provide the host with enough immunological memory to resist re-infections with HPAIV. In order to experimentally study the role of pre-existing host immunity, chickens previously infected with H7N2 LPAIV were subsequently challenged with H7N1 HPAIV. Pre-infection of chickens with H7N2 LAPIV conferred protection against the lethal challenge with H7N1 HPAIV, dramatically reducing the viral shedding, the clinical signs and the pathological outcome. Correlating with the protection afforded, sera from chickens primed with H7N2 LPAIV reacted with the H7-AIV subtype in hemagglutination inhibition assay and specifically with the N2-neuraminidase antigen. Conversely, subsequent exposure to H5N1 HPAIV resulted in a two days-delay on the onset of disease but all chickens died by 7 days post-challenge. Lack of protection correlated with the absence of H5-hemagglutining inhibitory antibodies prior to H5N1 HPAIV challenge. Our data suggest that in naturally occurring outbreaks of HPAIV, birds with pre-existing immunity to LPAIV could survive lethal infections with HA-homologous HPAIV but not subsequent re-infections with HA-heterologous HPAIV. These results could be useful to better understand the dynamics of AIV in chickens and might help in future vaccine formulations.

  17. Avian Influenza A (H5N1)

    Centers for Disease Control (CDC) Podcasts

    2009-05-27

    In this podcast, CDC's Dr. Tim Uyeki discusses H5N1, a subtype of influenza A virus. This highly pathogenic H5N1 virus doesn't usually infect people, although some rare infections with H5N1 viruses have occurred in humans. We need to use a comprehensive strategy to prevent the spread of H5N1 virus among birds, including having human health and animal health work closely together.  Created: 5/27/2009 by Emerging Infectious Diseases.   Date Released: 5/27/2009.

  18. Avian influenza viruses that cause highly virulent infections in humans exhibit distinct replicative properties in contrast to human H1N1 viruses

    Science.gov (United States)

    Simon, Philippe F.; de La Vega, Marc-Antoine; Paradis, Éric; Mendoza, Emelissa; Coombs, Kevin M.; Kobasa, Darwyn; Beauchemin, Catherine A. A.

    2016-04-01

    Avian influenza viruses present an emerging epidemiological concern as some strains of H5N1 avian influenza can cause severe infections in humans with lethality rates of up to 60%. These have been in circulation since 1997 and recently a novel H7N9-subtyped virus has been causing epizootics in China with lethality rates around 20%. To better understand the replication kinetics of these viruses, we combined several extensive viral kinetics experiments with mathematical modelling of in vitro infections in human A549 cells. We extracted fundamental replication parameters revealing that, while both the H5N1 and H7N9 viruses replicate faster and to higher titers than two low-pathogenicity H1N1 strains, they accomplish this via different mechanisms. While the H7N9 virions exhibit a faster rate of infection, the H5N1 virions are produced at a higher rate. Of the two H1N1 strains studied, the 2009 pandemic H1N1 strain exhibits the longest eclipse phase, possibly indicative of a less effective neuraminidase activity, but causes infection more rapidly than the seasonal strain. This explains, in part, the pandemic strain’s generally slower growth kinetics and permissiveness to accept mutations causing neuraminidase inhibitor resistance without significant loss in fitness. Our results highlight differential growth properties of H1N1, H5N1 and H7N9 influenza viruses.

  19. Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark.

    Science.gov (United States)

    Trebbien, Ramona; Bragstad, Karoline; Larsen, Lars Erik; Nielsen, Jens; Bøtner, Anette; Heegaard, Peter M H; Fomsgaard, Anders; Viuff, Birgitte; Hjulsager, Charlotte Kristiane

    2013-09-18

    The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically and the infection dynamics compared to an "avian-like" H1N1 virus by an experimental infection study. Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an "avian-like" H1N1 virus, respectively, followed by inoculation with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European "avian-like" H1-gene and a European "swine-like" N2-gene, thus being genetically distinct from most H1N2 viruses circulating in Europe, but similar to viruses reported in 2009/2010 in Sweden and Italy. Sequence analyses of the internal genes revealed that the reassortment probably arose between circulating Danish "avian-like" H1N1 and H3N2 SIVs. Infected pigs developed cross-reactive antibodies, and increased levels of acute phase proteins after inoculations. Pigs inoculated with H1N2 exhibited nasal virus excretion for seven days, peaking day 1 after inoculation two days earlier than H1N1 infected pigs and at a six times higher level. The difference, however, was not statistically significant. Pigs euthanized on day 4 after inoculation, had a high virus load in all lung lobes. After the second inoculation, the nasal virus excretion was minimal. There were no clinical sign except elevated body temperature under the experimental conditions. The "avian-like" H1N2 subtype, which has been established in the Danish pig population at least since 2003, is a reassortant between circulating swine "avian-like" H1N1 and H3N2. The Danish

  20. Treatment and Prevention of Pandemic H1N1 Influenza.

    Science.gov (United States)

    Rewar, Suresh; Mirdha, Dashrath; Rewar, Prahlad

    2015-01-01

    Swine influenza is a respiratory infection common to pigs worldwide caused by type A influenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. The Centers for Disease Control and Prevention recommends use of oseltamivir (Tamiflu, Genentech) or zanamivir (Relenza, GlaxoSmithKline). Prevention of swine influenza has 3 components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans. Because of limited treatment options, high risk for secondary infection, and frequent need for intensive care of individuals with H1N1 pneumonia, environmental control, including vaccination of high-risk populations and public education are critical to control of swine influenza out breaks. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Identification and Epidemiology of Severe Respiratory Disease due to Novel Swine-Origin Influenza A (H1N1 Virus Infection in Alberta

    Directory of Open Access Journals (Sweden)

    George Zahariadis

    2010-01-01

    Full Text Available BACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1 strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1 in Canada.

  2. Subclinical avian influenza A(H5N1) virus infection in human, Vietnam

    NARCIS (Netherlands)

    Le, Mai Quynh; Horby, Peter; Fox, Annette; Nguyen, Hien Tran; Le Nguyen, Hang Khanh; Hoang, Phuong Mai Vu; Nguyen, Khanh Cong; de Jong, Menno D.; Jeeninga, Rienk E.; Rogier van Doorn, H.; Farrar, Jeremy; Wertheim, Heiman F. L.

    2013-01-01

    Laboratory-confirmed cases of subclinical infection with avian influenza A(H5N1) virus in humans are rare, and the true number of these cases is unknown. We describe the identification of a laboratory-confirmed subclinical case in a woman during an influenza A(H5N1) contact investigation in northern

  3. Acute immune thrombocytopenic purpura in an adolescent with 2009 novel H1N1 influenza A virus infection

    Directory of Open Access Journals (Sweden)

    Chun-Yi Lee

    2011-09-01

    Full Text Available Although both leukopenia and thrombocytopenia are not uncommon hematological findings among patients with novel 2009 H1N1 influenza virus infection, immune thrombocytopenic purpura has rarely been shown to be associated with this novel influenza A infection. Here, we describe a previously healthy adolescent who presented with fever, influenza-like symptoms and acute onset of generalized petechiae and active oral mucosa bleeding on the third day of his illness. Severe leukopenia and thrombocytopenia were found. There was neither malignancy nor blast cells found by bone marrow aspiration. Real-time reverse transcriptase polymerase chain reaction was positive for novel 2009 H1N1 influenza infection. Novel influenza-associated atypical immune thrombocytopenic purpura was diagnosed. The patient recovered uneventfully after oseltamivir and methylprednisolone therapy.

  4. Highly (H5N1 and low (H7N2 pathogenic avian influenza virus infection in falcons via nasochoanal route and ingestion of experimentally infected prey.

    Directory of Open Access Journals (Sweden)

    Kateri Bertran

    Full Text Available An experimental infection with highly pathogenic avian influenza (HPAI and low pathogenic avian influenza (LPAI viruses was carried out on falcons in order to examine the effects of these viruses in terms of pathogenesis, viral distribution in tissues and viral shedding. The distribution pattern of influenza virus receptors was also assessed. Captive-reared gyr-saker (Falco rusticolus x Falco cherrug hybrid falcons were challenged with a HPAI H5N1 virus (A/Great crested grebe/Basque Country/06.03249/2006 or a LPAI H7N2 virus (A/Anas plathyrhynchos/Spain/1877/2009, both via the nasochoanal route and by ingestion of previously infected specific pathogen free chicks. Infected falcons exhibited similar infection dynamics despite the different routes of exposure, demonstrating the effectiveness of in vivo feeding route. H5N1 infected falcons died, or were euthanized, between 5-7 days post-infection (dpi after showing acute severe neurological signs. Presence of viral antigen in several tissues was confirmed by immunohistochemistry and real time RT-PCR (RRT-PCR, which were generally associated with significant microscopical lesions, mostly in the brain. Neither clinical signs, nor histopathological findings were observed in any of the H7N2 LPAI infected falcons, although all of them had seroconverted by 11 dpi. Avian receptors were strongly present in the upper respiratory tract of the falcons, in accordance with the consistent oral viral shedding detected by RRT-PCR in both H5N1 HPAI and H7N2 LPAI infected falcons. The present study demonstrates that gyr-saker hybrid falcons are highly susceptible to H5N1 HPAI virus infection, as previously observed, and that they may play a major role in the spreading of both HPAI and LPAI viruses. For the first time in raptors, natural infection by feeding on infected prey was successfully reproduced. The use of avian prey species in falconry husbandry and wildlife rehabilitation facilities could put valuable birds

  5. Highly (H5N1) and low (H7N2) pathogenic avian influenza virus infection in falcons via nasochoanal route and ingestion of experimentally infected prey.

    Science.gov (United States)

    Bertran, Kateri; Busquets, Núria; Abad, Francesc Xavier; García de la Fuente, Jorge; Solanes, David; Cordón, Iván; Costa, Taiana; Dolz, Roser; Majó, Natàlia

    2012-01-01

    An experimental infection with highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) viruses was carried out on falcons in order to examine the effects of these viruses in terms of pathogenesis, viral distribution in tissues and viral shedding. The distribution pattern of influenza virus receptors was also assessed. Captive-reared gyr-saker (Falco rusticolus x Falco cherrug) hybrid falcons were challenged with a HPAI H5N1 virus (A/Great crested grebe/Basque Country/06.03249/2006) or a LPAI H7N2 virus (A/Anas plathyrhynchos/Spain/1877/2009), both via the nasochoanal route and by ingestion of previously infected specific pathogen free chicks. Infected falcons exhibited similar infection dynamics despite the different routes of exposure, demonstrating the effectiveness of in vivo feeding route. H5N1 infected falcons died, or were euthanized, between 5-7 days post-infection (dpi) after showing acute severe neurological signs. Presence of viral antigen in several tissues was confirmed by immunohistochemistry and real time RT-PCR (RRT-PCR), which were generally associated with significant microscopical lesions, mostly in the brain. Neither clinical signs, nor histopathological findings were observed in any of the H7N2 LPAI infected falcons, although all of them had seroconverted by 11 dpi. Avian receptors were strongly present in the upper respiratory tract of the falcons, in accordance with the consistent oral viral shedding detected by RRT-PCR in both H5N1 HPAI and H7N2 LPAI infected falcons. The present study demonstrates that gyr-saker hybrid falcons are highly susceptible to H5N1 HPAI virus infection, as previously observed, and that they may play a major role in the spreading of both HPAI and LPAI viruses. For the first time in raptors, natural infection by feeding on infected prey was successfully reproduced. The use of avian prey species in falconry husbandry and wildlife rehabilitation facilities could put valuable birds of prey and

  6. Chest Radiographic Findings of Novel Swine-Origin Influenza A (H1N1) Virus Infection in Children

    Energy Technology Data Exchange (ETDEWEB)

    Bae, So Young; Hong, Eun Sook; Paik, Sang Hyun; Park, Seong Jin; Cha, Jang Gyu; Lee, Hae Kyung [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Jang, Yun Woo [Dept. of Radiology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2011-06-15

    To analyze chest radiographic findings in children infected with laboratory confirmed novel swine-origin influenza A (H1N1) virus. Three hundred seventy-two out of 2,014 children with laboratory confirmed H1N1 infection and who also underwent a chest radiograph from September to November 2009 were enrolled in this study. Patients were divided into in-patients, out-patients, and patients with co-infections and further subdivided into with underlying disease and without underlying disease as well as age (<2 years old, 2-5 years, 5-10 years, 10-18 years old). The initial radiographs were evaluated for radiographic findings and the anatomic distribution of abnormalities. The initial radiographs were abnormal in 154 (41.39%) patients. The predominant radiographic findings were peribronchial wall opacity found in 85 (22.84%) patients and hyperinflation observed in 69 (18.54%) patients. Further, 75 (71.42%) patients exhibited central predominance and the right lower lung zone was also commonly involved. There were statistically significant differences in the radiological findings between in-patient and out-patient groups. However, there were no significant differences in the radiographic findings between in-patients and the co-infection group with respect the presence of underlying disease and age. Initial radiographs of children with laboratory confirmed H1N1 virus were abnormal in 41.39% of cases. The common radiographic findings included peribronchial opacities, hyperinflation, lower lung zonal distribution, and central predominance

  7. Recurrent Spontaneous Pneumothorax during the Recovery Phase of ARDS Due to H1N1 Infection

    Directory of Open Access Journals (Sweden)

    Canan Bor

    2013-03-01

    Full Text Available The pregnant patients are prone to influenza A (H1N1 virus infection, which may rapidly progress to lower respiratory tract infection and subsequent respiratory failure and acute respiratory distress syndrome (ARDS. Pneumothorax might develop in ARDS under mechanical ventilation. But post-ARDS pneumothorax in spontaneously breathing patient has not been reported in the literature. We report a 31-year old pregnant woman infected with influenza A (H1N1 virus and progressed to ARDS. Mechanical ventilation with high PEEP improved patient's gas exchange parameters within 3 weeks. However spontaneous pneumothorax was developed one week after she weaned off the ventilator. After successful drainage therapy, the patient was discharged. However she re-admitted to the hospital because of a recurrent pneumothorax one week later. She was discharged in good health after being treated with negative continuous pleural aspiration for 10 days. Influenza might cause severe pulmonary infection and death. In addition to diffuse alveolar damage, sub-pleural and intrapulmonary air cysts might occur in influenza-related ARDS and may lead to spontaneous pneumothorax. This complication should always be considered during the recovery period of ARDS and a long-term close follow-up is necessary.

  8. Influenza A H5N1 and HIV co-infection: case report

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    Simmons Cameron

    2010-06-01

    Full Text Available Abstract Background The role of adaptive immunity in severe influenza is poorly understood. The occurrence of influenza A/H5N1 in a patient with HIV provided a rare opportunity to investigate this. Case Presentation A 30-year-old male was admitted on day 4 of influenza-like-illness with tachycardia, tachypnea, hypoxemia and bilateral pulmonary infiltrates. Influenza A/H5N1 and HIV tests were positive and the patient was treated with Oseltamivir and broad-spectrum antibiotics. Initially his condition improved coinciding with virus clearance by day 6. He clinically deteriorated as of day 10 with fever recrudescence and increasing neutrophil counts and died on day 16. His admission CD4 count was 100/μl and decreased until virus was cleared. CD8 T cells shifted to a CD27+CD28- phenotype. Plasma chemokine and cytokine levels were similar to those found previously in fatal H5N1. Conclusions The course of H5N1 infection was not notably different from other cases. Virus was cleared despite profound CD4 T cell depletion and aberrant CD8 T cell activation but this may have increased susceptibility to a fatal secondary infection.

  9. Clinical Profile of Suspected and Confirmed H1N1 Influenza Infection in Patients admitted at a Tertiary Care Teaching Hospital

    Directory of Open Access Journals (Sweden)

    Basavaraju Jayadeva

    2015-11-01

    Full Text Available Introduction: This study aimed to evaluate the clinical profile and outcomes of adult patients screened and diagnosed with H1N1 influenza infection at a tertiary care hospital in India. Materials and Methods: This retrospective  study was conducted on all adult patients suspected of H1N1 influenza admitted at a teaching hospital during the epidemic period of January-March 2015. Patients were screened and classified into three categories of A, B, and C based on international guidelines. Home confinement was recommended for patients in category A, and subjects in category B received treatment with Oseltamivir capsules. In addition, patients in category C received inpatient treatment with oseltamivir capsules. Results: In total, 695 patients were screened for H1N1 influenza infection during the epidemic, out of whom 380 patients (54.6% were in category A, 264 (37.9% were in category B, and 51 (7.3% were in category C. Throat swabs were collected and examined for 192 ( 27.6% patients, and 59 ( 8.4% cases were positive for H1N1 infection. Conclusion: According to the results of this study, close vigilance over the symptoms of patients infected with H1N1 influenza is more important than treatment and screening of suspicious cases during the epidemics of this infection. This is a retrospective cross sectional study. Hence, there were no comparative controls. The limitation of this study is,  thus the lack of control.

  10. Productive infection of human skeletal muscle cells by pandemic and seasonal influenza A(H1N1 viruses.

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    Marion Desdouits

    Full Text Available Besides the classical respiratory and systemic symptoms, unusual complications of influenza A infection in humans involve the skeletal muscles. Numerous cases of acute myopathy and/or rhabdomyolysis have been reported, particularly following the outbreak of pandemic influenza A(H1N1 in 2009. The pathogenesis of these influenza-associated myopathies (IAM remains unkown, although the direct infection of muscle cells is suspected. Here, we studied the susceptibility of cultured human primary muscle cells to a 2009 pandemic and a 2008 seasonal influenza A(H1N1 isolate. Using cells from different donors, we found that differentiated muscle cells (i. e. myotubes were highly susceptible to infection by both influenza A(H1N1 isolates, whereas undifferentiated cells (i. e. myoblasts were partially resistant. The receptors for influenza viruses, α2-6 and α2-3 linked sialic acids, were detected on the surface of myotubes and myoblasts. Time line of viral nucleoprotein (NP expression and nuclear export showed that the first steps of the viral replication cycle could take place in muscle cells. Infected myotubes and myoblasts exhibited budding virions and nuclear inclusions as observed by transmission electron microscopy and correlative light and electron microscopy. Myotubes, but not myoblasts, yielded infectious virus progeny that could further infect naive muscle cells after proteolytic treatment. Infection led to a cytopathic effect with the lysis of muscle cells, as characterized by the release of lactate dehydrogenase. The secretion of proinflammatory cytokines by muscle cells was not affected following infection. Our results are compatible with the hypothesis of a direct muscle infection causing rhabdomyolysis in IAM patients.

  11. Genetic and biological characterisation of an avian-like H1N2 swine influenza virus generated by reassortment of circulating avian-like H1N1 and H3N2 subtypes in Denmark

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Bragstad, Karoline; Larsen, Lars Erik

    2013-01-01

    BACKGROUND: The influenza A virus subtypes H1N1, H1N2 and H3N2 are the most prevalent subtypes in swine. In 2003, a reassorted H1N2 swine influenza virus (SIV) subtype appeared and became prevalent in Denmark. In the present study, the reassortant H1N2 subtype was characterised genetically...... and the infection dynamics compared to an “avian-like” H1N1 virus by an experimental infection study. METHODS: Sequence analyses were performed of the H1N2 virus. Two groups of pigs were inoculated with the reassortant H1N2 virus and an “avian-like” H1N1 virus, respectively, followed by inoculation...... with the opposite subtype four weeks later. Measurements of HI antibodies and acute phase proteins were performed. Nasal virus excretion and virus load in lungs were determined by real-time RT-PCR. RESULTS: The phylogenetic analysis revealed that the reassorted H1N2 virus contained a European “avian-like” H1-gene...

  12. Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009--associated encephalopathy in children.

    Science.gov (United States)

    Ishida, Yu; Kawashima, Hisashi; Morichi, Shinichiro; Yamanaka, Gaku; Okumura, Akihisa; Nakagawa, Satoshi; Morishima, Tsuneo

    2015-02-01

    Pandemic influenza A (H1N1) 2009 has been shown to be associated more with neurological complications than the seasonal influenza virus. In this study, we focused on the clinical usefulness of magnetic resonance imaging (MRI) in the acute phase of influenza A (H1N1) 2009-associated encephalopathy. A questionnaire was distributed to pediatric and general hospitals in Japan that treat children with encephalopathy. We conducted a questionnaire-based study involving the collection of information regarding 207 patients with encephalopathy. Brain MRI was performed in 97 of these 207 patients in the age group of 9 months to 15 years (mean, 7.5 years) within 48 hours after the development of encephalopathy symptoms. Sixty-six patients (68%) showed normal imaging. Diffuse brain edema was visible in five patients and an abnormal signal in the deep gray matter in two patients which is consistent with acute necrotizing encephalopathy. Abnormal signals of the splenial lesion, subcortical white matter (bright tree appearance), and cortical area were observed in 15, 1, and 8 patients, respectively. From our findings based on the questionnaire results, we suggest that MRI is useful for determining fatal cases of pandemic influenza A (H1N1) 2009 infection when performed in the acute phase. However, MRI is not useful in predicting the development of sequelae. Georg Thieme Verlag KG Stuttgart · New York.

  13. An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

    Science.gov (United States)

    Leung, Ho-Chuen; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Zhao, Han-Jun; Cheung, Chung-Yan; Ng, Fai; Huang, Jian-Dong; Zheng, Bo-Jian

    2015-04-01

    In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

  14. Acceptance and tolerability of an adjuvanted nH1N1 vaccine in HIV-infected patients in the cologne-bonn cohort

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    Steffens B

    2011-07-01

    Full Text Available Abstract Objective To evaluate the acceptance and tolerability of the nH1N1 2009 vaccine in HIV-positive individuals. Method 758 patients were included in this prospective study. Different study populations were formed: The Tolerability Study Group consists of HIV-infected patients who visited three outpatient clinics (Cologne, Bonn, Freiburg during a predefined time period. Patients were offered nH1N1 vaccination. Those accepting were administered a standard dose AS03 adjuvant nH1N1 vaccine. Questionnaires to report side effects occurring within 7 days after immunization were handed out. In a substudy conducted during the same time period, acceptance towards immunization was recorded. This Acceptance Study Group consists of all HIV-infected patients visiting the Cologne clinic. They were offered vaccination. In case of refusal, motivation was recorded. Results In the Tolerability Study Group, a total of 475 patient diaries returned in the three study centres could be evaluated, 119 of those (25% reported no side effects. Distribution of symptoms was as follows: Pain 285/475 patients (60%, swelling 96 (20%, redness 54 (11%, fever 48/475 (10%, muscle/joint ache 173 (36%, headache 127 (27%, and fatigue 210 (44%. Association of side effects with clinical data was calculated for patients in Cologne and Bonn. Incidence of side effects was significantly associated with CDC stages A, B compared to C, and with a detectable viral load (> 50 copies/mL. No correlation was noted for CD4 cell count, age, gender or ethnicity. In the Acceptance Study Group, 538 HIV-infected patients were offered vaccination, 402 (75% accepted, while 136 (25% rejected. Main reasons for rejection were: Negative media coverage (35%, indecisiveness with preference to wait until a later date (23%, influenza not seen as personal threat (19% and scepticism towards immunization in general (10%. Conclusion A total of 622 HIV-infected patients were vaccinated against nH1N1-influenza in

  15. Surveillance of hospitalizations with pandemic A(H1N1 2009 influenza infection in Queensland, Australia

    Directory of Open Access Journals (Sweden)

    Frances Birrell

    2011-05-01

    Full Text Available Objective : To describe the demographic and clinical characteristics of patients hospitalized with pandemic A(H1N1 2009 infection in Queensland, Australia between 25 May and 3 October 2009 and to examine the relationship between timing of antiviral treatment and severity of illness.Method: Using data from the Queensland Health EpiLog information system, descriptive analysis and logistic regression modelling were used to describe and model factors which influence patient outcomes (death, admission to intensive care unit and/or special care unit. Data on patients admitted to hospital in Queensland with confirmed pandemic A(H1N1 2009 infection were included in this analysis.Results: 1236 patients with pandemic A(H1N1 2009 infection were admitted to hospitals in Queensland during the study period. Of the total group: 15% were admitted to an intensive care unit or special care unit; 3% died; 34% were under the age of 18 years and 8% were 65 years of age or older; and 55% had at least one underlying medical condition. Among the 842 patients for whom data were available regarding the use of antiviral drugs, antiviral treatment was initiated in 737 (87.5% patients with treatment commencing at a median of one day (range 1–33 days after onset of illness. Admission to an intensive care unit or special care unit (ICU/SCU or death was significantly associated with increased age, lack of timeliness of antiviral treatment, chronic renal disease and morbid obesity.Discussion: Early antiviral treatment was significantly associated with lower likelihood of ICU/SCU admission or death. Early antiviral treatment for influenza cases may therefore have important public health implications.

  16. Pandemic influenza A (H1N1)

    African Journals Online (AJOL)

    ... in Port Shepstone, South Africa. Introduction. Influenza A (H1N1) 2009 'swine flu' variant is currently a global pandemic.1 The infection associated with this virus is usually a mild, self-limiting illness. However, it may progress to severe pneumonia requiring intensive care unit (ICU) therapy in 31% of patients.2 This may.

  17. Presence of serum antibodies to influenza A subtypes H5 and N1 in swans and ibises in French wetlands, irrespective of highly pathogenic H5N1 natural infection.

    Science.gov (United States)

    Niqueux, Eric; Guionie, Olivier; Schmitz, Audrey; Hars, Jean; Jestin, Véronique

    2010-03-01

    Highly pathogenic (HP) avian influenza A viruses (AIVs) subtype H5N1 (subclade 2.2) were detected in wild birds during outbreaks in France during winter 2006 and summer 2007 in la Dombes wetlands (eastern France) and in Moselle wetlands (northeastern France), respectively. Blood samples from apparently healthy wild birds were collected in 2006 and 2007 from the end of the outbreak to several weeks after the influenza A outbreak inside and outside the contaminated areas, and in 2008 outside the contaminated areas. The samples were tested for the presence and/or quantitation of serum antibodies to influenza A subtypes H5 and N1 using hemagglutination inhibition tests (HITs), a commercial N1-specific enzyme-linked immunosorbent assay kit, and virus neutralization assay. In the HIT, low pathogenicity (LP) and HP H5 AIVs (belonging to H5N1, H5N2, and H5N3 subtypes) were used as antigens. One hundred mute swans were bled in the la Dombes outbreak area in 2006. During 2007, 46 mallards, 69 common pochards, and 59 mute swans were sampled in the Moselle outbreak area. For comparison, blood samples were also collected in 2007 from 60 mute swans from the Marne department where no HP H5N1 influenza A cases have been reported, and in 2008 from 111 sacred ibises in western France where no HP H5N1 influenza A infections in wild birds have been reported either. Mute swans (irrespective of their origin and time of sampling) and sacred ibises (from an area with no known outbreaks) had the highest prevalence of positive sera in the H5 HIT (49-69% and 64%, respectively). The prevalence of anti-H5 antibodies in mallards and common pochards was lower (28% and 27%, respectively). Positive H5- and N1-antibody responses were also significantly associated in swans (irrespective of their origin and time of sampling) and in sacred ibises. However, in swans from the area without outbreaks, the HIT titer against an H5N1 LPAIV was significantly higher than against an H5N1 2.2.1 HPAIV, whereas no

  18. Comparative evaluation of acute respiratory distress syndrome in patients with and without H1N1 infection at a tertiary care referral center

    Directory of Open Access Journals (Sweden)

    Tanvir Samra

    2011-01-01

    Full Text Available H1N1 subtype of influenza A virus has clinical presentation ranging from mild flu like illness to severe lung injury and acute respiratory distress syndrome (ARDS. The aim of our study was to compare the demographic characteristics, clinical presentation, and mortality of critically ill patients with (H1N1+ and without H1N1 infection (H1N1-. We retrospectively analyzed medical charts of patients admitted in "Swine Flu ICU" with ARDS from August 2009 to May 2010. Real-time reverse transcriptase polymerase chain reaction (RT-PCR assay was used for detection of H1N1 virus in the respiratory specimens. Clinical data from 106 (H1N1 , 45; H1N1+, 61 patients was collected and compared. Mean delay in presentation to our hospital was 5.7 ± 3.1 days and co-morbidities were present in two-fifth of the total admissions. Sequential Organ Failure Assessment (SOFA score of patients with and without H1N1 infection was comparable; 7.8 ± 3.5 and 6.6 ± 3.1 on day 1 and 7.2 ± 4.5 and 6.5 ± 3.1 on day 3, respectively. H1N1+ patients were relatively younger in age (34.2 ± 12.9 years vs. 42.8 ± 18.1, P = 0.005 but presented with significantly lower PaO 2 :FiO 2 ratio (87.3 ± 48.7 vs. 114 ± 51.7 in comparison to those who subsequently tested as H1N1 . The total leucocyte counts were significantly lower in H1N1+ patients during the first four days of illness but incidence of renal failure (P = 0.02 was higher in H1N1+ patients. The mortality in both the groups was high (H1N1+, 77%; H1N1, 68% but comparable. There was a mean delay of 5.7 ± 3.1 days in initiation of antivirals. Patients with H1N1 infection were relatively younger in age and with a significantly higher incidence of refractory hypoxia and acute renal failure. Mortality from ARDS reported in our study in both the groups was high but comparable.

  19. Molecular characterization of pandemic H1N1 influenza viruses isolated from turkeys and pathogenicity of a human pH1N1 isolate in turkeys.

    Science.gov (United States)

    Berhane, Yohannes; Ojkic, Davor; Neufeld, James; Leith, Marsha; Hisanaga, Tamiko; Kehler, Helen; Ferencz, Arpad; Wojcinski, Helen; Cottam-Birt, Colleen; Suderman, Matthew; Handel, Katherine; Alexandersen, Soren; Pasick, John

    2010-12-01

    Suspected human-to-animal transmission of the 2009 pandemic H1N1 (pH1N1) virus has been reported in several animal species, including pigs, dogs, cats, ferrets, and turkeys. In this study we describe the genetic characterization of pH1N1 viruses isolated from breeder turkeys that was associated with a progressive drop in egg production. Sequence analysis of all eight gene segments from three viruses isolated from this outbreak demonstrated homology with other human and swine pH1N1 isolates. The susceptibility of turkeys to a human pH1N1 isolate was further evaluated experimentally. The 50% turkey infectious dose (TID50) for the human isolate A/Mexico/LnDRE/4487/2009 was determined by inoculating groups of 8-10-week-old turkeys with serial 10-fold dilutions of virus by oronasal and cloacal routes. We estimated the TID50 to be between 1 x 10(5) and 1 x 10(6) TCID50. The pathogenesis of pH1N1 in oronasally or cloacally inoculated juvenile turkeys was also examined. None of the turkeys exhibited clinical signs, and no significant difference in virus shedding or seroconversion was observed between the two inoculation groups. More than 50% of the turkeys in both oronasal and cloacal groups shed virus beginning at 2 days postinoculation (dpi). All birds that actively shed virus seroconverted by 14 dpi. Virus antigen was demonstrated by immunohistochemistry in the cecal tonsils and bursa of Fabricius in two of the birds that were infected by the cloacal route. Virus transmission to naive contact turkeys was at best doubtful. This report provides additional evidence that pH1N1 can cross the species barrier and cause disease outbreaks in domestic turkeys. However, it appears that the reproductive status of the host as well as environmental factors such as concurrent infections, stress, the presence or absence of litter, and stocking density may also contribute to efficient infection and transmission of this agent.

  20. Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection

    International Nuclear Information System (INIS)

    Yun, Tae Jin; Kwon, Gu Jin; Oh, Mi Kyeong; Woo, Sung Koo; Park, Seung Hoon; Choi, Seung Hong; Lee, Hyun Ju; Goo, Jin Mo; Yim, Jae Joon; Kim, Jong Sung; Park, Chang Min

    2010-01-01

    To describe detailed clinical and radiological features of the pandemic H1N1 2009 influenza viral infection among healthy young males in a semiclosed institutionalized setting. A total of 18 patients confirmed with the pandemic H1N1 2009 influenza virus infection from July 18 to July 30, 2009 were enrolled in this study. Each patient underwent an evaluation to determine detailed clinical and radiological features. All patients presented with high fever (> 38.0..C), with accompanying symptoms of cough, rhinorrhea, sore throat, myalgia and diarrhea, and increased C-reactive protein (CRP) values with no leukocytosis nor elevated erythrocyte sedimentation rate (ESR). All patients, including one patient who progressed into acute respiratory distress syndrome, were treated with oseltamivir phosphate and quickly recovered from their symptoms. Chest radiographs showed abnormalities of small nodules and lobar consolidation in only two out of 18 patients. However, six of 12 patients who underwent thin-section CT examinations showed abnormal findings for small ground-glass opacities (GGOs) in addition to poorly-defined nodules with upper lobe predominance. In a population of healthy young adults, elevated CRP with normal ESR and white blood cell levels combined with GGOs and nodules on thin section CT scans may indicate early signs of infection by the pandemic H1N1 2009 influenza virus

  1. Human infection with highly pathogenic H5N1 influenza virus

    NARCIS (Netherlands)

    Gambotto, Andrea; Barratt-Boyes, Simon M.; de Jong, Menno D.; Neumann, Gabriele; Kawaoka, Yoshihiro

    2008-01-01

    Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of

  2. Central nervous system manifestations in pediatric patients with influenza A H1N1 infection during the 2009 pandemic.

    Science.gov (United States)

    Wilking, Ashley N; Elliott, Elizabeth; Garcia, Melissa N; Murray, Kristy O; Munoz, Flor M

    2014-09-01

    A novel H1N1 influenza A virus (A(H1N1)pdm09) particularly affected individuals central nervous system complications associated with pandemic influenza in the pediatric population. Retrospective review of patients with laboratory-confirmed influenza A(H1N1)pdm09 infection and central nervous system manifestations at Texas Children's Hospital between April 2009 and June 2010. Among 365 patients with influenza A(H1N1)pdm09, 32 (8.8%) had central nervous system manifestations at a median age of 4 years. Eight (25.0%) were previously healthy, and 12 (37.5%) had neurological pre-existing conditions. Of the 32 cases of influenza with neurological complications, seizure (n = 17; 53.1%) was the most common central nervous system manifestation, followed by encephalitis (n = 4; 12.5%), meningitis (n = 4; 12.5%), encephalopathy (n = 3; 9.4%), meningismus (n = 3; 9.4%), focal hemorrhagic brain lesions (n = 2; 6.3%), brain infarction (n = 1; 3.1%), and sensorineural hearing loss (n = 1; 3.1%). Two patients demonstrated two or more types of central nervous system complications. One patient had abnormal cerebrospinal fluid with pleocytosis. Almost two thirds of the children with central nervous system manifestations required intensive care unit admission and nearly half required mechanical ventilation. There were no deaths. Patients with pre-existing neurological conditions were at greater risk for central nervous system manifestations during pandemic influenza infection. Patients with central nervous system manifestations were more likely to experience severe illness, characterized by intensive care unit admission and mechanical ventilation, although overall outcomes were good. Influenza prevention in patients with underlying medical conditions, particularly those with neurological conditions, is important. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Early Detection of Pandemic (H1N1) 2009, Bangladesh

    Science.gov (United States)

    Rahman, Mustafizur; Al Mamun, Abdullah; Haider, Mohammad Sabbir; Zaman, Rashid Uz; Karmakar, Polash Chandra; Nasreen, Sharifa; Muneer, Syeda Mah-E; Homaira, Nusrat; Goswami, Doli Rani; Ahmed, Be-Nazir; Husain, Mohammad Mushtuq; Jamil, Khondokar Mahbuba; Khatun, Selina; Ahmed, Mujaddeed; Chakraborty, Apurba; Fry, Alicia; Widdowson, Marc-Alain; Bresee, Joseph; Azim, Tasnim; Alamgir, A.S.M.; Brooks, Abdullah; Hossain, Mohamed Jahangir; Klimov, Alexander; Rahman, Mahmudur; Luby, Stephen P.

    2012-01-01

    To explore Bangladesh’s ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June–July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population. PMID:22257637

  4. Determinants of vaccine immunogenicity in HIV-infected pregnant women: analysis of B and T cell responses to pandemic H1N1 monovalent vaccine.

    Directory of Open Access Journals (Sweden)

    Adriana Weinberg

    Full Text Available Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1 vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1 antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ and granzyme B (GrB T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem increased, IFNγ-effector T-cells (Teff decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact, high CD8+CD39+ regulatory T cells (Treg, and low CD19+CD27-CD21- exhausted B cells (Bexhaust. IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but

  5. A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

    OpenAIRE

    Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui

    2010-01-01

    Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same a...

  6. Clinical differences between H3N2 and H1N1 influenza 2012 and lower respiratory tract infection found using a statistical classification approach

    Directory of Open Access Journals (Sweden)

    Petridis D

    2014-02-01

    drug for only for 1 day, 19 patients for 5 days, and 8 patients from 2 to 10 days. Conclusion: Clusters of symptoms can be used to identify different types of influenza and disease severity. Patients with vaccination had pneumonia, whereas patients without vaccination had influenza A. Patients more than 54.5 years old had H3N2 and patients less than 54.5 years had H1N1. White blood cell count values increased from normal to elevated in H3N2 patients but still remained abnormal in lower tract infection and H1N1 patients. Keywords: H3N2, H1N1, influenza outbreak, respiratory infection, vaccination

  7. Pneumonia in novel swine-origin influenza A (H1N1) virus infection: High-resolution CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Li Ping, E-mail: pinglee_2000@yahoo.com [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Su Dongju, E-mail: hyd_sdj@yahoo.com.cn [Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Zhang Jifeng, E-mail: zjf2005520@163.com [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Xia Xudong, E-mail: xiaxd888@163.com [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Sui Hong, E-mail: suisuihong@126.com [Department of Statistics, Harbin Medical University, 240 Xue Fu Road, Harbin 150086 (China); Zhao Donghui, E-mail: yhwoooooo@yahoo.com.cn [Centers for Disease Control and Prevention of Heilongjiang, 187 Xiang An Street, Harbin 150036 (China)

    2011-11-15

    Objective: The purpose of our study was to review the initial high-resolution CT (HRCT) findings in pneumonia patients with presumed/laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection and detect pneumonia earlier. Materials and methods: High-resolution CT (HRCT) findings of 106 patients with presumed/laboratory-confirmed novel S-OIV (H1N1) infection were reviewed. The 106 patients were divided into two groups according to the serious condition of the diseases. The pattern (consolidation, ground-glass, nodules, and reticulation), distribution, and extent of abnormality on the HRCT were evaluated in both groups. The dates of the onset of symptoms of the patients were recorded. Results: The predominant CT findings in the patients at presentation were unilateral or bilateral multifocal asymmetric ground-glass opacities alone (n = 29, 27.4%), with unilateral or bilateral consolidation (n = 50, 47.2%). The consolidation had peribronchovascular and subpleural predominance. The areas of consolidation were found mainly in the posterior, middle and lower regions of the lungs. Reticular opacities were found in 6 cases of the initial MDCT scan. The extent of disease was greater in group 1 patients requiring advanced mechanical ventilation, with diffuse involvement in 19 patients (63.3%) of group 1 patients, and only 15/76 (19.7%) of group 2 patients (p < 0.01, {chi}{sup 2} test). 20 cases (19%) of the 106 patients had small bilateral or unilateral pleural effusions. None had evidence of hilar or mediastinal lymph node enlargement on CT performed at admission or later. Conclusions: The most common radiographic and CT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On HRCT, the ground-glass opacities had a predominant peribronchovascular and subpleural distribution. CT plays an important role in the early recognition of severe S

  8. Pneumonia in novel swine-origin influenza A (H1N1) virus infection: High-resolution CT findings

    International Nuclear Information System (INIS)

    Li Ping; Su Dongju; Zhang Jifeng; Xia Xudong; Sui Hong; Zhao Donghui

    2011-01-01

    Objective: The purpose of our study was to review the initial high-resolution CT (HRCT) findings in pneumonia patients with presumed/laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection and detect pneumonia earlier. Materials and methods: High-resolution CT (HRCT) findings of 106 patients with presumed/laboratory-confirmed novel S-OIV (H1N1) infection were reviewed. The 106 patients were divided into two groups according to the serious condition of the diseases. The pattern (consolidation, ground-glass, nodules, and reticulation), distribution, and extent of abnormality on the HRCT were evaluated in both groups. The dates of the onset of symptoms of the patients were recorded. Results: The predominant CT findings in the patients at presentation were unilateral or bilateral multifocal asymmetric ground-glass opacities alone (n = 29, 27.4%), with unilateral or bilateral consolidation (n = 50, 47.2%). The consolidation had peribronchovascular and subpleural predominance. The areas of consolidation were found mainly in the posterior, middle and lower regions of the lungs. Reticular opacities were found in 6 cases of the initial MDCT scan. The extent of disease was greater in group 1 patients requiring advanced mechanical ventilation, with diffuse involvement in 19 patients (63.3%) of group 1 patients, and only 15/76 (19.7%) of group 2 patients (p 2 test). 20 cases (19%) of the 106 patients had small bilateral or unilateral pleural effusions. None had evidence of hilar or mediastinal lymph node enlargement on CT performed at admission or later. Conclusions: The most common radiographic and CT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On HRCT, the ground-glass opacities had a predominant peribronchovascular and subpleural distribution. CT plays an important role in the early recognition of severe S-OIV (H1N1).

  9. Multiplex RT-PCR assay for differentiating European swine influenza virus subtypes H1N1, H1N2 and H3N2.

    Science.gov (United States)

    Chiapponi, Chiara; Moreno, Ana; Barbieri, Ilaria; Merenda, Marianna; Foni, Emanuela

    2012-09-01

    In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2) have been isolated in pigs. Developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. This study describes two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe. The HA PCR was able to identify the lineage (avian or human) of the HA of H1 subtypes. The analytical sensitivity of the test, considered to be unique, was assessed using three reference viruses. The detection limit corresponded to 1×10(-1) TCID(50)/200μl for avian-like H1N1, 1×10(0) TCID(50)/200μl for human-like H1N2 and 1×10(1) TCID(50)/200μl for H3N2 SIV. The multiplex RT-PCR was first carried out on a collection of 70 isolated viruses showing 100% specificity and then on clinical samples, from which viruses had previously been isolated, resulting in an 89% positive specificity of the viral subtype. Finally, the test was able to identify the viral subtype correctly in 56% of influenza A positive samples, from which SIV had not been isolated previously. It was also possible to identify mixed viral infections and the circulation of a reassortant strain before performing genomic studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Influence of Novel Highly Pathogenic Avian Influenza A (H5N1 Virus Infection on Migrating Whooper Swans Fecal Microbiota

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    Na Zhao

    2018-02-01

    Full Text Available The migration of wild birds plays an important role in the transmission and spread of H5 highly pathogenic avian influenza (HPAI virus, posing a severe risk to animal and human health. Substantial evidence suggests that altered gut microbial community is implicated in the infection of respiratory influenza virus. However, the influence of H5N1 infection in gut microbiota of migratory birds remains unknown. In January 2015, a novel recombinant H5N1 virus emerged and killed about 100 migratory birds, mainly including whooper swans in Sanmenxia Reservoir Area of China. Here, we describe the first fecal microbiome diversity study of H5N1-infected migratory birds. By investigating the influence of H5N1 infection on fecal bacterial communities in infected and uninfected individuals, we found that H5N1 infection shaped the gut microbiota composition by a difference in the dominance of some genera, such as Aeromonas and Lactobacillus. We also found a decreased α diversity and increased β diversity in infectious individuals. Our results highlight that increases in changes in pathogen-containing gut communities occur when individuals become infected with H5N1. Our study may provide the first evidence that there are statistical association among H5N1 presence and fecal microbiota compositional shifts, and properties of the fecal microbiota may serve as the risk of gut-linked disease in migrates with H5N1 and further aggravate the disease transmission.

  11. Influence of Novel Highly Pathogenic Avian Influenza A (H5N1) Virus Infection on Migrating Whooper Swans Fecal Microbiota.

    Science.gov (United States)

    Zhao, Na; Wang, Supen; Li, Hongyi; Liu, Shelan; Li, Meng; Luo, Jing; Su, Wen; He, Hongxuan

    2018-01-01

    The migration of wild birds plays an important role in the transmission and spread of H5 highly pathogenic avian influenza (HPAI) virus, posing a severe risk to animal and human health. Substantial evidence suggests that altered gut microbial community is implicated in the infection of respiratory influenza virus. However, the influence of H5N1 infection in gut microbiota of migratory birds remains unknown. In January 2015, a novel recombinant H5N1 virus emerged and killed about 100 migratory birds, mainly including whooper swans in Sanmenxia Reservoir Area of China. Here, we describe the first fecal microbiome diversity study of H5N1-infected migratory birds. By investigating the influence of H5N1 infection on fecal bacterial communities in infected and uninfected individuals, we found that H5N1 infection shaped the gut microbiota composition by a difference in the dominance of some genera, such as Aeromonas and Lactobacillus . We also found a decreased α diversity and increased β diversity in infectious individuals. Our results highlight that increases in changes in pathogen-containing gut communities occur when individuals become infected with H5N1. Our study may provide the first evidence that there are statistical association among H5N1 presence and fecal microbiota compositional shifts, and properties of the fecal microbiota may serve as the risk of gut-linked disease in migrates with H5N1 and further aggravate the disease transmission.

  12. Community-acquired pneumonia due to pandemic A(H1N12009 influenzavirus and methicillin resistant Staphylococcus aureus co-infection.

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    Ronan J Murray

    Full Text Available BACKGROUND: Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N12009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection. METHODOLOGY/PRINCIPAL FINDINGS: Patients with community-acquired pneumonia (CAP caused by co-infection with pandemic A(H1N12009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N12009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N12009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N12009/cMRSA co-infection were identified on post-mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL. CONCLUSIONS/SIGNIFICANCE: Clinicians managing patients with pandemic A(H1N12009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic

  13. Antigen-specific H1N1 influenza antibody responses in acute respiratory tract infections and their relation to influenza infection and disease course.

    Science.gov (United States)

    Haran, John Patrick; Hoaglin, David C; Chen, Huaiqing; Boyer, Edward W; Lu, Shan

    2014-08-01

    Early antibody responses to influenza infection are important in both clearance of virus and fighting the disease. Acute influenza antibody titers directed toward H1-antigens and their relation to infection type and patient outcomes have not been well investigated. Using hemagglutination inhibition (HI) assays, we aimed to characterize the H1-specific antibody titers in patients with influenza infection or another respiratory infection before and after the H1N1-pandemic influenza outbreak. Among patients with acute influenza infection we related duration of illness, severity of symptoms, and need for hospitalization to antibody titers. There were 134 adult patients (average age 34.7) who presented to an urban academic emergency department (ED) from October through March during the 2008-2011 influenza seasons with symptoms of fever and a cough. Nasal aspirates were tested by viral culture, and peripheral blood serum was run in seven H1-subtype HI assays. Acutely infected influenza patients had markedly lower antibody titers for six of the seven pseudotype viruses. For the average over the seven titers (log units, base 2) their mean was 7.24 (95% CI 6.88, 7.61) compared with 8.60 (95% CI 8.27, 8.92) among patients who had a non-influenza respiratory illness, pinfection, titers of some antibodies correlated with severity of symptoms and with total duration of illness (pacute respiratory infections, lower concentrations of H1-influenza-specific antibodies were associated with influenza infection. Among influenza-infected patients, higher antibody titers were present in patients with a longer duration of illness and with higher severity-of-symptom scores. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Clinical features and risk factors for severe and critical pregnant women with 2009 pandemic H1N1 influenza infection in China

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    Zhang Peng-jun

    2012-02-01

    Full Text Available Abstract Background 2009 pandemic H1N1 (pH1N1 influenza posed an increased risk of severe illness among pregnant women. Data on risk factors associated with death of pregnant women and neonates with pH1N1 infections are limited outside of developed countries. Methods Retrospective observational study in 394 severe or critical pregnant women admitted to a hospital with pH1N1 influenza from Sep. 1, 2009 to Dec. 31, 2009. rRT-PCR testing was used to confirm infection. In-hospital mortality was the primary endpoint of this study. Univariable logistic analysis and multivariate logistic regression analysis were used to investigate the potential factors on admission that might be associated with the maternal and neonatal mortality. Results 394 pregnant women were included, 286 were infected with pH1N1 in the third trimester. 351 had pneumonia, and 77 died. A PaO2/FiO2 ≤ 200 (odds ratio (OR, 27.16; 95% confidence interval (CI, 2.64-279.70 and higher BMI (i.e. ≥ 30 on admission (OR, 1.26; 95% CI, 1.09 to 1.47 were independent risk factors for maternal death. Of 211 deliveries, 146 neonates survived. Premature delivery (OR, 4.17; 95% CI, 1.19-14.56 was associated neonatal mortality. Among 186 patients who received mechanical ventilation, 83 patients were treated with non-invasive ventilation (NIV and 38 were successful with NIV. The death rate was lower among patients who initially received NIV than those who were initially intubated (24/83, 28.9% vs 43/87, 49.4%; p = 0.006. Septic shock was an independent risk factor for failure of NIV. Conclusions Severe hypoxemia and higher BMI on admission were associated with adverse outcomes for pregnant women. Preterm delivery was a risk factor for neonatal death among pregnant women with pH1N1 influenza infection. NIV may be useful in selected pregnant women without septic shock.

  15. Epidemiology of Travel-associated Pandemic (H1N1) 2009 Infection in 116 Patients, Singapore

    OpenAIRE

    Mukherjee, Pratik; Lim, Poh Lian; Chow, Angela; Barkham, Timothy; Seow, Eillyne; Win, Mar Kyaw; Chua, Arlene; Leo, Yee Sin; Chen, Mark I-Cheng

    2010-01-01

    In June 2009, during Singapore?s pandemic influenza plan containment phase, pandemic (H1N1) 2009 was introduced into the country through imported cases. To understand how travel patterns affected the initial outbreak, we examined epidemiologic and travel data for the first 116 case-patients admitted to Tan Tock Seng Hospital, Singapore, with travel-associated infection. Sixty-one percent and 54% of patients, respectively, met US Centers for Disease Control and Prevention and World Health Orga...

  16. Influenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation.

    Directory of Open Access Journals (Sweden)

    Renee W Y Chan

    Full Text Available Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004 and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998, the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of alpha2-6-linked sialic acid receptors and human airway trypsin-like (HAT protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the

  17. Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

    Science.gov (United States)

    Yu, Xuelian; Zhang, Xi; Zhao, Baihui; Wang, Jiayu; Zhu, Zhaokui; Teng, Zheng; Shao, Junjie; Shen, Jiaren; Gao, Ye; Yuan, Zhengan; Wu, Fan

    2011-01-01

    The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity. We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression. A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further detailed investigations.

  18. Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

    Directory of Open Access Journals (Sweden)

    Xuelian Yu

    Full Text Available BACKGROUND: The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1 are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1 patients and identified cytokines related to disease severity. METHODS AND PRINCIPAL FINDINGS: We retrieved 77, 59, 26 and 26 sera samples from P(H1N1 and non-flu influenza like illness (non-ILIs cases with mild symptoms (mild patients, P(H1N1 vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1 and non-ILIs patients with severe symptoms (severe patients. Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1 patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1 patients. Higher IL-10 secretion in P(H1N1 vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression. CONCLUSION AND SIGNIFICANCE: A comprehensive innate immune response was activated at the early stage of P(H1N1 infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1 patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1 patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression, but the underlying mechanism awaits

  19. Corneal Opacity in Domestic Ducks Experimentally Infected With H5N1 Highly Pathogenic Avian Influenza Virus.

    Science.gov (United States)

    Yamamoto, Y; Nakamura, K; Yamada, M; Mase, M

    2016-01-01

    Domestic ducks can be a key factor in the regional spread of H5N1 highly pathogenic avian influenza (HPAI) virus in Asia. The authors performed experimental infections to examine the relationship between corneal opacity and H5N1 HPAI virus infection in domestic ducks (Anas platyrhyncha var domestica). A total of 99 domestic ducks, including 3 control birds, were used in the study. In experiment 1, when domestic ducks were inoculated intranasally with 2 H5N1 HPAI viruses, corneal opacity appeared more frequently than neurologic signs and mortality. Corneal ulceration and exophthalmos were rare findings. Histopathologic examinations of the eyes of domestic ducks in experiment 2 revealed that corneal opacity was due to the loss of corneal endothelial cells and subsequent keratitis with edema. Influenza viral antigen was detected in corneal endothelial cells and some other ocular cells by immunohistochemistry. Results suggest that corneal opacity is a characteristic and frequent finding in domestic ducks infected with the H5N1 HPAI virus. Confirming this ocular change may improve the detection rate of infected domestic ducks in the field. © The Author(s) 2015.

  20. Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratory-confirmed cases.

    Science.gov (United States)

    Cowling, Benjamin J; Jin, Lianmei; Lau, Eric H Y; Liao, Qiaohong; Wu, Peng; Jiang, Hui; Tsang, Tim K; Zheng, Jiandong; Fang, Vicky J; Chang, Zhaorui; Ni, Michael Y; Zhang, Qian; Ip, Dennis K M; Yu, Jianxing; Li, Yu; Wang, Liping; Tu, Wenxiao; Meng, Ling; Wu, Joseph T; Luo, Huiming; Li, Qun; Shu, Yuelong; Li, Zhongjie; Feng, Zijian; Yang, Weizhong; Wang, Yu; Leung, Gabriel M; Yu, Hongjie

    2013-07-13

    The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26-45) for H7N9 and 70% (56-83%) for H5N1. The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection--a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses

  1. Seroprevalence of three influenza A viruses (H1N1, H3N2, and H3N8) in pet dogs presented to a veterinary hospital in Ohio.

    Science.gov (United States)

    Jang, Hyesun; Jackson, Yasmine K; Daniels, Joshua B; Ali, Ahmed; Kang, Kyung-Il; Elaish, Mohamed; Lee, Chang-Won

    2017-08-31

    The prevalence of canine H3N8 influenza and human H1N1 and H3N2 influenza in dogs in Ohio was estimated by conducting serologic tests on 1,082 canine serum samples. In addition, risk factors, such as health status and age were examined. The prevalences of human H1N1, H3N2, and canine H3N8 influenzas were 4.0%, 2.4%, and 2.3%, respectively. Two samples were seropositive for two subtypes (H1N1 and H3N2; H1N1 and canine influenza virus [CIV] H3N8). Compared to healthy dogs, dogs with respiratory signs were 5.795 times more likely to be seropositive against H1N1 virus ( p = 0.042). The prevalence of human flu infection increased with dog age and varied by serum collection month. The commercial enzyme-linked immunosorbent assay used in this study did not detect nucleoprotein-specific antibodies from many hemagglutination inhibition positive sera, which indicates a need for the development and validation of rapid tests for influenza screening in canine populations. In summary, we observed low exposure of dogs to CIV and human influenza viruses in Ohio but identified potential risk factors for consideration in future investigations. Our findings support the need for establishment of reliable diagnostic standards for serologic detection of influenza infection in canine species.

  2. Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab'2 in mice

    Directory of Open Access Journals (Sweden)

    Li Yanbin

    2006-03-01

    Full Text Available Abstract Background Avian influenza virus H5N1 has demonstrated considerable pandemic potential. Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy may be an alternative strategy. To investigate the possible therapeutic effect of antibody against highly pathogenic H5N1 virus on a mammal host, we prepared specific equine anti-H5N1 IgGs from horses vaccinated with inactivated H5N1 virus, and then obtained the F(ab'2 fragments by pepsin digestion of IgGs. Methods The horses were vaccinated with inactivated H5N1 vaccine to prepare anti-H5N1 IgGs. The F(ab'2 fragments were purified from anti-H5N1 hyperimmune sera by a protocol for 'enhanced pepsin digestion'. The protective effect of the F(ab'2 fragments against H5N1 virus infection was determined in cultured MDCK cells by cytopathic effect (CPE assay and in a BALB/c mouse model by survival rate assay. Results By the protocol for 'enhanced pepsin digestion', total 16 g F(ab'2 fragments were finally obtained from one liter equine antisera with the purity of over 90%. The H5N1-specific F(ab'2 fragments had a HI titer of 1:1024, and the neutralization titre of F(ab'2 reached 1: 2048. The in vivo assay showed that 100 μg of the F(ab'2 fragments could protect BALB/c mice infected with a lethal dose of influenza H5N1 virus. Conclusion The availability of highly purified H5N1-specific F(ab'2 fragments may be promising for treatment of influenza H5N1 infection. Our work has provided experimental support for the application of the therapeutic equine immunoglobulin in future large primate or human trials.

  3. Dual Infection of Novel Influenza Viruses A/H1N1 and A/H3N2 in a Cluster of Cambodian Patients

    Science.gov (United States)

    2011-01-01

    influenza viruses as well as the avian influenza virus A/H5N1...on full genome sequencing. This incident confirms dual influenza virus infections and highlights the risk of zoonotic and seasonal influenza viruses ...North American swine influenza viruses , North American avian influenza viruses , human influenza viruses , and a Eurasian swine influenza virus . 18

  4. The prevalence of enteroviruses that cause respiratory infections in patients with influenzavirus A/H1N1 hospitalized in the Lublin province

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    Jarzynski Adrian

    2014-09-01

    Full Text Available Viruses that cause respiratory tract infections are the most common agents of infectious diseases in humans throughout the world. A virus that infects the respiratory system, may induce various clinical symptoms. What is more, the same symptoms may be caused by different viruses. The aim of the study was to analyze the prevalence of enteroviruses that cause respiratory infections in patients with influenzavirus A/H1N1 hospitalized in the Lublin province. The experimental material was throat and nose swabs taken from patients hospitalized in Lublin and Tomaszow Lubelski. In the group of 44 patients (20 women and 24 men infected with influenza A/H1N1, the genetic material of enteroviruses was detected in 13 patients (29.5%. Respiratory viruses co-infections are very common in hospitalized patients. Studies show that co-infection with influenza virus and enterovirus are more common in children than in adults. Moreover, viral respiratory tract infections are independent from the patients’ gender.

  5. Experimental infection of highly pathogenic avian influenza virus H5N1 in black-headed gulls (Chroicocephalus ridibundus)

    OpenAIRE

    Ramis , Antonio; van Amerongen , Geert; van de Bildt , Marco; Leijten , Loneke; Vanderstichel , Raphael; Osterhaus , Albert; Kuiken , Thijs

    2014-01-01

    Historically, highly pathogenic avian influenza viruses (HPAIV) rarely resulted in infection or clinical disease in wild birds. However, since 2002, disease and mortality from natural HPAIV H5N1 infection have been observed in wild birds including gulls. We performed an experimental HPAIV H5N1 infection of black-headed gulls (Chroicocephalus ridibundus) to determine their susceptibility to infection and disease from this virus, pattern of viral shedding, clinical signs, pathological changes a...

  6. Defining Moments in MMWR History: Swine Influenza A (H1N1) Infection in Two Children, Southern California, March-April 2009

    Centers for Disease Control (CDC) Podcasts

    In 2009, novel influenza A H1N1 virus infection in two children from southern California was first identified. This marked the beginning of the 2009 H1N1 influenza pandemic. MMWR was the first scientific publication to break the news of these cases and went on to publish critical findings from the pandemic. In this podcast, Dr. Dan Jernigan discusses this historic public health event.

  7. Effect of the novel influenza A (H1N1 virus in the human immune system.

    Directory of Open Access Journals (Sweden)

    Evangelos J Giamarellos-Bourboulis

    Full Text Available BACKGROUND: The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. METHODOLOGY/PRINCIPAL FINDINGS: Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL-1beta, IL-6, IL-18, interferon (FN-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs. CONCLUSIONS/SIGNIFICANCE: Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

  8. Effect of the novel influenza A (H1N1) virus in the human immune system.

    Science.gov (United States)

    Giamarellos-Bourboulis, Evangelos J; Raftogiannis, Maria; Antonopoulou, Anastasia; Baziaka, Fotini; Koutoukas, Pantelis; Savva, Athina; Kanni, Theodora; Georgitsi, Marianna; Pistiki, Aikaterini; Tsaganos, Thomas; Pelekanos, Nikolaos; Athanassia, Sofia; Galani, Labrini; Giannitsioti, Efthymia; Kavatha, Dimitra; Kontopidou, Flora; Mouktaroudi, Maria; Poulakou, Garyfallia; Sakka, Vissaria; Panagopoulos, Periklis; Papadopoulos, Antonios; Kanellakopoulou, Kyriaki; Giamarellou, Helen

    2009-12-23

    The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs). Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

  9. Risk of Human Infections With Highly Pathogenic H5N2 and Low Pathogenic H7N1 Avian Influenza Strains During Outbreaks in Ostriches in South Africa.

    Science.gov (United States)

    Venter, Marietjie; Treurnicht, Florette K; Buys, Amelia; Tempia, Stefano; Samudzi, Rudo; McAnerney, Johanna; Jacobs, Charlene A; Thomas, Juno; Blumberg, Lucille

    2017-09-15

    Risk factors for human infection with highly pathogenic (HP) and low-pathogenic (LP) avian influenza (AI) H5N2 and H7N1 were investigated during outbreaks in ostriches in the Western Cape province, South Africa. Serum surveys were conducted for veterinarians, farmworkers, and laboratory and abattoir workers involved in 2 AI outbreaks in the Western Cape province: (1) controlling and culling of 42000 ostriches during (HPAI)H5N2 outbreaks in ostriches (2011) (n = 207); (2) movement control during (LPAI)H7N1 outbreaks in 2012 (n = 66). A third serosurvey was conducted on state veterinarians from across the country in 2012 tasked with disease control in general (n = 37). Antibodies to H5 and H7 were measured by means of hemagglutination inhibition and microneutralization assays, with microneutralization assay titers >40 considered positive. Two of 207 (1%) participants were seropositive for H5 and 4 of 207 (2%) for H7 in 2011, compared with 1 of 66 (1.5%) and 8 of 66 (13%) in 2012. Although individuals in all professions tested seropositive, abattoir workers (10 of 97; 10.3%) were significantly more at risk of influenza A(H7N1) infection (P = .001) than those in other professions (2 of 171;1.2%). Among state veterinarians, 4 of 37(11%) were seropositive for H7 and 1 of 37 (2.7%) for H5. Investigations of (LP)H7N1-associated fatalities in wild birds and quarantined exotic birds in Gauteng, AI outbreaks in poultry in KwaZulu-Natal, and ostriches in Western Cape province provide possible exposure events. (LPAI)H7N1 strains pose a greater infection-risk than (HPAI)H5N2 strains to persons involved in control of outbreaks in infected birds, with ostrich abattoir workers at highest risk. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  10. The critical role of Notch ligand Delta-like 1 in the pathogenesis of influenza A virus (H1N1 infection.

    Directory of Open Access Journals (Sweden)

    Toshihiro Ito

    2011-11-01

    Full Text Available Influenza A viral infections have been identified as the etiologic agents for historic pandemics, and contribute to the annual mortality associated with acute viral pneumonia. While both innate and acquired immunity are important in combating influenza virus infection, the mechanism connecting these arms of the immune system remains unknown. Recent data have indicated that the Notch system is an important bridge between antigen-presenting cells (APCs and T cell communication circuits and plays a central role in driving the immune system to overcome disease. In the present study, we examine the role of Notch signaling during influenza H1N1 virus infection, focusing on APCs. We demonstrate here that macrophages, but not dendritic cells (DCs, increased Notch ligand Delta-like 1 (Dll1 expression following influenza virus challenge. Dll1 expression on macrophages was dependent on retinoic acid-inducible gene-I (RIG-I induced type-I IFN pathway, and not on the TLR3-TRIF pathway. We also found that IFNα-Receptor knockout mice failed to induce Dll1 expression on lung macrophages and had enhanced mortality during influenza virus infection. Our results further showed that specific neutralization of Dll1 during influenza virus challenge induced higher mortality, impaired viral clearance, and decreased levels of IFN-γ. In addition, we blocked Notch signaling by using γ-secretase inhibitor (GSI, a Notch signaling inhibitor. Intranasal administration of GSI during influenza infection also led to higher mortality, and higher virus load with excessive inflammation and an impaired production of IFN-γ in lungs. Moreover, Dll1 expression on macrophages specifically regulates IFN-γ levels from CD4(+and CD8(+T cells, which are important for anti-viral immunity. Together, the results of this study show that Dll1 positively influences the development of anti-viral immunity, and may provide mechanistic approaches for modifying and controlling the immune response

  11. Features of pathology in mice experimentally infected with highly pathogenic H5N1 influenza virus

    International Nuclear Information System (INIS)

    Ryabchikova, E. I.; Taranov, O. S.; Malkova, E. M.; Gritsyk, O. B.; Demina, O. K.

    2009-01-01

    Avian influenza became a new threat and has set people thinking about possibility of new influenza pandemic which may be caused by highly pathogenic H5N1 influenza virus. The virus could acquire ability of fast spreading between the humans and new pandemics could kill millions. Influenza virus H5N1 exhibited its deadly essence by taking out many millions of birds in nature and aviculture; other millions of chicks and ducks were killed to prevent spread of the epizootic. The strains isolated in Russia belong to Qinghai group of H5N1 influenza virus, and were imported to Russia by migratory birds. We examined time-course changes in mice blood and lungs after intranasal infection with strains A /Chicken/ Kurgan/ 05/2005, A/ Duck/ Kurgan/08/ 2005 and A/ Chicken/ Suzdalka/ Nov-11/2005 differing in virulence for this animal species. Development of leucopenia and severe damage of hemopoiesis were found in mice infected with all H5N1 influenza virus strains. Pathological changes in mice lungs during the infection with above mentioned strains, and strain-specific features have been examined. Main characteristics of lung pathology in all mice were focal nature of the alterations, severe damage of bronchial epithelium and pronounced alteration of lung vasculature. Strain A/Chicken/Suzdalka/Nov-11/2005 induced massive apoptosis of infected bronchial cells which may be a part of mechanism responsible for avirulent properties of this strain. The most interesting finding was absence of serious direct virus damage of the lung evidencing for principal role of the host humoral mechanisms in pathogenesis of H5N1 influenza in mice.(author)

  12. A metagenomic analysis of pandemic influenza A (2009 H1N1 infection in patients from North America.

    Directory of Open Access Journals (Sweden)

    Alexander L Greninger

    2010-10-01

    Full Text Available Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17, the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%, with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings.

  13. The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Davey, Richard T; Lynfield, Ruth; Dwyer, Dominic E

    2013-01-01

    Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment wer...

  14. New Orf virus (Parapoxvirus) recombinant expressing H5 hemagglutinin protects mice against H5N1 and H1N1 influenza A virus.

    Science.gov (United States)

    Rohde, Jörg; Amann, Ralf; Rziha, Hanns-Joachim

    2013-01-01

    Previously we demonstrated the versatile utility of the Parapoxvirus Orf virus (ORFV) as a vector platform for the development of potent recombinant vaccines. In this study we present the generation of new ORFV recombinants expressing the hemagglutinin (HA) or nucleoprotein (NP) of the highly pathogenic avian influenza virus (HPAIV) H5N1. Correct foreign gene expression was examined in vitro by immunofluorescence, Western blotting and flow cytometry. The protective potential of both recombinants was evaluated in the mouse challenge model. Despite adequate expression of NP, the recombinant D1701-V-NPh5 completely failed to protect mice from lethal challenge. However, the H5 HA-expressing recombinant D1701-V-HAh5n mediated solid protection in a dose-dependent manner. Two intramuscular (i.m.) injections of the HA-expressing recombinant protected all animals from lethal HPAIV infection without loss of body weight. Notably, the immunized mice resisted cross-clade H5N1 and heterologous H1N1 (strain PR8) influenza virus challenge. In vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T-cell subpopulations during immunization and/or challenge infection implicated the relevance of CD4-positive T-cells for induction of protective immunity by D1701-V-HAh5n, whereas the absence of CD8-positive T-cells did not significantly influence protection. In summary, this study validates the potential of the ORFV vectored vaccines also to combat HPAIV.

  15. New Orf virus (Parapoxvirus recombinant expressing H5 hemagglutinin protects mice against H5N1 and H1N1 influenza A virus.

    Directory of Open Access Journals (Sweden)

    Jörg Rohde

    Full Text Available Previously we demonstrated the versatile utility of the Parapoxvirus Orf virus (ORFV as a vector platform for the development of potent recombinant vaccines. In this study we present the generation of new ORFV recombinants expressing the hemagglutinin (HA or nucleoprotein (NP of the highly pathogenic avian influenza virus (HPAIV H5N1. Correct foreign gene expression was examined in vitro by immunofluorescence, Western blotting and flow cytometry. The protective potential of both recombinants was evaluated in the mouse challenge model. Despite adequate expression of NP, the recombinant D1701-V-NPh5 completely failed to protect mice from lethal challenge. However, the H5 HA-expressing recombinant D1701-V-HAh5n mediated solid protection in a dose-dependent manner. Two intramuscular (i.m. injections of the HA-expressing recombinant protected all animals from lethal HPAIV infection without loss of body weight. Notably, the immunized mice resisted cross-clade H5N1 and heterologous H1N1 (strain PR8 influenza virus challenge. In vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T-cell subpopulations during immunization and/or challenge infection implicated the relevance of CD4-positive T-cells for induction of protective immunity by D1701-V-HAh5n, whereas the absence of CD8-positive T-cells did not significantly influence protection. In summary, this study validates the potential of the ORFV vectored vaccines also to combat HPAIV.

  16. The seroprevalence of pandemic influenza H1N1 (2009 virus in China.

    Directory of Open Access Journals (Sweden)

    Cuiling Xu

    2011-04-01

    Full Text Available Mainland China experienced pandemic influenza H1N1 (2009 virus (pH1N1 with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1.Stored serum samples (n = 2,379 collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40 was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%. Among unvaccinated participants, those aged 6-15 years (32.9% and 16-24 years (30.3% had higher seroprevalence compared with participants aged 25-59 years (10.7% and ≥60 years (9.9%, P<0.0001. Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively. We estimated that 207.7 million individuals (15.9% experienced pH1N1 infection in China.The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

  17. Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets.

    Science.gov (United States)

    Vidaña, Beatriz; Martínez, Jorge; Martorell, Jaime; Montoya, María; Córdoba, Lorena; Pérez, Mónica; Majó, Natàlia

    2016-11-08

    Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3.

  18. Inactivation of influenza A virus H1N1 by disinfection process.

    Science.gov (United States)

    Jeong, Eun Kyo; Bae, Jung Eun; Kim, In Seop

    2010-06-01

    Because any patient, health care worker, or visitor is capable of transmitting influenza to susceptible persons within hospitals, hospital-acquired influenza has been a clinical concern. Disinfection and cleaning of medical equipment, surgical instruments, and hospital environment are important measures to prevent transmission of influenza virus from hospitals to individuals. This study was conducted to evaluate the efficacy of disinfection processes, which can be easily operated at hospitals, in inactivating influenza A virus H1N1 (H1N1). The effects of 0.1 mol/L NaOH, 70% ethanol, 70% 1-propanol, solvent/detergent (S/D) using 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100, heat, and ethylene oxide (EO) treatments in inactivating H1N1 were determined. Inactivation of H1N1 was kinetically determined by the treatment of disinfectants to virus solution. Also, a surface test method, which involved drying an amount of virus on a surface and then applying the inactivation methods for 1 minute of contact time, was used to determine the virucidal activity. H1N1 was completely inactivated to undetectable levels in 1 minute of 70% ethanol, 70% 1-propanol, and solvent/detergent treatments in the surface tests as well as in the suspension tests. H1N1 was completely inactivated in 1 minute of 0.1 mol/L NaOH treatment in the suspension tests and also effectively inactivated in the surface tests with the log reduction factor of 3.7. H1N1 was inactivated to undetectable levels within 5 minutes, 2.5 minutes, and 1 minute of heat treatment at 70, 80, and 90 degrees C, respectively in the suspension tests. Also, H1N1 was completely inactivated by EO treatment in the surface tests. Common disinfectants, heat, and EO tested in this study were effective at inactivating H1N1. These results would be helpful in implementing effective disinfecting measures to prevent hospital-acquired infections. Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc

  19. A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

    Directory of Open Access Journals (Sweden)

    Qin E-de

    2010-06-01

    Full Text Available Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009 influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.

  20. Pandemic H1N1 2009 virus in Norwegian pigs naïve to influenza A viruses

    DEFF Research Database (Denmark)

    Germundsson, A.; Gjerset, B.; Hjulsager, Charlotte Kristiane

    In March-April 2009, a novel pandemic influenza A (H1N1) virus (pH1N1-09v) emerged in the human population. The first case of pH1N1v infection in pigs was reported from Canada in May 2009. In Norway, pH1N1v infection was recorded in a swine herd on the 10th of October of 2009. Here, we report...... isolated from a confirmed human case at the farm. The majority of the positive herds had a history of contact with humans that were diagnosed with pandemic influenza or with ILI. This suggests that infected humans are the most likely source for introduction of pH1N1-09v to the Norwegian pig herds...

  1. Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses.

    Science.gov (United States)

    Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

    2017-09-01

    In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up

  2. Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection: Evidence of competitive advantage of pandemic H1N1 influenza versus seasonal influenza.

    Science.gov (United States)

    Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas

    2009-08-24

    On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains.

  3. Homosubtypic and heterosubtypic antibodies against highly pathogenic avian influenza H5N1 recombinant proteins in H5N1 survivors and non-H5N1 subjects.

    Science.gov (United States)

    Noisumdaeng, Pirom; Pooruk, Phisanu; Prasertsopon, Jarunee; Assanasen, Susan; Kitphati, Rungrueng; Auewarakul, Prasert; Puthavathana, Pilaipan

    2014-04-01

    Six recombinant vaccinia viruses containing HA, NA, NP, M or NS gene insert derived from a highly pathogenic avian influenza H5N1 virus, and the recombinant vaccinia virus harboring plasmid backbone as the virus control were constructed. The recombinant proteins were characterized for their expression and subcellular locations in TK(-) cells. Antibodies to the five recombinant proteins were detected in all 13 sequential serum samples collected from four H5N1 survivors during four years of follow-up; and those directed to rVac-H5 HA and rVac-NA proteins were found in higher titers than those directed to the internal proteins as revealed by indirect immunofluorescence assay. Although all 28 non-H5N1 subjects had no neutralizing antibodies against H5N1 virus, they did have cross-reactive antibodies to those five recombinant proteins. A significant increase in cross-reactive antibody titer to rVac-H5 HA and rVac-NA was found in paired blood samples from patients infected with the 2009 pandemic virus. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Molecular characterization of a novel reassortant H1N2 influenza virus containing genes from the 2009 pandemic human H1N1 virus in swine from eastern China.

    Science.gov (United States)

    Peng, Xiuming; Wu, Haibo; Xu, Lihua; Peng, Xiaorong; Cheng, Linfang; Jin, Changzhong; Xie, Tiansheng; Lu, Xiangyun; Wu, Nanping

    2016-06-01

    Pandemic outbreaks of H1N1 swine influenza virus have been reported since 2009. Reassortant H1N2 viruses that contain genes from the pandemic H1N1 virus have been isolated in Italy and the United States. However, there is limited information regarding the molecular characteristics of reassortant H1N2 swine influenza viruses in eastern China. Active influenza surveillance programs in Zhejiang Province identified a novel H1N2 influenza virus isolated from pigs displaying clinical signs of influenza virus infection. Whole-genome sequencing was performed and this strain was compared with other influenza viruses available in GenBank. Phylogenetic analysis suggested that the novel strain contained genes from the 2009 pandemic human H1N1 and swine H3N2 viruses. BALB/c mice were infected with the isolated virus to assess its virulence in mice. While the novel H1N2 isolate replicated well in mice, it was found to be less virulent. These results provide additional evidence that swine serve as intermediate hosts or 'mixing vessels' for novel influenza viruses. They also emphasize the importance of surveillance in the swine population for use as an early warning system for influenza outbreaks in swine and human populations.

  5. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza

    NARCIS (Netherlands)

    Cheng, Zhongshan; Zhou, Jie; To, Kelvin Kai-Wang; Chu, Hin; Li, Cun; Wang, Dong; Yang, Dong; Zheng, Shufa; Hao, Ke; Bosse, Yohan; Obeidat, Ma'en; Brandsma, Corry-Anke; Song, You-Qiang; Chen, Yu; Zheng, Bo-Jian; Li, Lanjuan; Yuen, Kwok-Yung

    2015-01-01

    The genetic predisposition to severe A(H1N1) 2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung

  6. Defining Moments in MMWR History: Swine Influenza A (H1N1) Infection in Two Children, Southern California, March-April 2009

    Centers for Disease Control (CDC) Podcasts

    2017-07-17

    In 2009, novel influenza A H1N1 virus infection in two children from southern California was first identified. This marked the beginning of the 2009 H1N1 influenza pandemic. MMWR was the first scientific publication to break the news of these cases and went on to publish critical findings from the pandemic. In this podcast, Dr. Dan Jernigan discusses this historic public health event.  Created: 7/17/2017 by MMWR.   Date Released: 7/17/2017.

  7. Co-infection of turkeys with Escherichia coli (O78) and H6N1 avian influenza virus.

    Science.gov (United States)

    Umar, Sajid; Delverdier, Maxence; Delpont, Mattias; Belkasmi, Sakhia F Z; Teillaud, Angélique; Bleuart, Céline; Pardo, Isabelle; El Houadfi, Mohammed; Guérin, Jean-Luc; Ducatez, Mariette F

    2018-03-28

    Respiratory diseases are responsible for major economic losses in poultry farms. While in most cases a single pathogen is not alone responsible for the clinical outcome, the impact of co-infections is not well known, especially in turkeys. The purpose of this study was to assess the possible synergism between Escherichia coli (O78) and low pathogenic avian influenza virus (LPAIV, H6N1), in the turkey model. Four-week-old commercial turkeys were inoculated with either H6N1, O78 or both agents simultaneously or three days apart. We have established an experimental infection model of turkeys using aerosolization that better mimics field infections. Birds were observed clinically and swabbed on a daily basis. Necropsies were performed at 4 and 14 days post single or dual inoculation and followed by histological and immunohistochemical analyses. Combined LPAIV/E. coli infections resulted in more severe clinical signs, were associated with higher mortality and respiratory organ lesions (mucous or fibrinous exudative material in lungs and air sacs), in comparison with the groups given single infections (P  0.05) respiratory signs were observed in turkeys of the E. coli followed by H6N1 inoculated group. Microscopic lesions and immunohistochemical staining supported clinical and macroscopic findings. Efficient virus and bacteria replication was observed in all inoculated groups. E. coli and H6N1 thus exercise an additive or synergistic pathogenic effect in the reproduction of respiratory disease.

  8. DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans

    International Nuclear Information System (INIS)

    Wang, S.-F.; Huang, Jason C.; Lee, Y.-M.; Liu, S.-J.; Chan, Yu-Jiun; Chau, Y.-P.; Chong, P.; Chen, Y.-M.A.

    2008-01-01

    DC-SIGN, a C-type lectin receptor expressed in dendritic cells (DCs), has been identified as a receptor for human immunodeficiency virus type 1, hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, and the SARS coronavirus. We used H5N1 pseudotyped and reverse-genetics (RG) virus particles to study their ability to bind with DC-SIGN. Electronic microscopy and functional assay results indicate that pseudotyped viruses containing both HA and NA proteins express hemagglutination and are capable of infecting cells expressing α-2,3-linked sialic acid receptors. Results from a capture assay show that DC-SIGN-expressing cells (including B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) and peripheral blood dendritic cells are capable of transferring H5N1 pseudotyped and RG virus particles to target cells; this action can be blocked by anti-DC-SIGN monoclonal antibodies. In summary, (a) DC-SIGN acts as a capture or attachment molecule for avian H5N1 virus, and (b) DC-SIGN mediates infections in cis and in trans

  9. Epidemiological survey on pandemic influenza A (H1N1) virus infection in Kurdistan province, Islamic Republic of Iran, 2009.

    Science.gov (United States)

    Afrasiabian, S; Mohsenpour, B; Bagheri, K H; Barari, M; Ghaderi, E; Hashemi, R; Garibi, F

    2014-04-03

    This study evaluated the epidemiology of suspected cases of pandemic influenza A (H1N1) virus infection in 2009-2010 in Kurdistan province, a frontier province of the Islamic Republic of Iran. A questionnaire covering demographic characteristics, clinical presentation and outcome, and history of exposure and travel was completed by patients attending health centres and hospitals in the province. Nasal and throat swabs were analysed by RT-PCR. A total of 1059 suspected cases were assessed; H1N1 influenza A was confirmed in 157 (14.8%). The highest proportion of confirmed cases was 30.0%, among children aged Kurdistan.

  10. Characterization of functional antibody and memory B-cell responses to pH1N1 monovalent vaccine in HIV-infected children and youth.

    Directory of Open Access Journals (Sweden)

    Donna J Curtis

    Full Text Available We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI titers, avidity indices (AI, B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.At entry, 26 (29% subjects had pH1N1 protective HAI titers (≥1:40. pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05, but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent

  11. Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase.

    Science.gov (United States)

    Pavlova, Sophia P; Veits, Jutta; Keil, Günther M; Mettenleiter, Thomas C; Fuchs, Walter

    2009-01-29

    Attenuated vaccine strains of the alphaherpesvirus causing infectious laryngotracheitis of chickens (ILTV, gallid herpesvirus 1) can be used for mass application. Previously, we showed that live virus vaccination with recombinant ILTV expressing hemagglutinin of highly pathogenic avian influenza viruses (HPAIV) protected chickens against ILT and fowl plague caused by HPAIV carrying the corresponding hemagglutinin subtypes [Lüschow D, Werner O, Mettenleiter TC, Fuchs W. Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene. Vaccine 2001;19(30):4249-59; Veits J, Lüschow D, Kindermann K, Werner O, Teifke JP, Mettenleiter TC, et al. Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT) virus leads to attenuation in chickens, and UL0 mutants expressing influenza virus haemagglutinin (H7) protect against ILT and fowl plague. J Gen Virol 2003;84(12):3343-52]. However, protection against H5N1 HPAIV was not satisfactory. Therefore, a newly designed dUTPase-negative ILTV vector was used for rapid insertion of the H5-hemagglutinin, or N1-neuraminidase genes of a recent H5N1 HPAIV isolate. Compared to our previous constructs, protein expression was considerably enhanced by insertion of synthetic introns downstream of the human cytomegalovirus immediate-early promoter within the 5'-nontranslated region of the transgenes. Deletion of the viral dUTPase gene did not affect in vitro replication of the ILTV recombinants, but led to sufficient attenuation in vivo. After a single ocular immunization, all chickens developed H5- or N1-specific serum antibodies. Nevertheless, animals immunized with N1-ILTV died after subsequent H5N1 HPAIV challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either H5-ILTV alone, or H5- and N1-ILTV simultaneously, survived

  12. Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

    Science.gov (United States)

    Bao, Yanyan; Gao, Yingjie; Shi, Yujing; Cui, Xiaolan

    2017-06-01

    H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

  13. Hospitalizations Associated with Pandemic Influenza A (H1N1) 2009 in Asthmatic Children in Japan

    OpenAIRE

    Toshio Katsunuma; Takehiko Matsui; Tsutomu Iwata; Mitsuhiko Nambu; Naomi Kondo

    2012-01-01

    Background: The pandemic influenza A (H1N1) 2009 [pdm (H1N1) 2009] spread through the world in 2009, producing a serious epidemic in Japan. Since it was suggested early that asthma is a risk factor for an increased severity of the infection, the Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) organized a working group for countermeasures, and investigated asthmatic children admitted to the hospitals for pdm (H1N1) 2009 infection. Methods: An appeal was made on the ho...

  14. Calculating the potential for within-flight transmission of influenza A (H1N1

    Directory of Open Access Journals (Sweden)

    Blower Sally

    2009-12-01

    Full Text Available Abstract Background Clearly air travel, by transporting infectious individuals from one geographic location to another, significantly affects the rate of spread of influenza A (H1N1. However, the possibility of within-flight transmission of H1N1 has not been evaluated; although it is known that smallpox, measles, tuberculosis, SARS and seasonal influenza can be transmitted during commercial flights. Here we present the first quantitative risk assessment to assess the potential for within-flight transmission of H1N1. Methods We model airborne transmission of infectious viral particles of H1N1 within a Boeing 747 using methodology from the field of quantitative microbial risk assessment. Results The risk of catching H1N1 will essentially be confined to passengers travelling in the same cabin as the source case. Not surprisingly, we find that the longer the flight the greater the number of infections that can be expected. We calculate that H1N1, even during long flights, poses a low to moderate within-flight transmission risk if the source case travels First Class. Specifically, 0-1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and 2-5 during a 17 hour flight. However, within-flight transmission could be significant, particularly during long flights, if the source case travels in Economy Class. Specifically, two to five infections could occur during a 5 hour flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the aircraft is only partially loaded, under certain conditions more infections could occur in First Class than in Economy Class. During a 17 hour flight, a greater number of infections would occur in First Class than in Economy if the First Class Cabin is fully occupied, but Economy class is less than 30% full. Conclusions Our results provide insights into the potential utility of air travel restrictions on controlling influenza pandemics in the winter of 2009/2010. They show travel by one

  15. Vγ4+γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A

    Directory of Open Access Journals (Sweden)

    Chunxue Xue

    2017-08-01

    Full Text Available The influenza A (H1N1 pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI and acute respiratory distress syndrome (ARDS are the major outcomes among severely infected patients. Our previous study found that interleukin (IL-17A production by humans or mice infected with influenza A (H1N1 pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1 pdm09 infection remained unknown. In this study, a mouse model of severe influenza A (H1N1 pdm09 infection was established. Our results show that, in the lungs of infected mice, the percentage of γδT cells, but not the percentages of CD4+Th and CD8+Tc cells, gradually increased and peaked at 3 days post-infection (dpi. Further analysis revealed that the Vγ4+γδT subset, but not the Vγ1+γδT subset, was significantly increased among the γδT cells. At 3 dpi, the virus induced significant increases in IL-17A in the bronchoalveolar lavage fluid (BALF and serum. IL-17A was predominantly secreted by γδT cells (especially the Vγ4+γδT subset, but not CD4+Th and CD8+Tc cells at the early stage of infection, and IL-1β and/or IL-23 were sufficient to induce IL-17A production by γδT cells. In addition to secreting IL-17A, γδT cells secreted interferon (IFN-γ and expressed both an activation-associated molecule, natural killer group 2, member D (NKG2D, and an apoptosis-associated molecule, FasL. Depletion of γδT cells or the Vγ4+γδT subset significantly rescued the virus-induced weight loss and improved the survival rate by decreasing IL-17A secretion and reducing immunopathological injury. This study demonstrated that, by secreting IL-17A, lung Vγ4+γδT cells, at least, in part mediated influenza A (H1N1 pdm09-induced immunopathological injury. This mechanism might serve as a

  16. La influenza A (H1N1: estado actual del conocimiento Influenza A (H1N1 virus: current information

    Directory of Open Access Journals (Sweden)

    Laura Margarita González Valdés

    2010-03-01

    Full Text Available Se revisó la bibliografía actualizada sobre el tema a partir de los principales buscadores, y reuniones internacionales realizadas sobre la pandemia de la influenza A (H1N1. Se tratan los aspectos relacionados con la historia, la aparición de la pandemia, la biología de la enfermedad, la epidemiología, el cuadro clínico, el tratamiento y el pronóstico y la prevención. La gripe A (H1N1 es una pandemia causada por una variante nueva del virus de la Influenza A que ha sufrido cambios antigénicos en la hemaglutinina y la neuraminidasa. Esto hace que la población sea altamente vulnerable a la infección y produce una sobrecarga temporal enorme a los servicios de salud. El virus se trasmite como otros virus Influenza. Su letalidad es similar a la de la influenza estacional, pero puede incrementarse en personas con factores de riesgo y en adultos jóvenes sanos. El asma y el embarazo parecen ser condiciones de base importantes para incrementar la severidad de la infección. Puede existir cierta protección por inmunidad cruzada con cepas que circularon en el pasado. El espectro clínico va desde personas asintomáticas hasta las formas graves que requieren internación en cuidados intensivos, con rápido deterioro hasta llegar a la insuficiencia respiratoria en un plazo de 24 horas. La vacunación durante la pandemia no parece ser suficientemente efectiva. Son necesarios antivirales (oseltamivir y zanamivir, y las medidas preventivas higiénico-sanitarias son muy eficaces.An updated review using the main search motors and international meetings already celebrated related to Influenza A H1N1 pandemics. Items related to the history, the appearance of the pandemics, the biology of the disease, its epidemiology, clinics, treatment, prognosis and prevention. Grippe A H1N1 is a pandemic caused by a new variant of the Influenza A virus that has suffered antigenic changes in haemaglutinin and neuraminidase. This turns populations more susceptible to

  17. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1 Virus Impairs the Human T Cell Response

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    Nuriban Valero-Pacheco

    2013-01-01

    Full Text Available PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 virus induced PD-L1 expression on human dendritic cells (DCs and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

  18. Immune response after one or two doses of pandemic influenza A (H1N1) monovalent, AS03-adjuvanted vaccine in HIV infected adults

    DEFF Research Database (Denmark)

    Bybeck Nielsen, Allan; Nielsen, Henriette Schjønning; Nielsen, Lars

    2012-01-01

    INTRODUCTION: Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients. METHOD......: Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n=60), one (n=31) or two (n=128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared...... to pre-pandemic antibody titers analyzed from serum samples in a local storage facility. RESULTS: 4-9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97...

  19. Influenza A(H1N1)pdm09 in critically ill children admitted to a ...

    African Journals Online (AJOL)

    tes. Fig. 1. The prevalence of seasonal and pandemic H1N1 (pH1N1) influenza A at RCWMCH and ... Full approval for the study was obtained from the Human Research ... respiratory virus infection, had not received prophylactic oseltamivir,.

  20. Experimental infection of swans and geese with highly pathogenic avian influenza virus (H5N1) of Asian lineage.

    Science.gov (United States)

    Brown, Justin D; Stallknecht, David E; Swayne, David E

    2008-01-01

    The role of wild birds in the epidemiology of the Asian lineage highly pathogenic avian influenza (HPAI) virus subtype H5N1 epizootic and their contribution to the spread of the responsible viruses in Eurasia and Africa are unclear. To better understand the potential role of swans and geese in the epidemiology of this virus, we infected 4 species of swans and 2 species of geese with an HPAI virus of Asian lineage recovered from a whooper swan in Mongolia in 2005, A/whooper swan/Mongolia/244/2005 (H5N1). The highest mortality rates were observed in swans, and species-related differences in clinical illness and viral shedding were evident. These results suggest that the potential for HPAI (H5N1) viral shedding and the movement of infected birds may be species-dependent and can help explain observed deaths associated with HPAI (H5N1) infection in anseriforms in Eurasia.

  1. Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey

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    Blumental Sophie

    2011-11-01

    Full Text Available Abstract Background During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. Methods From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR and probable (positive influenza A antigen or culture pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. Results During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%, concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002 and a higher mortality rate (4% vs 0%, p = 0.06. Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. Conclusion Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

  2. Influenza A H1N1 pneumonia: radiograph and CT features of children

    International Nuclear Information System (INIS)

    Cheng Hua; Duan Xiaomin; Peng Yun; Zeng Jinjin; Sun Guoqiang

    2010-01-01

    Objective: To explore the imaging features on chest radiograph and CT in children with Influenza A H1N1 pneumonia. Methods: The imaging data of chest radiograph and CT in six children with Influenza A H1N1 pneumonia confirmed by real-time RT-PCR assay was retrospectively analysis. All patients had chest radiograph at first examination and 4 of them re-examed. One children took CT. Results: All cases showed thick lung markings with varied degrees of pulmonary infiltration and interstitial changes on chest radiograph. Among them, 3 cases showed bilateral pulmonary infiltration and 3 cases showed infiltration in left lung; enlarged hilar was observed in 3 cases. The imaging findings of the pneumonia changed quickly during the follow-up accompanied with the improvement of clinical symptoms. The only one chest CT examination showed bilateral infiltration, multiple ground-glass opacities, small subpleural nodulars, right pleural effusion and lymphadenopathy of lung hila and mediastinum. Conclusions: Chest radiograph and CT revealed certain typical imaging features in the children with influenza A H1N1 pneumonia. However, the final diagnosis of influenza A H1N1 pneumonia still should be made based on epidemiology and laboratory examination. (authors)

  3. The chest X-ray manifestations of children with highly pathogenic H5N1 avian influenza virus infection (a report of 1 final diagnosis case and 1 borderline case)

    International Nuclear Information System (INIS)

    Jin Ke; Chen Hua; Tan Lihua; Yuan Youhong; Xiao Enhua; Luo Ruping; Li Wanging; Xu Heping

    2006-01-01

    Objective: To describe the chest X-ray manifestations of children with highly pathogenic H5N1 avian influenza virus infection. Methods: The pulmonary X-ray findings in 1 patient was confirmed by the World Health Organization infected H5N1 avian influenza vires and 1 borderline patient was retrospectively analyzed. Results: Both sides of lung field showed the cloudy and massive infiltration in chest X-ray film. The lesions of lung distributed extensively and symmetrically. Radiological dynamic changes showed the variation of the lesions of lung was quick in a short time. It had a characteristic of roving around. The lesions of lung appeared fibrosis at the period of the end. Conclusion: There are some radiographic characteristics in children with H5N1 avian influenza vires infection. It will be helpful for its diagnosis when getting familiar with its X-ray manifestations, but the final diagnosis is dependent on the epidemiology history and laboratory results. (authors)

  4. A historical perspective of influenza A(H1N2) virus.

    Science.gov (United States)

    Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin

    2014-01-01

    The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.

  5. Lethal infection by a novel reassortant H5N1 avian influenza A virus in a zoo-housed tiger.

    Science.gov (United States)

    He, Shang; Shi, Jianzhong; Qi, Xian; Huang, Guoqing; Chen, Hualan; Lu, Chengping

    2015-01-01

    In early 2013, a Bengal tiger (Panthera tigris) in a zoo died of respiratory distress. All specimens from the tiger were positive for HPAI H5N1, which were detected by real-time PCR, including nose swab, throat swab, tracheal swab, heart, liver, spleen, lung, kidney, aquae pericardii and cerebrospinal fluid. One stain of virus, A/Tiger/JS/1/2013, was isolated from the lung sample. Pathogenicity experiments showed that the isolate was able to replicate and cause death in mice. Phylogenetic analysis indicated that HA and NA of A/Tiger/JS/1/2013 clustered with A/duck/Vietnam/OIE-2202/2012 (H5N1), which belongs to clade 2.3.2.1. Interestingly, the gene segment PB2 shared 98% homology with A/wild duck/Korea/CSM-28/20/2010 (H4N6), which suggested that A/Tiger/JS/1/2013 is a novel reassortant H5N1 subtype virus. Immunohistochemical analysis also confirmed that the tiger was infected by this new reassortant HPAI H5N1 virus. Overall, our results showed that this Bengal tiger was infected by a novel reassortant H5N1, suggesting that the H5N1 virus can successfully cross species barriers from avian to mammal through reassortment. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  6. Household transmission of 2009 H1N1 influenza virus in Yazd, Iran

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    F. Behnaz

    2012-08-01

    Full Text Available Summary: Objectives: The 2009 pandemic influenza A (H1N1 virus is a public health challenge. Notably, laboratory-confirmed cases do not represent the age group most susceptible to infection. To characterize the age distribution of all cases of H1N1 influenza, we studied the personal contacts of confirmed cases to identify the age group at the highest risk. Methods: We investigated the family members of 162 laboratory-confirmed cases of 2009 H1N1 in Yazd, Iran. Family members were retrospectively asked whether they had ≥2 respiratory symptoms within 7 days of the last contact with the associated index cases. The ages and symptoms of the patients as well as the interval between diagnosis and the onset of symptoms among household contacts were determined using a questionnaire. Results: We identified 596 family members of index cases, 83 (13.9% of whom developed acute respiratory illness. No acute respiratory illness was found in 104 families (64%; however, there were 2 cases in 15 families (9.3% and ≥3 cases in 4 families (24%. Household contacts from 5 to 18 years old were more susceptible to acute respiratory illness than those who were ≥51 years old (RR = 3.174, 95% CI 1.313–7.675 P-value = 0.01. Conclusion: Individuals ≤18 years old were most susceptible to infection by the H1N1 virus. Therefore, in low-income populations, prevention of the spread of H1N1 to this age group should be emphasized. Keywords: Household transmission, 2009 Influenza A (H1N1 virus

  7. Experimental infection of a North American raptor, American kestrel (Falco sparverius), with highly pathogenic avian influenza virus (H5N1)

    Science.gov (United States)

    Hall, Jeffrey S.; Ip, Hon S.; Franson, J.C.; Meteyer, C.; Nashold, Sean W.; Teslaa, Joshua L.; French, J.; Redig, P.; Brand, C.

    2009-01-01

    Several species of wild raptors have been found in Eurasia infected with highly pathogenic avian influenza virus (HPAIV) subtype H5N1. Should HPAIV (H5N1) reach North America in migratory birds, species of raptors are at risk not only from environmental exposure, but also from consuming infected birds and carcasses. In this study we used American kestrels as a representative species of a North American raptor to examine the effects of HPAIV (H5N1) infection in terms of dose response, viral shedding, pathology, and survival. Our data showed that kestrels are highly susceptible to HPAIV (H5N1). All birds typically died or were euthanized due to severe neurologic disease within 4-5 days of inoculation and shed significant amounts of virus both orally and cloacally, regardless of dose administered. The most consistent microscopic lesions were necrosis in the brain and pancreas. This is the first experimental study of HPAIV infection in a North American raptor and highlights the potential risks to birds of prey if HPAIV (H5N1) is introduced into North America.

  8. HIV-1 and its gp120 inhibits the influenza A(H1N1)pdm09 life cycle in an IFITM3-dependent fashion.

    Science.gov (United States)

    Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q; Abrantes, Juliana L; Costa, Eduardo; Temerozo, Jairo R; Siqueira, Marilda M; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L

    2014-01-01

    HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.

  9. HIV-1 and its gp120 inhibits the influenza A(H1N1pdm09 life cycle in an IFITM3-dependent fashion.

    Directory of Open Access Journals (Sweden)

    Milene Mesquita

    Full Text Available HIV-1-infected patients co-infected with A(H1N1pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1pdm09 life cycle in vitro. We show here that exposure of A(H1N1pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA gene from in vitro experiments and from samples of HIV-1/A(H1N1pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1pdm09 co-infected patients during the recent influenza form 2009/2010.

  10. Outbreaks of avian influenza A (H5N2), (H5N8), and (H5N1) among birds--United States, December 2014-January 2015.

    Science.gov (United States)

    Jhung, Michael A; Nelson, Deborah I

    2015-02-06

    During December 15, 2014-January 16, 2015, the U.S. Department of Agriculture received 14 reports of birds infected with Asian-origin, highly pathogenic avian influenza A (HPAI) (H5N2), (H5N8), and (H5N1) viruses. These reports represent the first reported infections with these viruses in U.S. wild or domestic birds. Although these viruses are not known to have caused disease in humans, their appearance in North America might increase the likelihood of human infection in the United States. Human infection with other avian influenza viruses, such as HPAI (H5N1) and (H5N6) viruses and (H7N9) virus, has been associated with severe, sometimes fatal, disease, usually following contact with poultry.

  11. H1N1 influenza (Swine flu)

    Science.gov (United States)

    Swine flu; H1N1 type A influenza ... The H1N1 virus is now considered a regular flu virus. It is one of the three viruses included in the regular (seasonal) flu vaccine . You cannot get H1N1 flu virus from ...

  12. Experiences after Twenty Months with Pandemic Influenza A (H1N1) 2009 Infection in the Naïve Norwegian Pig Population

    Science.gov (United States)

    Gjerset, B.; Er, C.; Løtvedt, S.; Jørgensen, A.; Hungnes, O.; Lium, B.; Germundsson, A.

    2011-01-01

    Pandemic (H1N1) 2009 influenza A virus was detected in Norwegian pigs in October 2009. Until then, Norway was regarded free of swine influenza. Intensified screening revealed 91 positive herds within three months. The virus was rapidly transmitted to the susceptible population, including closed breeding herds with high biosecurity. Humans were important for the introduction as well as spread of the virus to pigs. Mild or no clinical signs were observed in infected pigs. Surveillance of SIV in 2010 revealed that 41% of all the Norwegian pig herds had antibodies to pandemic (H1N1) 2009 virus. Furthermore, this surveillance indicated that pigs born in positive herds after the active phase did not seroconvert, suggesting no ongoing infection in the herds. However, results from surveillance in 2011 show a continuing spread of the infection in many herds, either caused by new introduction or by virus circulation since 2009. PMID:23074654

  13. Clinical aspects of influenza A (H1N1 in HIV-infected individuals in São Paulo during the pandemic of 2009

    Directory of Open Access Journals (Sweden)

    Rosana Del Bianco

    Full Text Available OBJECTIVE: To describe the clinical aspects of H1N1 among HIV coinfected patients seen at a reference center for AIDS treatment in São Paulo, Brazil. Design: Observational and prospective cohort study. METHODS: Descriptive study of clinical and laboratory investigation of HIV-infected patients with confirmed diagnosis of influenza A (H1N1 in 2009. We analyzed patients monitored in CRT/DST/AIDS, a specialized service for people living with HIV, located in São Paulo, Brazil. RESULTS: 108 individuals presented with symptoms of H1N1 infection at the CRT DST/AIDS in 2009. Eighteen patients (16.7% had confirmation of the diagnosis of influenza A. Among the confirmed cases, ten (55.6% were hospitalized and eight (44.4% were outpatients. Dyspnea was present in nine patients (50%, hemoptysis in three (16%. Six patients (60% required therapy with supplemental oxygen. All patients had good clinical outcomes and none died. CONCLUSIONS: In our hospital, the symptoms that led patients to seek medical care were similar to the common flu. Hospital admission and the early introduction of antibiotics associated with oseltamivir may have been the cause of the favorable outcome of our cases.

  14. Don't let the flu catch you: agency assignment in printed educational materials about the H1N1 influenza virus.

    Science.gov (United States)

    McGlone, Matthew S; Bell, Robert A; Zaitchik, Sarah T; McGlynn, Joseph

    2013-01-01

    In English and in other languages, the agency for viral transmission can be grammatically assigned to people (e.g., Thousands may contract H1N1) or to the virus itself (e.g., H1N1 may infect thousands). These assignment options shape different conceptions of transmission as attributable either to social contact within one's control or to pursuit of an active predator. The authors tested the effect of agency assignment and agentic images on young adults' (N = 246) reactions to educational materials about H1N1 influenza. The authors hypothesized that assigning agency to the virus would heighten perceived severity and personal susceptibility relative to human agency assignment. Results were consistent with this hypothesis, indicating that virus agency increased perceptions of severity, personal susceptibility, and reported intentions to seek vaccination relative to human agency. The image manipulation did not directly affect these factors. The findings suggest that strategic agency assignment can improve the effectiveness of educational materials about influenza and other health threats.

  15. Research of H5N6 Treatment by Comparing with H6N1 and H10N8 by Using Decision Tree and Apriori Algorithm

    Directory of Open Access Journals (Sweden)

    Kim Sunghyun

    2016-01-01

    Full Text Available Since 2003, 608 people in 15 countries have infected with human-infectious AI viruses and 359 of them died. Especially, in China, H6N1 and H10N8 viruses were wide-spread and a lot of people were infected and died. Recently, H5N6 virus emerged in China and the number of patients has been increasing gradually. Therefore, this research compared amino acid strain of Matrix Protein, Hemagglutinin, Neuraminidase and Nucleoprotein of H5N6, H6N1 and H10N8, by using Decision tree and Apriori Algorithm, to figure out their similarity and devise the treatment. In result, Matrix protein and Nucleoprotein sequences of H5N6 were similar with those of H6N1 and H10N8. Therefore, this research concluded that the treatment targeting those proteins of H6N1 and H10N8 will be also effective to H5N6.

  16. An Outbreak of 2009 Pandemic Influenza A (H1N1) Virus Infection in an Elementary School in Pennsylvania

    Science.gov (United States)

    Bhattarai, Achuyt; Fagan, Ryan P.; Ostroff, Stephen; Sodha, Samir V.; Moll, Mària E.; Lee, Bruce Y.; Chang, Chung-Chou H.; Ennis, Brent; Britz, Phyllis; Fiore, Anthony; Nguyen, Michael; Palekar, Rakhee; Archer, W. Roodly; Gift, Thomas L.; Leap, Rebecca; Nygren, Benjamin L.; Cauchemez, Simon; Angulo, Frederick J.; Swerdlow, David

    2011-01-01

    In May 2009, one of the earliest outbreaks of 2009 pandemic influenza A virus (pH1N1) infection resulted in the closure of a semi-rural Pennsylvania elementary school. Two sequential telephone surveys were administered to 1345 students (85% of the students enrolled in the school) and household members in 313 households to collect data on influenza-like illness (ILI). A total of 167 persons (12.4%) among those in the surveyed households, including 93 (24.0%) of the School A students, reported ILI. Students were 3.1 times more likely than were other household members to develop ILI (95% confidence interval [CI], 2.3–4.1). Fourth-grade students were more likely to be affected than were students in other grades (relative risk, 2.2; 95% CI, 1.2–3.9). pH1N1 was confirmed in 26 (72.2%) of the individuals tested by real-time reverse-transcriptase polymerase chain reaction. The outbreak did not resume upon the reopening of the school after the 7-day closure. This investigation found that pH1N1 outbreaks at schools can have substantial attack rates; however, grades and classrooms are affected variably. Additioanl study is warranted to determine the effectiveness of school closure during outbreaks. PMID:21342888

  17. Pathogenesis of highly pathogenic avian influenza A/turkey/Turkey/1/2005 H5N1 in Pekin ducks (Anas platyrhynchos) infected experimentally.

    Science.gov (United States)

    Löndt, Brandon Z; Nunez, Alejandro; Banks, Jill; Nili, Hassan; Johnson, Linda K; Alexander, Dennis J

    2008-12-01

    Asian H5N1 (hereafter referred to as panzootic H5N1) highly pathogenic avian influenza (HPAI) virus has caused large numbers of deaths in both poultry and wild-bird populations. Recent isolates of this virus have been reported to cause disease and death in commercial ducks, which has not been seen with other HPAI viruses. However, little is known about either the dissemination of this H5N1 within the organs or the cause of death in infected ducks. Nineteen 4-week-old Pekin ducks were infected with 10(6.7) median egg infectious doses of HPAI A/turkey/Turkey/1/05 (H5N1, clade 2.2) in 0.1ml via the intranasal and intraocular routes. Cloacal and oropharyngeal swabs were taken daily before three animals were selected randomly and killed humanely for postmortem examination, when samples of tissues were taken for real-time reverse transcriptase-polymerase chain reaction, histopathological examination and immunohistochemistry. Clinical signs were first observed 4 days post infection (d.p.i.) and included depression, reluctance to feed, in-coordination and torticollis resulting in the death of all the birds remaining on 5d.p.i. Higher levels of virus shedding were detected from oropharyngeal swabs than from cloacal swabs. Real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry identified peak levels of virus at 2d.p.i. in several organs. In the spleen, lung, kidney, caecal tonsils, breast muscle and thigh muscle the levels were greatly reduced at 3d.p.i. However, the highest viral loads were detected in the heart and brain from 3d.p.i. and coincided with the appearance of clinical signs and death. Our experimental results demonstrate the systemic spread of this HPAI H5N1 virus in Pekin ducks, and the localization of virus in the brain and heart tissue preceding death.

  18. Risk of influenza A (H5N1) infection among poultry workers, Hong Kong, 1997-1998.

    Science.gov (United States)

    Bridges, Carolyn Buxton; Lim, Wilina; Hu-Primmer, Jean; Sims, Les; Fukuda, Keiji; Mak, K H; Rowe, Thomas; Thompson, William W; Conn, Laura; Lu, Xiuhua; Cox, Nancy J; Katz, Jacqueline M

    2002-04-15

    In 1997, outbreaks of highly pathogenic influenza A (H5N1) among poultry coincided with 18 documented human cases of H5N1 illness. Although exposure to live poultry was associated with human illness, no cases were documented among poultry workers (PWs). To evaluate the potential for avian-to-human transmission of H5N1, a cohort study was conducted among 293 Hong Kong government workers (GWs) who participated in a poultry culling operation and among 1525 PWs. Paired serum samples collected from GWs and single serum samples collected from PWs were considered to be anti-H5 antibody positive if they were positive by both microneutralization and Western blot testing. Among GWs, 3% were seropositive, and 1 seroconversion was documented. Among PWs, approximately 10% had anti-H5 antibody. More-intensive poultry exposure, such as butchering and exposure to ill poultry, was associated with having anti-H5 antibody. These findings suggest an increased risk for avian influenza infection from occupational exposure.

  19. A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

    Science.gov (United States)

    Yang, Ji-Rong; Chen, Chih-Yuan; Kuo, Chuan-Yi; Cheng, Chieh-Yu; Lee, Min-Shiuh; Cheng, Ming-Chu; Yang, Yu-Chih; Wu, Chia-Ying; Wu, Ho-Sheng; Liu, Ming-Tsan; Hsiao, Pei-Wen

    2016-02-01

    Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid.

    Science.gov (United States)

    You, Huey-Ling; Huang, Chao-Chun; Chen, Chung-Jen; Chang, Cheng-Chin; Liao, Pei-Lin; Huang, Sheng-Teng

    2018-05-01

    The pandemic influenza A (H1N1) virus has spread worldwide and infected a large proportion of the human population. Discovery of new and effective drugs for the treatment of influenza is a crucial issue for the global medical community. According to our previous study, TSL-1, a fraction of the aqueous extract from the tender leaf of Toonasinensis, has demonstrated antiviral activities against pandemic influenza A (H1N1) through the down-regulation of adhesion molecules and chemokine to prevent viral attachment. The aim of the present study was to identify the active compounds in TSL-1 which exert anti-influenza A (H1N1) virus effects. XTT assay was used to detect the cell viability. Meanwhile, the inhibitory effect on the pandemic influenza A (H1N1) virus was analyzed by observing plaque formation, qRT-PCR, neuraminidase activity, and immunofluorescence staining of influenza A-specific glycoprotein. Both catechin and gallic acid were found to be potent inhibitors in terms of influenza virus mRNA replication and MDCK plaque formation. Additionally, both compounds inhibited neuraminidase activities and viral glycoprotein. The 50% effective inhibition concentration (EC 50 ) of catechin and gallic acid for the influenza A (H1N1) virus were 18.4 μg/mL and 2.6 μg/mL, respectively; whereas the 50% cytotoxic concentrations (CC 50 ) of catechin and gallic acid were >100 μg/mL and 22.1 μg/mL, respectively. Thus, the selectivity indexes (SI) of catechin and gallic acid were >5.6 and 22.1, respectively. The present study demonstrates that catechin might be a safe reagent for long-term use to prevent influenza A (H1N1) virus infection; whereas gallic acid might be a sensitive reagent to inhibit influenza virus infection. We conclude that these two phyto-chemicals in TSL-1 are responsible for exerting anti-pandemic influenza A (H1N1) virus effects. Copyright © 2017. Published by Elsevier Taiwan LLC.

  1. Experimental infection of a North American raptor, American Kestrel (Falco sparverius, with highly pathogenic avian influenza virus (H5N1.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Hall

    2009-10-01

    Full Text Available Several species of wild raptors have been found in Eurasia infected with highly pathogenic avian influenza virus (HPAIV subtype H5N1. Should HPAIV (H5N1 reach North America in migratory birds, species of raptors are at risk not only from environmental exposure, but also from consuming infected birds and carcasses. In this study we used American kestrels as a representative species of a North American raptor to examine the effects of HPAIV (H5N1 infection in terms of dose response, viral shedding, pathology, and survival. Our data showed that kestrels are highly susceptible to HPAIV (H5N1. All birds typically died or were euthanized due to severe neurologic disease within 4-5 days of inoculation and shed significant amounts of virus both orally and cloacally, regardless of dose administered. The most consistent microscopic lesions were necrosis in the brain and pancreas. This is the first experimental study of HPAIV infection in a North American raptor and highlights the potential risks to birds of prey if HPAIV (H5N1 is introduced into North America.

  2. Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans.

    Science.gov (United States)

    Kalthoff, Donata; Breithaupt, Angele; Teifke, Jens P; Globig, Anja; Harder, Timm; Mettenleiter, Thomas C; Beer, Martin

    2008-08-01

    Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity.

  3. Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: the INSIGHT FLU 002 and FLU 003 studies

    DEFF Research Database (Denmark)

    Dwyer, Dominic E; Nielsen, Henrik Ib

    2011-01-01

    The novel pandemic influenza A (H1H1) 2009 virus spread rapidly around the world in 2009. The paucity of prospective international epidemiologic data on predictors of clinical outcomes with pandemic (H1N1) 2009 virus infection stimulated the INSIGHT network, an international network of community...... and hospital-based investigators, to commence two worldwide clinical observational studies to describe pandemic (H1N1) 2009 virus activity. The purpose of these two studies was to estimate the percent of adult patients with illness due to laboratory-confirmed pandemic (H1N1) 2009 virus infection...

  4. Corticosteroid treatment ameliorates acute lung injury induced by 2009 swine origin influenza A (H1N1 virus in mice.

    Directory of Open Access Journals (Sweden)

    Chenggang Li

    Full Text Available BACKGROUND: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection. METHODOLOGY/PRINCIPAL FINDINGS: We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection. CONCLUSIONS/SIGNIFICANCE: Using the established, very susceptible 2009 Pandemic Influenza A (H1N1 mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1 pandemics.

  5. Protection from the 2009 H1N1 pandemic influenza by an antibody from combinatorial survivor-based libraries.

    Directory of Open Access Journals (Sweden)

    Arun K Kashyap

    2010-07-01

    Full Text Available Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06 against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 "Swine" H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population.

  6. Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case–control study

    Directory of Open Access Journals (Sweden)

    Morales-García Guadalupe

    2012-11-01

    Full Text Available Abstract Background Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Methods Case–control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR and the 95% confidence interval (95% CI were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Results Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77; LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32; TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64; additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13. Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05; those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05. The IL1B rs16944 AA

  7. Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study.

    Science.gov (United States)

    Morales-García, Guadalupe; Falfán-Valencia, Ramcés; García-Ramírez, Román Alejandro; Camarena, Ángel; Ramirez-Venegas, Alejandra; Castillejos-López, Manuel; Pérez-Rodríguez, Martha; González-Bonilla, César; Grajales-Muñíz, Concepción; Borja-Aburto, Víctor; Mejía-Aranguré, Juan Manuel

    2012-11-13

    Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Case-control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07-1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82-10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48-12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of

  8. Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case–control study

    Science.gov (United States)

    2012-01-01

    Background Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. Methods Case–control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. Results Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07–1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82–10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48–12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated

  9. Pandemic influenza A/H1N1 virus incursion into Africa: countries ...

    African Journals Online (AJOL)

    Pandemic influenza A/H1N1 virus incursion into Africa: countries, hosts and ... features are important for planning control measures between countries and to ... in humans, infections in pigs earlier reported in America, Europe and Asia were ...

  10. Protection of guinea pigs by vaccination with a recombinant swinepox virus co-expressing HA1 genes of swine H1N1 and H3N2 influenza viruses.

    Science.gov (United States)

    Xu, Jiarong; Yang, Deji; Huang, Dongyan; Xu, Jiaping; Liu, Shichao; Lin, Huixing; Zhu, Haodan; Liu, Bao; Lu, Chengping

    2013-03-01

    Swine influenza (SI) is an acute respiratory infectious disease of swine caused by swine influenza virus (SIV). SIV is not only an important respiratory pathogen in pigs but also a potent threat to human health. Here, we report the construction of a recombinant swinepox virus (rSPV/H3-2A-H1) co-expressing hemagglutinin (HA1) of SIV subtypes H1N1 and H3N2. Immune responses and protection efficacy of the rSPV/H3-2A-H1 were evaluated in guinea pigs. Inoculation of rSPV/H3-2A-H1 yielded neutralizing antibodies against SIV H1N1 and H3N2. The IFN-γ and IL-4 concentrations in the supernatant of lymphocytes stimulated with purified SIV HA1 antigen were significantly higher (P guinea pigs against SIV H1N1 or H3N2 challenge was observed. No SIV shedding was detected from guinea pigs vaccinated with rSPV/H3-2A-H1 after challenge. Most importantly, the guinea pigs immunized with rSPV/H3-2A-H1 did not show gross and micrographic lung lesions. However, the control guinea pigs experienced distinct gross and micrographic lung lesions at 7 days post-challenge. Our data suggest that the recombinant swinepox virus encoding HA1 of SIV H1N1 and H3N2 might serve as a promising candidate vaccine for protection against SIV H1N1 and H3N2 infections.

  11. Susceptibility of turkeys to pandemic-H1N1 virus by reproductive tract insemination

    Directory of Open Access Journals (Sweden)

    Suarez David L

    2010-02-01

    Full Text Available Abstract The current pandemic influenza A H1N1 2009 (pH1N1 was first recognized in humans with acute respiratory diseases in April 2009 in Mexico, in swine in Canada in June, 2009 with respiratory disease, and in turkeys in Chile in June 2009 with a severe drop in egg production. Several experimental studies attempted to reproduce the disease in turkeys, but failed to produce respiratory infection in turkeys using standard inoculation routes. We demonstrated that pH1N1 virus can infect the reproductive tract of turkey hens after experimental intrauterine inoculation, causing decreased egg production. This route of exposure is realistic in modern turkey production because turkey hens are handled once a week for intrauterine insemination in order to produce fertile eggs. This understanding of virus exposure provides an improved understanding of the pathogenesis of the disease and can improve poultry husbandry to prevent disease outbreaks.

  12. Avian influenza A H5N1 infections in Bali Province, Indonesia: a behavioral, virological and seroepidemiological study.

    Science.gov (United States)

    Santhia, Ketut; Ramy, Ayu; Jayaningsih, Putri; Samaan, Gina; Putra, Anak Agung Gde; Dibia, Nyoman; Sulaimin, Cynthia; Joni, Gusti; Leung, Connie Y H; Sriyal, Joseph; Peiris, Malik; Wandra, Toni; Kandun, Nyoman

    2009-05-01

    Bali Province was affected by avian influenza H5N1 outbreaks in birds in October 2003. Despite ongoing circulation of the virus, no human infection had been identified by December 2005. To assess behavioral patterns associated with poultry rearing in Bali, and to identify potential risk factors for H5N1 infection in humans and in household chickens, ducks and pigs. A behavioral, virological and seroepidemiologic survey in 38 villages and three live bird markets was completed in December 2005. A multi-stage cluster design was used to select 291 households with 841 participants from all nine districts in Bali. Specimens were collected from participants as well as a maximum of three pigs, chickens and ducks from each household. Eighty-seven market vendors participated, where specimens were collected from participants as well as chickens and ducks. Twenty out of the 38 villages sampled had H5N1 outbreaks. Despite exposure to H5N1 outbreaks, none of the participants from villages or markets were seropositive for H5N1. None of the pigs tested were positive for H5N1. Virus isolation rate in ducks and chicken in markets was higher than in households. Transport of poultry in or out of villages was a risk factor for outbreaks in household chickens and ducks. The study highlighted that the market chain and associated behaviors may play a role in maintaining the virus in household flocks. The study adds evidence that transmission of H5N1 to humans remains a rare event despite high level handling of both healthy and sick birds.

  13. The comparative clinical course of pregnant and non-pregnant women hospitalised with influenza A(H1N1pdm09 infection.

    Directory of Open Access Journals (Sweden)

    Gayle P Dolan

    Full Text Available The Influenza Clinical Information Network (FLU-CIN was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy.A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15-44 years, using univariate and multivariable techniques.Of the 395 women aged 15-44 years, 82 (21% were pregnant; 73 (89% in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30-0.82, require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20-0.80, or have underlying co-morbidities (p-trend <0.001. However, they were equally likely to be admitted to high dependency (Level 2 or intensive care (Level 3 and/or to die, after adjustment for potential confounders (adj. OR = 0.93 (95% CI: 0.46-1.92. Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died.Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups.

  14. Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

    Science.gov (United States)

    Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

    2011-09-28

    Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Antigenically Diverse Swine Origin H1N1 Variant Influenza Viruses Exhibit Differential Ferret Pathogenesis and Transmission Phenotypes.

    Science.gov (United States)

    Pulit-Penaloza, Joanna A; Jones, Joyce; Sun, Xiangjie; Jang, Yunho; Thor, Sharmi; Belser, Jessica A; Zanders, Natosha; Creager, Hannah M; Ridenour, Callie; Wang, Li; Stark, Thomas J; Garten, Rebecca; Chen, Li-Mei; Barnes, John; Tumpey, Terrence M; Wentworth, David E; Maines, Taronna R; Davis, C Todd

    2018-06-01

    Influenza A(H1) viruses circulating in swine represent an emerging virus threat, as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed. Antigenic analysis of the virus isolated from the fatal case, A/Ohio/09/2015, demonstrated significant antigenic drift away from the classical swine H1N1 variant viruses and H1N1 pandemic 2009 viruses. A substitution in the H1 hemagglutinin (G155E) was identified that likely impacted antigenicity, and reverse genetics was employed to understand the molecular mechanism of antibody escape. Reversion of the substitution to 155G, in a reverse genetics A/Ohio/09/2015 virus, showed that this residue was central to the loss of hemagglutination inhibition by ferret antisera raised against a prototypical H1N1 pandemic 2009 virus (A/California/07/2009), as well as gamma lineage classical swine H1N1 viruses, demonstrating the importance of this residue for antibody recognition of this H1 lineage. When analyzed in the ferret model, A/Ohio/09/2015 and another H1N1v virus, A/Iowa/39/2015, as well as A/California/07/2009, replicated efficiently in the respiratory tract of ferrets. The two H1N1v viruses transmitted efficiently among cohoused ferrets, but respiratory droplet transmission studies showed that A/California/07/2009 transmitted through the air more efficiently. Preexisting immunity to A/California/07/2009 did not fully protect ferrets from challenge with A/Ohio/09/2015. IMPORTANCE Human infections with classical swine influenza A(H1N1) viruses that circulate in pigs continue to occur in the United States following exposure to swine. To

  16. Immunomorphologic Manifestations in Mice Liver Infected with Influenza A/H5N1, A/Goose/Krasnoozerskoye/627/05 Strain

    Directory of Open Access Journals (Sweden)

    Oxana V. Potapova

    2013-01-01

    Full Text Available Highly pathogenic avian influenza H5N1 (HPAI H5N1 viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate. In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses. The changes in mice liver infected with HPAI H5N1 virus A/goose/Krasnoozerskoye/627/05 have been studied. It has been shown that the virus persistence in the liver leads to the expression of proinflammatory cytokines (TNF-α, IL-6 and intracellular proteases (lysozyme, cathepsin D, and myeloperoxidase by Kupffer cells. Defective antiviral response exacerbates destructive processes in the liver accelerating the development of liver failure.

  17. A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

    Directory of Open Access Journals (Sweden)

    Hana Apsari Pawestri

    2016-07-01

    Full Text Available Abstrak Tujuan. Protein PB1-F2 (polymerase basic 1-frame 2 adalah protein terbaru yang ditemukan pada virus Influenza dan telah terbukti berperan dalam induksi kematian sel dan patogenitas. Tujuan dari tulisan ini adalah untuk menganalisis protein PB1-F2 pada virus Influenza A/H5N1 dan A/H1N1pdm09. Metode. Kami melakukan pencarian data yang relevan yaitu sekuens gen virus Influenza A/H5N1 dan A/H1N1pdm09 dari Gen Bank National Center for Biotechnology Information (NCBI selama tahun 1997-2015. Data yang digunakan adalah data sekuens nukleotida gen PB1 (polymerase basic1 virus influenza A/H5N1 dan A/H1N1pdm09. Kemudian dilakukan analisis alignment untuk mengetahui variasi protein dan mutasi yang berhubungan dengan patogenitas dan virulensi. Hasil. Kami melakukan penelitian terhadap sekuens PB1-F2 sebanyak 3262 influenza A/H5N1 dan 2472 Influenza A/H1N1pdm09. Hasil analisis menunjukkan bahwa semua sekuens A/H5N1 memiliki panjang yang penuh sebanyak 90 asam amino, kecuali influenza pandemi 2009 hanya memiliki panjang 87 asam amino. Kemudian, ditemukan mutasi yang berhubungan dengan virulensi yang ditunjukan dengan perubahan asam amino Asparagin (N menjadi Serin (S. Mutasi tersebut terjadi pada Influenza A/H5N1 sebanyak 8.5% dan Influenza A/H1N1pdm09 sebanyak 0.5%. Kesimpulan. Ditemukan beberapa variasi panjang asam amino dan mutasi penting pada sekuens PB1-F2 dari subtipe yang berbeda yaitu influenza A/H5N1 dan A/H1N1pdm09  yang mengindikasikan seleksi spesifik karena introduksi dan adaptasi terhadap inang yang berbeda. Diperlukan penelitian lanjutan untuk lebih memahami variasi dan kontribusi protein PB1-F2 tersebut terhadap virulensi dan patogenitas virus Influenza. Kata kunci : Patogenesis, Virus Influenza, Protein  PB1-F2 Abstract Aim. Influenza virus PB1-F2 (polymerase basic 1-frame 2 protein is a novel protein previously shown to be involved in cell death induction and pathogenesis. Here we analysis the PB1-F2 protein of Influenza virus A/H

  18. A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

    Directory of Open Access Journals (Sweden)

    Hana Apsari Pawestri

    2016-07-01

    Full Text Available Abstrak Tujuan. Protein PB1-F2 (polymerase basic 1-frame 2 adalah protein terbaru yang ditemukan pada virus Influenza dan telah terbukti berperan dalam induksi kematian sel dan patogenitas. Tujuan dari tulisan ini adalah untuk menganalisis protein PB1-F2 pada virus Influenza A/H5N1 dan A/H1N1pdm09. Metode. Kami melakukan pencarian data yang relevan yaitu sekuens gen virus Influenza A/H5N1 dan A/H1N1pdm09 dari Gen Bank National Center for Biotechnology Information (NCBI selama tahun 1997-2015. Data yang digunakan adalah data sekuens nukleotida gen PB1 (polymerase basic1 virus influenza A/H5N1 dan A/H1N1pdm09. Kemudian dilakukan analisis alignment untuk mengetahui variasi protein dan mutasi yang berhubungan dengan patogenitas dan virulensi. Hasil. Kami melakukan penelitian terhadap sekuens PB1-F2 sebanyak 3262 influenza A/H5N1 dan 2472 Influenza A/H1N1pdm09. Hasil analisis menunjukkan bahwa semua sekuens A/H5N1 memiliki panjang yang penuh sebanyak 90 asam amino, kecuali influenza pandemi 2009 hanya memiliki panjang 87 asam amino. Kemudian, ditemukan mutasi yang berhubungan dengan virulensi yang ditunjukan dengan perubahan asam amino Asparagin (N menjadi Serin (S. Mutasi tersebut terjadi pada Influenza A/H5N1 sebanyak 8.5% dan Influenza A/H1N1pdm09 sebanyak 0.5%. Kesimpulan. Ditemukan beberapa variasi panjang asam amino dan mutasi penting pada sekuens PB1-F2 dari subtipe yang berbeda yaitu influenza A/H5N1 dan A/H1N1pdm09  yang mengindikasikan seleksi spesifik karena introduksi dan adaptasi terhadap inang yang berbeda. Diperlukan penelitian lanjutan untuk lebih memahami variasi dan kontribusi protein PB1-F2 tersebut terhadap virulensi dan patogenitas virus Influenza. Kata kunci : Patogenesis, Virus Influenza, Protein  PB1-F2 Abstract Aim. Influenza virus PB1-F2 (polymerase basic 1-frame 2 protein is a novel protein previously shown to be involved in cell death induction and pathogenesis. Here we analysis the PB1-F2 protein of Influenza virus A/H

  19. 2009 H1N1 Flu Vaccine Facts

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of ... the H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials ...

  20. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Paquette, Stéphane G. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Banner, David [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Chi, Le Thi Bao [Department of Microbiology, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Carlo Urbani Centre, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Leon, Alberto J. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); Xu, Luoling; Ran, Longsi [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Huang, Stephen S.H. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Farooqui, Amber [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); and others

    2014-01-05

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development.

  1. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    International Nuclear Information System (INIS)

    Paquette, Stéphane G.; Banner, David; Chi, Le Thi Bao; Leon, Alberto J.; Xu, Luoling; Ran, Longsi; Huang, Stephen S.H.; Farooqui, Amber

    2014-01-01

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development

  2. Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility.

    Directory of Open Access Journals (Sweden)

    Stefano Merler

    Full Text Available BACKGROUND: A common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated. METHODS: The level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40, was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model. RESULTS: By comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%. Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI. CONCLUSIONS: Our results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in

  3. Pathogenicity of Highly Pathogenic Avian Influenza Virus H5N1 in Naturally Infected Poultry in Egypt.

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    Ibrahim Thabet Hagag

    Full Text Available Highly pathogenic avian influenza virus (HPAIV H5N1 has been endemic in Egypt since 2006, and there is increasing concern for its potential to become highly transmissible among humans. Infection by HPAIV H5N1 has been described in experimentally challenged birds. However, the pathogenicity of the H5N1 isolated in Egypt has never been reported in naturally infected chickens and ducks. Here we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck for chickens, and nervous signs (torticollis for ducks. Within 48-72 hrs of the onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of chickens and ducks were collected for analyses with cross-section immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts. While viral RNA was detected in nearly all tissues and sera collected, viral nucleoprotein was detected almost ubiquitously in all tissues, including testis. Interestingly, viral antigen was also observed in endothelial cells of most organs in chickens, and clearly detected in the trachea and brain in particular. Viral nucleoprotein was also detected in mononuclear cells of various organs, especially pulmonary tissue. We performed phylogenetic analyses and compared the genomic sequences of the hemagglutinin (HA and nonstructural proteins (NS among the isolated viruses, the HPAIV circulated in Egypt in the past and currently, and some available vaccine strains. Further analysis of deduced amino acids of both HA and NS1 revealed that our isolates carried molecular determinants of HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF in the cleavage site in HA and glutamate at position 92 (D92E in NS1. This is the first report of the pathogenicity

  4. Outcomes of influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E

    2014-01-01

    BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were...

  5. Pandemic H1N1 2009 ('swine flu'): diagnostic and other challenges.

    Science.gov (United States)

    Burkardt, Hans-Joachim

    2011-01-01

    Pandemic H1N1 2009 ('swine flu') virus was 'the virus of the year 2009' because it affected the lives of many people in this year. H1N1 was first described in California in April 2009 and spread very rapidly all over the globe. The fast global penetration of the swine flu caused the WHO in Geneva to call the infection with H1N1 a new pandemic with a rapid escalation of the different pandemic phases that ended on 11 June 2009, with the declaration of phase 6 (full-blown pandemic). This had far-reaching consequences for the local health authorities in the different affected countries and created awareness in the public and fear in the experts and even more so in many lay people. The consequences were: setting up reliable diagnostic tests as soon as possible; enhanced production, distribution and stock creation of the few drugs that were available to treat newly infected persons; and development, production, distribution and stock creation of new and appropriate anti-H1N1 swine flu vaccines. This all resulted in enormous costs in the local healthcare systems and also required smart and diligent logistics, because demand for all this was, in most cases, much higher than availability. Fortunately, the pandemic ended quite quickly (there was no 'second wave' as had been anticipated by some experts) and the death toll was moderate, compared with other influenza pandemic in the past and even to the regular annual appearance of the seasonal flu. This favorable outcome, however, provoked some harsh criticism that the WHO and healthcare systems in general had over-reacted and by doing so, a lot of money was thrown out of the window. This article describes the history of the H1N1 pandemic, the diagnostic challenges and resolutions, touches on treatment and vaccination very briefly and also comments on the criticism and arguments that came up immediately at the end and following the termination of the pandemic situation.

  6. Swine-origin influenza A viral (H1N1) infection in children. Chest computed tomography findings

    International Nuclear Information System (INIS)

    Im, Soo-Ah; Kim, Hyo-Lim; Yoon, Jong-seo; Kang, Jin-Han; Lee, Joon-Sung; Chun, Ho-Jong

    2011-01-01

    The aim of this study was to review the chest computed tomography (CT) findings in children with swine-origin influenza (H1N1) virus (S-OIV) infection. The radiologists retrospectively reviewed chest CT findings in 12 children with S-OIV infection and recorded the following findings: ground-glass opacities (GGO), consolidation, nodules, reticular opacities, peribronchial cuffing, and air trapping; distribution; affected lobes. The presence of pleural effusions, pneumomediastinum, pulmonary interstitial emphysema (PIE), and lymphadenopathy was also recorded. Chest CT revealed GGO (67%), consolidation (67%), nodules (25%), peribronchial cuffing (42%), and air trapping (33%). The distribution of the lesions was random (75%), peribronchial (17%), or subpleural (8%). The lobes affected were the lower (92%), upper (58%), and middle (17%) lobes. There were associated pleural effusions (42%), PIE (42%), pneumomediastinum (33%), and lymphadenopathy (75%). Among five patients with air-leak complications, three had a history of allergies and three required the intensive care unit. Chest CT findings in children with S-OIV infection were peribronchial thickening and a mixture of airspace consolidation and GGO with random distribution and lower lobe predominance. Pleural effusion, lymphadenopathy, PIE, and pneumomediastinum may be associated findings. (author)

  7. Genetic divergence of influenza A NS1 gene in pandemic 2009 H1N1 isolates with respect to H1N1 and H3N2 isolates from previous seasonal epidemics

    Directory of Open Access Journals (Sweden)

    Campanini Giulia

    2010-09-01

    Full Text Available Abstract Background The Influenza A pandemic sustained by a new H1N1 variant (H1N1v started in Mexico and the USA at the end of April 2009 spreading worldwide in a few weeks. In this study we investigate the variability of the NS1 gene of the pandemic H1N1v strain with respect to previous seasonal strains circulating in humans and the potential selection of virus variants through isolation in cell culture. Methods During the period April 27th 2009-Jan 15th 2010, 1633 potential 2009 H1N1v cases have been screened at our center using the CDC detection and typing realtime RT-PCR assays. Virus isolation on MDCK cells was systematically performed in 1/10 positive cases. A subset of 51 H1N1v strains isolated in the period May-September 2009 was selected for NS1 gene sequencing. In addition, 15 H1N1 and 47 H3N2 virus isolates from three previous seasonal epidemics (2006-2009 were analyzed in parallel. Results A low variability in the NS1 amino acid (aa sequence among H1N1v isolates was shown (aa identity 99.5%. A slightly higher NS1 variability was observed among H1N1 and H3N2 strains from previous epidemics (aa identity 98.6% and 98.9%, respectively. The H1N1v strains were closely related (aa identity 92.1% to swine reference strain (A/swine/Oklahoma/042169/2008. In contrast, substantial divergence (aa identity 83.4% with respect to human reference strain A/Brevig Mission/1/1918 and previous epidemic strains H1N1 and H3N2 (aa identity 78.9% and 77.6%, respectively was shown. Specific sequence signatures of uncertain significance in the new virus variant were a C-terminus deletion and a T215P substitution. Conclusions The H1N1v NS1 gene was more conserved than that of previous epidemic strains. In addition, a closer genetic identity of H1N1v with the swine than the human reference strains was shown. Hot-spots were shown in the H1N1v NS1 aa sequence whose biologic relevance remains to be investigated.

  8. Oseltamivir for treatment and prevention of pandemic influenza A/H1N1 virus infection in households, Milwaukee, 2009

    Directory of Open Access Journals (Sweden)

    Miller Joel C

    2010-07-01

    Full Text Available Abstract Background During an influenza pandemic, a substantial proportion of transmission is thought to occur in households. We used data on influenza progression in individuals and their contacts collected by the City of Milwaukee Health Department (MHD to study the transmission of pandemic influenza A/H1N1 virus in 362 households in Milwaukee, WI, and the effects of oseltamivir treatment and chemoprophylaxis. Methods 135 households had chronological information on symptoms and oseltamivir usage for all household members. The effect of oseltamivir treatment and other factors on the household secondary attack rate was estimated using univariate and multivariate logistic regression with households as the unit of analysis. The effect of oseltamivir treatment and other factors on the individual secondary attack rate was estimated using univariate and multivariate logistic regression with individual household contacts as the unit of analysis, and a generalized estimating equations approach was used to fit the model to allow for clustering within households. Results Oseltamivir index treatment on onset day or the following day (early treatment was associated with a 42% reduction (OR: 0.58, 95% CI: 0.19, 1.73 in the odds of one or more secondary infections in a household and a 50% reduction (OR: 0.5, 95% CI: 0.17, 1.46 in the odds of a secondary infection in individual contacts. The confidence bounds are wide due to a small sample of households with early oseltamivir index usage - in 29 such households, 5 had a secondary attack. Younger household contacts were at higher risk of infection (OR: 2.79, 95% CI: 1.50-5.20. Conclusions Early oseltamivir treatment may be beneficial in preventing H1N1pdm influenza transmission; this may have relevance to future control measures for influenza pandemics. Larger randomized trials are needed to confirm this finding statistically.

  9. High mortality from respiratory failure secondary to swine-origin influenza A (H1N1) in South Africa.

    Science.gov (United States)

    Koegelenberg, C F N; Irusen, E M; Cooper, R; Diacon, A H; Taljaard, J J; Mowlana, A; von Groote-Bidlingmaier, F; Bolliger, C T

    2010-05-01

    The novel influenza A (H1N1) pandemic affected South Africa late during the 2009 Southern hemisphere winter and placed an extra burden on a health care system already dealing with a high prevalence of chronic lung diseases and human immunodeficiency virus (HIV) infection. The aim of this study was to describe the epidemiological characteristics, clinical features, management and outcomes of patients with confirmed influenza A (H1N1) infection complicated by respiratory failure. We included all adult patients with confirmed influenza A (H1N1) infection that were referred to the medical intensive care unit of a large academic hospital in Cape Town for ventilatory support in this prospective observational study. A total of 19 patients (39.5 +/- 14.8 years) needed ventilatory support over a 6-week period. Of these, 15 were female and 16 had identifiable risk factors for severe disease, including pregnancy (n = 6), type 2 diabetes mellitus (n = 6), obesity (n = 4), HIV infection (n = 3), immunosuppressive therapy (n = 3) and active pulmonary tuberculosis (n = 2). The most frequent complications were acute renal failure (n = 13), acute respiratory distress syndrome (n = 12) and ventilator associated pneumonia (n = 10). Thirteen patients died (mortality: 68.4%). Fatal cases were significantly associated with an APACHE II score >or=20 (P = 0.034), but not with a P(a)O(2)/F(I)O(2) or=12 (P = 0.134). The majority of patients with respiratory failure secondary to influenza A (H1N1) infection were young females and had an underlying risk factor for severe disease. The condition had a high mortality, particularly amongst patients with an APACHE II score >or=20.

  10. Pathogenesis of Highly Pathogenic Avian Influenza (HPAI) A/turkey/Turkey/1/2005 H5N1 in Pekin ducks (Anas platyrhynchos) infected experimentally

    OpenAIRE

    Löndt , Brandon Z.; Nunez , Alejandro; Banks , Jill; Nili , Hassan; Johnson , Linda K; Alexander , Dennis

    2008-01-01

    Abstract Asian H5N1 (hereafter referred to as panzootic H5N1) highly pathogenic avian influenza (HPAI) virus has caused large numbers of deaths in both poultry and wild bird populations. Recent isolates of this virus have been reported to cause disease and death in commercial ducks, which has not been seen with other HPAI viruses. However, little is known about the dissemination of this H5N1 within the organs and the cause of death in infected ducks. Nineteen 4-week-old Pekin ducks...

  11. Novel virus influenza A (H1N1sw in South-Eastern France, April-August 2009.

    Directory of Open Access Journals (Sweden)

    Antoine Nougairède

    Full Text Available BACKGROUND: In April 2009, the first cases of pandemic (H1N1-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones. METHODOLOGY/PRINCIPAL FINDINGS: We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i Nasal swabs were tested using rapid influenza diagnostic test (RIDT and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus and distribution in age groups and results of RIDT were analyzed. (ii 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii One early (May 2009 and one late (July 2009 viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed. CONCLUSIONS/SIGNIFICANCE: This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in

  12. Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril; Thomsen, Joakim S.

    2011-01-01

    Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13-23. Background Alternative influenza vaccines...... and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change...... in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were...

  13. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003.

    Science.gov (United States)

    Van Reeth, Kristien; Brown, Ian H; Dürrwald, Ralf; Foni, Emanuela; Labarque, Geoffrey; Lenihan, Patrick; Maldonado, Jaime; Markowska-Daniel, Iwona; Pensaert, Maurice; Pospisil, Zdenek; Koch, Guus

    2008-05-01

    Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance Network for Influenza in Pigs 1', aimed to determine the seroprevalence of the H1N2 virus in different European regions and to compare the relative prevalences of each SIV between regions. Laboratories from Belgium, the Czech Republic, Germany, Italy, Ireland, Poland and Spain participated in an international serosurvey. A total of 4190 sow sera from 651 farms were collected in 2002-2003 and examined in haemagglutination inhibition tests against H1N1, H3N2 and H1N2. In Belgium, Germany, Italy and Spain seroprevalence rates to each of the three SIV subtypes were high (> or =30% of the sows seropositive) to very high (> or =50%), except for a lower H1N2 seroprevalence rate in Italy (13.8%). Most sows in these countries with high pig populations had antibodies to two or three subtypes. In Ireland, the Czech Republic and Poland, where swine farming is less intensive, H1N1 was the dominant subtype (8.0-11.7% seropositives) and H1N2 and H3N2 antibodies were rare (0-4.2% seropositives). Thus, SIV of H1N1, H3N2 and H1N2 subtype are enzootic in swine producing regions of Western Europe. In Central Europe, SIV activity is low and the circulation of H3N2 and H1N2 remains to be confirmed. The evolution and epidemiology of SIV throughout Europe is being further monitored through a second 'European Surveillance Network for Influenza in Pigs'.

  14. Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection

    Directory of Open Access Journals (Sweden)

    Yi Jin

    2013-01-01

    Full Text Available The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In this study, we evaluated the immunomodulatory activities and protective effect of Eupatorium adenophorum polysaccharide (EAP against the highly pathogenic H5N1 subtype influenza virus. EAP treatment significantly increased the production of IL-6, TNF-α, and IFN-γ both in vivo and in vitro as measured by qPCR and ELISA. In a mouse infection model, intranasal administration of EAP at a dose of 25 mg/kg body weight prior to H5N1 viral challenge efficiently inhibited viral replication, decreased lung lesions, and increased survival rate. We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR. These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products.

  15. Experimentally infected domestic ducks show efficient transmission of Indonesian H5N1 highly pathogenic avian influenza virus, but lack persistent viral shedding.

    Science.gov (United States)

    Wibawa, Hendra; Bingham, John; Nuradji, Harimurti; Lowther, Sue; Payne, Jean; Harper, Jenni; Junaidi, Akhmad; Middleton, Deborah; Meers, Joanne

    2014-01-01

    Ducks are important maintenance hosts for avian influenza, including H5N1 highly pathogenic avian influenza viruses. A previous study indicated that persistence of H5N1 viruses in ducks after the development of humoral immunity may drive viral evolution following immune selection. As H5N1 HPAI is endemic in Indonesia, this mechanism may be important in understanding H5N1 evolution in that region. To determine the capability of domestic ducks to maintain prolonged shedding of Indonesian clade 2.1 H5N1 virus, two groups of Pekin ducks were inoculated through the eyes, nostrils and oropharynx and viral shedding and transmission investigated. Inoculated ducks (n = 15), which were mostly asymptomatic, shed infectious virus from the oral route from 1 to 8 days post inoculation, and from the cloacal route from 2-8 dpi. Viral ribonucleic acid was detected from 1-15 days post inoculation from the oral route and 1-24 days post inoculation from the cloacal route (cycle threshold ducks seroconverted in a range of serological tests by 15 days post inoculation. Virus was efficiently transmitted during acute infection (5 inoculation-infected to all 5 contact ducks). However, no evidence for transmission, as determined by seroconversion and viral shedding, was found between an inoculation-infected group (n = 10) and contact ducks (n = 9) when the two groups only had contact after 10 days post inoculation. Clinical disease was more frequent and more severe in contact-infected (2 of 5) than inoculation-infected ducks (1 of 15). We conclude that Indonesian clade 2.1 H5N1 highly pathogenic avian influenza virus does not persist in individual ducks after acute infection.

  16. Pathogenesis and transmissibility of highly (H7N1 and low (H7N9 pathogenic avian influenza virus infection in red-legged partridge (Alectoris rufa

    Directory of Open Access Journals (Sweden)

    Bertran Kateri

    2011-02-01

    Full Text Available Abstract An experimental infection with highly pathogenic avian influenza virus (HPAIV and low pathogenic avian influenza virus (LPAIV was carried out in red-legged partridges (Alectoris rufa in order to study clinical signs, gross and microscopic lesions, and viral distribution in tissues and viral shedding. Birds were infected with a HPAIV subtype H7N1 (A/Chicken/Italy/5093/1999 and a LPAIV subtype H7N9 (A/Anas crecca/Spain/1460/2008. Uninoculated birds were included as contacts in both groups. In HPAIV infected birds, the first clinical signs were observed at 3 dpi, and mortality started at 4 dpi, reaching 100% at 8 dpi. The presence of viral antigen in tissues and viral shedding were confirmed by immunohistochemistry and quantitative real time RT-PCR (qRRT-PCR, respectively, in all birds infected with HPAIV. However, neither clinical signs nor histopathological findings were observed in LPAIV infected partridges. In addition, only short-term viral shedding together with seroconversion was detected in some LPAIV inoculated animals. The present study demonstrates that the red-legged partridge is highly susceptible to the H7N1 HPAIV strain, causing severe disease, mortality and abundant viral shedding and thus contributing to the spread of a potential local outbreak of this virus. In contrast, our results concerning H7N9 LPAIV suggest that the red-legged partridge is not a reservoir species for this virus.

  17. Pathogenesis and transmissibility of highly (H7N1) and low (H7N9) pathogenic avian influenza virus infection in red-legged partridge (Alectoris rufa).

    Science.gov (United States)

    Bertran, Kateri; Pérez-Ramírez, Elisa; Busquets, Núria; Dolz, Roser; Ramis, Antonio; Darji, Ayub; Abad, Francesc Xavier; Valle, Rosa; Chaves, Aida; Vergara-Alert, Júlia; Barral, Marta; Höfle, Ursula; Majó, Natàlia

    2011-02-07

    An experimental infection with highly pathogenic avian influenza virus (HPAIV) and low pathogenic avian influenza virus (LPAIV) was carried out in red-legged partridges (Alectoris rufa) in order to study clinical signs, gross and microscopic lesions, and viral distribution in tissues and viral shedding. Birds were infected with a HPAIV subtype H7N1 (A/Chicken/Italy/5093/1999) and a LPAIV subtype H7N9 (A/Anas crecca/Spain/1460/2008). Uninoculated birds were included as contacts in both groups. In HPAIV infected birds, the first clinical signs were observed at 3 dpi, and mortality started at 4 dpi, reaching 100% at 8 dpi. The presence of viral antigen in tissues and viral shedding were confirmed by immunohistochemistry and quantitative real time RT-PCR (qRRT-PCR), respectively, in all birds infected with HPAIV. However, neither clinical signs nor histopathological findings were observed in LPAIV infected partridges. In addition, only short-term viral shedding together with seroconversion was detected in some LPAIV inoculated animals. The present study demonstrates that the red-legged partridge is highly susceptible to the H7N1 HPAIV strain, causing severe disease, mortality and abundant viral shedding and thus contributing to the spread of a potential local outbreak of this virus. In contrast, our results concerning H7N9 LPAIV suggest that the red-legged partridge is not a reservoir species for this virus.

  18. Seasonal patterns in human A (H5N1 virus infection: analysis of global cases.

    Directory of Open Access Journals (Sweden)

    Maya B Mathur

    Full Text Available Human cases of highly pathogenic avian influenza (HPAI A (H5N1 have high mortality. Despite abundant data on seasonal patterns in influenza epidemics, it is unknown whether similar patterns exist for human HPAI H5N1 cases worldwide. Such knowledge could help decrease avian-to-human transmission through increased prevention and control activities during peak periods.We performed a systematic search of published human HPAI H5N1 cases to date, collecting month, year, country, season, hemisphere, and climate data. We used negative binomial regression to predict changes in case incidence as a function of season. To investigate hemisphere as a potential moderator, we used AIC and the likelihood-ratio test to compare the season-only model to nested models including a main effect or interaction with hemisphere. Finally, we visually assessed replication of seasonal patterns across climate groups based on the Köppen-Geiger climate classification.We identified 617 human cases (611 with complete seasonal data occurring in 15 countries in Southeast Asia, Africa, and the Middle East. Case occurrence was much higher in winter (n = 285, p = 0.03 than summer (n = 64, and the winter peak occurred across diverse climate groups. There was no significant interaction between hemisphere and season.Across diverse climates, HPAI H5N1 virus infection in humans increases significantly in winter. This is consistent with increased poultry outbreaks and HPAI H5N1 virus transmission during cold and dry conditions. Prioritizing prevention and control activities among poultry and focusing public health messaging to reduce poultry exposures during winter months may help to reduce zoonotic transmission of HPAI H5N1 virus in resource-limited settings.

  19. Radiologic Findings of Influenza A (H1N1) Pneumonia: Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jin Kyoung; Ahn, Myeong Im; Jung, Jung Im; Han, Dae Hee; Park, Seog Hee; Park, Chan Kwon; Kim, Young Kyoon [Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

    2010-08-15

    Novel influenza A (H1N1) infection is a highly infectious disease, which has been rapidly spreading worldwide since it was first documented in March of 2009 in Mexico. We experienced and report two cases of Influenza A (H1N1) pneumonia, accompanied by chest radiographic and CT findings. The chest radiographs revealed diffuse haziness and extensive airspace consolidation, whereas the CT scans demonstrated multifocal areas of ground glass opacity and airspace consolidation with a CT halo sign.

  20. A Historical Perspective of Influenza A(H1N2) Virus

    OpenAIRE

    Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin

    2014-01-01

    The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase ...

  1. Broadly-reactive human monoclonal antibodies elicited following pandemic H1N1 influenza virus exposure protect mice from highly pathogenic H5N1 challenge.

    Science.gov (United States)

    Nachbagauer, Raffael; Shore, David; Yang, Hua; Johnson, Scott K; Gabbard, Jon D; Tompkins, S Mark; Wrammert, Jens; Wilson, Patrick C; Stevens, James; Ahmed, Rafi; Krammer, Florian; Ellebedy, Ali H

    2018-06-13

    Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the mAbs bound HAs from multiple strains of group 1 viruses, and one mAb, 05-2G02, bound to both group 1 and group 2 influenza A HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two mAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One mAb, 70-1F02, was co-crystallized with H5 HA and showed similar heavy chain only interactions as a the previously described anti-stalk antibody CR6261. Finally, we showed that antibodies that compete with these mAbs are prevalent in serum from an individual recently infected with A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections with zoonotic or emerging pandemic influenza viruses. IMPORTANCE The rise in zoonotic infections of humans with emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually

  2. In silico approach towards H5N1 virus protein and transcriptomics ...

    African Journals Online (AJOL)

    H5N1 influenza A virus is a serious threat to human population. With a considerable mortality rate, strategies for coping with the infection are being developed. Our research group and some others investigated the potential therapeutic and preventive measures for tackling H5N1 infections. Protein based and transcriptomics ...

  3. 1H-1H correlations across N-H···N hydrogen bonds in nucleic acids

    International Nuclear Information System (INIS)

    Majumdar, Ananya; Gosser, Yuying; Patel, Dinshaw J.

    2001-01-01

    In 2H J NN -COSY experiments, which correlate protons with donor/acceptor nitrogens across N d ···HN a bonds, the receptor nitrogen needs to be assigned in order to unambiguously identify the hydrogen bond. For many situations this is a non-trivial task which is further complicated by poor dispersion of (N a ,N d ) resonances. To address these problems, we present pulse sequences to obtain direct, internucleotide correlations between protons in uniformly 13 C/ 15 N labeled nucleic acids containing N d ···HN a hydrogen bonds. Specifically, the pulse sequence H2(N1N3)H3 correlates H2(A,ω 1 ):H3(U,ω 2 ) protons across Watson-Crick A-U and mismatched G·A base pairs, the sequences H5(N3N1)H1/H6(N3N1)H1 correlate H5(C,ω 1 )/H6(C,ω 1 ):H1(G,ω 2 ) protons across Watson-Crick G-C base pairs, and the H 2 (N2N7)H8 sequence correlates NH 2 (G,A,C;ω 1 ):H8(G,A;ω 2 ) protons across G·G, A·A, sheared G·A and other mismatch pairs. These 1 H- 1 H connectivities circumvent the need for independent assignment of the donor/acceptor nitrogen and related degeneracy issues associated with poorly dispersed nitrogen resonances. The methodology is demonstrated on uniformly 13 C/ 15 N labeled samples of (a) an RNA regulatory element involving the HIV-1 TAR RNA fragment, (b) a multi-stranded DNA architecture involving a G·(C-A) triad-containing G-quadruplex and (c) a peptide-RNA complex involving an evolved peptide bound to the HIV-1 Rev response element (RRE) RNA fragment

  4. Pathogenesis and transmissibility of highly (H7N1) and low (H7N9) pathogenic avian influenza virus infection in red-legged partridge (Alectoris rufa)

    OpenAIRE

    Bertran, Kateri; Pérez-Ramírez, Elisa; Busquets, Núria; Dolz, Roser; Ramis, Antoni; Abad, Francesc Xavier; Chaves, Aida; Vergara-Alert, Júlia; Barral, Marta; Höfle, Ursula; Majó, Natàlia

    2011-01-01

    Abstract An experimental infection with highly pathogenic avian influenza virus (HPAIV) and low pathogenic avian influenza virus (LPAIV) was carried out in red-legged partridges (Alectoris rufa) in order to study clinical signs, gross and microscopic lesions, and viral distribution in tissues and viral shedding. Birds were infected with a HPAIV subtype H7N1 (A/Chicken/Italy/5093/1999) and a LPAIV subtype H7N9 (A/Anas crecca/Spain/1460/2008). Uninoculated birds were included as contacts in bot...

  5. Mortality, severe acute respiratory infection, and influenza-like illness associated with influenza A(H1N1pdm09 in Argentina, 2009.

    Directory of Open Access Journals (Sweden)

    Eduardo Azziz-Baumgartner

    Full Text Available INTRODUCTION: While there is much information about the burden of influenza A(H1N1pdm09 in North America, little data exist on its burden in South America. METHODS: During April to December 2009, we actively searched for persons with severe acute respiratory infection and influenza-like illness (ILI in three sentinel cities. A proportion of case-patients provided swabs for influenza testing. We estimated the number of case-patients that would have tested positive for influenza by multiplying the number of untested case-patients by the proportion who tested positive. We estimated rates by dividing the estimated number of case-patients by the census population after adjusting for the proportion of case-patients with missing illness onset information and ILI case-patients who visited physicians multiple times for one illness event. RESULTS: We estimated that the influenza A(H1N1pdm09 mortality rate per 100,000 person-years (py ranged from 1.5 among persons aged 5-44 years to 5.6 among persons aged ≥ 65 years. A(H1N1pdm09 hospitalization rates per 100,000 py ranged between 26.9 among children aged <5 years to 41.8 among persons aged ≥ 65 years. Influenza A(H1N1pdm09 ILI rates per 100 py ranged between 1.6 among children aged <5 to 17.1 among persons aged 45-64 years. While 9 (53% of 17 influenza A(H1N1pdm09 decedents with available data had obesity and 7 (17% of 40 had diabetes, less than 4% of surviving influenza A(H1N1pdm09 case-patients had these pre-existing conditions (p ≤ 0.001. CONCLUSION: Influenza A(H1N1pdm09 caused a similar burden of disease in Argentina as in other countries. Such disease burden suggests the potential value of timely influenza vaccinations.

  6. Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1 2009 virus infected patients in Spain, 2009-2010.

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    Fernando González-Candelas

    Full Text Available The emergence and pandemic spread of a new strain of influenza A (H1N1 virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1 virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1 2009 were determined to be obesity (BMI≥40, with an odds-ratio [OR] 14.27, hematological neoplasia (OR 10.71, chronic heart disease, COPD (OR 5.16 and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88 and high risk conditions raise this value markedly (OR 6.43. The risk of hospitalization increased proportionally when for two (OR 2.08 or for three or more (OR 4.86 risk factors were simultaneously present in the same patient. These findings should be considered when a new influenza virus appears in the human population.

  7. Avian influenza A (H5N1)

    NARCIS (Netherlands)

    de Jong, Menno D.; Hien, Tran Tinh

    2006-01-01

    Since their reemergence in 2003, highly pathogenic avian influenza A (H5N1) viruses have reached endemic levels among poultry in several southeast Asian countries and have caused a still increasing number of more than 100 reported human infections with high mortality. These developments have ignited

  8. Experimental infection of highly pathogenic avian influenza virus H5N1 in black-headed gulls (Chroicocephalus ridibundus).

    Science.gov (United States)

    Ramis, Antonio; van Amerongen, Geert; van de Bildt, Marco; Leijten, Loneke; Vanderstichel, Raphael; Osterhaus, Albert; Kuiken, Thijs

    2014-08-19

    Historically, highly pathogenic avian influenza viruses (HPAIV) rarely resulted in infection or clinical disease in wild birds. However, since 2002, disease and mortality from natural HPAIV H5N1 infection have been observed in wild birds including gulls. We performed an experimental HPAIV H5N1 infection of black-headed gulls (Chroicocephalus ridibundus) to determine their susceptibility to infection and disease from this virus, pattern of viral shedding, clinical signs, pathological changes and viral tissue distribution. We inoculated sixteen black-headed gulls with 1 × 10(4) median tissue culture infectious dose HPAIV H5N1 (A/turkey/Turkey/1/2005) intratracheally and intraesophageally. Birds were monitored daily until 12 days post inoculation (dpi). Oropharyngeal and cloacal swabs were collected daily to detect viral shedding. Necropsies from birds were performed at 2, 4, 5, 6, 7, and 12 dpi. Sampling from selected tissues was done for histopathology, immunohistochemical detection of viral antigen, PCR, and viral isolation. Our study shows that all inoculated birds were productively infected, developed systemic disease, and had a high morbidity and mortality rate. Virus was detected mainly in the respiratory tract on the first days after inoculation, and then concentrated more in pancreas and central nervous system from 4 dpi onwards. Birds shed infectious virus until 7 dpi from the pharynx and 6 dpi from the cloaca. We conclude that black-headed gulls are highly susceptible to disease with a high mortality rate and are thus more likely to act as sentinel species for the presence of the virus than as long-distance carriers of the virus to new geographical areas.

  9. Infecção pelo vírus Influenza A (H1N1 de origem suína: como reconhecer, diagnosticar e prevenir How to prevent, recognize and diagnose infection with the swine-origin Influenza A (H1N1 virus in humans

    Directory of Open Access Journals (Sweden)

    Alcyone Artioli Machado

    2009-05-01

    Full Text Available Em março de 2009, houve o início de uma epidemia de gripe no México que, em pouco tempo, levou ao surgimento de casos semelhantes em outros países, alertando as autoridades sanitárias para o risco de uma pandemia. Neste artigo, descrevemos os principais sinais e sintomas da infecção pelo vírus Influenza A (H1N1 de origem suína, as medidas a serem tomadas para os casos suspeitos ou confirmados e como proceder em relação aos contactantes. Comentamos também quais drogas são utilizadas para o tratamento e profilaxia.In March of 2009, a flu epidemic began in Mexico. Shortly thereafter, similar cases appeared in other countries, alerting authorities to the risk of a pandemic. This article details the principal signs and symptoms of infection with the swine-origin Influenza A (H1N1 virus. In addition, the measures to be taken in suspected or confirmed cases are addressed, as are the procedures to follow in relation to contacts. Furthermore, the drugs used in the prophylaxis against and the treatment of infection with the H1N1 virus are described.

  10. Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian Influenza virus (H5N1, H7N7 and swine-origin H1N1 (S-OIV

    Directory of Open Access Journals (Sweden)

    Schoop Roland

    2009-11-01

    Full Text Available Abstract Background Influenza virus (IV infections are a major threat to human welfare and animal health worldwide. Anti-viral therapy includes vaccines and a few anti-viral drugs. However vaccines are not always available in time, as demonstrated by the emergence of the new 2009 H1N1-type pandemic strain of swine origin (S-OIV in April 2009, and the acquisition of resistance to neuraminidase inhibitors such as Tamiflu® (oseltamivir is a potential problem. Therefore the prospects for the control of IV by existing anti-viral drugs are limited. As an alternative approach to the common anti-virals we studied in more detail a commercial standardized extract of the widely used herb Echinacea purpurea (Echinaforce®, EF in order to elucidate the nature of its anti-IV activity. Results Human H1N1-type IV, highly pathogenic avian IV (HPAIV of the H5- and H7-types, as well as swine origin IV (S-OIV, H1N1, were all inactivated in cell culture assays by the EF preparation at concentrations ranging from the recommended dose for oral consumption to several orders of magnitude lower. Detailed studies with the H5N1 HPAIV strain indicated that direct contact between EF and virus was required, prior to infection, in order to obtain maximum inhibition in virus replication. Hemagglutination assays showed that the extract inhibited the receptor binding activity of the virus, suggesting that the extract interferes with the viral entry into cells. In sequential passage studies under treatment in cell culture with the H5N1 virus no EF-resistant variants emerged, in contrast to Tamiflu®, which produced resistant viruses upon passaging. Furthermore, the Tamiflu®-resistant virus was just as susceptible to EF as the wild type virus. Conclusion As a result of these investigations, we believe that this standard Echinacea preparation, used at the recommended dose for oral consumption, could be a useful, readily available and affordable addition to existing control options

  11. Polymorphism of HLA class I and class II alleles in influenza A(H1N1)pdm09 virus infected population of Assam, Northeast India.

    Science.gov (United States)

    Dutta, Mousumi; Dutta, Prafulla; Medhi, Subhash; Borkakoty, Biswajyoti; Biswas, Dipankar

    2018-05-01

    Human leucocyte antigen (HLA) represents one of the most highly polymorphic systems which plays a central role in the immune response. Genetic polymorphism of HLA in influenza A(H1N1)pdm09 infected population may be an important factor in disease progression and severity that needs further probing. In this study, a total of 110 Influenza like illness patients were recruited from the population of Assam, Northeast India, from which 35 cases infected by A(H1N1)pdm09 viruses and 35 controls were typed for HLA-A, B and DRB1 locus by PCR-SSP method. A total of seven alleles of HLA-A, 16 alleles of HLA-B, and 11 alleles of HLA-DRB1 locus were identified. The most common alleles within each locus in cases were HLA-A*11 (85.71%, P = 0.046), HLA-B*35 (25%, P = 0.0001), and HLA-DRB1*15 (49.35%,  P = 0.133) as compared to the controls, HLA-A*11 (40.82%), HLA-B*35 (0.00%), and HLA-DRB1*15 (67.53%). The frequency of HLA-A*11 and HLA-B*35 were significantly higher in cases as compared to the controls. In DRB1 locus, HLA-DRB1*10 was significantly higher in cases (20.78%, P = 0.005) than that of controls (0.00%). Whereas, HLA-DRB1*15 showed a higher frequency in controls than in cases. In addition, HLA-DRB3*01 (P = 0.053), DRB4*01 (P = 1.000), and DRB5*01(P = 0.591) were also identified along with HLA-DRB1 haplotype. From this preliminary study, it is suspected that there may be a role of HLA-A*11, HLA-B*35 and HLA-DRB1*10 in conferring susceptibility to influenza A(H1N1)pdm09 infection in the study population. A larger extended study on HLA polymorphism may explain the association between HLA and influenza A(H1N1)pdm09 infection and provide insights for HLA restricted peptide based vaccines. © 2018 Wiley Periodicals, Inc.

  12. Estimating the disease burden of 2009 pandemic influenza A(H1N1 from surveillance and household surveys in Greece.

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    Vana Sypsa

    Full Text Available The aim of this study was to assess the disease burden of the 2009 pandemic influenza A(H1N1 in Greece.Data on influenza-like illness (ILI, collected through cross-sectional nationwide telephone surveys of 1,000 households in Greece repeated for 25 consecutive weeks, were combined with data from H1N1 virologic surveillance to estimate the incidence and the clinical attack rate (CAR of influenza A(H1N1. Alternative definitions of ILI (cough or sore throat and fever>38°C [ILI-38] or fever 37.1-38°C [ILI-37] were used to estimate the number of symptomatic infections. The infection attack rate (IAR was approximated using estimates from published studies on the frequency of fever in infected individuals. Data on H1N1 morbidity and mortality were used to estimate ICU admission and case fatality (CFR rates. The epidemic peaked on week 48/2009 with approximately 750-1,500 new cases/100,000 population per week, depending on ILI-38 or ILI-37 case definition, respectively. By week 6/2010, 7.1%-15.6% of the population in Greece was estimated to be symptomatically infected with H1N1. Children 5-19 years represented the most affected population group (CAR:27%-54%, whereas individuals older than 64 years were the least affected (CAR:0.6%-2.2%. The IAR (95% CI of influenza A(H1N1 was estimated to be 19.7% (13.3%, 26.1%. Per 1,000 symptomatic cases, based on ILI-38 case definition, 416 attended health services, 108 visited hospital emergency departments and 15 were admitted to hospitals. ICU admission rate and CFR were 37 and 17.5 per 100,000 symptomatic cases or 13.4 and 6.3 per 100,000 infections, respectively.Influenza A(H1N1 infected one fifth and caused symptomatic infection in up to 15% of the Greek population. Although individuals older than 65 years were the least affected age group in terms of attack rate, they had 55 and 185 times higher risk of ICU admission and CFR, respectively.

  13. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Science.gov (United States)

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  14. A polyvalent influenza A DNA vaccine induces heterologous immunity and protects pigs against pandemic A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Vinner, Lasse; Hansen, Mette Sif

    2013-01-01

    seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs...... intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA...... of this DNA vaccine to limit virus shedding may have an impact on virus spread among pigs which could possibly extend to humans as well, thereby diminishing the risk for epidemics and pandemics to evolve....

  15. Neurovirulence of H5N1 infection in ferrets is mediated by multifocal replication in distinct permissive neuronal cell regions.

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    Jennifer R Plourde

    Full Text Available Highly pathogenic avian influenza A (HPAI, subtype H5N1, remains an emergent threat to the human population. While respiratory disease is a hallmark of influenza infection, H5N1 has a high incidence of neurological sequelae in many animal species and sporadically in humans. We elucidate the temporal/spatial infection of H5N1 in the brain of ferrets following a low dose, intranasal infection of two HPAI strains of varying neurovirulence and lethality. A/Vietnam/1203/2004 (VN1203 induced mortality in 100% of infected ferrets while A/Hong Kong/483/1997 (HK483 induced lethality in only 20% of ferrets, with death occurring significantly later following infection. Neurological signs were prominent in VN1203 infection, but not HK483, with seizures observed three days post challenge and torticollis or paresis at later time points. VN1203 and HK483 replication kinetics were similar in primary differentiated ferret nasal turbinate cells, and similar viral titers were measured in the nasal turbinates of infected ferrets. Pulmonary viral titers were not different between strains and pathological findings in the lungs were similar in severity. VN1203 replicated to high titers in the olfactory bulb, cerebral cortex, and brain stem; whereas HK483 was not recovered in these tissues. VN1203 was identified adjacent to and within the olfactory nerve tract, and multifocal infection was observed throughout the frontal cortex and cerebrum. VN1203 was also detected throughout the cerebellum, specifically in Purkinje cells and regions that coordinate voluntary movements. These findings suggest the increased lethality of VN1203 in ferrets is due to increased replication in brain regions important in higher order function and explains the neurological signs observed during H5N1 neurovirulence.

  16. Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian 'avian-like' H1N1 swine viruses in mice.

    Science.gov (United States)

    Castrucci, Maria R; Facchini, Marzia; Di Mario, Giuseppina; Garulli, Bruno; Sciaraffia, Ester; Meola, Monica; Fabiani, Concetta; De Marco, Maria A; Cordioli, Paolo; Siccardi, Antonio; Kawaoka, Yoshihiro; Donatelli, Isabella

    2014-05-01

    To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian "avian-like" (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs. Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice. Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study. Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses. Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge. Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans. © 2013 The Authors Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  17. Experimental infection of highly pathogenic avian influenza virus H5N1 in black-headed gulls (Chroicocephalus ridibundus)

    NARCIS (Netherlands)

    A. Ramis (Antonio); G. van Amerongen (Geert); M.W.G. van de Bildt (Marco); L.M.E. Leijten (Lonneke); R. Vanderstichel (R.); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2014-01-01

    textabstractHistorically, highly pathogenic avian influenza viruses (HPAIV) rarely resulted in infection or clinical disease in wild birds. However, since 2002, disease and mortality from natural HPAIV H5N1 infection have been observed in wild birds including gulls. We performed an experimental

  18. Usefulness of Ct value in acute respiratory infections caused by respiratory syncytial virus A and B and influenza virus A (H1N1)pdm09, A (H3N2) and B.

    Science.gov (United States)

    Reina, Jordi; Morales, Carmen; Busquets, María; Norte, Cristina

    2017-06-07

    Acute respiratory infections of viral cause are very frequent entities. The difficulty in evaluating the detection of a virus in these entities could be solved by determining the viral load. A prospective study on the mean Ct value (cycle threshold value) detected against RSV-A, RSV-B and influenza A (H1N1)pdm09, A (H3N2) and B viruses in patients of different origin and age was performed. Detection was performed using a commercial molecular amplification (RT-PCR) technique. Different mean Ct values were detected for each virus. In RSV infections, no differences were observed between those caused by RSV-A or RSV-B in children. Depending on the patient's age, the only statistical significance was observed in those included in the 0-4 month groups for RSV-A and this group and the 5-12 months group for RSV-B (higher values). A lower viral load was detected in adult patients than in paediatric patients. In influenza infections, no statistical significance was observed in the mean values detected in patients from the Red Centinela («sentinel network», a Spanish network of doctors aimed at research and surveillance of diseases), those diagnosed in the adult emergency room or in hospital admissions. In the adult patients admitted to the ICU, only a slightly lower mean value was observed in those infected with influenza A (H1N1)pdm09, but without statistical significance. There were no patients admitted to the ICU with influenza B infection. The detection of viral load could be a good tool for the evaluation, monitoring and prognosis of acute viral respiratory infections. With the exception of those caused by RSV, no significant differences were observed in influenza infections except in younger paediatric patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Directory of Open Access Journals (Sweden)

    Helena Grgić

    Full Text Available The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1pdm09. One H1N2 isolate had hemagglutinin (HA, polymerase A (PA and non-structural (NS genes closely related to A(H1N1pdm09, and neuraminidase (NA, matrix (M, polymerase B1 (PB1, polymerase B2 (PB2, and nucleoprotein (NP genes originating from a triple-reassortant H3N2 virus (tr H3N2. The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  20. An Analysis of 332 Fatalities Infected with Pandemic 2009 Influenza A (H1N1) in Argentina

    Science.gov (United States)

    Balanzat, Ana M.; Hertlein, Christian; Apezteguia, Carlos; Bonvehi, Pablo; Cámera, Luis; Gentile, Angela; Rizzo, Oscar; Gómez-Carrillo, Manuel; Coronado, Fatima; Azziz-Baumgartner, Eduardo; Chávez, Pollyanna R.; Widdowson, Marc-Alain

    2012-01-01

    Background The apparent high number of deaths in Argentina during the 2009 pandemic led to concern that the influenza A H1N1pdm disease was different there. We report the characteristics and risk factors for influenza A H1N1pdm fatalities. Methods We identified laboratory-confirmed influenza A H1N1pdm fatalities occurring during June-July 2009. Physicians abstracted data on age, sex, time of onset of illness, medical history, clinical presentation at admission, laboratory, treatment, and outcomes using standardize questionnaires. We explored the characteristics of fatalities according to their age and risk group. Results Of 332 influenza A H1N1pdm fatalities, 226 (68%) were among persons aged Argentina, though timeliness of antiviral treatment improved during the pandemic. PMID:22506006

  1. Preventive Activity against Influenza (H1N1 Virus by Intranasally Delivered RNA-Hydrolyzing Antibody in Respiratory Epithelial Cells of Mice

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    Seungchan Cho

    2015-09-01

    Full Text Available The antiviral effect of a catalytic RNA-hydrolyzing antibody, 3D8 scFv, for intranasal administration against avian influenza virus (H1N1 was described. The recombinant 3D8 scFv protein prevented BALB/c mice against H1N1 influenza virus infection by degradation of the viral RNA genome through its intrinsic RNA-hydrolyzing activity. Intranasal administration of 3D8 scFv (50 μg/day for five days prior to infection demonstrated an antiviral activity (70% survival against H1N1 infection. The antiviral ability of 3D8 scFv to penetrate into epithelial cells from bronchial cavity via the respiratory mucosal layer was confirmed by immunohistochemistry, qRT-PCR, and histopathological examination. The antiviral activity of 3D8 scFv against H1N1 virus infection was not due to host immune cytokines or chemokines, but rather to direct antiviral RNA-hydrolyzing activity of 3D8 scFv against the viral RNA genome. Taken together, our results suggest that the RNase activity of 3D8 scFv, coupled with its ability to penetrate epithelial cells through the respiratory mucosal layer, directly prevents H1N1 virus infection in a mouse model system.

  2. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

    Science.gov (United States)

    Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

    2010-01-01

    Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

  3. Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults.

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    Nelson Lee

    Full Text Available BACKGROUND: Studying cytokine/chemokine responses in severe influenza infections caused by different virus subtypes may improve understanding on pathogenesis. METHODS: Adults hospitalized for laboratory-confirmed seasonal and pandemic 2009 A/H1N1 (pH1N1 influenza were studied. Plasma concentrations of 13 cytokines/chemokines were measured at presentation and then serially, using cytometric-bead-array with flow-cytometry and ELISA. PBMCs from influenza patients were studied for cytokine/chemokine expression using ex-vivo culture (Whole Blood Assay,±PHA/LPS stimulation. Clinical variables were prospectively recorded and analyzed. RESULTS: 63 pH1N1 and 53 seasonal influenza patients were studied. pH1N1 patients were younger (mean±S.D. 42.8±19.2 vs 70.5±16.7 years, and fewer had comorbidities. Respiratory/cardiovascular complications were common in both groups (71.4% vs 81.1%, although severe pneumonia with hypoxemia (54.0% vs 28.3% and ICU admissions (25.4% vs 1.9% were more frequent with pH1N1. Hyperactivation of the proinflammatory cytokines IL-6, CXCL8/IL-8, CCL2/MCP-1 and sTNFR-1 was found in pH1N1 pneumonia (2-15 times normal and in complicated seasonal influenza, but not in milder pH1N1 infections. The adaptive-immunity (Th1/Th17-related CXCL10/IP-10, CXCL9/MIG and IL-17A however, were markedly suppressed in severe pH1N1 pneumonia (2-27 times lower than seasonal influenza; P-values<0.01. This pattern was further confirmed with serial measurements. Hypercytokinemia tended to be sustained in pH1N1 pneumonia, associated with a slower viral clearance [PCR-negativity: day 3-4, 55% vs 85%; day 6-7, 67% vs 100%]. Elevated proinflammatory cytokines, particularly IL-6, predicted ICU admission (adjusted OR 12.6, 95%CI 2.6-61.5, per log(10unit increase; P = 0.002, and correlated with fever, tachypnoea, deoxygenation, and length-of-stay (Spearman's rho, P-values<0.01 in influenza infections. PBMCs in seasonal influenza patients were activated and

  4. Primary study on the lesions and specific proteins in BEAS-2B cells induced with the 2009 A (H1N1) influenza virus.

    Science.gov (United States)

    Fang, Shisong; Zhang, Kaining; Wang, Ting; Wang, Xin; Lu, Xing; Peng, Bo; Wu, Weihua; Zhang, Ran; Chen, Shiju; Zhang, Renli; Xue, Hong; Yu, Muhua; Cheng, Jinquan

    2014-12-01

    In order to investigate the lesions and proteins with differential expression in cells infected with the 2009 A (H1N1) virus and to determine the specific proteins involved in cell damage, the present study has been performed. BEAS-2B cells were infected with the 2009 A (H1N1) influenza virus or the seasonal H1N1 influenza virus for 12, 24, 48, and 72 h, and cell cycle and apoptosis were analyzed with flow cytometry. Total cellular proteins were extracted and underwent two-dimensional gel electrophoresis. The differentially expressed proteins underwent mass spectrometry for identification. The results showed that after 12 h, cells infected with the virus strain sourced from severe cases had the highest apoptosis rate (P cells infected with the virus strain sourced from fatal cases and severe cases had the highest apoptosis rate (P cells infected with virus strains from fatal cases and ordinary cases had the highest apoptosis rate (P cell cycle arrest mainly at the G0/G1 phase. Eighteen differentially expressed proteins were identified, including galectin-1, cofilin-1, protein DJ-1, proteasome subunit α type-5, macrophage migration inhibitory factor, translationally controlled tumor protein, profilin 1, and interferon α-2. Galectin-1 was specifically observed in BEAS-2B infected with 2009 A (H1N1) influenza viruses, and cofilin-1 was specifically observed in BEAS-2B cells in the late stage of 2009 A (H1N1) influenza virus infection. In conclusion, differential effects of the 2009 A (H1N1) influenza virus and seasonal H1N1 influenza virus were identified on the cell cycle and apoptosis, and galectin-1 may play a role in cell apoptosis induced by 2009 A (H1N1) influenza virus.

  5. H5N1 surveillance in migratory birds in Java, Indonesia.

    Science.gov (United States)

    Stoops, Arthur C; Barbara, Katie A; Indrawan, Mochamad; Ibrahim, Ima N; Petrus, Wicaksana B; Wijaya, Susan; Farzeli, Arik; Antonjaya, Ungke; Sin, Lim W; Hidayatullah, N; Kristanto, Ige; Tampubolon, A M; Purnama, S; Supriatna, Adam; Burgess, Timothy H; Williams, Maya; Putnam, Shannon D; Tobias, Steve; Blair, Patrick J

    2009-12-01

    We sought to elucidate the role of migratory birds in transmission of H5N1 in an enzoonotic area. Resident, captive, and migratory birds were sampled at five sites in Java, Indonesia. Mist nets were used to trap birds. Birds were identified to species. RNA was extracted from swabs and reverse transcriptase polymerase chain reaction (RT-PCR) conducted for the HA and M genes of H5N1. Antibodies were detected by enzyme-linked immunosorbent assay and hemagglutination inhibition test. Between October 2006 and September 2007, a total of 4,067 captive, resident, and migratory birds comprising 98 species in 23 genera were sampled. The most commonly collected birds were the common sandpiper (6% of total), striated heron (3%), and the domestic chicken (14%). The overall prevalence of H5N1 antibodies was 5.3%. A significantly higher percentage of captive birds (16.1%) showed antibody evidence of H5N1 exposure when compared to migratory or resident birds. The greatest number of seropositive birds in each category were Muschovy duck (captive), striated heron (resident), and the Pacific golden plover (migratory). Seven apparently well captive birds yielded molecular evidence of H5N1 infection. Following amplification, the HA, NA, and M genes were analyzed. Phylogenetic analysis of the HA gene showed that the isolates were 97% similar to EU124153.1 A/chicken/West Java/Garut May 2006, an isolate obtained in a similar region of West Java. While no known markers of neuraminidase inhibitor resistance were found within the NA gene, M segment analysis revealed the V27A mutation known to confer resistance to adamantanes. Our results demonstrate moderate serologic evidence of H5N1 infection in captive birds, sampled in five sites in Java, Indonesia, but only occasional infection in resident and migratory birds. These data imply that in an enzoonotic region of Indonesia the role of migratory birds in transmission of H5N1 is limited.

  6. Reduced experimental infectivity and transmissibility of intercontinental H5 (H5N8 and H5N2) compared to Eurasian H5N1 highly pathogenic avian influenza viruses for chickens, turkeys, and Japanese quail

    Science.gov (United States)

    H5N1 high pathogenicity avian influenza (HPAI) virus (HPAIV) emerged in 1996 in Guangdong China and has since spread to infect and cause deaths in wild birds, poultry and humans in over 63 countries in Asia, Europe and Africa; and more recently a reassortant H5N8 clade 2.3.4.4 HPAI virus has spread ...

  7. Evaluation of twenty rapid antigen tests for the detection of human influenza A H5N1, H3N2, H1N1, and B viruses.

    Science.gov (United States)

    Taylor, Janette; McPhie, Kenneth; Druce, Julian; Birch, Chris; Dwyer, Dominic E

    2009-11-01

    Twenty rapid antigen assays were compared for their ability to detect influenza using dilutions of virus culture supernatants from human isolates of influenza A H5N1 (clade 1 and 2 strains), H3N2 and H1N1 viruses, and influenza B. There was variation amongst the rapid antigen assays in their ability to detect different influenza viruses. Six of the 12 assays labeled as distinguishing between influenza A and B had comparable analytical sensitivities for detecting both influenza A H5N1 strains, although their ability to detect influenza A H3N2 and H1N1 strains varied. The two assays claiming H5 specificity did not detect either influenza A H5N1 strains, and the two avian influenza-specific assays detected influenza A H5N1, but missed some influenza A H3N2 virus supernatants. Clinical trials of rapid antigen tests for influenza A H5N1 are limited. For use in a pandemic where novel influenza strains are circulating (such as the current novel influenza A H1N1 09 virus), rapid antigen tests should ideally have comparable sensitivity and specificity for the new strains as for co-circulating seasonal influenza strains.

  8. The transmissibility and control of pandemic influenza A (H1N1) virus.

    Science.gov (United States)

    Yang, Yang; Sugimoto, Jonathan D; Halloran, M Elizabeth; Basta, Nicole E; Chao, Dennis L; Matrajt, Laura; Potter, Gail; Kenah, Eben; Longini, Ira M

    2009-10-30

    Pandemic influenza A (H1N1) 2009 (pandemic H1N1) is spreading throughout the planet. It has become the dominant strain in the Southern Hemisphere, where the influenza season has now ended. Here, on the basis of reported case clusters in the United States, we estimated the household secondary attack rate for pandemic H1N1 to be 27.3% [95% confidence interval (CI) from 12.2% to 50.5%]. From a school outbreak, we estimated that a typical schoolchild infects 2.4 (95% CI from 1.8 to 3.2) other children within the school. We estimated the basic reproductive number, R0, to range from 1.3 to 1.7 and the generation interval to range from 2.6 to 3.2 days. We used a simulation model to evaluate the effectiveness of vaccination strategies in the United States for fall 2009. If a vaccine were available soon enough, vaccination of children, followed by adults, reaching 70% overall coverage, in addition to high-risk and essential workforce groups, could mitigate a severe epidemic.

  9. Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

    DEFF Research Database (Denmark)

    Brookes, Sharon M; Nunez, Alejandor; Choudhury, Bhudipa

    2010-01-01

    The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment...... and evolution within swine worldwide [3]. A key public and veterinary health consideration in the context of the evolving pandemic is whether the H1N1/09 virus could become established in pig populations [4]. We performed an infection and transmission study in pigs with A/California/07/09. In combination......, with clearly demonstrable pulmonary pathology, there was apparent selection of a virus variant with glycine (225G). These findings provide potential clues to the existence and biological significance of viral receptor-binding variants with 225D and 225G during the 1918 pandemic [5]....

  10. Pathology of whooper swans (Cygnus cygnus) infected with H5N1 avian influenza virus in Akita, Japan, in 2008.

    Science.gov (United States)

    Ogawa, Shuji; Yamamoto, Yu; Yamada, Manabu; Mase, Masaji; Nakamura, Kikuyasu

    2009-10-01

    Two (1 adult and 1 young bird) of 4 H5N1-highly-pathogenic-avian-influenza (HPAI)-virus-infected whooper swans in Akita, Japan, in 2008 were investigated pathologically. Macroscopically, white spots with hemorrhages were scattered in the pancreas in the adult bird. Histologically, the adult bird had severe necrotizing pancreatitis and mild nonpurulent encephalitis. The young bird had severe nonpurulent encephalitis and nonpurulent enteric ganglionitis, and intestinal venous wall thickening. Virus antigens were detected in the lesions of pancreatitis in the adult bird and of encephalitis in adult and young birds. These findings suggest that the swans died or became moribund due to neurological disorders and necrotizing pancreatitis caused by H5N1 HPAI virus infection.

  11. No evidence of transmission of H5N1 highly pathogenic avian influenza to humans after unprotected contact with infected wild swans.

    Science.gov (United States)

    Wallensten, A; Salter, M; Bennett, S; Brown, I; Hoschler, K; Oliver, I

    2010-02-01

    Highly pathogenic avian influenza (HPAI) subtype H5N1 remains a public health threat as long as it circulates in wild and domestic birds. Information on the transmissibility of H5N1 HPAI from wild birds is needed for evidence-based public health advice. We investigated if transmission of H5N1 HPAI had taken place in people that had unprotected contact with infected wild mute swans during an incident at the Abbotsbury Swannery in Dorset, England. Thirteen people who had been exposed to infected swans were contacted and actively followed up for symptoms. Serology was taken after 30 days. We did not find evidence of transmission of H5N1 HPAI to humans during the incident. The incident provided a rare opportunity to study the transmissibility of the virus from wild birds to humans.

  12. Clinical outcomes of seasonal influenza and pandemic influenza A (H1N1 in pediatric inpatients

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    Budd Alicia

    2010-10-01

    Full Text Available Abstract Background In April 2009, a novel influenza A H1N1 (nH1N1 virus emerged and spread rapidly worldwide. News of the pandemic led to a heightened awareness of the consequences of influenza and generally resulted in enhanced infection control practices and strengthened vaccination efforts for both healthcare workers and the general population. Seasonal influenza (SI illness in the pediatric population has been previously shown to result in significant morbidity, mortality, and substantial hospital resource utilization. Although influenza pandemics have the possibility of resulting in considerable illness, we must not ignore the impact that we can experience annually with SI. Methods We compared the outcomes of pediatric patients ≤18 years of age at a large urban hospital with laboratory confirmed influenza and an influenza-like illness (ILI during the 2009 pandemic and two prior influenza seasons. The primary outcome measure was hospital length of stay (LOS. All variables potentially associated with LOS based on univariable analysis, previous studies, or hypothesized relationships were included in the regression models to ensure adjustment for their effects. Results There were 133 pediatric cases of nH1N1 admitted during 2009 and 133 cases of SI admitted during the prior 2 influenza seasons (2007-8 and 2008-9. Thirty-six percent of children with SI and 18% of children with nH1N1 had no preexisting medical conditions (p = 0.14. Children admitted with SI had 1.73 times longer adjusted LOS than children admitted for nH1N1 (95% CI 1.35 - 2.13. There was a trend towards more children with SI requiring mechanical ventilation compared with nH1N1 (16 vs.7, p = 0.08. Conclusions This study strengthens the growing body of evidence demonstrating that SI results in significant morbidity in the pediatric population. Pandemic H1N1 received considerable attention with strong media messages urging people to undergo vaccination and encouraging improved

  13. Detection of H5N1 high-pathogenicity avian influenza virus in meat and tracheal samples from experimentally infected chickens.

    Science.gov (United States)

    Das, Amaresh; Spackman, Erica; Thomas, Colleen; Swayne, David E; Suarez, David L

    2008-03-01

    The Asian H5N1 highly pathogenic avian influenza (HPAI) virus causes a systemic disease with high mortality of poultry and is potentially zoonotic. In both chickens and ducks, the virus has been demonstrated to replicate in both cardiac and skeletal muscle cells. Experimentally, H5N1 HPAI virus has been transmitted to chickens through the consumption of raw infected meat. In this study, we investigated virus replication in cardiac and skeletal muscle and in the trachea of chickens after experimental intranasal inoculation with the H5N1 HPAI virus. The virus was detected in tissues by real-time reverse transcription-polymerase chain reaction (RRT-PCR) and virus isolation, and in the trachea by RRT-PCR and a commercial avian influenza (AI) viral antigen detection test. A modified RNA extraction protocol was developed for rapid detection of the virus in tissues by RRT-PCR. The H5N1 HPAI virus was sporadically detected in meat and the tracheas of infected birds without any clinical sign of disease as early as 6 hr postinfection (PI), and was detected in all samples tested at 24 hr PI and later. No differences in sensitivity were seen between virus isolation and RRT-PCR in meat samples. The AI viral antigen detection test on tracheal swabs was a useful method for identifying infected chickens when they were sick or dead, but was less sensitive in detecting infected birds when they were preclinical. This study provides data indicating that preslaughter tracheal swab testing can identify birds infected with HPAI among the daily mortality and prevent infected flocks from being sent to processing plants. In addition, the modified RNA extraction and RRT-PCR test on meat samples provide a rapid and sensitive method of identifying HPAI virus in illegal contraband or domestic meat samples.

  14. Analysis of Viral Genetics for Estimating Diffusion of Influenza A H6N1

    OpenAIRE

    Scotch, Matthew; Suchard, Marc A.; Rabinowitz, Peter M.

    2015-01-01

    H6N1 influenza A is an avian virus but in 2013 infected a human in Taiwan. We studied the phylogeography of avian origin H6N1 viruses in the Influenza Research Database and the Global Initiative on Sharing Avian Influenza Data EpiFlu Database in order to characterize their recent evolutionary spread. Our results suggest that the H6N1 virus that infected a human in Taiwan is derived from a diversity of avian strains of H6N1 that have circulated for at least seven years in this region. Understa...

  15. Live bird markets of Bangladesh: H9N2 viruses and the near absence of highly pathogenic H5N1 influenza.

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    Nicholas J Negovetich

    2011-04-01

    Full Text Available Avian influenza surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results of an active surveillance effort focusing on the live-bird markets are presented. Prevalence of influenza infection in the birds of the live bird markets is 23.0%, which is similar to that in poultry markets in other countries. Nearly all of the isolates (94% were of the non-pathogenic H9N2 subtype, but viruses of the H1N2, H1N3, H3N6, H4N2, H5N1, and H10N7 subtypes were also observed. The highly pathogenic H5N1-subtype virus was observed at extremely low prevalence in the surveillance samples (0.08%, and we suggest that the current risk of infection for humans in the retail poultry markets in Bangladesh is negligible. However, the high prevalence of the H9 subtype and its potential for interaction with the highly pathogenic H5N1-subtype, i.e., reassortment and attenuation of host morbidity, highlight the importance of active surveillance of the poultry markets.

  16. Adaptation of Pandemic H1N1 Influenza Viruses in Mice▿

    Science.gov (United States)

    Ilyushina, Natalia A.; Khalenkov, Alexey M.; Seiler, Jon P.; Forrest, Heather L.; Bovin, Nicolai V.; Marjuki, Henju; Barman, Subrata; Webster, Robert G.; Webby, Richard J.

    2010-01-01

    The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to α2,3 together with decreasing binding to α2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals. PMID:20592084

  17. Seroprevalence of H1N1, H3N2 and H1N2 influenza viruses in pigs in seven European countries in 2002-2003

    NARCIS (Netherlands)

    Reeth, K.; Brown, I.H.; Durrwald, R.; Foni, E.; Labarque, G.; Lenihan, P.; Maldonado, J.; Markowska-Daniel, I.; Pensaert, M.; Pospisil, Z.; Koch, G.

    2008-01-01

    Objectives Avian-like H1N1 and human-like H3N2 swine influenza viruses (SIV) have been considered widespread among pigs in Western Europe since the 1980s, and a novel H1N2 reassortant with a human-like H1 emerged in the mid 1990s. This study, which was part of the EC-funded 'European Surveillance

  18. Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

    Directory of Open Access Journals (Sweden)

    Farooqui Amber

    2012-06-01

    Full Text Available Abstract Background Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. Results This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA of viral genomes that might correlate with their different phenotypic behavior. Conclusions The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.

  19. (H1N1) Influenza in Saurashtra, India

    African Journals Online (AJOL)

    Mexico in April, 2009,[1] and then in United States (US).[2,3]. This was originally ... duration of hospital stay of such patients was 2‑32 days. All admitted A (H1N1) .... Because of limited resources, only 2009 A (H1N1) influenza virus was tested ...

  20. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

    Science.gov (United States)

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-09-01

    We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  1. Coinfection with influenza A(H1N1pdm09 and dengue virus in fatal cases

    Directory of Open Access Journals (Sweden)

    Anne Carolinne Bezerra Perdigão

    2016-01-01

    Full Text Available Abstract We report on four patients with fatal influenza A(H1N1pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses’ epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4. Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998. As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015. In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm, caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010. In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013. The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013. The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  2. First reported detection of influenza A (H1N1)pdm09 in turkeys in the United Kingdom.

    Science.gov (United States)

    Reid, Scott M; Cox, William J; Ceeraz, Vanessa; Sutton, David; Essen, Steve C; Howard, Wendy A; Slomka, Marek J; Irvine, Richard M; Brown, Ian H

    2012-12-01

    We report the first occurrence of pandemic (H1N1) 2009 virus [A(H1N1)pdm09] infection on two epidemiologically linked turkey breeder premises in the United Kingdom during December 2010 and January 2011. Clinically, the birds showed only mild signs of disease, with the major presenting sign being an acute and marked reduction in egg production, leading to the prompt reporting of suspected avian notifiable disease for official investigation. Presence of A(H1N1)pdm09 infection in the United Kingdom turkey breeder flocks was confirmed by detailed laboratory investigations including virus isolation in embryonated specific pathogen-free fowls' eggs, two validated real-time reverse transcription-PCR tests, and nucleotide sequencing of the hemagglutinin and neuraminidase genes. These investigations revealed high nucleotide identity with currently circulating human A(H1N1)pdm09 strains, suggesting that human-to-poultry transmission (reverse zoonosis) was the most likely route of infection. Peak levels of human influenza-like illness community transmission also coincided with the onset of clinical signs in both affected turkey breeder flocks. This case demonstrated the value of the existing passive surveillance framework and associated veterinary and laboratory infrastructure that enables the detection and management of both exotic and new and emerging disease hazards and risks. The case also presents further evidence of the susceptibility of turkeys to infection with influenza A viruses of nonavian origin.

  3. Clinical and epidemiologic characteristics of an outbreak of novel H1N1 (swine origin) influenza A virus among United States military beneficiaries.

    Science.gov (United States)

    Crum-Cianflone, Nancy F; Blair, Patrick J; Faix, Dennis; Arnold, John; Echols, Sara; Sherman, Sterling S; Tueller, John E; Warkentien, Tyler; Sanguineti, Gabriela; Bavaro, Mary; Hale, Braden R

    2009-12-15

    A novel swine-origin influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. The San Diego region was an early focal point of the emerging pandemic. We describe the clinical and epidemiologic characteristics of this novel strain in a military population to assist in future outbreak prevention and control efforts. We performed an epidemiologic evaluation of novel H1N1 virus infections diagnosed in San Diego County among 96,258 local US military beneficiaries. The structured military medical system afforded the ability to obtain precise epidemiologic information on the impact on H1N1 virus infection in a population. The novel H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 21 April through 8 May 2009, 761 patients presented with influenza-like illness and underwent rRT-PCR testing. Of these patients, 97 had confirmed novel H1N1 virus infection, with an incidence rate of 101 cases per 100,000 persons. The median age of H1N1 patients with H1N1 virus infection was 21 years (interquartile range, 15-25 years). Fever was a universal symptom in patients with H1N1 virus infection; other symptoms included cough (present in 96% of patients), myalgia or arthralgia (57%), and sore throat (51%). Sixty-eight (70%) of our patients had an identifiable epidemiologic link to another confirmed patient. The largest cluster of cases of H1N1 virus infection occurred on a Navy ship and involved 32 (8%) of 402 crew members; the secondary attack rate was 6%-14%. The rapid influenza testing that was used during this outbreak had a sensitivity of 51% and specificity of 98%, compared with rRT-PCR. Only 1 patient was hospitalized, and there were no deaths. A novel H1N1 influenza A virus caused a significant outbreak among military beneficiaries in San Diego County, including a significant cluster of cases onboard a Navy ship. The outbreak described here primarily affected adolescents and young

  4. The infection of chicken tracheal epithelial cells with a H6N1 avian influenza virus.

    Directory of Open Access Journals (Sweden)

    Ching-I Shen

    Full Text Available Sialic acids (SAs linked to galactose (Gal in α2,3- and α2,6-configurations are the receptors for avian and human influenza viruses, respectively. We demonstrate that chicken tracheal ciliated cells express α2,3-linked SA, while goblet cells mainly express α2,6-linked SA. In addition, the plant lectin MAL-II, but not MAA/MAL-I, is bound to the surface of goblet cells, suggesting that SA2,3-linked oligosaccharides with Galβ1-3GalNAc subterminal residues are specifically present on the goblet cells. Moreover, both α2,3- and α2,6-linked SAs are detected on single tracheal basal cells. At a low multiplicity of infection (MOI avian influenza virus H6N1 is exclusively detected in the ciliated cells, suggesting that the ciliated cell is the major target cell of the H6N1 virus. At a MOI of 1, ciliated, goblet and basal cells are all permissive to the AIV infection. This result clearly elucidates the receptor distribution for the avian influenza virus among chicken tracheal epithelial cells and illustrates a primary cell model for evaluating the cell tropisms of respiratory viruses in poultry.

  5. Streptococcus pneumoniae Coinfection Is Correlated with the Severity of H1N1 Pandemic Influenza

    Science.gov (United States)

    Cisterna, Daniel; Savji, Nazir; Bussetti, Ana Valeria; Kapoor, Vishal; Hui, Jeffrey; Tokarz, Rafal; Briese, Thomas; Baumeister, Elsa; Lipkin, W. Ian

    2009-01-01

    Background Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease. Methods/Principal Findings We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0

  6. Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus.

    Science.gov (United States)

    Ogiwara, Haru; Yasui, Fumihiko; Munekata, Keisuke; Takagi-Kamiya, Asako; Munakata, Tsubasa; Nomura, Namiko; Shibasaki, Futoshi; Kuwahara, Kazuhiko; Sakaguchi, Nobuo; Sakoda, Yoshihiro; Kida, Hiroshi; Kohara, Michinori

    2014-01-01

    Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    Directory of Open Access Journals (Sweden)

    Paola Faverio

    2014-01-01

    Full Text Available We present the results of bronchoalveolar lavage (BAL performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS. Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage.

  8. Willingness to accept H1N1 pandemic influenza vaccine: A cross-sectional study of Hong Kong community nurses

    Directory of Open Access Journals (Sweden)

    Wong Carmen

    2010-10-01

    Full Text Available Abstract Background The 2009 pandemic of influenza A (H1N1 infection has alerted many governments to make preparedness plan to control the spread of influenza A (H1N1 infection. Vaccination for influenza is one of the most important primary preventative measures to reduce the disease burden. Our study aims to assess the willingness of nurses who work for the community nursing service (CNS in Hong Kong on their acceptance of influenza A (H1N1 influenza vaccination. Methods 401 questionnaires were posted from June 24, 2009 to June 30, 2009 to community nurses with 67% response rate. Results of the 267 respondents on their willingness to accept influenza A (H1N1 vaccine were analyzed. Results Twenty-seven percent of respondents were willing to accept influenza vaccination if vaccines were available. Having been vaccinated for seasonable influenza in the previous 12 months were significantly independently associated with their willingness to accept influenza A (H1N1 vaccination (OR = 4.03; 95% CI: 2.03-7.98. Conclusions Similar to previous findings conducted in hospital healthcare workers and nurses, we confirmed that the willingness of community nurses to accept influenza A (H1N1 vaccination is low. Future studies that evaluate interventions to address nurses' specific concerns or interventions that aim to raise the awareness among nurses on the importance of influenza A (H1N1 vaccination to protect vulnerable patient populations is needed.

  9. Impact of Body Mass Index on Immunogenicity of Pandemic H1N1 Vaccine in Children and Adults

    Science.gov (United States)

    Callahan, S. Todd; Wolff, Mark; Hill, Heather R.; Edwards, Kathryn M.; Keitel, Wendy; Atmar, Robert; Patel, Shital; Sahly, Hana El; Munoz, Flor; Paul Glezen, W.; Brady, Rebecca; Frenck, Robert; Bernstein, David; Harrison, Christopher; Jackson, Mary Anne; Swanson, Douglas; Newland, Jason; Myers, Angela; Livingston, Robyn A; Walter, Emmanuel; Dolor, Rowena; Schmader, Kenneth; Mulligan, Mark J.; Edupuganti, Srilatha; Rouphael, Nadine; Whitaker, Jennifer; Spearman, Paul; Keyserling, Harry; Shane, Andi; Eckard, Allison Ross; Jackson, Lisa A.; Frey, Sharon E.; Belshe, Robert B.; Graham, Irene; Anderson, Edwin; Englund, Janet A.; Healy, Sara; Winokur, Patricia; Stapleton, Jack; Meier, Jeffrey; Kotloff, Karen; Chen, Wilbur; Hutter, Julia; Stephens, Ina; Wooten, Susan; Wald, Anna; Johnston, Christine; Edwards, Kathryn M.; Buddy Creech, C.; Todd Callahan, S.

    2014-01-01

    Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses. PMID:24795475

  10. Temperature sensitivity on growth and/or replication of H1N1, H1N2 and H3N2 influenza A viruses isolated from pigs and birds in mammalian cells.

    Science.gov (United States)

    Massin, Pascale; Kuntz-Simon, Gaëlle; Barbezange, Cyril; Deblanc, Céline; Oger, Aurélie; Marquet-Blouin, Estelle; Bougeard, Stéphanie; van der Werf, Sylvie; Jestin, Véronique

    2010-05-19

    Influenza A viruses have been isolated from a wide range of animal species, aquatic birds being the reservoir for their genetic diversity. Avian influenza viruses can be transmitted to humans, directly or indirectly through an intermediate host like pig. This study aimed to define in vitro conditions that could prove useful to evaluate the potential of influenza viruses to adapt to a different host. Growth of H1N1, H1N2 and H3N2 influenza viruses belonging to different lineages isolated from birds or pigs prior to 2005 was tested on MDCK or NPTr cell lines in the presence or absence of exogenous trypsin. Virus multiplication was compared at 33, 37 and 40 degrees C, the infection site temperatures in human, swine and avian hosts, respectively. Temperature sensitivity of PB2-, NP- and M-RNA replication was also tested by quantitative real-time PCR. Multiplication of avian viruses was cold-sensitive, whatever cell type. By contrast, temperature sensitivity of swine viruses was found to depend on the virus and the host cell: for an H1N1 swine isolate from 1982, multiplication was cold-sensitive on NPTr cells and undetectable at 40 degrees C. From genetic analyses, it appears that temperature sensitivity could involve other residues than PB2 residue 627 and could affect other steps of the replication cycle than replication. Copyright 2009 Elsevier B.V. All rights reserved.

  11. Clinical profile and predictors of mortality of severe pandemic (H1N1 2009 virus infection needing intensive care: A multi-centre prospective study from South India

    Directory of Open Access Journals (Sweden)

    Kartik Ramakrishna

    2012-01-01

    Full Text Available Background: This multi-center study from India details the profile and outcomes of patients admitted to the intensive care unit (ICU with pandemic Influenza A (H1N1 2009 virus [P(H1N12009v] infection. Materials and Methods: Over 4 months, adult patients diagnosed to have P(H1N12009v infection by real-time RT-PCR of respiratory specimens and requiring ICU admission were followed up until death or hospital discharge. Sequential organ failure assessment (SOFA scores were calculated daily. Results: Of the 1902 patients screened, 464 (24.4% tested positive for P(H1N12009v; 106 (22.8% patients aged 35±11.9 (mean±SD years required ICU admission 5.8±2.7 days after onset of illness. Common symptoms were fever (96.2%, cough (88.7%, and breathlessness (85.9%. The admission APACHE-II and SOFA scores were 14.4±6.5 and 5.5±3.1, respectively. Ninety-six (90.6% patients required ventilation for 10.1±7.5 days. Of these, 34/96 (35.4% were non-invasively ventilated; 16/34 were weaned successfully whilst 18/34 required intubation. Sixteen patients (15.1% needed dialysis. The duration of hospitalization was 14.0±8.0 days. Hospital mortality was 49%. Mortality in pregnant/puerperal women was 52.6% (10/19. Patients requiring invasive ventilation at admission had a higher mortality than those managed with non-invasive ventilation and those not requiring ventilation (44/62 vs. 8/44, P<0.001. Need for dialysis was independently associated with mortality (P=0.019. Although admission APACHE-II and SOFA scores were significantly (P<0.02 higher in non-survivors compared with survivors on univariate analysis, individually, neither were predictive on multivariate analysis. Conclusions: In our setting, a high mortality was observed in patients admitted to ICU with severe P(H1N12009v infection. The need for invasive ventilation and dialysis were associated with a poor outcome.

  12. Different neuraminidase inhibitor susceptibilities of human H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany from 2001 to 2005/2006.

    Science.gov (United States)

    Bauer, Katja; Richter, Martina; Wutzler, Peter; Schmidtke, Michaela

    2009-04-01

    In the flu season 2005/2006 amantadine-resistant human influenza A viruses (FLUAV) of subtype H3N2 circulated in Germany. This raises questions on the neuraminidase inhibitor (NAI) susceptibility of FLUAV. To get an answer, chemiluminescence-based neuraminidase inhibition assays were performed with 51 H1N1, H1N2, and H3N2 FLUAV isolated in Germany from 2001 to 2005/2006. According to the mean IC(50) values (0.38-0.91 nM for oseltamivir and 0.76-1.13 nM for zanamivir) most H1N1 and H3N2 FLUAV were NAI-susceptible. But, about four times higher zanamivir concentrations were necessary to inhibit neuraminidase activity of H1N2 viruses. Two H1N1 isolates were less susceptible to both drugs in NA inhibition as well as virus yield reduction assays. Results from sequence analysis of viral hemagglutinin and neuraminidase genes and evolutionary analysis of N2 gene revealed (i) different subclades for N2 in H1N2 and H3N2 FLUAV that could explain the differences in zanamivir susceptibility among these viruses and (ii) specific amino acid substitutions in the neuraminidase segment of the two less NAI-susceptible H1N1 isolates. One H3N2 was isolate proved to be a mixture of a NA deletion mutant and full-length NA viruses.

  13. 64 multidetector CT findings of influenza A (H1N1) virus in patients with hematologic malignancies

    International Nuclear Information System (INIS)

    El-Badrawy, Adel; Zeidan, Amany; Ebrahim, Mohamed A.

    2012-01-01

    Background. The pandemic of swine-origin H1N1 influenza that began in early 2009 has provided evidence that radiology can assist in the early diagnosis of severe cases. Immunocompromised patients are at increased risk for morbidity and mortality. MDCT is superior to radiography in showing the distribution of the disease. Purpose. To review the 64 multidetector CT thoracic findings of novel swine-origin influenza A (H1N1) virus in patients with hematologic malignancies. Material and Methods. This study included 12 patients (3 women, 9 men; mean age, 32.2 years). All patients proved to be infected with influenza A (H1N1) virus. The hematologic malignancies were acute myeloid leukemia (n = 8), chronic lymphocytic leukemia (n = 2), multiple myeloma (n = 1), and myelodysplastic syndrome (n = 1). All the patients underwent CT scanning using a 64 multidetector CT scanner. Chest CT scans were reviewed for ground-glass opacities (GGOs), consolidation, airway thickening/dilatation, nodules, mediastinal lymphadenopathy, and pleural effusion. Results. More than one CT finding was detected in every patient. Pulmonary affection was bilateral, more on the left side. The affections were mainly peribronchial. Airway wall thickening and dilatation were detected in all 12 patients, GGO in 9/12 patients, nodules in 6/12 patients, consolidation in 6/12 patients, hilar lymphadenopathy in 3/12 patients, and pleural effusion in 2/12 patients. Conclusion. Acute myeloid leukemia is the most common hematologic malignancy affected by influenza A (H1N1) virus. The left lung is affected more than the right one. The most common multidetector CT findings are unilateral or bilateral airway thickening and dilatation. Multidetector CT can be used for early and accurate assessment of pulmonary affection with influenza A H1N1 virus infection

  14. 64 multidetector CT findings of influenza A (H1N1) virus in patients with hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    El-Badrawy, Adel [Dept. of Radiology, Mansoura Faculty of Medicine, Mansoura (Egypt)], E-mail: adelelbadrawy@hotmail.com; Zeidan, Amany [Dept. of Thoracic Medicine, Mansoura Faculty of Medicine, Mansoura (Egypt); Ebrahim, Mohamed A. [Dept. of Medical Oncology, Mansoura Faculty of Medicine, Mansoura (Egypt)

    2012-07-15

    Background. The pandemic of swine-origin H1N1 influenza that began in early 2009 has provided evidence that radiology can assist in the early diagnosis of severe cases. Immunocompromised patients are at increased risk for morbidity and mortality. MDCT is superior to radiography in showing the distribution of the disease. Purpose. To review the 64 multidetector CT thoracic findings of novel swine-origin influenza A (H1N1) virus in patients with hematologic malignancies. Material and Methods. This study included 12 patients (3 women, 9 men; mean age, 32.2 years). All patients proved to be infected with influenza A (H1N1) virus. The hematologic malignancies were acute myeloid leukemia (n = 8), chronic lymphocytic leukemia (n = 2), multiple myeloma (n = 1), and myelodysplastic syndrome (n = 1). All the patients underwent CT scanning using a 64 multidetector CT scanner. Chest CT scans were reviewed for ground-glass opacities (GGOs), consolidation, airway thickening/dilatation, nodules, mediastinal lymphadenopathy, and pleural effusion. Results. More than one CT finding was detected in every patient. Pulmonary affection was bilateral, more on the left side. The affections were mainly peribronchial. Airway wall thickening and dilatation were detected in all 12 patients, GGO in 9/12 patients, nodules in 6/12 patients, consolidation in 6/12 patients, hilar lymphadenopathy in 3/12 patients, and pleural effusion in 2/12 patients. Conclusion. Acute myeloid leukemia is the most common hematologic malignancy affected by influenza A (H1N1) virus. The left lung is affected more than the right one. The most common multidetector CT findings are unilateral or bilateral airway thickening and dilatation. Multidetector CT can be used for early and accurate assessment of pulmonary affection with influenza A H1N1 virus infection.

  15. Nosocomial Pandemic (H1N1) 2009, United Kingdom, 2009–2010

    Science.gov (United States)

    Myles, Puja R.; Openshaw, Peter J.M.; Gadd, Elaine M.; Lim, Wei Shen; Semple, Malcolm G.; Read, Robert C.; Taylor, Bruce L.; McMenamin, James; Armstrong, Colin; Bannister, Barbara; Nicholson, Karl G.; Nguyen-Van-Tam, Jonathan S.

    2011-01-01

    To determine clinical characteristics of patients hospitalized in the United Kingdom with pandemic (H1N1) 2009, we studied 1,520 patients in 75 National Health Service hospitals. We characterized patients who acquired influenza nosocomially during the pandemic (H1N1) 2009 outbreak. Of 30 patients, 12 (80%) of 15 adults and 14 (93%) of 15 children had serious underlying illnesses. Only 12 (57%) of 21 patients who received antiviral therapy did so within 48 hours after symptom onset, but 53% needed escalated care or mechanical ventilation; 8 (27%) of 30 died. Despite national guidelines and standardized infection control procedures, nosocomial transmission remains a problem when influenza is prevalent. Health care workers should be routinely offered influenza vaccine, and vaccination should be prioritized for all patients at high risk. Staff should remain alert to the possibility of influenza in patients with complex clinical problems and be ready to institute antiviral therapy while awaiting diagnosis during influenza outbreaks. PMID:21470446

  16. INFECCIÓN POR VIRUS DE LA GRIPE A H1N1NV EN ELCOMPLEJO ASISTENCIAL UNIVERSITARIO DE BURGOSDESDE DICIEMBRE DE 2010 A MARZO DE 2011

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    Megías Lobón G

    2012-01-01

    Full Text Available SUMMARY: INFLUENZA A H1N1NV INFECTION IN A BURGOS HOSPITAL FROM DECEMBER 2010 TO MARCH 2011 Introduction: Monitoring and characterization of infection with pandemic (H1N1nv 2009 is an essential part of monitoring the evolution, epidemiology and severity of a pandemic. The aim of this paper is to describe and analyze the clinical characteristics and risk factors of patients admitted to our hospital the 2010-2011 season. Methods: Detection of influenza A H1N1nv virus in 266 respiratory specimens (242 patients with suspected infection and descriptive and comparative analysis of data collected from each patient: age, sex, service, reason for admission, risk factors and treatment with antivirals. Results: The most common reason for admission (52.47% was the presence of clinical respiratory signs. 69.4% of patients had risk factors, with chronic respiratory disease (CRD, the most frequent (20.2%. 14.2% were pediatric patients. The infection of Influenza A H1N1nv was confirmed in 26,4% of patients. The mean age among the infected patients was 36 years versus 44.85 years in non-infected. This difference was statistically significant (p = 0.011. 75% of infected patients had risk factors. Of these, 68.7% had CRD only factor being predominant. 6% of patients with infection were vaccinated. Conclusion: The positivity rate was similar to that observed in the previous season. There was a greater involvement among young-adult population. The CRD is the most common risk factor. Vaccine coverage was low.

  17. Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.

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    Cameron P Simmons

    2007-05-01

    Full Text Available New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs and tested their efficacy for prophylaxis and therapy in a murine model of infection.Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1 in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1. mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1.These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1

  18. Protection level of AI H5N1 vaccine clade 2.1.3 commercial against AI H5N1 clade 2.3.2 virus from Ducks to SPF chicken in laboratory conditions

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    Indriani R

    2015-03-01

    Full Text Available Highly Pathogenic Avian Influenza (HPAI subtype H5N1 clade 2.3.2 has infected chickens in farms, causing mortality and a decrease in egg production. Vaccination is one of the strategies to control disease of AI subtype H5N1. AI H5N1 clade 2.1.3 vaccine is available commercially. The effectiveness of two vaccines of AI H5N1 clade 2.1.3 (product A and B, and AI H5N1 clade 2.3.2 (Sukoharjo against AI H5N1 clade 2.3.2 (Sukoharjo virus SPF chickens was tested in laboratory. Four groups of SPF chickens were used in this study, there were (1 vaccinated with H5N1 clade 2.1.3 (product A, (2 vaccinated with H5N1 clade 2.1.3 (product B, (3 vaccinated with AI H5N1 clade 2.3.2 and (4 unvaccinated (as a control. Each vaccinated group consisted of 10 chicken except 8 chicken for control group. SPF chicken were vaccinated with 1 dose of vaccine at 3 weeks olds, and then after 3 weeks post vaccination (at 6 weeks olds. All group of chicken were challenged with 106 EID50 per 0.1 ml via intranasal. The results showed, chicken vaccinated with H5N1 clade 2.1.3 product A and B gave 100 and 80% protection respectively, but showed challenged virus shedding, whereas vaccine of H5N1 clade 2.3.2 gave 100% protection from mortality and without virus shedding. Vaccines of AI H5N1 clade 2.1.3 product A was better than vaccine product B, and when chicken vaccinated against H5N1 clade 2.3.2, H5N1 clade 2.3.2 vaccine was the best to be used. In order to protect chicken from AI subtype H5N1 clade 2.1.3 and 2.3.2 in the field, a bivalent vaccine of H5N1 clade 2.1.3 and 2.3.2 subtypes should be developed.

  19. Predicting H1N1 vaccine uptake and H1N1-related health beliefs: the role of individual difference in consideration of future consequences.

    Science.gov (United States)

    Nan, Xiaoli; Kim, Jarim

    2014-01-01

    This research examines the influence of individual difference in consideration of future consequences on H1N1 vaccine uptake and H1N1-related health beliefs (i.e., perceived susceptibility to and severity of the H1N1 flu, perceived efficacy and safety of the H1N1 vaccine, and perceived self-efficacy in obtaining the H1N1 vaccine). A survey of 411 college students showed that consideration of future consequences had no direct effect on vaccine uptake, but higher consideration of future consequences was associated with greater perceived severity of the flu, higher perceived effectiveness of the vaccine, and greater perceived self-efficacy. Additional analysis suggested that consideration of future consequences had a significant indirect effect on vaccine uptake through perceived vaccine efficacy. Results of the study also revealed gender and racial differences in some of the H1N1-related health beliefs. Implications of the findings for vaccine risk communication are discussed.

  20. An analysis of 332 fatalities infected with pandemic 2009 influenza A (H1N1 in Argentina.

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    Ana M Balanzat

    Full Text Available The apparent high number of deaths in Argentina during the 2009 pandemic led to concern that the influenza A H1N1pdm disease was different there. We report the characteristics and risk factors for influenza A H1N1pdm fatalities.We identified laboratory-confirmed influenza A H1N1pdm fatalities occurring during June-July 2009. Physicians abstracted data on age, sex, time of onset of illness, medical history, clinical presentation at admission, laboratory, treatment, and outcomes using standardize questionnaires. We explored the characteristics of fatalities according to their age and risk group.Of 332 influenza A H1N1pdm fatalities, 226 (68% were among persons aged <50 years. Acute respiratory failure was the leading cause of death. Of all cases, 249 (75% had at least one comorbidity as defined by Advisory Committee on Immunization Practices. Obesity was reported in 32% with data and chronic pulmonary disease in 28%. Among the 40 deaths in children aged <5 years, chronic pulmonary disease (42% and neonatal pathologies (35% were the most common co-morbidities. Twenty (6% fatalities were among pregnant or postpartum women of which only 47% had diagnosed co-morbidities. Only 13% of patients received antiviral treatment within 48 hours of symptom onset. None of children aged <5 years or the pregnant women received antivirals within 48 h of symptom onset. As the pandemic progressed, the time from symptom-onset to medical care and to antiviral treatment decreased significantly among case-patients who subsequently died (p<0.001.Persons with co-morbidities, pregnant and who received antivirals late were over-represented among influenza A H1N1pdm deaths in Argentina, though timeliness of antiviral treatment improved during the pandemic.

  1. Oseltamivir-resistant pandemic (H1N12009 in Yemen - case report

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    Al-Kohlani Abdulhakeem

    2010-05-01

    Full Text Available Abstract Background During the influenza season of 2007-08, oseltamivir-resistant influenza A (H1N1 viruses emerged in several countries in Europe, North America, and Asia. Despite substantial prevalence of oseltamivir-resistant viruses, few data are available on the clinical profile of subjects infected with these viruses. Objectives: to describe the first oseltamivir-resistant (H1N1 influenza virus pandemic 2009 from the Eastern Mediterranean Region including Yemen and to determine the evidence by clinical presentation of children infected with these oseltamivir - resistant viruses. Methodology History, physical examination and laboratory investigations including Complete Blood Count, chest x-ray, blood cultures, CSF examination, LFTs, RFTs, blood for sugar, H1N1 test and oseltamivir resistance test. Results Nasal swabs indicated positivity on both H1N1 test and the RNP gene (Human R Nase P gene that serves as internal positive control for Human RNA. Both clinical specimens presented the mutation S31N in the M2 gene associated with resistance to adamantanes and H274Y in NA gene associated with resistance to oseltamivir. This was the first diagnosed case of resistance to oseltamivir in Yemen and also it is the first reported case of oseltamivir resistance virus in the Eastern Mediterranean Region. Conclusion The pattern of resistance found in the oseltamivir resistant isolate collected from Yemen is the same as has been reported elsewhere in other WHO regions. Clinical description and outcomes are not different from what is described elsewhere.

  2. Endothelial cell tropism is a determinant of H5N1 pathogenesis in mammalian species.

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    Smanla Tundup

    2017-03-01

    Full Text Available The cellular and molecular mechanisms underpinning the unusually high virulence of highly pathogenic avian influenza H5N1 viruses in mammalian species remains unknown. Here, we investigated if the cell tropism of H5N1 virus is a determinant of enhanced virulence in mammalian species. We engineered H5N1 viruses with restricted cell tropism through the exploitation of cell type-specific microRNA expression by incorporating microRNA target sites into the viral genome. Restriction of H5N1 replication in endothelial cells via miR-126 ameliorated disease symptoms, prevented systemic viral spread and limited mortality, despite showing similar levels of peak viral replication in the lungs as compared to control virus-infected mice. Similarly, restriction of H5N1 replication in endothelial cells resulted in ameliorated disease symptoms and decreased viral spread in ferrets. Our studies demonstrate that H5N1 infection of endothelial cells results in excessive production of cytokines and reduces endothelial barrier integrity in the lungs, which culminates in vascular leakage and viral pneumonia. Importantly, our studies suggest a need for a combinational therapy that targets viral components, suppresses host immune responses, and improves endothelial barrier integrity for the treatment of highly pathogenic H5N1 virus infections.

  3. Molecular evolution of H1N1 swine influenza in Guangdong, China, 2016-2017.

    Science.gov (United States)

    Cai, Mengkai; Huang, Junming; Bu, Dexin; Yu, Zhiqing; Fu, Xinliang; Ji, Chihai; Zhou, Pei; Zhang, Guihong

    2018-06-01

    Swine are the main host of the H1N1 swine influenza virus (SIV), however, H1N1 can also infect humans and occasionally cause serious respiratory disease. To trace the evolution of the SIV in Guangdong, China, we performed an epidemic investigation during the period of 2016-2017. Nine H1N1 influenza viruses were isolated from swine nasal swabs. Antigenic analysis revealed that these viruses belonged to two distinct antigenic groups, represented by A/Swine/Guangdong/101/2016 and A/Swine/Guangdong/52/2017. Additionally, three genotypes, known as GD52/17-like, GD493/17-like and GD101/16-like, were identified by phylogenetic analysis. Importantly, the genotypes including a minimum of 4 pdm/09-origin internal genes have become prevalent in China in recent years. A total of 2966 swine serum samples were used to perform hemagglutination inhibition (HI) tests, and the results showed that the seroprevalence values of SW/GD/101/16 (32.2% in 2016, 32.1% in 2017) were significantly higher than the seroprevalence values of SW/GD/52/17 (18.0% in 2016, 16.7% in 2017). Our study showed that the three reassortant genotypes of H1N1 SIV currently circulating in China are stable, but H1N1pdm09 poses challenges to human health by the introduction of internal genes into these reassortant genotypes. Strengthening SIV surveillance is therefore critical for SIV control and minimizing its potential threat to public health. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

    Science.gov (United States)

    Li, Zhuo; Mooney, Alaina J.; Gabbard, Jon D.; Gao, Xiudan; Xu, Pei; Place, Ryan J.; Hogan, Robert J.; Tompkins, S. Mark

    2013-01-01

    A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine. PMID:23077314

  5. Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France.

    Science.gov (United States)

    Dauvilliers, Yves; Arnulf, Isabelle; Lecendreux, Michel; Monaca Charley, Christelle; Franco, Patricia; Drouot, Xavier; d'Ortho, Marie-Pia; Launois, Sandrine; Lignot, Séverine; Bourgin, Patrice; Nogues, Béatrice; Rey, Marc; Bayard, Sophie; Scholz, Sabine; Lavault, Sophie; Tubert-Bitter, Pascale; Saussier, Cristel; Pariente, Antoine

    2013-08-01

    An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects agedvaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association

  6. High-resolution Computed Tomography Findings of H1N1 Influenza-Associated Pneumonia in Korea

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    Lee, Byung Chan; Choi, Song; Kim, Jin Woong; Lim, Hyo Soon [Dept. of Radiology, Chonnam National University Hospital, Chonnam National University School of Medicine, Kwangju (Korea, Republic of); Seon, Hyung Joo; Shin, Sang Soo [Dept. of Radiology, Chonnam National University Hospital, Chonnam National University School of Medicine, Kwangju (Korea, Republic of); Kim, Yun Hyeon; Park, Kyung Hwa [Dept. of Internal Medicine, Chonnam National University Hospital, Chonnam National University School of Medicine, Kwangju (Korea, Republic of)

    2011-04-15

    To evaluate and compare the high-resolution computed tomography (HRCT) findings of patients with H1N1 influenza-associated pneumonia compared usual community acquired pneumonia (CAP), to determine whether there were any useful common HRCT findings predicting their prognosis. HRCT findings of 31 patients (M:F = 16:15, mean age 42 yrs) with Influenza A (H1N1) infection were retrospectively reviewed for abnormal HRCT findings and compared to HRCT findings of CAP in matched patients. Patients were matched according to age and sex, from 2009 to January 2010. The predominant HRCT findings of pneumonia consisted of areas of consolidation and/or groundglass opacity (GGO) which showed no statistically significant differences when comparing the two groups. However, the abnormalities of H1N1-related pneumonia showed higher bilaterality and multilobar or multisegmental involvement compared with CAP (p < 0.05). Internal low attenuation or air-densities in pulmonary infiltration /or lymphadenopathy was observed only in patients with CAP (p < 0.05). HRCT findings in 8 patients with poor clinical outcome had bilaterality (p=0.015), multilobar, and multisegmental involvement. The predominant HRCT findings of H1N1-related pneumonia were areas of consolidation and/or GGO. In addition, H1N1-related pneumonia showed higher bilaterality or multilobar/multisegmental involvement compared with CAP. The patients who presented bilaterality had a worse clinical outcome.

  7. The effect of age on the pathogenesis of a highly pathogenic avian influenza (HPAI) H5N1 virus in Pekin ducks (Anas platyrhynchos) infected experimentally

    OpenAIRE

    L?ndt, Brandon Z.; N??ez, Alejandro.; Banks, Jill; Alexander, Dennis J.; Russell, Christine; Richard? L?ndt, Angela C.; Brown, Ian H.

    2009-01-01

    Background? Highly pathogenic avian influenza (HPAI) H5N1 viruses have recently displayed increased virulence for wild waterfowl. Objectives? To study the effect of host age on the shedding and tissue dissemination of a HPAI H5N1 virus in infected Pekin ducks. Methods? Pekin ducks in two age?matched groups (n?=?18), 8 and 12?weeks old (wo) were each infected with 106 EID50/0?1?ml of HPAI A/turkey/Turkey/1/05 (H5N1, clade 2?2). Each day for 5?days, birds were monitored clinically, and cloacal ...

  8. Will the community nurse continue to function during H1N1 influenza pandemic: a cross-sectional study of Hong Kong community nurses?

    Science.gov (United States)

    Wong, Eliza L Y; Wong, Samuel Y S; Kung, Kenny; Cheung, Annie W L; Gao, Tiffany T; Griffiths, Sian

    2010-04-30

    Healthcare workers have been identified as one of the high risk groups for being infected with influenza during influenza pandemic. Potential levels of absenteeism among healthcare workers in hospital settings are high. However, there was no study to explore the attitudes of healthcare workers in community setting towards the preparedness to the novel H1N1 influenza pandemic. The aim of this study was to explore the willingness of community nurses in Hong Kong to work during H1N1 influenza pandemic. A cross-sectional survey was conducted among all 401 community nurses employed by the Hospital Authority in Hong Kong when the WHO pandemic alert level was 6. The response rate of this study was 66.6%. 76.9% participants reported being "not willing" (33.3%) or "not sure" (43.6%) to take care of patients during H1N1 influenza pandemic. The self-reported reasons for being unwilling to report to duty during H1N1 influenza pandemic were psychological stress (55.0%) and fear of being infected H1N1 influenza (29.2%). The reported unwillingness to report to duty was marginally significantly associated with the request for further training of using infection control clinical guideline (OR: 0.057; CI: 0.25-1.02). Those who reported unwillingness or not being sure about taking care of the patients during H1N1 influenza pandemic were more depressed (p work more emotionally stressful (p < 0.001). Interventions to provide infection control training and address community nurses' psychological needs might increase their willingness to provide care to patients in the community during H1N1 influenza pandemic. This would help to ensure an effective and appropriate health system response during the H1N1 influenza pandemic.

  9. Will the community nurse continue to function during H1N1 influenza pandemic: a cross-sectional study of Hong Kong community nurses?

    Directory of Open Access Journals (Sweden)

    Gao Tiffany T

    2010-04-01

    Full Text Available Abstract Background Healthcare workers have been identified as one of the high risk groups for being infected with influenza during influenza pandemic. Potential levels of absenteeism among healthcare workers in hospital settings are high. However, there was no study to explore the attitudes of healthcare workers in community setting towards the preparedness to the novel H1N1 influenza pandemic. The aim of this study was to explore the willingness of community nurses in Hong Kong to work during H1N1 influenza pandemic. Methods A cross-sectional survey was conducted among all 401 community nurses employed by the Hospital Authority in Hong Kong when the WHO pandemic alert level was 6. Results The response rate of this study was 66.6%. 76.9% participants reported being "not willing" (33.3% or "not sure" (43.6% to take care of patients during H1N1 influenza pandemic. The self-reported reasons for being unwilling to report to duty during H1N1 influenza pandemic were psychological stress (55.0% and fear of being infected H1N1 influenza (29.2%. The reported unwillingness to report to duty was marginally significantly associated with the request for further training of using infection control clinical guideline (OR: 0.057; CI: 0.25-1.02. Those who reported unwillingness or not being sure about taking care of the patients during H1N1 influenza pandemic were more depressed (p Conclusions Interventions to provide infection control training and address community nurses' psychological needs might increase their willingness to provide care to patients in the community during H1N1 influenza pandemic. This would help to ensure an effective and appropriate health system response during the H1N1 influenza pandemic.

  10. Identification of swine H1N2/pandemic H1N1 reassortant influenza virus in pigs, United States.

    Science.gov (United States)

    Ali, Ahmed; Khatri, Mahesh; Wang, Leyi; Saif, Yehia M; Lee, Chang-Won

    2012-07-06

    In October and November 2010, novel H1N2 reassortant influenza viruses were identified from pigs showing mild respiratory signs that included cough and depression. Sequence and phylogenetic analysis showed that the novel H1N2 reassortants possesses HA and NA genes derived from recent H1N2 swine isolates similar to those isolated from Midwest. Compared to the majority of reported reassortants, both viruses preserved human-like host restrictive and putative antigenic sites in their HA and NA genes. The four internal genes, PB2, PB1, PA, and NS were similar to the contemporary swine triple reassortant viruses' internal genes (TRIG). Interestingly, NP and M genes of the novel reassortants were derived from the 2009 pandemic H1N1. The NP and M proteins of the two isolates demonstrated one (E16G) and four (G34A, D53E, I109T, and V313I) amino acid changes in the M2 and NP proteins, respectively. Similar amino acid changes were also noticed upon incorporation of the 2009 pandemic H1N1 NP in other reassortant viruses reported in the U.S. Thus the role of those amino acids in relation to host adaptation need to be further investigated. The reassortments of pandemic H1N1 with swine influenza viruses and the potential of interspecies transmission of these reassortants from swine to other species including human indicate the importance of systematic surveillance of swine population to determine the origin, the prevalence of similar reassortants in the U.S. and their impact on both swine production and public health. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Clinical profile and outcome of critically ill pregnant females with H1N1 influenza

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    Minal Shastri

    2016-12-01

    Full Text Available Background Record based review of the 2009 H1N1 Influenza pandemic suggests that pregnant women are at higher risk for hospitalization and death due to H1N1 Influenza. Aims To study the clinical profile and outcome of critically ill pregnant females admitted in intensive care unit (ICU with real-time recombinant polymerase chain reaction (rRT-PCR proven positive H1N1 cases. Methods A retrospective record-review based study was conducted at Sir SayajiRao General Hospital (SSGH and Medical College, Vadodara on data of confirmed rRT-PCR H1N1 pregnant females admitted during the pandemics of 2010and 2015. Demographics, clinical profile and laboratory investigations were recorded and outcomes (survived or expired were analysed. Results There were a total of 20 H1N1 positive pregnant females requiring ICU admission. With equal demographic distribution among rural and urban population, cough and fever were the most common presenting complaints. 65 per cent were in third trimester, the subgroup which also had the highest mortality. Mean days from onset until presentation was 5.05 days. 12 (60 per cent patients’ required invasive mode of ventilation and all died. Average hospital stay was 7 days. Foetus had favourable outcome in patients who recovered from H1N1 acute illness. Conclusion Pregnant females in our study had 60 per cent mortality. Thus, awareness, early diagnosis and treatment should be provided to them. Guidelines, policy changes and government protocols are required specifically for pregnant females with H1N1 Influenza A infection. Our study was an observational study and comparisons with non-pregnant females were not done, conclusions applicable to entire pregnant population was not derived.

  12. Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza.

    Science.gov (United States)

    Qiu, Yu; De Hert, Karl; Van Reeth, Kristien

    2015-09-24

    Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs.

  13. Full genomic analysis of an influenza A (H1N2) virus identified during 2009 pandemic in Eastern India: evidence of reassortment event between co-circulating A(H1N1)pdm09 and A/Brisbane/10/2007-like H3N2 strains.

    Science.gov (United States)

    Mukherjee, Tapasi Roy; Agrawal, Anurodh S; Chakrabarti, Sekhar; Chawla-Sarkar, Mamta

    2012-10-11

    During the pandemic [Influenza A(H1N1)pdm09] period in 2009-2010, an influenza A (Inf-A) virus with H1N2 subtype (designated as A/Eastern India/N-1289/2009) was detected from a 25 years old male from Mizoram (North-eastern India). To characterize full genome of the H1N2 influenza virus. For initial detection of Influenza viruses, amplification of matrix protein (M) gene of Inf-A and B viruses was carried out by real time RT-PCR. Influenza A positive viruses are then further subtyped with HA and NA gene specific primers. Sequencing and the phylogenetic analysis was performed for the H1N2 strain to understand its origin. The outcome of this full genome study revealed a unique reassortment event where the N-1289 virus acquired it's HA gene from a 2009 pandemic H1N1 virus with swine origin and the other genes from H3N2-like viruses of human origin. This study provides information on possibility of occurrence of reassortment events during influenza season when infectivity is high and two different subtypes of Inf-A viruses co-circulate in same geographical location.

  14. Continued dominance of pandemic A(H1N1 2009 influenza in Victoria, Australia in 2010

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    James E. Fielding

    2011-08-01

    Full Text Available The 2010 Victorian influenza season was characterized by normal seasonal influenza activity and the dominance of the pandemic A(H1N1 2009 strain. General Practice Sentinel Surveillance rates peaked at 9.4 ILI cases per 1000 consultations in week 36 for metropolitan practices, and at 10.5 ILI cases per 1000 in the following week for rural practices. Of the 678 ILI cases, 23% were vaccinated, a significantly higher percentage than in previous years. A significantly higher percentage of ILI patients were swabbed in 2010 compared to 2003–2008, but similar to 2009, with a similar percentage being positive for influenza as in previous years. Vaccination rates increased with patient age. Melbourne Medical Deputising Service rates peaked in week 35 at 19.1 ILI cases per 1000 consultations. Of the 1914 cases of influenza notified to the Department of Health, Victoria, 1812 (95% were influenza A infections - 1001 (55% pandemic A(H1N1 2009, 4 (<1% A(H3N2 and 807 (45% not subtyped; 88 (5% were influenza B; and 14 (< 1% were influenza A and B co-infections. The World Health Organization Collaborating Centre for Reference and Research on Influenza tested 403 isolates of which 261 were positive for influenza, 250 of which were influenza A and 11 were influenza B. Ninety-two per cent of the influenza A viruses were pandemic A(H1N1 2009, and following antigenic analysis all of these were found to be similar to the current vaccine strain. Three viruses (0.9% were found to be oseltamivir resistant due to an H275Y mutation in the neuraminidase gene.

  15. Influenza A (H1N1) neuraminidase inhibitors from Vitis amurensis

    DEFF Research Database (Denmark)

    Nguyen, Ngoc Anh; Dao, Trong Tuan; Tung, Bui Thanh

    2011-01-01

    Recently, a novel H1N1 influenza A virus (H1N1/09 virus) was identified and considered a strong candidate for a novel influenza pandemic. As part of an ongoing anti-influenza screening programme on natural products, eight oligostilbenes were isolated as active principles from the methanol extract...... of Vitis amurensis. This manuscript reports the isolation, structural elucidation, and anti-viral activities of eight compounds on various neuraminidases from influenza A/PR/8/34 (H1N1), novel swine-origin influenza A (H1N1), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells...

  16. The new school absentees reporting system for pandemic influenza A/H1N1 2009 infection in Japan.

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    Takeshi Suzue

    Full Text Available To evaluate the new Japanese School Absentees Reporting System for Infectious Disease (SARSID for pandemic influenza A/H1N1 2009 infection in comparison with the National epidemiological Surveillance of Infectious Disease (NESID.We used data of 53,223 students (97.7% in Takamatsu city Japan. Data regarding school absentees in SARSID was compared with that in NESID from Oct 13, 2009 to Jan 12, 2010.Similar trends were observed both in SARSID and NESID. However, the epidemic trend for influenza in SARSID was thought to be more sensitive than that in NESID.The epidemic trend for influenza among school-aged children could be easily and rapidly assessed by SARSID compared to NESID. SARSID might be useful for detecting the epidemic trend of influenza.

  17. Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients

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    Cristiana C. Garcia

    2018-05-01

    Full Text Available Influenza A virus (IAV infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks are central signaling enzymes, involved in cell growth, survival, and migration. Class IB PI3K or phosphatidyl inositol 3 kinase-gamma (PI3Kγ, mainly expressed by leukocytes, is involved in cell migration during inflammation. Here, we investigated the contribution of PI3Kγ for the inflammatory and antiviral responses to IAV. PI3Kγ knockout (KO mice were highly susceptible to lethality following infection with influenza A/WSN/33 H1N1. In the early time points of infection, infiltration of neutrophils was higher than WT mice whereas type-I and type-III IFN expression and p38 activation were reduced in PI3Kγ KO mice resulting in higher viral loads when compared with WT mice. Blockade of p38 in WT macrophages infected with IAV reduced levels of interferon-stimulated gene 15 protein to those induced in PI3Kγ KO macrophages, suggesting that p38 is downstream of antiviral responses mediated by PI3Kγ. PI3Kγ KO-derived fibroblasts or macrophages showed reduced type-I IFN transcription and altered pro-inflammatory cytokines suggesting a cell autonomous imbalance between inflammatory and antiviral responses. Seven days after IAV infection, there were reduced infiltration of natural killer cells and CD8+ T lymphocytes, increased concentration of inflammatory cytokines in bronchoalveolar fluid, reduced numbers of resolving macrophages, and IL-10 levels in PI3Kγ KO. This imbalanced environment in PI3Kγ KO-infected mice culminated in enhanced lung neutrophil infiltration, reactive oxygen species release, and lung damage that together with the increased viral loads, contributed to higher mortality in PI3Kγ KO mice compared with WT mice. In humans, we tested the genetic association of disease severity in influenza A/H1N1pdm09-infected patients with three potentially functional PIK3CG single

  18. Narcolepsy with cataplexy and hyperthyroidism sudden appeared after H1N1 vaccination

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    Silvia Leiva

    Full Text Available Narcolepsy type 1 (NT1 is a chronic sleep disorder, characterized by excessive daytime sleepiness, cataplexy and fragmented nocturnal sleep. It is caused by a hypocretin deficiency due to a significant reduction of the neurons producing it. In the last years, it has been postulated that an autoimmune mechanism would be responsible for the destruction of these neurons in those genetically predisposed patients. The increased incidence of narcolepsy after the pandemic H1N1 influenza vaccination campaign in 2009-2010 is known. We present below the case of an adult patient who, 10 days after receiving H1N1 vaccination, suffers a traffic accident after falling asleep. Subsequent studies revealed hyperthyroidism due to Graves disease. In spite of the treatment, the patient persisted with daily and disabling daytime sleepiness, sleep attacks and episodes of generalized muscle atony with preservation of consciousness. A nocturnal polysomnography and multiple sleep latency test (MSLT were performed with a diagnosis of NT1. The particularity of this case is the presentation of 2 autoimmune diseases triggered by an H1N1 vaccine without adjuvant, so far there is only evidence of NT1 associated with vaccines with adjuvant and viral infection. The association of both entities has made us reflect on the autoimmune mechanism, reinforcing the theory of its role in the onset of the disease.

  19. Highly pathogenic avian influenza (H5N1: pathways of exposure at the animal-human interface, a systematic review.

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    Maria D Van Kerkhove

    Full Text Available BACKGROUND: The threat posed by highly pathogenic avian influenza A H5N1 viruses to humans remains significant, given the continued occurrence of sporadic human cases (499 human cases in 15 countries with a high case fatality rate (approximately 60%, the endemicity in poultry populations in several countries, and the potential for reassortment with the newly emerging 2009 H1N1 pandemic strain. Therefore, we review risk factors for H5N1 infection in humans. METHODS AND FINDINGS: Several epidemiologic studies have evaluated the risk factors associated with increased risk of H5N1 infection among humans who were exposed to H5N1 viruses. Our review shows that most H5N1 cases are attributed to exposure to sick poultry. Most cases are sporadic, while occasional limited human-to-human transmission occurs. The most commonly identified factors associated with H5N1 virus infection included exposure through contact with infected blood or bodily fluids of infected poultry via food preparation practices; touching and caring for infected poultry; [corrected] exposure to H5N1 via swimming or bathing in potentially virus laden ponds; and exposure to H5N1 at live bird markets. CONCLUSIONS: Research has demonstrated that despite frequent and widespread contact with poultry, transmission of the H5N1 virus from poultry to humans is rare. Available research has identified several risk factors that may be associated with infection including close direct contact with poultry and transmission via the environment. However, several important data gaps remain that limit our understanding of the epidemiology of H5N1 in humans. Although infection in humans with H5N1 remains rare, human cases continue to be reported and H5N1 is now considered endemic among poultry in parts of Asia and in Egypt, providing opportunities for additional human infections and for the acquisition of virus mutations that may lead to more efficient spread among humans and other mammalian species

  20. Searching for sharp drops in the incidence of pandemic A/H1N1 influenza by single year of age.

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    Jessica Hartman Jacobs

    Full Text Available During the 2009 H1N1 pandemic (pH1N1, morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52-53 years old in 2009, but the precise range of ages affected has not been delineated.To test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available, and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951-1959 (hospitalized and 1953-1960 (not hospitalized.The reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957.

  1. ‘Presenting CXR phenotype of H1N1’ flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks’

    International Nuclear Information System (INIS)

    Minns, F.C.; Nimhuineachain, A; Beek, E.J.R. van; Ritchie, G.; Hill, A.; Murchison, J.T.

    2015-01-01

    Highlights: • Patients with H1N1 pneumonia demonstrated more opacified zones on chest x-ray than patients with non-H1N1 pneumonias. • A particular ‘phenotype’ of chest x-ray changes was identified in H1N1 patients. • This H1N1 ‘phenotype’ was the same for the two evaluated ‘flu seasons, during both pandemic and post pandemic stages. - Abstract: Aims: To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). Methods: We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were ‘blinded’ to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. Results: Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p = 0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p = 0.001). H1N1 radiographs were more likely to be ‘patchy’ versus ‘confluent’ changes of non-H1N1 CAP (p = 0.03) and more often demonstrated peripheral distribution (p = 0.01). H1N1 patients tended to stay in hospital longer (not significant; p = 0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p = 0.02). The findings were the same for the two evaluated seasons. Conclusion: H1N1 patients demonstrated more extensive disease, which was more likely bilateral, ‘patchy’, and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients

  2. ‘Presenting CXR phenotype of H1N1’ flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks’

    Energy Technology Data Exchange (ETDEWEB)

    Minns, F.C., E-mail: Fiona.Minns@nhslothian.scot.nhs.uk [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom); Nimhuineachain, A, E-mail: draideen@gmail.com [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom); Beek, E.J.R. van, E-mail: Edwin-vanbeek@ed.ac.uk [Clinical Research Imaging Centre, University of Edinburgh, 47 Little France Crescent, Edinburgh, Midlothian EH16 4TJ (United Kingdom); Ritchie, G., E-mail: drgillritchie@hotmail.com [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom); Hill, A., E-mail: adam.hill318@nhs.net [Department of Respiratory Medicine, New Royal Infirmary, Edinburgh (United Kingdom); Murchison, J.T., E-mail: john.murchison@nhslothian.scot.nhs.uk [Department of Radiology, New Royal Infirmary Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (United Kingdom)

    2015-09-15

    Highlights: • Patients with H1N1 pneumonia demonstrated more opacified zones on chest x-ray than patients with non-H1N1 pneumonias. • A particular ‘phenotype’ of chest x-ray changes was identified in H1N1 patients. • This H1N1 ‘phenotype’ was the same for the two evaluated ‘flu seasons, during both pandemic and post pandemic stages. - Abstract: Aims: To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). Methods: We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were ‘blinded’ to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. Results: Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p = 0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p = 0.001). H1N1 radiographs were more likely to be ‘patchy’ versus ‘confluent’ changes of non-H1N1 CAP (p = 0.03) and more often demonstrated peripheral distribution (p = 0.01). H1N1 patients tended to stay in hospital longer (not significant; p = 0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p = 0.02). The findings were the same for the two evaluated seasons. Conclusion: H1N1 patients demonstrated more extensive disease, which was more likely bilateral, ‘patchy’, and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients

  3. Neuraminidase and hemagglutinin matching patterns of a highly pathogenic avian and two pandemic H1N1 influenza A viruses.

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    Yonghui Zhang

    Full Text Available BACKGROUND: Influenza A virus displays strong reassortment characteristics, which enable it to achieve adaptation in human infection. Surveying the reassortment and virulence of novel viruses is important in the prevention and control of an influenza pandemic. Meanwhile, studying the mechanism of reassortment may accelerate the development of anti-influenza strategies. METHODOLOGY/PRINCIPAL FINDINGS: The hemagglutinin (HA and neuraminidase (NA matching patterns of two pandemic H1N1 viruses (the 1918 and current 2009 strains and a highly pathogenic avian influenza A virus (H5N1 were studied using a pseudotyped particle (pp system. Our data showed that four of the six chimeric HA/NA combinations could produce infectious pps, and that some of the chimeric pps had greater infectivity than did their ancestors, raising the possibility of reassortment among these viruses. The NA of H5N1 (A/Anhui/1/2005 could hardly reassort with the HAs of the two H1N1 viruses. Many biological characteristics of HA and NA, including infectivity, hemagglutinating ability, and NA activity, are dependent on their matching pattern. CONCLUSIONS/SIGNIFICANCE: Our data suggest the existence of an interaction between HA and NA, and the HA NA matching pattern is critical for valid viral reassortment.

  4. Information Needs and Seeking Behavior During the H1N1 Virus Outbreak

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    Majid, Shaheen

    2013-03-01

    Full Text Available Timely access to quality healthcare information during an outbreak plays an important role in curtailing its spread. The aim of this study was to investigate the information needs and seeking behavior of the general public in Singapore during the H1N1 pandemic. A pre-tested questionnaire was used for data collection. The convenience snowball sampling method was used and 260 working adults and tertiary-level students participated in this study. The most crucial information needs of a majority of the participants were: symptoms of H1N1, causes of the infection, preventive measures, and possible treatments. Data analysis also revealed that mass media such as television, newspapers, and radio were most frequently used for seeking the needed information. The use of human information sources was also quite high while only a small number of the respondents accessed online news and healthcare websites. About three-quarters of the participants indicated that the gathered information helped them to stay vigilant and take necessary precautionary measures. A major problem identified by the participants in using H1N1 information was the lack of understanding of certain terms used in public communications. This paper suggests certain measures for strengthening health information communication during future outbreaks.

  5. H1N1 influenza in an Irish population: patterns of chest radiograph abnormality in patients testing positive.

    LENUS (Irish Health Repository)

    O'Sullivan, K

    2012-02-29

    The winter of 2010\\/2011 saw a second peak in the number of H1N1 cases detected in Ireland. The purpose of this study was to investigate the radiological characteristics of patients diagnosed during this period. A retrospective analysis of these cases was performed. Chest radiographs were classified as normal or abnormal. A total of 37 patients were included. Of these, 22 (59%) of chest radiographs were abnormal and 15 (41%) were normal. In the 7 paediatric patients, 4 (57%) had a perihilar distribution of disease, 2 (28%) had peripherally based disease with 1 (14%) having a mixed distribution. A series of radiographs was available for 9 patients, 6 of these showed a radiographic deterioration from the initial study. The majority of chest radiographs of patients with confirmed H1N1 infection will be abnormal. In children, disease is more likely to be perihilar in distribution. Chest radiography is an important initial investigation in patients with H1N1 infection and is useful to track progression of disease in the subset of patients requiring hospitalization for severe disease.

  6. High-resolution computed tomography findings from adult patients with Influenza A (H1N1) virus-associated pneumonia

    International Nuclear Information System (INIS)

    Marchiori, Edson; Zanetti, Glaucia; Hochhegger, Bruno; Rodrigues, Rosana Souza; Fontes, Cristina Asvolinsque Pantaleao; Nobre, Luiz Felipe; Dias Mancano, Alexandre; Meirelles, Gustavo; Irion, Klaus Loureiro

    2010-01-01

    Objective: The aim of this study was to assess the high-resolution computed tomography (HRCT) findings at presentation in patients diagnosed with Influenza A (H1N1) virus-associated pneumonia. Materials and methods: We reviewed the HRCT findings from 20 patients diagnosed with Influenza A (H1N1) and compared their HRCT scans with chest radiographs, obtained on the same day. The imaging studies were obtained 4-9 days after the onset of symptoms. The patients included 11 men and 9 women (ages 24-62 years; mean 42.7 years). All patients had a body temperature greater than 100.4 deg. F (>38 deg. C), tachypnea, and cough. Other common symptoms included diarrhea (60%) and sore throat (30%). The radiographs and HRCT scans were reviewed independently by two observers who reached a consensus decision. Results: The predominant HRCT findings consisted of bilateral ground-glass opacities (n = 12), bilateral areas of consolidation (n = 2), or a mixed bilateral pattern of ground-glass opacities and areas of consolidation (n = 6). The abnormalities were bilateral in all of the 20 patients, had a predominantly sub-pleural distribution in 13 patients, and had a random distribution in the remaining 7 patients. The predominant radiographic findings were consolidations. Normal radiographs were found in 4 out of the 20 patients. Conclusion: HRCT may reveal parenchymal abnormalities in patients with Influenza A (H1N1) infection who have normal findings on radiographs. The predominant HRCT findings were bilateral, peripheral, ground-glass opacities and/or bilateral areas of consolidation. The patients who presented consolidations had more severe clinical course.

  7. High-resolution computed tomography findings from adult patients with Influenza A (H1N1) virus-associated pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Marchiori, Edson [Fluminense Federal University, Rio de Janeiro (Brazil); Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)], E-mail: edmarchiori@gmail.com; Zanetti, Glaucia [Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)], E-mail: glauciazanetti@gmail.com; Hochhegger, Bruno [Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)], E-mail: brunohochhegger@gmail.com; Rodrigues, Rosana Souza [Federal University of Rio de Janeiro, Rio de Janeiro (Brazil); D' OR Institute for Research and Education, Rio de Janeiro (Brazil)], E-mail: rosana.souzarodrigues@gmail.com; Fontes, Cristina Asvolinsque Pantaleao [Fluminense Federal University, Rio de Janeiro (Brazil)], E-mail: cristinasvolinsque@gmail.com; Nobre, Luiz Felipe [Santa Catarina Federal University, Florianopolis (Brazil)], E-mail: luizfelipenobresc@gmail.com; Dias Mancano, Alexandre [Anchieta Hospital, Taguatinga, DF (Brazil)], E-mail: alex.manzano1@gmail.com; Meirelles, Gustavo [Sao Paulo Federal University, Sao Paulo (Brazil)], E-mail: gmeirelles@gmail.com; Irion, Klaus Loureiro [Liverpool Heart and Chest Hospital NHS Trust, Liverpool (United Kingdom); Royal Liverpool and Broadgreen University Hospital NHS, Liverpool (United Kingdom)], E-mail: klaus.irion@btinternet.com

    2010-04-15

    Objective: The aim of this study was to assess the high-resolution computed tomography (HRCT) findings at presentation in patients diagnosed with Influenza A (H1N1) virus-associated pneumonia. Materials and methods: We reviewed the HRCT findings from 20 patients diagnosed with Influenza A (H1N1) and compared their HRCT scans with chest radiographs, obtained on the same day. The imaging studies were obtained 4-9 days after the onset of symptoms. The patients included 11 men and 9 women (ages 24-62 years; mean 42.7 years). All patients had a body temperature greater than 100.4 deg. F (>38 deg. C), tachypnea, and cough. Other common symptoms included diarrhea (60%) and sore throat (30%). The radiographs and HRCT scans were reviewed independently by two observers who reached a consensus decision. Results: The predominant HRCT findings consisted of bilateral ground-glass opacities (n = 12), bilateral areas of consolidation (n = 2), or a mixed bilateral pattern of ground-glass opacities and areas of consolidation (n = 6). The abnormalities were bilateral in all of the 20 patients, had a predominantly sub-pleural distribution in 13 patients, and had a random distribution in the remaining 7 patients. The predominant radiographic findings were consolidations. Normal radiographs were found in 4 out of the 20 patients. Conclusion: HRCT may reveal parenchymal abnormalities in patients with Influenza A (H1N1) infection who have normal findings on radiographs. The predominant HRCT findings were bilateral, peripheral, ground-glass opacities and/or bilateral areas of consolidation. The patients who presented consolidations had more severe clinical course.

  8. Full genomic analysis of an influenza A (H1N2 virus identified during 2009 pandemic in Eastern India: evidence of reassortment event between co-circulating A(H1N1pdm09 and A/Brisbane/10/2007-like H3N2 strains

    Directory of Open Access Journals (Sweden)

    Mukherjee Tapasi Roy

    2012-10-01

    Full Text Available Abstract Background During the pandemic [Influenza A(H1N1pdm09] period in 2009-2010, an influenza A (Inf-A virus with H1N2 subtype (designated as A/Eastern India/N-1289/2009 was detected from a 25 years old male from Mizoram (North-eastern India. Objective To characterize full genome of the H1N2 influenza virus. Methods For initial detection of Influenza viruses, amplification of matrix protein (M gene of Inf-A and B viruses was carried out by real time RT-PCR. Influenza A positive viruses are then further subtyped with HA and NA gene specific primers. Sequencing and the phylogenetic analysis was performed for the H1N2 strain to understand its origin. Results The outcome of this full genome study revealed a unique reassortment event where the N-1289 virus acquired it’s HA gene from a 2009 pandemic H1N1 virus with swine origin and the other genes from H3N2-like viruses of human origin. Conclusions This study provides information on possibility of occurrence of reassortment events during influenza season when infectivity is high and two different subtypes of Inf-A viruses co-circulate in same geographical location.

  9. Diversity of the murine antibody response targeting influenza A(H1N1pdm09) hemagglutinin.

    Science.gov (United States)

    Wilson, Jason R; Tzeng, Wen-Pin; Spesock, April; Music, Nedzad; Guo, Zhu; Barrington, Robert; Stevens, James; Donis, Ruben O; Katz, Jacqueline M; York, Ian A

    2014-06-01

    We infected mice with the 2009 influenza A pandemic virus (H1N1pdm09), boosted with an inactivated vaccine, and cloned immunoglobulins (Igs) from HA-specific B cells. Based on the redundancy in germline gene utilization, we inferred that between 72-130 unique IgH VDJ and 35 different IgL VJ combinations comprised the anti-HA recall response. The IgH VH1 and IgL VK14 variable gene families were employed most frequently. A representative panel of antibodies were cloned and expressed to confirm reactivity with H1N1pdm09 HA. The majority of the recombinant antibodies were of high avidity and capable of inhibiting H1N1pdm09 hemagglutination. Three of these antibodies were subtype-specific cross-reactive, binding to the HA of A/South Carolina/1/1918(H1N1), and one further reacted with A/swine/Iowa/15/1930(H1N1). These results help to define the genetic diversity of the influenza anti-HA antibody repertoire profile induced following infection and vaccination, which may facilitate the development of influenza vaccines that are more protective and broadly neutralizing. Protection against influenza viruses is mediated mainly by antibodies, and in most cases this antibody response is narrow, only providing protection against closely related viruses. In spite of this limited range of protection, recent findings indicate that individuals immune to one influenza virus may contain antibodies (generally a minority of the overall response) that are more broadly reactive. These findings have raised the possibility that influenza vaccines could induce a more broadly protective response, reducing the need for frequent vaccine strain changes. However, interpretation of these observations is hampered by the lack of quantitative characterization of the antibody repertoire. In this study, we used single-cell cloning of influenza HA-specific B cells to assess the diversity and nature of the antibody response to influenza hemagglutinin in mice. Our findings help to put bounds on the

  10. Isolation and genetic characterization of avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China.

    Science.gov (United States)

    Yu, Hai; Zhang, Peng-Chao; Zhou, Yan-Jun; Li, Guo-Xin; Pan, Jie; Yan, Li-Ping; Shi, Xiao-Xiao; Liu, Hui-Li; Tong, Guang-Zhi

    2009-08-21

    As pigs are susceptible to both human and avian influenza viruses, they have been proposed to be intermediate hosts or mixing vessels for the generation of pandemic influenza viruses through reassortment or adaptation to the mammalian host. In this study, we reported avian-like H1N1 and novel ressortant H1N2 influenza viruses from pigs in China. Homology and phylogenetic analyses showed that the H1N1 virus (A/swine/Zhejiang/1/07) was closely to avian-like H1N1 viruses and seemed to be derived from the European swine H1N1 viruses, which was for the first time reported in China; and the two H1N2 viruses (A/swine/Shanghai/1/07 and A/swine/Guangxi/13/06) were novel ressortant H1N2 influenza viruses containing genes from the classical swine (HA, NP, M and NS), human (NA and PB1) and avian (PB2 and PA) lineages, which indicted that the reassortment among human, avian, and swine influenza viruses had taken place in pigs in China and resulted in the generation of new viruses. The isolation of avian-like H1N1 influenza virus originated from the European swine H1N1 viruses, especially the emergence of two novel ressortant H1N2 influenza viruses provides further evidence that pigs serve as intermediate hosts or "mixing vessels", and swine influenza virus surveillance in China should be given a high priority.

  11. Cost-effectiveness of 2009 pandemic influenza A(H1N1 vaccination in the United States.

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    Lisa A Prosser

    Full Text Available Pandemic influenza A(H1N1 (pH1N1 was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination.A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY gained. Sensitivity analyses were conducted.For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000-$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery.Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of

  12. Reassortant H9N2 influenza viruses containing H5N1-like PB1 genes isolated from black-billed magpies in Southern China.

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    Guoying Dong

    Full Text Available H9N2 influenza A viruses have become endemic in different types of terrestrial poultry and wild birds in Asia, and are occasionally transmitted to humans and pigs. To evaluate the role of black-billed magpies (Pica pica in the evolution of influenza A virus, we conducted two epidemic surveys on avian influenza viruses in wild black-billed magpies in Guangxi, China in 2005 and characterized three isolated black-billed magpie H9N2 viruses (BbM viruses. Phylogenetic analysis indicated that three BbM viruses were almost identical with 99.7 to 100% nucleotide homology in their whole genomes, and were reassortants containing BJ94-like (Ck/BJ/1/94 HA, NA, M, and NS genes, SH/F/98-like (Ck/SH/F/98 PB2, PA, and NP genes, and H5N1-like (Ck/YN/1252/03, clade 1 PB1 genes. Genetic analysis showed that BbM viruses were most likely the result of multiple reassortments between co-circulating H9N2-like and H5N1-like viruses, and were genetically different from other H9N2 viruses because of the existence of H5N1-like PB1 genes. Genotypical analysis revealed that BbM viruses evolved from diverse sources and belonged to a novel genotype (B46 discovered in our recent study. Molecular analysis suggested that BbM viruses were likely low pathogenic reassortants. However, results of our pathogenicity study demonstrated that BbM viruses replicated efficiently in chickens and a mammalian mouse model but were not lethal for infected chickens and mice. Antigenic analysis showed that BbM viruses were antigenic heterologous with the H9N2 vaccine strain. Our study is probably the first report to document and characterize H9N2 influenza viruses isolated from black-billed magpies in southern China. Our results suggest that black-billed magpies were susceptible to H9N2 influenza viruses, which raise concerns over possible transmissions of reassortant H9N2 viruses among poultry and wild birds.

  13. A comparative evaluation of feathers, oropharyngeal swabs, and cloacal swabs for the detection of H5N1 highly pathogenic avian influenza virus infection in experimentally infected chickens and ducks.

    Science.gov (United States)

    Nuradji, Harimurti; Bingham, John; Lowther, Sue; Wibawa, Hendra; Colling, Axel; Long, Ngo Thanh; Meers, Joanne

    2015-11-01

    Oropharyngeal and cloacal swabs have been widely used for the detection of H5N1 highly pathogenic avian Influenza A virus (HPAI virus) in birds. Previous studies have shown that the feather calamus is a site of H5N1 virus replication and therefore has potential for diagnosis of avian influenza. However, studies characterizing the value of feathers for this purpose are not available, to our knowledge; herein we present a study investigating feathers for detection of H5N1 virus. Ducks and chickens were experimentally infected with H5N1 HPAI virus belonging to 1 of 3 clades (Indonesian clades 2.1.1 and 2.1.3, Vietnamese clade 1). Different types of feathers and oropharyngeal and cloacal swab samples were compared by virus isolation. In chickens, virus was detected from all sample types: oral and cloacal swabs, and immature pectorosternal, flight, and tail feathers. During clinical disease, the viral titers were higher in feathers than swabs. In ducks, the proportion of virus-positive samples was variable depending on viral strain and time from challenge; cloacal swabs and mature pectorosternal feathers were clearly inferior to oral swabs and immature pectorosternal, tail, and flight feathers. In ducks infected with Indonesian strains, in which most birds did not develop clinical signs, all sampling methods gave intermittent positive results; 3-23% of immature pectorosternal feathers were positive during the acute infection period; oropharyngeal swabs had slightly higher positivity during early infection, while feathers performed better during late infection. Our results indicate that immature feathers are an alternative sample for the diagnosis of HPAI in chickens and ducks. © 2015 The Author(s).

  14. MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.

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    Joost H C M Kreijtz

    Full Text Available Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.

  15. Identification of Human H1N2 and Human-Swine Reassortant H1N2 and H1N1 Influenza A Viruses among Pigs in Ontario, Canada (2003 to 2005)†

    OpenAIRE

    Karasin, Alexander I.; Carman, Suzanne; Olsen, Christopher W.

    2006-01-01

    Since 2003, three novel genotypes of H1 influenza viruses have been recovered from Canadian pigs, including a wholly human H1N2 virus and human-swine reassortants. These isolates demonstrate that human-lineage H1N2 viruses are infectious for pigs and that viruses with a human PB1/swine PA/swine PB2 polymerase complex can replicate in pigs.

  16. High burden of non-influenza viruses in influenza-like illness in the early weeks of H1N1v epidemic in France.

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    Nathalie Schnepf

    Full Text Available BACKGROUND: Influenza-like illness (ILI may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5% were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9% were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%, followed by parainfluenza viruses (24.2% and adenovirus (5.3%. 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.

  17. Psychosocial effects assocPsychosocial effects associated with highly pathogenic avian influenza (H5N1 in Nigeriaiated with highly pathogenic avian influenza (H5N1 in Nigeria

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    Chiara Rafanelli

    2010-12-01

    Full Text Available Highly pathogenic avian influenza H5N1 (HPAI H5N1 infected poultry in Nigeria in 2006. The outbreaks caused significant economic losses and had serious zoonotic repercussions. The outbreaks have also had psychosocial effects on Nigerian farmers. To date, empirical data on the effect of outbreaks on humans are scarce. In this study, field data on HPAI H5N1 in Nigeria were analysed. Although only one human case leading to death was reported in Nigeria, the fact that HPAI H5N1 caused a human death created a disruption in social order and in the well-being of farmers (stress, altered livelihood and trauma and affected the rural economy. The implication of the above on health communication, the importance of successful control measures in poultry and policy implementation are stressed. Further studies are encouraged.

  18. Avian influenza virus (H5N1; effects of physico-chemical factors on its survival

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    Hameed Sajid

    2009-03-01

    Full Text Available Abstract Present study was performed to determine the effects of physical and chemical agents on infective potential of highly pathogenic avian influenza (HPAI H5N1 (local strain virus recently isolated in Pakistan during 2006 outbreak. H5N1 virus having titer 108.3 ELD50/ml was mixed with sterilized peptone water to get final dilution of 4HA units and then exposed to physical (temperature, pH and ultraviolet light and chemical (formalin, phenol crystals, iodine crystals, CID 20, virkon®-S, zeptin 10%, KEPCIDE 300, KEPCIDE 400, lifebuoy, surf excel and caustic soda agents. Harvested amnio-allantoic fluid (AAF from embryonated chicken eggs inoculated with H5N1 treated virus (0.2 ml/egg was subjected to haemagglutination (HA and haemagglutination inhibition (HI tests. H5N1 virus lost infectivity after 30 min at 56°C, after 1 day at 28°C but remained viable for more than 100 days at 4°C. Acidic pH (1, 3 and basic pH (11, 13 were virucidal after 6 h contact time; however virus retained infectivity at pH 5 (18 h, 7 and 9 (more than 24 h. UV light was proved ineffectual in inactivating virus completely even after 60 min. Soap (lifebuoy®, detergent (surf excel® and alkali (caustic soda destroyed infectivity after 5 min at 0.1, 0.2 and 0.3% dilution. All commercially available disinfectants inactivated virus at recommended concentrations. Results of present study would be helpful in implementing bio-security measures at farms/hatcheries levels in the wake of avian influenza virus (AIV outbreak.

  19. Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus.

    Science.gov (United States)

    Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A

    2011-03-24

    Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.

  20. Demographic and clinical predictors of mortality from highly pathogenic avian influenza A (H5N1 virus infection: CART analysis of international cases.

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    Rita B Patel

    Full Text Available Human infections with highly pathogenic avian influenza (HPAI A (H5N1 viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions.We included all cases of human HPAI H5N1 reported in World Health Organization Global Alert and Response updates and those identified through a systematic search of multiple databases (PubMed, Scopus, and Google Scholar, including articles in all languages. We abstracted predefined clinical and demographic predictors and mortality and used bivariate logistic regression analyses to examine the relationship of each candidate predictor with mortality. We developed and pruned a decision tree using nonparametric Classification and Regression Tree methods to create risk strata for mortality.We identified 617 human cases of HPAI H5N1 occurring between December 1997 and April 2013. The median age of subjects was 18 years (interquartile range 6-29 years and 54% were female. HPAI H5N1 case-fatality proportion was 59%. The final decision tree for mortality included age, country, per capita government health expenditure, and delay from symptom onset to hospitalization, with an area under the receiver operator characteristic (ROC curve of 0.81 (95% CI: 0.76-0.86.A model defined by four clinical and demographic predictors successfully estimated the probability of mortality from HPAI H5N1 illness. These parameters highlight the importance of early diagnosis and treatment and may enable early, targeted pharmaceutical therapy and supportive care for symptomatic patients with HPAI H5N1 virus infection.

  1. Virulence of H5N1 Influenza Virus in Cattle Egrets (Bubulcus Ibis)

    DEFF Research Database (Denmark)

    Phuong, Do Quy; Dung, Nguyen Tien; Jørgensen, Poul Henrik

    2011-01-01

    for insect control in households. In this study, six Cattle Egrets were experimentally infected intranasally with highly pathogenic avian influenza (AI) A/duck/Vietnam/40D/04 (H5N1) to investigate a possible epidemiologic role for Cattle Egrets in outbreaks of H5N1 AI in Vietnam. The Cattle Egrets were...

  2. Epidemia de influenza A(H1N1 en la Argentina: Experiencia del Hospital Nacional Profesor Alejandro Posadas Influenza A(H1N1 epidemic in Argentina: Experience in a National General Hospital (Hospital Nacional Profesor Alejandro Posadas

    Directory of Open Access Journals (Sweden)

    2009-10-01

    clinical or X-ray differences between 21/49 confirmed and non confirmed A(H1N1 cases. Treatment: oseltamivir, ampicillin-sulbactam, and clarithromycin. ICU: 28 severe pneumonia patients were admitted (21 with associated conditions; 24 with acute respiratory distress syndrome received mechanical ventilation, 21 of them had shock; 8/9 acute renal failure cases required hemodialysis. Mortality: 14/28; 7/14 with confirmed A(H1N1 infection. Seventy A(H1N1 infected children were hospitalized (27 required ICU, 6 of them died. The children's median age was 11 months; 61.8% presented comorbidities (prematurity, asthma, broncho-pulmonary dysplasia and congenital heart disease. Oseltamivir and antibiotics were administered. Children's mortality: 8.6%.

  3. Specific Inhibitory Effect of κ-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus.

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    Qiang Shao

    Full Text Available The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. Carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. The aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. It was here demonstrated that κ-carrageenan had no cytotoxicity at concentrations below 1000 μg/ml. Hemagglutination, 50% tissue culture infectious dose (TCID50 and cytopathic effect (CPE inhibition assays showed that κ-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731 and A/California/04/2009 H1N1 (CA04 replication in a dose-dependent fashion. Mechanism studies show that the inhibition of SW731 multiplication and mRNA expression was maximized when κ-carrageenan was added before or during adsorption. The result of Hemagglutination inhibition assay indicate that κ-carrageenan specifically targeted HA of SW731 and CA04, both of which are pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8, A/WSN/1933 H1N1 (WSN, A/Swine/Beijing/26/2008 H1N1 (SW26, A/Chicken/Shandong/LY/2008 H9N2 (LY08, and A/Chicken/Shandong/ZB/2007 H9N2 (ZB07 viruses. Immunofluorescence assay and Western blot showed that κ-carrageenan also inhibited SW731 protein expression after its internalization into cells. These results suggest that κ-carrageenan can significantly inhibit SW731 replication by interfering with a few replication steps in the SW731 life cycles, including adsorption, transcription, and viral protein expression, especially interactions between HA and cells. In this way, κ-carrageenan might be a suitable alternative approach to therapy meant to address anti-IAV, which contains an HA homologous to that of SW731.

  4. Hemagglutinin pseudotyped lentiviral particles: characterization of a new method for avian H5N1 influenza sero-diagnosis.

    OpenAIRE

    Nefkens , Isabelle; Garcia , Jean-Michel; Ling , Chu Shui; Lagarde , Nadège; Nicholls , John; Tang , Dong Jiang; Peiris , Malik; Buchy , Philippe; Altmeyer , Ralf

    2007-01-01

    BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 has spread globally in birds and infected over 270 humans with an apparently high mortality rate. Serologic studies to determine the extent of asymptomatic H5N1 infection in humans and other mammals and to investigate the immunogenicity of current H5N1 vaccine candidates have been hampered by the biosafety requirements needed for H5N1 micro-neutralization tests. OBJECTIVE: Development of a serodiagnostic tool for highly pathogenic infl...

  5. Influenza A H5N1 immigration is filtered out at some international borders.

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    Robert G Wallace

    2008-02-01

    Full Text Available Geographic spread of highly pathogenic influenza A H5N1, the bird flu strain, appears a necessary condition for accelerating the evolution of a related human-to-human infection. As H5N1 spreads the virus diversifies in response to the variety of socioecological environments encountered, increasing the chance a human infection emerges. Genetic phylogenies have for the most part provided only qualitative evidence that localities differ in H5N1 diversity. For the first time H5N1 variation is quantified across geographic space.We constructed a statistical phylogeography of 481 H5N1 hemagglutinin genetic sequences from samples collected across 28 Eurasian and African localities through 2006. The MigraPhyla protocol showed southern China was a source of multiple H5N1 strains. Nested clade analysis indicated H5N1 was widely dispersed across southern China by both limited dispersal and long distance colonization. The UniFrac metric, a measure of shared phylogenetic history, grouped H5N1 from Indonesia, Japan, Thailand and Vietnam with those from southeastern Chinese provinces engaged in intensive international trade. Finally, H5N1's accumulative phylogenetic diversity was greatest in southern China and declined beyond. The gradient was interrupted by areas of greater and lesser phylogenetic dispersion, indicating H5N1 migration was restricted at some geopolitical borders. Thailand and Vietnam, just south of China, showed significant phylogenetic clustering, suggesting newly invasive H5N1 strains have been repeatedly filtered out at their northern borders even as both countries suffered recurring outbreaks of endemic strains. In contrast, Japan, while successful in controlling outbreaks, has been subjected to multiple introductions of the virus.The analysis demonstrates phylogenies can provide local health officials with more than hypotheses about relatedness. Pathogen dispersal, the functional relationships among disease ecologies across localities, and

  6. Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice.

    Science.gov (United States)

    Chandler, Joshua D; Hu, Xin; Ko, Eun-Ju; Park, Soojin; Lee, Young-Tae; Orr, Michael; Fernandes, Jolyn; Uppal, Karan; Kang, Sang-Moo; Jones, Dean P; Go, Young-Mi

    2016-11-01

    Influenza is a significant health concern worldwide. Viral infection induces local and systemic activation of the immune system causing attendant changes in metabolism. High-resolution metabolomics (HRM) uses advanced mass spectrometry and computational methods to measure thousands of metabolites inclusive of most metabolic pathways. We used HRM to identify metabolic pathways and clusters of association related to inflammatory cytokines in lungs of mice with H1N1 influenza virus infection. Infected mice showed progressive weight loss, decreased lung function, and severe lung inflammation with elevated cytokines [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ] and increased oxidative stress via cysteine oxidation. HRM showed prominent effects of influenza virus infection on tryptophan and other amino acids, and widespread effects on pathways including purines, pyrimidines, fatty acids, and glycerophospholipids. A metabolome-wide association study (MWAS) of the aforementioned inflammatory cytokines was used to determine the relationship of metabolic responses to inflammation during infection. This cytokine-MWAS (cMWAS) showed that metabolic associations consisted of distinct and shared clusters of 396 metabolites highly correlated with inflammatory cytokines. Strong negative associations of selected glycosphingolipid, linoleate, and tryptophan metabolites with IFN-γ contrasted strong positive associations of glycosphingolipid and bile acid metabolites with IL-1β, TNF-α, and IL-10. Anti-inflammatory cytokine IL-10 had strong positive associations with vitamin D, purine, and vitamin E metabolism. The detailed metabolic interactions with cytokines indicate that targeted metabolic interventions may be useful during life-threatening crises related to severe acute infection and inflammation. Copyright © 2016 the American Physiological Society.

  7. Outbreak of pandemic influenza A/H1N1 2009 in Nepal.

    Science.gov (United States)

    Adhikari, Bal Ram; Shakya, Geeta; Upadhyay, Bishnu Prasad; Prakash Kc, Khagendra; Shrestha, Sirjana Devi; Dhungana, Guna Raj

    2011-03-23

    The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1) 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Out of 609 collected samples, 302 (49.6%) were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3%) were positive for Pandemic influenza A/H1N1 and 130 (21.3%) were Seasonal influenza A. Most of the pandemic cases (53%) were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1)v type. The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1)v type.

  8. Outbreak of pandemic influenza A/H1N1 2009 in Nepal

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    Shrestha Sirjana

    2011-03-01

    Full Text Available Abstract Background The 2009 flu pandemic is a global outbreak of a new strain of H1N1 influenza virus. Pandemic influenza A (H1N1 2009 has posed a serious public health challenge world-wide. Nepal has started Laboratory diagnosis of Pandemic influenza A/H1N1 from mid June 2009 though active screening of febrile travellers with respiratory symptoms was started from April 27, 2009. Results Out of 609 collected samples, 302 (49.6% were Universal Influenza A positive. Among the influenza A positive samples, 172(28.3% were positive for Pandemic influenza A/H1N1 and 130 (21.3% were Seasonal influenza A. Most of the pandemic cases (53% were found among young people with ≤ 20 years. Case Fatality Ratio for Pandemic influenza A/H1N1 in Nepal was 1.74%. Upon Molecular characterization, all the isolated pandemic influenza A/H1N1 2009 virus found in Nepal were antigenically and genetically related to the novel influenza A/CALIFORNIA/07/2009-LIKE (H1N1v type. Conclusion The Pandemic 2009 influenza virus found in Nepal were antigenically and genetically related to the novel A/CALIFORNIA/07/2009-LIKE (H1N1v type.

  9. Mechanical ventilation in patients with most severe forms of influenza a H1N1

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    Romić Predrag

    2011-01-01

    Full Text Available Background/Aim. Pandemic of A H1N1 influenza is noted for its rapid spreading and life-threatening consequences like acute respiratory distress syndrome (ARDS which requires mechanical ventilation (MV and intensive therapy (IT. The aim of the study was to determine the significance of mechanical ventilation application in the presence of comorbidities on the outcome of the disease and patients with severe forms of acute influenza caused by A H1N1 virus. Methods. Five patients with acute respiratory failure caused by A H1N1 influenza that required MV were included in the study. Course and outcome of the treatment were monitored in relation to age and sex of the patients, concomitant diseases, time of influenza beginning, a time of admittance in an intensive care unit, a time of an endotracheal intubation and MV beginning, MV duration and occurrence of secondary infections. Results. Three patients were on a very prolonged MV (39, 43 and 20 days, respectively and they all survived. Two patients with a significantly shorter duration of MV (14 and 12 days, respectively died because of a very severe clinical course and concomitant diseases. Unexpectedly, we found a positive correlation between duration of MV and survival although two patients, who were on MV for the longest period of time (43 and 39 days, respectively, developed, as a complication, secondary bacterial pneumonia. Conclusion. Intensive therapy of patients with ARDS due to A H1N1 influenza virus requires MV which should be carried out according to guidelines of international expert forums. That is in accordance with our unexpected observation on negative correlation between duration of MV and fatal outcome. Intensive treatment of these patients, specially MV, can be very prolonged and, therefore, requires specialized teams of anesthesiologists, separate, isolated intensive therapy units and high level of medical staff protection, as was the case in this study, so no member of medical

  10. Enfermedad respiratoria grave en terapia intensiva durante la pandemia por el virus de influenza A (H1N1 2009 Severe respiratory disease in an intensive care unit during influenza A(H1N12009 pandemia

    Directory of Open Access Journals (Sweden)

    José Aquino-Esperanza

    2010-10-01

    A(H1N1 2009 in Argentina. We analyzed clinical data, severity scores, laboratory tests, microbiological and radiological findings at admission, clinical outcomes and in-hospital mortality. H1N1 was confirmed by RT-PCR. Data from positive and negative PCR patients were compared. We admitted 31 adult patients between June and July 2009; median age: 54 years (IQR 33-66. A 54% (17 had positive PCR; 16 patients presented underlying medical conditions. Bilateral interstitial opacities were observed in chest radiography in 20 cases; 5 had unilateral lobar consolidation. Bacterial co-infection (isolation or IgM antibodies for bacterial infections was found in 21 patients. Mechanical ventilation was required in 23 patients and 18 developed ARDS. Lymphopenia and increased creatine kinase levels were frequently observed (83% and 65% among PCR+ and PCR- respectively. Six patients died (19%; they were all over 75 years old, had cancer or immune-suppression. Early antiviral treatment (≤ 48 hours from symptoms onset was associated with less frequency of mechanical ventilation (54% vs. 89%, p: 0.043. There were no differences in analyzed variables when comparing H1N1 positive and H1N1 negative patients; which suggests this approach as a most correct in future epidemic outbreaks. H1N1 infection was associated with severe respiratory illness and ARDS. Fatal outcome was observed in very old patients, or in those with major co-morbidities.

  11. Ventilatory and ECMO treatment of H1N1-induced severe respiratory failure: results of an Italian referral ECMO center

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    Giovannini Valtere

    2011-01-01

    Full Text Available Abstract Background Since the first outbreak of a respiratory illness caused by H1N1 virus in Mexico, several reports have described the need of intensive care or extracorporeal membrane oxygenation (ECMO assistance in young and often healthy patients. Here we describe our experience in H1N1-induced ARDS using both ventilation strategy and ECMO assistance. Methods Following Italian Ministry of Health instructions, an Emergency Service was established at the Careggi Teaching Hospital (Florence, Italy for the novel pandemic influenza. From Sept 09 to Jan 10, all patients admitted to our Intensive Care Unit (ICU of the Emergency Department with ARDS due to H1N1 infection were studied. All ECMO treatments were veno-venous. H1N1 infection was confirmed by PCR assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage. Lung pathology was evaluated daily by lung ultrasound (LUS examination. Results A total of 12 patients were studied: 7 underwent ECMO treatment, and 5 responded to protective mechanical ventilation. Two patients had co-infection by Legionella Pneumophila. One woman was pregnant. In our series, PCR from bronchoalveolar lavage had a 100% sensitivity compared to 75% from pharyngeal swab samples. The routine use of LUS limited the number of chest X-ray examinations and decreased transportation to radiology for CT-scan, increasing patient safety and avoiding the transitory disconnection from ventilator. No major complications occurred during ECMO treatments. In three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions. Overall mortality rate was 8.3%. Conclusions In our experience, early ECMO assistance resulted safe and feasible, considering the life threatening condition, in H1N1-induced ARDS. Lung ultrasound is an effective mean for daily assessment of ARDS patients.

  12. Screening for Influenza A(H1N1)pdm09, Auckland International Airport, New Zealand

    Science.gov (United States)

    Hale, Michael J.; Baker, Michael G.

    2012-01-01

    Entry screening for influenza A(H1N1)pdm09 at Auckland International Airport, New Zealand, detected 4 cases, which were later confirmed, among 456,518 passengers arriving April 27–June 22, 2009. On the basis of national influenza surveillance data, which suggest that ≈69 infected travelers passed through the airport, sensitivity for screening was only 5.8%. PMID:22516105

  13. Early Outbreak of 2009 Influenza A (H1N1) in Mexico Prior to Identification of pH1N1 Virus

    Science.gov (United States)

    Hsieh, Ying-Hen; Ma, Stefan; Velasco Hernandez, Jorge X.; Lee, Vernon J.; Lim, Wei Yen

    2011-01-01

    Background In the aftermath of the global spread of 2009 influenza A (pH1N1) virus, still very little is known of the early stages of the outbreak in Mexico during the early months of the year, before the virus was identified. Methodology/Main Findings We fit a simple mathematical model, the Richards model, to the number of excess laboratory-confirmed influenza cases in Mexico and Mexico City during the first 15 weeks in 2009 over the average influenza case number of the previous five baseline years of 2004-2008 during the same period to ascertain the turning point (or the peak incidence) of a wave of early influenza infections, and to estimate the transmissibility of the virus during these early months in terms of its basic reproduction number. The results indicate that there may have been an early epidemic in Mexico City as well as in all of Mexico during February/March. Based on excess influenza cases, the estimated basic reproduction number R0 for the early outbreak was 1.59 (0.55 to 2.62) for Mexico City during weeks 5–9, and 1.25 (0.76, 1.74) for all of Mexico during weeks 5–14. Conclusions We established the existence of an early epidemic in Mexico City and in all of Mexico during February/March utilizing the routine influenza surveillance data, although the location of seeding is unknown. Moreover, estimates of R0 as well as the time of peak incidence (the turning point) for Mexico City and all of Mexico indicate that the early epidemic in Mexico City in February/March had been more transmissible (larger R0) and peaked earlier than the rest of the country. Our conclusion lends support to the possibility that the virus could have already spread to other continents prior to the identification of the virus and the reporting of lab-confirmed pH1N1 cases in North America in April. PMID:21909366

  14. Insights from investigating the interactions of adamantane-based drugs with the M2 proton channel from the H1N1 swine virus

    International Nuclear Information System (INIS)

    Wang, Jing-Fang; Wei, Dong-Qing; Chou, Kuo-Chen

    2009-01-01

    The M2 proton channel is one of indispensable components for the influenza A virus that plays a vital role in its life cycle and hence is an important target for drug design against the virus. In view of this, the three-dimensional structure of the H1N1-M2 channel was developed based on the primary sequence taken from a patient recently infected by the H1N1 (swine flu) virus. With an explicit water-membrane environment, molecular docking studies were performed for amantadine and rimantadine, the two commercial drugs generally used to treat influenza A infection. It was found that their binding affinity to the H1N1-M2 channel is significantly lower than that to the H5N1-M2 channel, fully consistent with the recent report that the H1N1 swine virus was resistant to the two drugs. The findings and the relevant analysis reported here might provide useful structural insights for developing effective drugs against the new swine flu virus.

  15. Perturbation of B Cell Gene Expression Persists in HIV-Infected Children Despite Effective Antiretroviral Therapy and Predicts H1N1 Response.

    Science.gov (United States)

    Cotugno, Nicola; De Armas, Lesley; Pallikkuth, Suresh; Rinaldi, Stefano; Issac, Biju; Cagigi, Alberto; Rossi, Paolo; Palma, Paolo; Pahwa, Savita

    2017-01-01

    Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine. To do so, we analyzed prevaccination transcriptional levels of a 96-gene panel in equal numbers of sort-purified B cell subsets (SPBS) isolated from peripheral blood mononuclear cells using multiplexed RT-PCR. Immune responses to H1N1 antigen were determined by hemaglutination inhibition and memory B cell ELISpot assays following trivalent-inactivated influenza vaccination (TIV) for all study participants. Although there were no differences in terms of cell frequencies of SPBS between HIV and HC, the groups were distinguishable based upon gene expression analyses. Indeed, a 28-gene signature, characterized by higher expression of genes involved in the inflammatory response and immune activation was observed in activated memory B cells (CD27 + CD21 - ) from HIV when compared to HC despite long-term viral control (>24 months). Further analysis, taking into account H1N1 responses after TIV in HIV participants, revealed that a 25-gene signature in resting memory (RM) B cells (CD27 + CD21 + ) was able to distinguish vaccine responders from non-responders (NR). In fact, prevaccination RM B cells of responders showed a higher expression of gene sets involved in B cell adaptive immune responses ( APRIL, BTK, BLIMP1 ) and

  16. Transforming growth factor-β: activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis.

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    Christina M Carlson

    2010-10-01

    Full Text Available Transforming growth factor-beta (TGF-β, a multifunctional cytokine regulating several immunologic processes, is expressed by virtually all cells as a biologically inactive molecule termed latent TGF-β (LTGF-β. We have previously shown that TGF-β activity increases during influenza virus infection in mice and suggested that the neuraminidase (NA protein mediates this activation. In the current study, we determined the mechanism of activation of LTGF-β by NA from the influenza virus A/Gray Teal/Australia/2/1979 by mobility shift and enzyme inhibition assays. We also investigated whether exogenous TGF-β administered via a replication-deficient adenovirus vector provides protection from H5N1 influenza pathogenesis and whether depletion of TGF-β during virus infection increases morbidity in mice. We found that both the influenza and bacterial NA activate LTGF-β by removing sialic acid motifs from LTGF-β, each NA being specific for the sialic acid linkages cleaved. Further, NA likely activates LTGF-β primarily via its enzymatic activity, but proteases might also play a role in this process. Several influenza A virus subtypes (H1N1, H1N2, H3N2, H5N9, H6N1, and H7N3 except the highly pathogenic H5N1 strains activated LTGF-β in vitro and in vivo. Addition of exogenous TGF-β to H5N1 influenza virus-infected mice delayed mortality and reduced viral titers whereas neutralization of TGF-β during H5N1 and pandemic 2009 H1N1 infection increased morbidity. Together, these data show that microbe-associated NAs can directly activate LTGF-β and that TGF-β plays a pivotal role protecting the host from influenza pathogenesis.

  17. EFSA Panel Animal Health and Welfare (AHAW); Scientific Opinion on the pandemic (H1N1) 2009 influenza and its potential implications for animal health

    DEFF Research Database (Denmark)

    Bøtner, Anette; Brown, Ian; Capua, Ilaria

    . Occasionally, pigs have been infected following exposure to pH1N1 infected humans. In pigs, a subclinical course was common and when clinical signs were seen (coughing, fever) they were generally mild. Presently, the clinical impact of pH1N1virus on the EU pig population is considered minimal. In poultry....... Such vaccines efficiently prevent disease by reducing virus replication in the lungs. However, voluntary vaccination of swine with these vaccines has not halted the circulation of SIV in swine. There is no urgency for vaccination of pigs against pH1N1 virus. Currently, no vaccines against H1 viruses for poultry...... are available but at present, there is no need to vaccinate poultry against pH1N1 virus. Monitoring of circulating influenza viruses in swine and poultry populations should be instigated to monitor the evolution of the pH1N1 virus including changes in virulence....

  18. Frequency of respiratory virus infections and next-generation analysis of influenza A/H1N1pdm09 dynamics in the lower respiratory tract of patients admitted to the ICU.

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    Antonio Piralla

    Full Text Available Recent molecular diagnostic methods have significantly improved the diagnosis of viral pneumonia in intensive care units (ICUs. It has been observed that 222G/N changes in the HA gene of H1N1pdm09 are associated with increased lower respiratory tract (LRT replication and worse clinical outcome. In the present study, the frequency of respiratory viruses was assessed in respiratory samples from 88 patients admitted to 16 ICUs during the 2014-2015 winter-spring season in Lombardy. Sixty-nine out of 88 (78.4% patients were positive for a respiratory viral infection at admission. Of these, 57/69 (82.6% were positive for influenza A (41 A/H1N1pdm09 and 15 A/H3N2, 8/69 (11.6% for HRV, 2/69 (2.9% for RSV and 2/69 (2.9% for influenza B. Phylogenetic analysis of influenza A/H1N1pdm09 strains from 28/41 ICU-patients and 21 patients with mild respiratory syndrome not requiring hospitalization, showed the clear predominance of subgroup 6B strains. The median influenza A load in LRT samples of ICU patients was higher than that observed in the upper respiratory tract (URT (p<0.05. Overall, a greater number of H1N1pdm09 virus variants were observed using next generation sequencing on partial HA sequences (codons 180-286 in clinical samples from the LRT as compared to URT. In addition, 222G/N/A mutations were observed in 30% of LRT samples from ICU patients. Finally, intra-host evolution analysis showed the presence of different dynamics of viral population in LRT of patients hospitalized in ICU with a severe influenza infection.

  19. Detection of extensive cross-neutralization between pandemic and seasonal A/H1N1 Influenza Viruses using a pseudotype neutralization assay.

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    Béatrice Labrosse

    Full Text Available BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007 and against pandemic A/H1N1 (A/California/04/2009 were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic.

  20. Pandemic H1N1 (2009) and renal failure: the experience of the Irish national tertiary referral centre.

    LENUS (Irish Health Repository)

    O Brien, F J

    2012-02-01

    INTRODUCTION: H1N1 influenza A, was first described in April 2009. A significant cohort of patients from this outbreak developed acute respiratory distress syndrome or pneumonia. H1N1 has since been transmitted across the world. Little has been described on the renal complications of this illness. METHODS: A retrospective review of all patients admitted to our institution with H1N1 infection was carried out from July to November 2009. Renal biochemistry, need for renal replacement therapy and hospital outcome was recorded. RESULTS: Thirty-four patients with H1N1 were admitted. Average length of admission was 10 days (3-84). Eleven patients (32%) developed acute kidney injury (AKI) as defined by the RIFLE criteria (creatinine range 120-610). Four patients required renal replacement therapy, for a range of 10-52 days. Seven patients developed AKI that responded to volume resuscitation. The commonest cause of AKI was sepsis with acute tubular necrosis. CONCLUSION: This study highlights the significance and frequency of renal complications associated with this illness.

  1. Understanding the cross-resistance of oseltamivir to H1N1 and H5N1 influenza A neuraminidase mutations using multidimensional computational analyses

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    Singh A

    2015-07-01

    Full Text Available Ashona Singh, Mahmoud E Soliman School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa Abstract: This study embarks on a comprehensive description of the conformational contributions to resistance of neuraminidase (N1 in H1N1 and H5N1 to oseltamivir, using comparative multiple molecular dynamic simulations. The available data with regard to elucidation of the mechanism of resistance as a result of mutations in H1N1 and H5N1 neuraminidases is not well established. Enhanced post-dynamic analysis, such as principal component analysis, solvent accessible surface area, free binding energy calculations, and radius of gyration were performed to gain a precise insight into the binding mode and origin of resistance of oseltamivir in H1N1 and H5N1 mutants. Three significant features reflecting resistance in the presence of mutations H274Y and I222K, of the protein complexed with the inhibitor are: reduced flexibility of the a-carbon backbone; an improved ΔEele of ~15 (kcal/mol for H1N1 coupled with an increase in ΔGsol­ (~13 kcal/mol from wild-type to mutation; a low binding affinity in comparison with the wild-type of ~2 (kcal/mol and ~7 (kcal/mol with respect to each mutation for the H5N1 systems; and reduced hydrophobicity of the overall surface structure due to an impaired hydrogen bonding network. We believe the results of this study will ultimately provide a useful insight into the structural landscape of neuraminidase-associated binding of oseltamivir. Furthermore, the results can be used in the design and development of potent inhibitors of neuraminidases. Keywords: neuraminidase, molecular dynamics, resistance, mutation, binding free energy

  2. Pathobiology of highly pathogenic avian influenza virus (H5N1) infection in mute swans (Cygnus olor).

    Science.gov (United States)

    Pálmai, Nimród; Erdélyi, Károly; Bálint, Adám; Márton, Lázár; Dán, Adám; Deim, Zoltán; Ursu, Krisztina; Löndt, Brandon Z; Brown, Ian H; Glávits, Róbert

    2007-06-01

    The results of pathological, virological and polymerase chain reaction examinations carried out on 35 mute swans (Cygnus olor) that succumbed to a highly pathogenic avian influenza virus (H5N1) infection during an outbreak in Southern Hungary are reported. The most frequently observed macroscopic lesions included: haemorrhages under the epicardium, in the proventricular and duodenal mucosa and pancreas; focal necrosis in the pancreas; myocardial degeneration; acute mucous enteritis; congestion of the spleen and lung, and the accumulation of sero-mucinous exudate in the body cavity. Histopathological lesions comprised: lymphocytic meningo-encephalomyelitis accompanied by gliosis and occasional perivascular haemorrhages; multi-focal myocardial necrosis with lympho-histiocytic infiltration; pancreatitis with focal necrosis; acute desquamative mucous enteritis; lung congestion and oedema; oedema of the tracheal mucosa and, in young birds, the atrophy of the bursa of Fabricius as a result of lymphocyte depletion and apoptosis. The observed lesions and the moderate to good body conditions were compatible with findings in acute highly pathogenic avian influenza infections of other bird species reported in the literature. Skin lesions and lesions typical for infections caused by strains of lower pathogenicity (low pathogenic avian influenza virus) such as emaciation or fibrinous changes in the reproductive and respiratory organs, sinuses and airsacs were not observed. The H5N1 subtype avian influenza virus was isolated in embryonated fowl eggs from all cases and it was identified by classical and molecular virological methods.

  3. Factors associated with post-seasonal serological titer and risk factors for infection with the pandemic A/H1N1 virus in the French general population.

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    Nathanael Lapidus

    Full Text Available The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households. The GMT for the general population was 47.1 (95% confidence interval (CI: 45.1, 49.2. According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.

  4. Clinical and microbiological evaluation of travel-associated respiratory tract infections in travelers returning from countries affected by pandemic A(H1N1) 2009 influenza.

    Science.gov (United States)

    Jauréguiberry, Stéphane; Boutolleau, David; Grandsire, Eric; Kofman, Tomek; Deback, Claire; Aït-Arkoub, Zaïna; Bricaire, François; Agut, Henri; Caumes, Eric

    2012-01-01

    Although acute respiratory tract infections (RTI) have been recognized as a significant cause of illness in returning travelers, few studies have specifically evaluated the etiologies of RTI in this population. This prospective investigation evaluated travelers returning from countries with endemic influenza A(H1N1) 2009, and who were seen in our department at the onset of the outbreak (April-July 2009). Patients were included if they presented with signs of RTI that occurred during travel or less than 7 days after return from overseas travel. Patients were evaluated for microbial agents with RespiFinder plus assay, and throat culture according to clinical presentation. A total of 113 travelers (M/F ratio 1.2:1; mean age 39 y) were included. They were mainly tourists (n = 50; 44.2%) mostly returning from North America (n = 65; 58%) and Mexico (n = 21; 18.5%). The median duration of travel was 23 days (range 2-540 d). The median lag time between return and onset of illness was 0.2 days (range 10 d prior to 7 d after). The main clinical presentation of RTI was influenza-like illness (n = 76; 67.3%). Among the 99 microbiologically evaluated patients, a pathogen was found by polymerase chain reaction (PCR) or throat culture in 65 patients (65.6%). The main etiological agents were influenza A(H1N1) 2009 (18%), influenza viruses (14%), and rhinovirus (20%). A univariate analysis was unable to show variables associated with influenza A(H1N1) 2009, whereas rhinorrhea was associated with viruses other than influenza (p = 0.04). Despite the A(H1N1) 2009 influenza pandemic, rhinovirus and other influenza viruses were also frequent causes of RTI in overseas travelers. Real-time reverse transcription-PCR and nasopharyngeal swab cultures are useful diagnostic tools for evaluating travelers with RTI. © 2011 International Society of Travel Medicine.

  5. MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape

    Energy Technology Data Exchange (ETDEWEB)

    Menachery, Vineet D.; Schafer, Alexandra; Burnum-Johnson, Kristin E.; Mitchell, Hugh D.; Eisfeld-Fenney, Amie J.; Walters, Kevin B.; Nicora, Carrie D.; Purvine, Samuel O.; Casey, Cameron P.; Monroe, Matthew E.; Weitz, Karl K.; Stratton, Kelly G.; Webb-Robertson, Bobbie-Jo M.; Gralinski, Lisa; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; Sims, Amy C.; Kawaoka, Yoshihiro; Baric, Ralph

    2018-01-16

    Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways in order to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems based approach, we examined differential regulation of IFNγ dependent genes following infection with highly pathogenic viruses including influenza (H5N1-VN1203, H1N1-CA04) and coronaviruses (SARS-CoV, MERS-CoV). Categorizing by function, we observed down regulation of genes associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down regulation of antigen presentation genes and was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation rather than histone modification plays a crucial role in MERS-CoV mediated antagonism of antigen presentation genes; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common approach utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.

  6. H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells.

    Science.gov (United States)

    Mazel-Sanchez, B; Boal-Carvalho, I; Silva, F; Dijkman, R; Schmolke, M

    2018-06-01

    Highly pathogenic influenza A viruses (IAV) from avian hosts were first reported to directly infect humans 20 years ago. However, such infections are rare events, and our understanding of factors promoting or restricting zoonotic transmission is still limited. One accessory protein of IAV, PB1-F2, was associated with pathogenicity of pandemic and zoonotic IAV. This short (90-amino-acid) peptide does not harbor an enzymatic function. We thus identified host factors interacting with H5N1 PB1-F2, which could explain its importance for virulence. PB1-F2 binds to HCLS1-associated protein X1 (HAX-1), a recently identified host restriction factor of the PA subunit of IAV polymerase complexes. We demonstrate that the PA of a mammal-adapted H1N1 IAV is resistant to HAX-1 imposed restriction, while the PA of an avian-origin H5N1 IAV remains sensitive. We also showed HAX-1 sensitivity for PAs of A/Brevig Mission/1/1918 (H1N1) and A/Shanghai/1/2013 (H7N9), two avian-origin zoonotic IAV. Inhibition of H5N1 polymerase by HAX-1 can be alleviated by its PB1-F2 through direct competition. Accordingly, replication of PB1-F2-deficient H5N1 IAV is attenuated in the presence of large amounts of HAX-1. Mammal-adapted H1N1 and H3N2 viruses do not display this dependence on PB1-F2 for efficient replication in the presence of HAX-1. We propose that PB1-F2 plays a key role in zoonotic transmission of avian H5N1 IAV into humans. IMPORTANCE Aquatic and shore birds are the natural reservoir of influenza A viruses from which the virus can jump into a variety of bird and mammal host species, including humans. H5N1 influenza viruses are a good model for this process. They pose an ongoing threat to human and animal health due to their high mortality rates. However, it is currently unclear what restricts these interspecies jumps on the host side or what promotes them on the virus side. Here we show that a short viral peptide, PB1-F2, helps H5N1 bird influenza viruses to overcome a human restriction

  7. A seroepidemiological study of pandemic A/H1N1(2009) influenza in a rural population of Mali.

    Science.gov (United States)

    Koita, O A; Sangare, L; Poudiougou, B; Aboubacar, B; Samake, Y; Coulibaly, T; Pronyk, P; Salez, N; Kieffer, A; Ninove, L; Flahault, A; de Lamballerie, X

    2012-10-01

    The swine-origin H1N1 influenza A virus (pH1N1(2009)) started to circulate worldwide in 2009, and cases were notified in a number of sub-Saharan African countries. However, no epidemiological data allowing estimation of the epidemic burden were available in this region, preventing comprehensive comparisons with other parts of the world. The CoPanFlu-Mali programme studied a cohort of 202 individuals living in the rural commune of Dioro (southern central Mali). Pre-pandemic and post-pandemic paired sera (sampled in 2006 and April 2010, respectively) were tested by the haemagglutination inhibition (HI) method. Different estimates of pH1N1(2009) infection during the 2009 first epidemic wave were used (increased prevalence of HI titre of ≥1/40 or ≥1/80, seroconversions) and provided convergent attack rate values (12.4-14.9%), the highest values being observed in the 0-19-year age group (16.0-18.4%). In all age groups, pre-pandemic HI titres of ≥1/40 were associated with complete absence of seroconversion; and geometric mean titres were 20 in others. Important variations in seroconversion rate existed among the different villages investigated. Despite limitations resulting from the size and composition of the sample analysed, this study provides strong evidence that the impact of the pH1N1(2009) first wave was more important than previously believed, and that the determinants of the epidemic spread in sub-Saharan populations were quite different from those observed in developed countries. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  8. Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

    African Journals Online (AJOL)

    Background: A novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in ...

  9. Epidemiological characteristics of Pandemic Influenza A (H1N1 ...

    African Journals Online (AJOL)

    ... novel influenza A virus strain (H1N1-2009) spread first in Mexico and the United Stated in late April 2009, leading to the first influenza pandemic of the 21st century. The objective of this study was to determine the epidemiological and virological characteristics of the pandemic influenza A (H1N1-2009) in Zhanjiang, China ...

  10. Comparative pathogenesis of an avian H5N2 and a swine H1N1 influenza virus in pigs.

    Directory of Open Access Journals (Sweden)

    Annebel De Vleeschauwer

    2009-08-01

    Full Text Available Pigs are considered intermediate hosts for the transmission of avian influenza viruses (AIVs to humans but the basic organ pathogenesis of AIVs in pigs has been barely studied. We have used 42 four-week-old influenza naive pigs and two different inoculation routes (intranasal and intratracheal to compare the pathogenesis of a low pathogenic (LP H5N2 AIV with that of an H1N1 swine influenza virus. The respiratory tract and selected extra-respiratory tissues were examined for virus replication by titration, immunofluorescence and RT-PCR throughout the course of infection. Both viruses caused a productive infection of the entire respiratory tract and epithelial cells in the lungs were the major target. Compared to the swine virus, the AIV produced lower virus titers and fewer antigen positive cells at all levels of the respiratory tract. The respiratory part of the nasal mucosa in particular showed only rare AIV positive cells and this was associated with reduced nasal shedding of the avian compared to the swine virus. The titers and distribution of the AIV varied extremely between individual pigs and were strongly affected by the route of inoculation. Gross lung lesions and clinical signs were milder with the avian than with the swine virus, corresponding with lower viral loads in the lungs. The brainstem was the single extra-respiratory tissue found positive for virus and viral RNA with both viruses. Our data do not reject the theory of the pig as an intermediate host for AIVs, but they suggest that AIVs need to undergo genetic changes to establish full replication potential in pigs. From a biomedical perspective, experimental LP H5 AIV infection of pigs may be useful to examine heterologous protection provided by H5 vaccines or other immunization strategies, as well as for further studies on the molecular pathogenesis and neurotropism of AIVs in mammals.

  11. Systems-level comparison of host responses induced by pandemic and seasonal influenza A H1N1 viruses in primary human type I-like alveolar epithelial cells in vitro

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    Guan Yi

    2010-10-01

    Full Text Available Abstract Background Pandemic influenza H1N1 (pdmH1N1 virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. Methods We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus. Results Overall, we found that most of the genes that induced by the pdmH1N1 were similarly regulated in response to seasonal H1N1 infection with respect to both trend and extent of gene expression. These commonly responsive genes were largely related to the interferon (IFN response. Expression of the type III IFN IL29 was more prominent than the type I IFN IFNβ and a similar pattern of expression of both IFN genes was seen in pdmH1N1 and seasonal H1N1 infection. Genes that were significantly down-regulated in response to seasonal H1N1 but not in response to pdmH1N1 included the zinc finger proteins and small nucleolar RNAs. Gene Ontology (GO and pathway over-representation analysis suggested that these genes were associated with DNA binding and transcription/translation related functions. Conclusions Both seasonal H1N1 and pdmH1N1 trigger similar host responses including IFN-based antiviral responses and cytokine responses. Unlike the avian H5N1 virus, pdmH1N1 virus does not have an intrinsic capacity for cytokine dysregulation. The differences between pdmH1N1 and seasonal H1N1 viruses

  12. Antiviral Prophylaxis and H1N1

    Centers for Disease Control (CDC) Podcasts

    2011-07-14

    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  13. Genetic diversity of the 2009 pandemic influenza A(H1N1 viruses in Finland.

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    Niina Ikonen

    Full Text Available BACKGROUND: In Finland, the first infections caused by the 2009 pandemic influenza A(H1N1 virus were identified on May 10. During the next three months almost all infections were found from patients who had recently traveled abroad. In September 2009 the pandemic virus started to spread in the general population, leading to localized outbreaks and peak epidemic activity was reached during weeks 43-48. METHODS/RESULTS: The nucleotide sequences of the hemagglutinin (HA and neuraminidase (NA genes from viruses collected from 138 patients were determined. The analyzed viruses represented mild and severe infections and different geographic regions and time periods. Based on HA and NA gene sequences, the Finnish pandemic viruses clustered in four groups. Finnish epidemic viruses and A/California/07/2009 vaccine virus strain varied from 2-8 and 0-5 amino acids in HA and NA molecules, respectively, giving a respective maximal evolution speed of 1.4% and 1.1%. Most amino acid changes in HA and NA molecules accumulated on the surface of the molecule and were partly located in antigenic sites. Three severe infections were detected with a mutation at HA residue 222, in two viruses with a change D222G, and in one virus D222Y. Also viruses with change D222E were identified. All Finnish pandemic viruses were sensitive to oseltamivir having the amino acid histidine at residue 275 of the neuraminidase molecule. CONCLUSIONS: The Finnish pandemic viruses were quite closely related to A/California/07/2009 vaccine virus. Neither in the HA nor in the NA were changes identified that may lead to the selection of a virus with increased epidemic potential or exceptionally high virulence. Continued laboratory-based surveillance of the 2009 pandemic influenza A(H1N1 is important in order to rapidly identify drug resistant viruses and/or virus variants with potential ability to cause severe forms of infection and an ability to circumvent vaccine-induced immunity.

  14. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: an ecological study.

    Science.gov (United States)

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2012-01-01

    The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.

  15. Advances and Future Challenges in Recombinant Adenoviral Vectored H5N1 Influenza Vaccines

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    Jianfeng Zhang

    2012-11-01

    Full Text Available The emergence of a highly pathogenic avian influenza virus H5N1 has increased the potential for a new pandemic to occur. This event highlights the necessity for developing a new generation of influenza vaccines to counteract influenza disease. These vaccines must be manufactured for mass immunization of humans in a timely manner. Poultry should be included in this policy, since persistent infected flocks are the major source of avian influenza for human infections. Recombinant adenoviral vectored H5N1 vaccines are an attractive alternative to the currently licensed influenza vaccines. This class of vaccines induces a broadly protective immunity against antigenically distinct H5N1, can be manufactured rapidly, and may allow mass immunization of human and poultry. Recombinant adenoviral vectors derived from both human and non-human adenoviruses are currently being investigated and appear promising both in nonclinical and clinical studies. This review will highlight the current status of various adenoviral vectored H5N1 vaccines and will outline novel approaches for the future.

  16. Novel reassortant influenza A(H1N2) virus derived from A(H1N1)pdm09 virus isolated from swine, Japan, 2012.

    Science.gov (United States)

    Kobayashi, Miho; Takayama, Ikuyo; Kageyama, Tsutomu; Tsukagoshi, Hiroyuki; Saitoh, Mika; Ishioka, Taisei; Yokota, Yoko; Kimura, Hirokazu; Tashiro, Masato; Kozawa, Kunihisa

    2013-12-01

    We isolated a novel influenza virus A(H1N2) strain from a pig on January 13, 2012, in Gunma Prefecture, Japan. Phylogenetic analysis showed that the strain was a novel type of double-reassortant virus derived from the swine influenza virus strains H1N1pdm09 and H1N2, which were prevalent in Gunma at that time.

  17. The effect of age on the pathogenesis of a highly pathogenic avian influenza (HPAI) H5N1 virus in Pekin ducks (Anas platyrhynchos) infected experimentally.

    Science.gov (United States)

    Löndt, Brandon Z; Núñez, Alejandro; Banks, Jill; Alexander, Dennis J; Russell, Christine; Richard-Löndt, Angela C; Brown, Ian H

    2010-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 viruses have recently displayed increased virulence for wild waterfowl. To study the effect of host age on the shedding and tissue dissemination of a HPAI H5N1 virus in infected Pekin ducks. Pekin ducks in two age-matched groups (n = 18), 8 and 12 weeks old (wo) were each infected with 10(6) EID(50)/0.1 ml of HPAI A/turkey/Turkey/1/05 (H5N1, clade 2.2). Each day for 5 days, birds were monitored clinically, and cloacal and oropharyngeal swabs collected, before three birds from each group were selected randomly for post-mortem examination. Tissue samples were collected for examination by real-time RT-PCR, histopathology and immunohistochemistry (IHC). Severe clinical signs, including incoordination and torticollis were observed in the 8 wo group resulting in 100% mortality by 4 dpi. Mild clinical signs were observed in the 12 wo group with no mortality. Real-time RT-PCR and IHC results demonstrated the systemic spread of H5N1 virus in birds of both age groups. Higher levels of virus shedding were detected in oropharyngeal swabs than in cloacal swabs, with similar levels of shedding detected in both age groups. Variations in level and temporal dissemination of virus within tissues of older ducks, and the presence of the virus in brain and heart were observed, which coincided with the appearance of clinical signs preceding death in younger birds. These results are consistent with reports of natural infections of wild waterfowl and poultry possibly indicating an age-related association with dissemination and clinical outcome in ducks following infection with H5N1 HPAI virus.

  18. Experimental infection of macaques with a wild water bird-derived highly pathogenic avian influenza virus (H5N1.

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    Tomoko Fujiyuki

    Full Text Available Highly pathogenic avian influenza virus (HPAIV continues to threaten human health. Non-human primate infection models of human influenza are desired. To establish an animal infection model with more natural transmission and to determine the pathogenicity of HPAIV isolated from a wild water bird in primates, we administered a Japanese isolate of HPAIV (A/whooper swan/Hokkaido/1/2008, H5N1 clade 2.3.2.1 to rhesus and cynomolgus monkeys, in droplet form, via the intratracheal route. Infection of the lower and upper respiratory tracts and viral shedding were observed in both macaques. Inoculation of rhesus monkeys with higher doses of the isolate resulted in stronger clinical symptoms of influenza. Our results demonstrate that HPAIV isolated from a water bird in Japan is pathogenic in monkeys by experimental inoculation, and provide a new method for HPAIV infection of non-human primate hosts, a good animal model for investigation of HPAIV pathogenicity.

  19. Avian Influenza Virus (H5N1): a Threat to Human Health

    OpenAIRE

    Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

    2007-01-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, ...

  20. PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection

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    Wang Qiang

    2012-06-01

    Full Text Available Abstract Background Although gene exchange is not likely to occur freely, reassortment between the H5N1 highly pathogenic avian influenza virus (HPAIV and currently circulating human viruses is a serious concern. The PA polymerase subunit of H5N1 HPAIV was recently reported to activate the influenza replicon activity. Methods The replicon activities of PR8 and WSN strains (H1N1 of influenza containing PA from HPAIV A/Cambodia/P0322095/2005 (H5N1 and the activity of the chimeric RNA polymerase were analyzed. A reassortant WSN virus containing the H5N1 Cambodia PA (C-PA was then reconstituted and its growth in cells and pathogenicity in mice examined. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities of C-PA-infected cells were compared with those of WSN-infected cells. Results The activity of the chimeric RNA polymerase was slightly higher than that of WSN, and C-PA replicated better than WSN in cells. However, the multi-step growth of C-PA and its pathogenicity in mice were lower than those of WSN. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities were strongly induced in early infection in C-PA-infected cells but not in WSN-infected cells. Conclusions Apoptosis and interferon were strongly induced early in C-PA infection, which protected the uninfected cells from expansion of viral infection. In this case, these classical host-virus interactions contributed to the attenuation of this strongly replicating virus.

  1. Evolutionary trends of A(H1N1 influenza virus hemagglutinin since 1918.

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    Jun Shen

    2009-11-01

    Full Text Available The Pandemic (H1N1 2009 is spreading to numerous countries and causing many human deaths. Although the symptoms in humans are mild at present, fears are that further mutations in the virus could lead to a potentially more dangerous outbreak in subsequent months. As the primary immunity-eliciting antigen, hemagglutinin (HA is the major agent for host-driven antigenic drift in A(H3N2 virus. However, whether and how the evolution of HA is influenced by existing immunity is poorly understood for A(H1N1. Here, by analyzing hundreds of A(H1N1 HA sequences since 1918, we show the first evidence that host selections are indeed present in A(H1N1 HAs. Among a subgroup of human A(H1N1 HAs between 1918 approximately 2008, we found strong diversifying (positive selection at HA(1 156 and 190. We also analyzed the evolutionary trends at HA(1 190 and 225 that are critical determinants for receptor-binding specificity of A(H1N1 HA. Different A(H1N1 viruses appeared to favor one of these two sites in host-driven antigenic drift: epidemic A(H1N1 HAs favor HA(1 190 while the 1918 pandemic and swine HAs favor HA(1 225. Thus, our results highlight the urgency to understand the interplay between antigenic drift and receptor binding in HA evolution, and provide molecular signatures for monitoring future antigenically drifted 2009 pandemic and seasonal A(H1N1 influenza viruses.

  2. Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season

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    Timen Aura

    2011-10-01

    Full Text Available Abstract Background In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1 2009 virus infection was performed. Methods The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season. Results A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02, and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005. Conclusions The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward

  3. Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model.

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    Benjamin P Holder

    2011-03-01

    Full Text Available In 2007, the A/Brisbane/59/2007 (H1N1 seasonal influenza virus strain acquired the oseltamivir-resistance mutation H275Y in its neuraminidase (NA gene. Although previous studies had demonstrated that this mutation impaired the replication capacity of the influenza virus in vitro and in vivo, the A/Brisbane/59/2007 H275Y oseltamivir-resistant mutant completely out-competed the wild-type (WT strain and was, in the 2008-2009 influenza season, the primary A/H1N1 circulating strain. Using a combination of plaque and viral yield assays, and a simple mathematical model, approximate values were extracted for two basic viral kinetics parameters of the in vitro infection. In the ST6GalI-MDCK cell line, the latent infection period (i.e., the time for a newly infected cell to start releasing virions was found to be 1-3 h for the WT strain and more than 7 h for the H275Y mutant. The infecting time (i.e., the time for a single infectious cell to cause the infection of another one was between 30 and 80 min for the WT, and less than 5 min for the H275Y mutant. Single-cycle viral yield experiments have provided qualitative confirmation of these findings. These results, though preliminary, suggest that the increased fitness success of the A/Brisbane/59/2007 H275Y mutant may be due to increased infectivity compensating for an impaired or delayed viral release, and are consistent with recent evidence for the mechanistic origins of fitness reduction and recovery in NA expression. The method applied here can reconcile seemingly contradictory results from the plaque and yield assays as two complementary views of replication kinetics, with both required to fully capture a strain's fitness.

  4. Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

    NARCIS (Netherlands)

    Meijer, A.; Swaan, C.M.; Voerknecht, M.; Jusic, E.; Brink, S. van den; Wijsman, L.A.; Voordouw, B.C.G.; Donker, G.A.; Sleven, J.; Dorigo-Zetsma, W.W.; Svraka, S.; Boven, M. van; Haverkate, M.R.; Timen, A.; Dissel, J.T. van; Koopmans, M.P.G.; Besteboer, T.M.; Fouchier, R.A.M.

    2018-01-01

    A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general

  5. Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

    NARCIS (Netherlands)

    Meijer, Adam; Swaan, Corien M; Voerknecht, Martin; Jusic, Edin; van den Brink, Sharon; Wijsman, Lisa A; Voordouw, Bettie Cg; Donker, Gé A; Sleven, Jacqueline; Dorigo-Zetsma, Wendelien W; Svraka, Sanela; van Boven, Michiel; Haverkate, Manon R; Timen, Aura; van Dissel, Jaap T; Koopmans, Marion Pg; Bestebroer, Theo M; Fouchier, Ron Am

    A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general

  6. Isolation and genetic characterization of a novel 2.2.1.2a H5N1 virus from a vaccinated meat-turkeys flock in Egypt.

    Science.gov (United States)

    Salaheldin, Ahmed H; Veits, Jutta; Abd El-Hamid, Hatem S; Harder, Timm C; Devrishov, Davud; Mettenleiter, Thomas C; Hafez, Hafez M; Abdelwhab, Elsayed M

    2017-03-09

    Vaccination of poultry to control highly pathogenic avian influenza virus (HPAIV) H5N1 is used in several countries. HPAIV H5N1 of clade 2.2.1 which is endemic in Egypt has diversified into two genetic clades. Clade 2.2.1.1 represents antigenic drift variants in vaccinated commercial poultry while clade 2.2.1.2 variants are detected in humans and backyard poultry. Little is known about H5N1 infection in vaccinated turkeys under field conditions. Here, we describe an HPAI H5N1 outbreak in a vaccinated meat-turkey flock in Egypt. Birds were vaccinated with inactivated H5N2 and H5N1 vaccines at 8 and 34 days of age, respectively. At 72 nd day of age (38 days post last vaccination), turkeys exhibited mild respiratory signs, cyanosis of snood and severe congestion of the internal organs. Survivors had a reduction in feed consumption and body gain. A mortality of ~29% cumulated within 10 days after the onset of clinical signs. Laboratory diagnosis using RT-qPCRs revealed presence of H5N1 but was negative for H7 and H9 subtypes. A substantial antigenic drift against different serum samples from clade 2.2.1.1 and clade 2.3.4.4 was observed. Based on full genome sequence analysis the virus belonged to clade 2.2.1.2 but clustered with recent H5N1 viruses from 2015 in poultry in Israel, Gaza and Egypt in a novel subclade designated here 2.2.1.2a which is distinct from 2014/2015 2.2.1.2 viruses. These viruses possess 2.2.1.2 clade-specific genetic signatures and also mutations in the HA similar to those in clade 2.2.1.1 that enabled evasion from humoral immune response. Taken together, this manuscript describes a recent HPAI H5N1 outbreak in vaccinated meat-turkeys in Egypt after infection with a virus representing novel distinct 2.2.1.2a subclade. Infection with HPAIV H5N1 in commercial turkeys resulted in significant morbidity and mortality despite of vaccination using H5 vaccines. The isolated virus showed antigenic drift and clustered in a novel cluster designated here

  7. Isolation of avian influenza H5N1 virus from vaccinated commercial layer flock in Egypt

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    El-Zoghby Elham F

    2012-11-01

    Full Text Available Abstract Background Uninterrupted transmission of highly pathogenic avian influenza virus (HPAIV H5N1 of clade 2.2.1 in Egypt since 2006 resulted in establishment of two main genetic clusters. The 2.2.1/C group where all recent human and majority of backyard origin viruses clustered together, meanwhile the majority of viruses derived from vaccinated poultry in commercial farms grouped in 2.2.1.1 clade. Findings In the present investigation, an HPAIV H5N1 was isolated from twenty weeks old layers chickens that were vaccinated with a homologous H5N1 vaccine at 1, 7 and 16 weeks old. At twenty weeks of age, birds showed cyanosis of comb and wattle, decrease in egg production and up to 27% mortality. Examined serum samples showed low antibody titer in HI test (Log2 3.2± 4.2. The hemagglutinin (HA and neuraminidase (NA genes of the isolated virus were closely related to viruses in 2.2.1/C group isolated from poultry in live bird market (LBM and backyards or from infected people. Conspicuous mutations in the HA and NA genes including a deletion within the receptor binding domain in the HA globular head region were observed. Conclusions Despite repeated vaccination of layer chickens using a homologous H5N1 vaccine, infection with HPAIV H5N1 resulted in significant morbidity and mortality. In endemic countries like Egypt, rigorous control measures including enforcement of biosecurity, culling of infected birds and constant update of vaccine virus strains are highly required to prevent circulation of HPAIV H5N1 between backyard birds, commercial poultry, LBM and humans.

  8. Assessing Google flu trends performance in the United States during the 2009 influenza virus A (H1N1 pandemic.

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    Samantha Cook

    Full Text Available BACKGROUND: Google Flu Trends (GFT uses anonymized, aggregated internet search activity to provide near-real time estimates of influenza activity. GFT estimates have shown a strong correlation with official influenza surveillance data. The 2009 influenza virus A (H1N1 pandemic [pH1N1] provided the first opportunity to evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an updated United States GFT model was developed using data from the beginning of pH1N1. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the accuracy of each U.S. GFT model by comparing weekly estimates of ILI (influenza-like illness activity with the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet. For each GFT model we calculated the correlation and RMSE (root mean square error between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1, Winter H1N1, and H1N1 overall (Mar 2009-Dec 2009. We also compared the number of queries, query volume, and types of queries (e.g., influenza symptoms, influenza complications in each model. Both models' estimates were highly correlated with ILINet pre-H1N1 and over the entire surveillance period, although the original model underestimated the magnitude of ILI activity during pH1N1. The updated model was more correlated with ILINet than the original model during Summer H1N1 (r = 0.95 and 0.29, respectively. The updated model included more search query terms than the original model, with more queries directly related to influenza infection, whereas the original model contained more queries related to influenza complications. CONCLUSIONS: Internet search behavior changed during pH1N1, particularly in the categories "influenza complications" and "term for influenza." The complications associated with pH1N1, the fact that pH1N1 began in the summer rather than winter, and changes in health-seeking behavior each may have played a part. Both GFT models performed well prior to and during pH1

  9. Assessing Google Flu Trends Performance in the United States during the 2009 Influenza Virus A (H1N1) Pandemic

    Science.gov (United States)

    Cook, Samantha; Conrad, Corrie; Fowlkes, Ashley L.; Mohebbi, Matthew H.

    2011-01-01

    Background Google Flu Trends (GFT) uses anonymized, aggregated internet search activity to provide near-real time estimates of influenza activity. GFT estimates have shown a strong correlation with official influenza surveillance data. The 2009 influenza virus A (H1N1) pandemic [pH1N1] provided the first opportunity to evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an updated United States GFT model was developed using data from the beginning of pH1N1. Methodology/Principal Findings We evaluated the accuracy of each U.S. GFT model by comparing weekly estimates of ILI (influenza-like illness) activity with the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet). For each GFT model we calculated the correlation and RMSE (root mean square error) between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1, Winter H1N1, and H1N1 overall (Mar 2009–Dec 2009). We also compared the number of queries, query volume, and types of queries (e.g., influenza symptoms, influenza complications) in each model. Both models' estimates were highly correlated with ILINet pre-H1N1 and over the entire surveillance period, although the original model underestimated the magnitude of ILI activity during pH1N1. The updated model was more correlated with ILINet than the original model during Summer H1N1 (r = 0.95 and 0.29, respectively). The updated model included more search query terms than the original model, with more queries directly related to influenza infection, whereas the original model contained more queries related to influenza complications. Conclusions Internet search behavior changed during pH1N1, particularly in the categories “influenza complications” and “term for influenza.” The complications associated with pH1N1, the fact that pH1N1 began in the summer rather than winter, and changes in health-seeking behavior each may have played a part. Both GFT models performed well prior to and during pH1N1

  10. Usefulness of CURB-65 and pneumonia severity index for influenza A H1N1v pneumonia.

    Science.gov (United States)

    Estella, A

    2012-01-01

    Usefulness of CURB-65 and pneumonia severity index for influenza A H1N1v pneumonia. A. Estella. Different prognostic scales have been documented to assess the severity and indications for hospitalization and ICU admissions of community acquired pneumonia. During the past two years Influenza A H1N1v infections have been commonly attended to in emergency departments. The aim of the study was to analyse the usefulness of the application of the Pneumonia Severity Index (PSI) and CURB-65 prognostic scales in patients with primary viral pneumonia caused by influenza A H1N1v. A retrospective study was performed at a community hospital with a 17 bed-intensive care unit. Patients admitted in hospital with influenza A H1N1v pneumonia over a two year period were analysed. CURB 65 and PSI scales were applied in the emergency department and outcome and destination of admission were analysed. 24 patients were registered, 19 required ICU admission and 5 patients were admitted in medical wards. Most of the patients admitted to the intensive care unit (78.9%) required mechanical ventilation. Mortality was 21.1%. Most patients admitted to the ICU had CURB 65 scale of 1 (60%), 13.3% obtained 0 and 26.7% 2. PSI scale resulted class I in a 20%, class II 40%, 26.7% class IV and 13.3% class V. The scales CURB 65 and PSI showed no differences in scores according to the destination of admission and mortality. Use of CURB-65 and PSI in the emergency department may underestimate the risk of patients with Influenza A H1N1v pneumonia. Based in our results, the ability of these scales to predict ICU admissions for Influenza A H1N1v pneumonia is questioned.

  11. Case of seasonal reassortant a(H1N2) influenza virus infection, the Netherlands, March 2018

    NARCIS (Netherlands)

    Meijer, A. (Adam); C. Swaan (Corien); Voerknecht, M. (Martin); E. Jusic (Edin); van den Brink, S. (Sharon); Wijsman, L.A. (Lisa A.); A.C.G. Voordouw (Bettie); G.A. Donker (Gé); Sleven, J. (Jacqueline); Dorigo-Zetsma, W.W. (Wendelien W.); S. Svraka-Latifovic (Sanela); M. van Boven (Michiel); Haverkate, M.R. (Manon R.); A. Timen (Aura); J.T. van Dissel (Jaap); M.P.G. Koopmans D.V.M. (Marion); T.M. Bestebroer (Theo); R.A.M. Fouchier (Ron)

    2018-01-01

    textabstractA seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general

  12. Ion chemistry of 1H-1,2,3-triazole.

    Science.gov (United States)

    Ichino, Takatoshi; Andrews, Django H; Rathbone, G Jeffery; Misaizu, Fuminori; Calvi, Ryan M D; Wren, Scott W; Kato, Shuji; Bierbaum, Veronica M; Lineberger, W Carl

    2008-01-17

    A combination of experimental methods, photoelectron-imaging spectroscopy, flowing afterglow-photoelectron spectroscopy and the flowing afterglow-selected ion flow tube technique, and electronic structure calculations at the B3LYP/6-311++G(d,p) level of density functional theory (DFT) have been employed to study the mechanism of the reaction of the hydroxide ion (HO-) with 1H-1,2,3-triazole. Four different product ion species have been identified experimentally, and the DFT calculations suggest that deprotonation by HO- at all sites of the triazole takes place to yield these products. Deprotonation of 1H-1,2,3-triazole at the N1-H site gives the major product ion, the 1,2,3-triazolide ion. The 335 nm photoelectron-imaging spectrum of the ion has been measured. The electron affinity (EA) of the 1,2,3-triazolyl radical has been determined to be 3.447 +/- 0.004 eV. This EA and the gas-phase acidity of 2H-1,2,3-triazole are combined in a negative ion thermochemical cycle to determine the N-H bond dissociation energy of 2H-1,2,3-triazole to be 112.2 +/- 0.6 kcal mol-1. The 363.8 nm photoelectron spectroscopic measurements have identified the other three product ions. Deprotonation of 1H-1,2,3-triazole at the C5 position initiates fragmentation of the ring structure to yield a minor product, the ketenimine anion. Another minor product, the iminodiazomethyl anion, is generated by deprotonation of 1H-1,2,3-triazole at the C4 position, followed by N1-N2 bond fission. Formation of the other minor product, the 2H-1,2,3-triazol-4-ide ion, can be rationalized by initial deprotonation of 1H-1,2,3-triazole at the N1-H site and subsequent proton exchanges within the ion-molecule complex. The EA of the 2H-1,2,3-triazol-4-yl radical is 1.865 +/- 0.004 eV.

  13. Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

    Science.gov (United States)

    Nicolini, A; Tonveronachi, E; Navalesi, P; Antonelli, M; Valentini, I; Melotti, R M; Pigna, A; Carrassi, A; Righini, P; Ferrari Bravo, M; Pelosi, P; Nicoli, F; Cosentini, R; Vaschetto, R; Faenza, S; Nava, S

    2012-12-01

    The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO229 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

  14. Identification of reassortant pandemic H1N1 influenza virus in Korean pigs.

    Science.gov (United States)

    Han, Jae Yeon; Park, Sung Jun; Kim, Hye Kwon; Rho, Semi; Nguyen, Giap Van; Song, Daesub; Kang, Bo Kyu; Moon, Hyung Jun; Yeom, Min Joo; Park, Bong Kyun

    2012-05-01

    Since the 2009 pandemic human H1N1 influenza A virus emerged in April 2009, novel reassortant strains have been identified throughout the world. This paper describes the detection and isolation of reassortant strains associated with human pandemic influenza H1N1 and swine influenza H1N2 (SIV) viruses in swine populations in South Korea. Two influenza H1N2 reassortants were detected, and subtyped by PCR. The strains were isolated using Madin- Darby canine kidney (MDCK) cells, and genetically characterized by phylogenetic analysis for genetic diversity. They consisted of human, avian, and swine virus genes that were originated from the 2009 pandemic H1N1 virus and a neuraminidase (NA) gene from H1N2 SIV previously isolated in North America. This identification of reassortment events in swine farms raises concern that reassortant strains may continuously circulate within swine populations, calling for the further study and surveillance of pandemic H1N1 among swine.

  15. Pandemic 2009 Influenza A (H1N1 virus infection in cancer and hematopoietic stem cell transplant recipients; a multicenter observational study. [v1; ref status: indexed, http://f1000r.es/4bi

    Directory of Open Access Journals (Sweden)

    Maria Cecilia Dignani

    2014-09-01

    Full Text Available Background: During March 2009 a novel Influenza A virus emerged in Mexico. We describe the clinical picture of the pandemic Influenza A (H1N1 Influenza in cancer patients during the 2009 influenza season. Methods: Twelve centers participated in a multicenter retrospective observational study of cancer patients with confirmed infection with the 2009 H1N1 Influenza A virus (influenza-like illness or pneumonia plus positive PCR for the 2009 H1N1 Influenza A virus  in respiratory secretions. Clinical data were obtained by retrospective chart review and analyzed.  Results: From May to August 2009, data of 65 patients were collected. Median age was 51 years, 57 % of the patients were female. Most patients (47 had onco-hematological cancers and 18 had solid tumors. Cancer treatment mainly consisted of chemotherapy (46, or stem cell transplantation (SCT (16. Only 19 of 64 patients had received the 2009 seasonal Influenza vaccine. Clinical presentation included pneumonia (43 and upper respiratory tract infection (22. Forty five of 58 ambulatory patients were admitted. Mechanical ventilation was required in 12 patients (18%. Treatment included oseltamivir monotherapy or in combination with amantadine for a median of 7 days. The global 30-day mortality rate was 18%. All 12 deaths were among the non-vaccinated patients. No deaths were observed among the 19 vaccinated patients. Oxygen saturation <96% at presentation was a predictor of mortality (OR 19.5; 95%CI: 2.28 to 165.9. Conclusions: In our cancer patient population, the pandemic 2009 Influenza A (H1N1 virus was associated with high incidence of pneumonia (66%, and 30-day mortality (18.5%. Saturation <96% was significantly associated with death. No deaths were observed among vaccinated patients.

  16. Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1 in experimentally infected chickens

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    Chaves Aida J

    2011-10-01

    Full Text Available Abstract In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV into the central nervous system (CNS of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF, nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood-CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaα2,3 Gal and Siaα2,6 Gal receptors in brain vascular endothelial cells, and Siaα2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF.

  17. Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1) in experimentally infected chickens.

    Science.gov (United States)

    Chaves, Aida J; Busquets, Núria; Valle, Rosa; Rivas, Raquel; Vergara-Alert, Júlia; Dolz, Roser; Ramis, Antonio; Darji, Ayub; Majó, Natàlia

    2011-10-07

    In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV) into the central nervous system (CNS) of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF), nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi) of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood-CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaα2,3 Gal and Siaα2,6 Gal receptors in brain vascular endothelial cells, and Siaα2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF.

  18. Enrichment of variations in KIR3DL1/S1 and KIR2DL2/L3 among H1N1/09 ICU patients: an exploratory study.

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    David La

    Full Text Available BACKGROUND: Infection by the pandemic influenza A (H1N1/09 virus resulted in significant pathology among specific ethnic groups worldwide. Natural Killer (NK cells are important in early innate immune responses to viral infections. Activation of NK cells, in part, depend on killer-cell immunoglobulin-like receptors (KIR and HLA class I ligand interactions. To study factors involved in NK cell dysfunction in overactive immune responses to H1N1 infection, KIR3DL1/S1 and KIR2DL2/L3 allotypes and cognate HLA ligands of H1N1/09 intensive-care unit (ICU patients were determined. METHODOLOGY AND FINDINGS: KIR3DL1/S1, KIR2DL2/L3, and HLA -B and -C of 51 H1N1/09 ICU patients and 105 H1N1-negative subjects (St. Theresa Point, Manitoba were characterized. We detected an increase of 3DL1 ligand-negative pairs (3DL1/S1(+ Bw6(+ Bw4(-, and a lack of 2DL1 HLA-C2 ligands, among ICU patients. They were also significantly enriched for 2DL2/L3 ligand-positive pairs (PVA, P=0.024, Pc=0.047; Odds Ratio:2.563, CI95%:1.109-5.923, 3DL1*00101 (Ab>VA, PSTh, P=0.034, Pc=0.268, and 3DL1*029 (Ab>STh, P=0.039, Pc=0.301. Aboriginal patients ligand-positive for 3DL1/S1 and 2DL1 had the lowest probabilities of death (R(d (R(d=28%, compared to patients that were 3DL1/S1 ligand-negative (R(d=52% or carried 3DL1*029 (R(d=52%. Relative to Caucasoids (CA, two allotypes were enriched among non-aboriginal ICU patients (NAb: 3DL1*00401 (NAb>CA, P<0.001, Pc<0.001 and 3DL1*01502 (CA1/S1, 2DL2/L3, and 2DL1 had the lowest probabilities of death (R(d=36%, compared to subjects with 3DL1*01502 (R(d=48% and/or 3DL1*00401 (R(d=58%. CONCLUSIONS: Specific KIR3DL1/S1 allotypes, 3DL1/S1 and 2DL1 ligand-negative pairs, and 2DL2/L3 ligand-positive pairs were enriched among ICU patients. This suggests a possible association with NK cell dysfunction in patients with overactive immune responses to H1N1/09, leading to

  19. H1N1, globalization and the epidemiology of inequality.

    Science.gov (United States)

    Sparke, Matthew; Anguelov, Dimitar

    2012-07-01

    This paper examines the lessons learned from the 2009 H1N1 pandemic in relation to wider work on globalization and the epidemiology of inequality. The media attention and economic resources diverted to the threats posed by H1N1 were significant inequalities themselves when contrasted with weaker responses to more lethal threats posed by other diseases associated with global inequality. However, the multiple inequalities revealed by H1N1 itself in 2009 still provide important insights into the future of global health in the context of market-led globalization. These lessons relate to at least four main forms of inequality: (1) inequalities in blame for the outbreak in the media; (2) inequalities in risk management; (3) inequalities in access to medicines; and (4) inequalities encoded in the actual emergence of new flu viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt.

    Science.gov (United States)

    Kim, Shin-Hee

    2018-03-09

    Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

  1. Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt

    Directory of Open Access Journals (Sweden)

    Shin-Hee Kim

    2018-03-01

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1 altering amino acids in hemagglutinin (HA that enable binding affinity to human-type receptors, (2 loss of the glycosylation site and 130 loop in the HA protein and (3 mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

  2. Pathogenesis of H5N1 influenza virus infections in mice and ferret models differ between respiratory and digestive system exposure

    Science.gov (United States)

    Background. Epidemiological, clinical and laboratory data suggests H5N1 influenza viruses are transmitted through and predominantly affect the respiratory system of mammals. Some data suggests digestive system involvement. However, direct evidence of alimentary transmission and infection in mammal...

  3. The environmental deposition of influenza virus from patients infected with influenza A(H1N1)pdm09: Implications for infection prevention and control.

    Science.gov (United States)

    Killingley, Benjamin; Greatorex, Jane; Digard, Paul; Wise, Helen; Garcia, Fayna; Varsani, Harsha; Cauchemez, Simon; Enstone, Joanne E; Hayward, Andrew; Curran, Martin D; Read, Robert C; Lim, Wei S; Nicholson, Karl G; Nguyen-Van-Tam, Jonathan S

    2016-01-01

    In a multi-center, prospective, observational study over two influenza seasons, we sought to quantify and correlate the amount of virus recovered from the nares of infected subjects with that recovered from their immediate environment in community and hospital settings. We recorded the symptoms of adults and children with A(H1N1)pdm09 infection, took nasal swabs, and sampled touched surfaces and room air. Forty-two infected subjects were followed up. The mean duration of virus shedding was 6.2 days by PCR (Polymerase Chain Reaction) and 4.2 days by culture. Surface swabs were collected from 39 settings; 16 (41%) subject locations were contaminated with virus. Overall, 33 of the 671 (4.9%) surface swabs were PCR positive for influenza, of which two (0.3%) yielded viable virus. On illness Day 3, subjects yielding positive surface samples had significantly higher nasal viral loads (geometric mean ratio 25.7; 95% CI 1.75, 376.0, p=0.021) and a positive correlation (r=0.47, p=0.006) was observed between subject nasal viral loads and viral loads recovered from the surfaces around them. Room air was sampled in the vicinity of 12 subjects, and PCR positive samples were obtained for five (42%) samples. Influenza virus shed by infected subjects did not detectably contaminate the vast majority of surfaces sampled. We question the relative importance of the indirect contact transmission of influenza via surfaces, though our data support the existence of super-spreaders via this route. The air sampling results add to the accumulating evidence that supports the potential for droplet nuclei (aerosol) transmission of influenza. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  4. Epidemiology, clinical characteristics and resource implications of pandemic (H1N1) 2009 in intensive care units in Ireland.

    LENUS (Irish Health Repository)

    Nicolay, Nathalie

    2010-12-01

    To describe the incidence, clinical characteristics and outcomes of critically ill patients in Ireland with pandemic (H1N1) 2009 infection, and to provide a dynamic assessment of the burden of such cases on Irish intensive care units.

  5. Memory immune responses against pandemic (H1N1 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.

    Directory of Open Access Journals (Sweden)

    Masahiko Arikata

    Full Text Available We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009 H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052:02, were used to analyze peptide-specific CD8(+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1 than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1 in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8(+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052:02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses

  6. Seroprevalence of avian influenza A (H5N1 virus among poultry workers in Jiangsu Province, China: an observational study

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    Huo Xiang

    2012-04-01

    Full Text Available Abstract Background Since 2003 to 06 Jan 2012, the number of laboratory confirmed human cases of infection with avian influenza in China was 41 and 27 were fatal. However, the official estimate of the H5N1 case-fatality rate has been described by some as an over estimation since there may be numerous undetected asymptomatic/mild cases of H5N1 infection. This study was conducted to better understand the real infection rate and evaluate the potential risk factors for the zoonotic spread of H5N1 viruses to humans. Methods A seroepidemiological survey was conducted in poultry workers, a group expected to have the highest level of exposure to H5N1-infected birds, from 3 counties with habitat lakes of wildfowl in Jiangsu province, China. Serum specimens were collected from 306 participants for H5N1 serological test. All participants were interviewed to collect information about poultry exposures. Results The overall seropositive rate was 2.61% for H5N1 antibodies. The poultry number was found associated with a 2.39-fold significantly increased subclinical infection risk after adjusted with age and gender. Conclusions Avian-to -human transmission of avian H5N1 virus remained low. Workers associated with raising larger poultry flocks have a higher risk on seroconversion.

  7. Bayesian estimation of the dynamics of pandemic (H1N1) 2009 influenza transmission in Queensland: A space-time SIR-based model.

    Science.gov (United States)

    Huang, Xiaodong; Clements, Archie C A; Williams, Gail; Mengersen, Kerrie; Tong, Shilu; Hu, Wenbiao

    2016-04-01

    A pandemic strain of influenza A spread rapidly around the world in 2009, now referred to as pandemic (H1N1) 2009. This study aimed to examine the spatiotemporal variation in the transmission rate of pandemic (H1N1) 2009 associated with changes in local socio-environmental conditions from May 7-December 31, 2009, at a postal area level in Queensland, Australia. We used the data on laboratory-confirmed H1N1 cases to examine the spatiotemporal dynamics of transmission using a flexible Bayesian, space-time, Susceptible-Infected-Recovered (SIR) modelling approach. The model incorporated parameters describing spatiotemporal variation in H1N1 infection and local socio-environmental factors. The weekly transmission rate of pandemic (H1N1) 2009 was negatively associated with the weekly area-mean maximum temperature at a lag of 1 week (LMXT) (posterior mean: -0.341; 95% credible interval (CI): -0.370--0.311) and the socio-economic index for area (SEIFA) (posterior mean: -0.003; 95% CI: -0.004--0.001), and was positively associated with the product of LMXT and the weekly area-mean vapour pressure at a lag of 1 week (LVAP) (posterior mean: 0.008; 95% CI: 0.007-0.009). There was substantial spatiotemporal variation in transmission rate of pandemic (H1N1) 2009 across Queensland over the epidemic period. High random effects of estimated transmission rates were apparent in remote areas and some postal areas with higher proportion of indigenous populations and smaller overall populations. Local SEIFA and local atmospheric conditions were associated with the transmission rate of pandemic (H1N1) 2009. The more populated regions displayed consistent and synchronized epidemics with low average transmission rates. The less populated regions had high average transmission rates with more variations during the H1N1 epidemic period. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

    Science.gov (United States)

    Nolan, Terry; Roy-Ghanta, Sumita; Montellano, May; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Safadi, Marco Aurélio Palazzi; Cruz-Valdez, Aurelio; Litao, Sandra; Lim, Fong Seng; de Los Santos, Abiel Mascareñas; Weber, Miguel Angel Rodriguez; Tinoco, Juan-Carlos; Mezerville, Marcela Hernandez-de; Faingezicht, Idis; Kosuwon, Pensri; Lopez, Pio; Borja-Tabora, Charissa; Li, Ping; Durviaux, Serge; Fries, Louis; Dubin, Gary; Breuer, Thomas; Innis, Bruce L.; Vaughn, David W.

    2014-01-01

    Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. PMID:24652494

  9. The pathogenecity of H5N1 highly pathogenic Avian Influenza (HPAI virus clade 2.3.2. in Indonesian indigenous chicken by contact tranmission with infected duck

    Directory of Open Access Journals (Sweden)

    R. Damayanti

    2017-05-01

    Full Text Available An experimental transmission study was conducted using nine healthy Indonesian indigenous chickens placed together with two 30 days old ducks which were experimentally infected with H5N1 HPAI clade 2.3.2 virus in the Biosafety Laboratory Level 3 (BSL-3 facilities. The aim of the study was to find out the pathogenicity of H5N1 HPAI virus clade 2.3.2 in Indonesian indigenous chickens. The study showed that within twenty four hours rearing, the chickens were exhibited mild clinical signs and by 48 hours, all of the chickens died, whereas the ducks survived but with severe clinical signs. The H5N1 HPAI virus has been successfully isolated from chickens and ducks swabs, confirming that those animals were infected by the virus. Histologically, the infected chicken encountered with severe inflammation reaction namely non suppuratives encephalitis, tracheitis, myocarditis, interstitial pneumonia, hepatitis, proventriculitis, enteritis, pancreatitis, nephritis and bursitis. Necrotizing spleen and pancreas were also prominent. Viral antigen was detected by immunohistochemistry staining in various affected visceral organs. This suggests that Indonesian indigenous chickens were susceptible to H5N1 HPAI virus clade 2.3.2 and it can be transmitted easily to Indonesian indigenous chickens by contact transmission with infected ducks.

  10. Emergence of influenza A (H1N1) PDM09 in the remote Islands of India--a molecular approach.

    Science.gov (United States)

    Muruganandam, N; Bhattacharya, D; Chaaithanya, I K; Bhattacharya, H; Reesu, R; Maile, A; Bharathi, G S J; Sugunan, A P; Vijayachari, P

    2015-01-01

    A disease outbreak of A (H1N1) PDM09 was reported in Andaman and Nicobar islands in 2009 with an attack rate of 33.5% among settler population and 26.3% among the aboriginal Nicobarese tribe. During the ongoing outbreak of A (H1N1) PDM09 disease in different parts of the world, a subject working in Dubai city of Saudi Arabia, came to Port Blair, following which the pandemic triggered for the first time in these Islands. During the period August 2009 to January 2011, 30 confirmed cases of Influenza A (H1N1) PDM09 virus infection was detected. To understand the genetic relationship, the NA gene sequences of the viruses were phylogenetically analysed together along with the virus sequence isolated from other parts of the world. Formation of multiple clusters were observed, with the sequences of Andaman Islands, mainland India, Mexico, Saudi Arabia and few other counties clustering together. The sequence analysis data revealed that there was no specific mutation conferring resistance to oseltamivir among the Andaman A (H1N1) PDM09 virus isolates. The result of phylogenetic analysis have also revealed that the A (H1N1) PDM09 virus might have spread in these remote Islands of India via the subject from Saudi Arabia/Dubai. A (H1N1) PDM09 Influenza outbreak have highlighted the need to strengthen the region-specific pandemic preparedness plans and surveillance strategies.

  11. Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States.

    Science.gov (United States)

    Vincent, Amy L; Ma, Wenjun; Lager, Kelly M; Gramer, Marie R; Richt, Juergen A; Janke, Bruce H

    2009-10-01

    H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.

  12. Generation, characterization and epitope mapping of two neutralizing and protective human recombinant antibodies against influenza A H5N1 viruses.

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    Lina Sun

    Full Text Available BACKGROUND: The development of new therapeutic targets and strategies to control highly pathogenic avian influenza (HPAI H5N1 virus infection in humans is urgently needed. Broadly cross-neutralizing recombinant human antibodies obtained from the survivors of H5N1 avian influenza provide an important role in immunotherapy for human H5N1 virus infection and definition of the critical epitopes for vaccine development. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized two recombinant baculovirus-expressed human antibodies (rhAbs, AVFluIgG01 and AVFluIgG03, generated by screening a Fab antibody phage library derived from a patient recovered from infection with a highly pathogenic avian influenza A H5N1 clade 2.3 virus. AVFluIgG01 cross-neutralized the most of clade 0, clade 1, and clade 2 viruses tested, in contrast, AVFluIgG03 only neutralized clade 2 viruses. Passive immunization of mice with either AVFluIgG01 or AVFluIgG03 antibody resulted in protection from a lethal H5N1 clade 2.3 virus infection. Furthermore, through epitope mapping, we identify two distinct epitopes on H5 HA molecule recognized by these rhAbs and demonstrate their potential to protect against a lethal H5N1 virus infection in a mouse model. CONCLUSIONS/SIGNIFICANCE: Importantly, localization of the epitopes recognized by these two neutralizing and protective antibodies has provided, for the first time, insight into the human antibody responses to H5N1 viruses which contribute to the H5 immunity in the recovered patient. These results highlight the potential of a rhAbs treatment strategy for human H5N1 virus infection and provide new insight for the development of effective H5N1 pandemic vaccines.

  13. Maternal and neonatal outcomes among pregnant women with 2009 pandemic influenza A(H1N1 illness in Florida, 2009-2010: a population-based cohort study.

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    Timothy J Doyle

    Full Text Available Pregnant women have been identified as a high risk group for severe illness with 2009 pandemic influenza A(H1N1 virus infection (pH1N1. Obesity has also been identified as a risk factor for severe illness, though this has not been thoroughly assessed among pregnant women. The objectives of this study were to provide risk estimates for adverse maternal and neonatal outcomes associated with pH1N1 illness during pregnancy and to assess the role of obesity in these outcomes.We established a retrospective population-based cohort of all live births occurring in Florida during the first 15 months of the pandemic. Illness with pH1N1 during pregnancy was ascertained through record linkage with the Florida state notifiable disease surveillance database. Data from the birth record, including pre-pregnancy body mass index, were analyzed to assess risk of adverse outcomes associated with pH1N1 illness.A total of 194 women were identified through surveillance with pH1N1 illness during pregnancy. Children born to women with pH1N1 illness during pregnancy were at increased risk for low birth weight [OR (95%CI: 1.78 (1.11-2.860], premature birth [2.21 (1.47-3.330], and infant death [4.46 (1.80-11.00], after adjusting for other factors. Women with pH1N1 illness during pregnancy were at increased risk for severe outcomes including admission to an intensive care unit. Obesity was an observed risk factor, both for the more severe pH1N1 illness detected through surveillance, and for severe maternal outcomes.Case-patients in this analysis likely represent the most severely ill subset of all women infected with pH1N1 during pregnancy, limiting the generalizability of these findings to more severely ill patients rather than influenza infection in general. Nevertheless, these results suggest that more severe pH1N1 illness during pregnancy is associated with adverse neonatal outcomes and that pregnant women should continue to be targeted for appropriate prophylaxis and

  14. Community-based measures for mitigating the 2009 H1N1 pandemic in China.

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    Sanyi Tang

    Full Text Available Since the emergence of influenza A/H1N1 pandemic virus in March-April 2009, very stringent interventions including Fengxiao were implemented to prevent importation of infected cases and decelerate the disease spread in mainland China. The extent to which these measures have been effective remains elusive. We sought to investigate the effectiveness of Fengxiao that may inform policy decisions on improving community-based interventions for management of on-going outbreaks in China, in particular during the Spring Festival in mid-February 2010 when nationwide traveling will be substantially increased. We obtained data on initial laboratory-confirmed cases of H1N1 in the province of Shaanxi and used Markov-chain Monte-Carlo (MCMC simulations to estimate the reproduction number. Given the estimates for the exposed and infectious periods of the novel H1N1 virus, we estimated a mean reproduction number of 1.68 (95% CI 1.45-1.92 and other A/H1N1 epidemiological parameters. Our results based on a spatially stratified population dynamical model show that the early implementation of Fengxiao can delay the epidemic peak significantly and prevent the disease spread to the general population but may also, if not implemented appropriately, cause more severe outbreak within universities/colleges, while late implementation of Fengxiao can achieve nothing more than no implementation. Strengthening local control strategies (quarantine and hygiene precaution is much more effective in mitigating outbreaks and inhibiting the successive waves than implementing Fengxiao. Either strong mobility or high transport-related transmission rate during the Spring Festival holiday will not reverse the ongoing outbreak, but both will result in a large new wave. The findings suggest that Fengxiao and travel precautions should not be relaxed unless strict measures of quarantine, isolation, and hygiene precaution practices are put in place. Integration and prompt implementation of

  15. EARLY IDENTIFICATION OF SWINE INFLUENZA A (H1N1- BASING ONEPIDEMIOLOGIC CLUE, CLINICAL PRESENTATION, IMAGING FINDINGS, PERIPHERAL LEUCOCYTE COUNTS AND SPO2 LEVELS

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    Venkateswararao Kopparti

    2017-11-01

    Full Text Available BACKGROUND The present study is a retrospective study of 22 cases of RT-PCR positive swine influenza spanning from 2014 to 20-09-2017 with main objective of early identification of influenza A H1N1 basing on epidemiological clue, clinical presentation, imaging findings and lab parameters as early antiviral therapy and judicious management of ARDS brings good outcome as per available literature. 1,2,3 MATERIAL AND METHODS 22 confirmed adult cases of swine influenza by throat/nasopharyngeal swab RT-PCR for H1N1 were studied in terms of clinical presentation, imaging findings, lab manifestations and SpO2 levels4 with particular emphasis on imaging findings. RESULTS 95% presented with symptoms of Influenza-Like Illness (ILI. Nearly, 80% of patients belonged to fourth to fifth decades. Leucocyte count was normal in 75% and 25% had low leucocyte count (<4000, SpO2 levels were normal in 25% and low in 75% cases. CXR was abnormal in 82% of cases of which 83% had mid/lower zone peripheral, patchy, pleural-based consolidations and 17% showed all lung zone opacities. HRCT chest done in 32% of cases showed similar features of chest xray findings with dominant mid/lower zone pleural-based consolidations to ground-glass haziness without pleural effusions and no mediastinal nodal involvement. CONCLUSION As intermittent outbreaks of swine influenza are still continuing in India with recent spurt in incidence in the months of April/May 2017, early diagnosis of H1N1 A is necessary for improved outcome. Early diagnosis is feasible by ILI presentation, normal or low leucocyte count, low SpO2 levels and characteristic radiologic findings of bilateral mid/lower zone pleural-based peripheral patchy opacities to consolidations. As this can be done at peripheral level, primary care physicians need to be sensitised in early diagnosis and treatment and prompt referral to higher centres when needed. Since, the present study is a retrospective one and of public health

  16. Identifikasi Secara Serologi Galur Virus Flu Burung Subtipe H5N1 Clade 2.1.3 dan Clade 2.3.2 pada Ayam Petelur (SEROLOGICAL IDENTIFICATION OF AVIAN INFLUENZA STRAIN VIRUS SUBTYPE H5N1 CLADE 2.1.3 AND CLADE 2.3.2 FROM LAYER

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    Aprilia Kusumastuti

    2015-10-01

    Full Text Available The aim of the study was to know avian influenza (AI infection in field by using serology test in threemarketing area of AI vaccines. Haemagglutination inhibition methode was used in this test. There werefour antigen strains of AI subtype H5N1 clade 2.1.3 (AIstrainA/Chicken/West Java/PWT-WIJ/2006, AIstrain A/Chicken/Garut/BBVW-223/2007, AI strain A/Chicken/West Java-Nagrak/30/2007, and AI strainA/Chicken/Pekalongan/BBVW-208/2007 and 2 antigen strains of AI subtype H5N1 clade 2.3.2 (AI strainA/duck/Sukoharjo/BBVW-1428-9/2012 and AI strain A/duck/Sleman/BBVW-1463-10/2012 was used inthis study for HI test. The result presents that 93,33% chicken farms in three marketing area of PT. SanbioLaboratories have positive antibody titre to AI subtype H5N1 clade 2.1.3. This titre may be obtained fromAI clade 2.1.3 vaccination. From 15 samples, 92,86% are positive to AI subtype H5N1 clade 2.3.2A/duck/Sukoharjo/BBVW-1428-9/2012 and 92,31% are positive to A/duck/Sleman/BBVW-1463-10/2012 evenwithout AI clade 2.3.2 vaccination. This antibody titre may be obtained from AI clade 2.1.3 vaccine crossprotection or field infection.

  17. MDA5 can be exploited as efficacious genetic adjuvant for DNA vaccination against lethal H5N1 influenza virus infection in chickens.

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    Matthias Liniger

    Full Text Available Chickens lack the retinoic acid-inducible gene I (RIG-I and sense avian influenza virus (AIV infections by means of the melanoma differentiation-associated gene 5 product (chMDA5. Plasmid-driven expression of the N-terminal half of chMDA5 containing the caspase activation and recruitment domains [chMDA5(1-483] triggers interferon-β responses in chicken cells. We hypothesized that mimicking virus infection by chMDA5(1-483 expression may enhance vaccine-induced adaptive immunity. In order to test this, the potential genetic adjuvant properties of chMDA5(1-483 were evaluated in vivo in combination with a suboptimal quantity of a plasmid DNA vaccine expressing haemagglutinin (HA of H5N1 AIV. Co-administration of the HA plasmid with plasmid DNA for chMDA5(1-483 expression resulted in approximately 10-fold higher HA-specific antibody responses than injection of the HA plasmid mixed with empty vector DNA as control. Accordingly, compared with HA DNA vaccination alone, the chMDA5(1-483-adjuvanted HA DNA vaccine mediated enhanced protection against a lethal H5N1 challenge infection in chickens, with reduced clinical signs and cloacal virus shedding. These data demonstrate that innate immune activation by expression of signaling domains of RIG-I-like receptors can be exploited to enhance vaccine efficacy.

  18. Molecular diagnosis of microbial copathogens with influenza A(H1N1pdm09 in Oaxaca, Mexico

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    Ramírez-Palacios LR

    2018-04-01

    Full Text Available Luis Román Ramírez-Palacios,1 Diana Reséndez-Pérez,2 Maria Cristina Rodríguez-Padilla,2 Santiago Saavedra-Alonso,2 Olga Real-Najarro,3 Nadia A Fernández-Santos,4 Mario A Rodriguez Perez4 1Laboratorio Estatal de Salud Pública de Oaxaca, Oaxaca, 2Departamento de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico; 3Consejería de Educación, Madrid, Spain; 4Instituto Politécnico Nacional (IPN, Centro de Biotecnología Genómica, Reynosa, Mexico Background: Multiple factors have been associated with the severity of infection by influenza A(H1N1pdm09. These include H1N1 cases with proven coinfections showing clinical association with bacterial contagions. Purpose: The objective was to identify H1N1 and copathogens in the Oaxaca (Mexico population. A cross-sectional survey was conducted from 2009 to 2012. A total of 88 study patients with confirmed H1N1 by quantitative RT-PCR were recruited. Methods: Total nucleic acid from clinical samples of study patients was analyzed using a TessArray RPM-Flu microarray assay to identify other respiratory pathogens. Results: High prevalence of copathogens (77.3%; 68 patients harbored one to three pathogens, predominantly from Streptococcus, Haemophilus, Neisseria, and Pseudomonas, were detected. Three patients (3.4% had four or five respiratory copathogens, whereas others (19.3% had no copathogens. Copathogenic occurrence with Staphylococcus aureus was 5.7%, Coxsackie virus 2.3%, Moraxella catarrhalis 1.1%, Klebsiella pneumoniae 1.1%, and parainfluenza virus 3 1.1%. The number of patients with copathogens was four times higher to those with H1N1 alone (80.68% and 19.32%, respectively. Four individuals (4.5%; two males, one female, and one infant who died due to H1N1 were observed to have harbored such copathogens as Streptococcus, Staphylococcus, Haemophilus, and Neisseria. Conclusion: In summary, copathogens were found in a

  19. Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015.

    Science.gov (United States)

    Bi, Yuhai; Zhang, Zhenjie; Liu, Wenjun; Yin, Yanbo; Hong, Jianmin; Li, Xiangdong; Wang, Haiming; Wong, Gary; Chen, Jianjun; Li, Yunfeng; Ru, Wendong; Gao, Ruyi; Liu, Di; Liu, Yingxia; Zhou, Boping; Gao, George F; Shi, Weifeng; Lei, Fumin

    2015-08-11

    Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.3.2.1c HA gene and a H9N2-derived PB2 gene. Sanmenxia Clade 2.3.2.1c-like H5N1 viruses possess the closest genetic identity to A/Alberta/01/2014 (H5N1), which recently caused a fatal respiratory infection in Canada with signs of meningoencephalitis, a highly unusual symptom with influenza infections in humans. Furthermore, this virus was shown to be highly pathogenic to both birds and mammals, and demonstrate tropism for the nervous system. Due to the geographical location of Sanmenxia, these novel H5N1 viruses also have the potential to be imported to other regions through the migration of wild birds, similar to the H5N1 outbreak amongst migratory birds in Qinghai Lake during 2005. Therefore, further investigation and monitoring is required to prevent this novel reassortant virus from becoming a new threat to public health.

  20. Epidemiological assessment of influenza (H1N1- A in patients hospitalized in Tohid hospital in Sanandaj, Iran during 2013-2014

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    Houshiyar Ghafouri

    2016-12-01

    Full Text Available Background: Influenza is an acute respiratory infection caused by influenza virus which is highly contagious and spread easily. Objectives: The aim of this study was to evaluate the epidemiology of influenza (H1N1 type A in patients admitted to Tohid hospital, Sanandaj, Iran during 2013-2014. Material and Methods: This study was descriptive. Data were collected using a questionnaire which was designed based on study goals. The questionnaires were completed via interview, observation and performing clinical tests. After clinical confirmation of influenza by a specialist, genotype was determined by PCR. Results: Of the total 76 cases, 36 cases (48.6% were male, mean age was 42.7 ± 16.3 and 13.5% were rural and 86.5 were urban dwellers. 52 patient (70.3% were hospitalized and 22 (29.7% were outpatients. Travel history was including, abroad 9.5%, domestic 16.2% and without traveling 75.3%. The average time between referring to the doctor and sampling for H1N1 was 2.7 days. The prevalence of influenza (H1N1 A was 1.4%. Conclusion: The low incidence of H1N1 influenza type A in this study was probably due to travel to infected areas. Considering virus mutation, the readiness of health services to prevent an epidemic of this disease is essential and recommended.

  1. High Level Antibody Response to Pandemic Influenza H1N1/09 Virus Is Associated With Interferon-Induced Transmembrane Protein-3 rs12252-CC in Young Adults

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    Ling Qin

    2018-05-01

    Full Text Available Background: The C allele of the interferon-induced transmembrane protein-3 (IFITM3 SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%, severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections.Cohort and Method: A total 99 young healthy volunteers (18–20 years were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2, A/California/7/2009 (pdm09H1N1 and B/Jeep/3073/2013-like virus (Flu-B]. Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination. Additionally, 68 elderlies (>65 years were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly. For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point.Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1 but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination. No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed. In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes. Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers.Conclusion:IFITM3-rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the

  2. Pneumococcal Pneumonia and Pandemic H1N1

    Centers for Disease Control (CDC) Podcasts

    2012-06-06

    Dr. George Nelson, a CDC medical officer, discusses the relationship between pneumococcal pneumonia and Pandemic H1N1.  Created: 6/6/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/6/2012.

  3. Differential host determinants contribute to the pathogenesis of 2009 pandemic H1N1 and human H5N1 influenza A viruses in experimental mouse models.

    Science.gov (United States)

    Otte, Anna; Sauter, Martina; Alleva, Lisa; Baumgarte, Sigrid; Klingel, Karin; Gabriel, Gülsah

    2011-07-01

    Influenza viruses are responsible for high morbidities in humans and may, eventually, cause pandemics. Herein, we compared the pathogenesis and host innate immune responses of a seasonal H1N1, two 2009 pandemic H1N1, and a human H5N1 influenza virus in experimental BALB/c and C57BL/6J mouse models. We found that both 2009 pandemic H1N1 isolates studied (A/Hamburg/05/09 and A/Hamburg/NY1580/09) were low pathogenic in BALB/c mice [log mouse lethal dose 50 (MLD(50)) >6 plaque-forming units (PFU)] but displayed remarkable differences in virulence in C57BL/6J mice. A/Hamburg/NY1580/09 was more virulent (logMLD(50) = 3.5 PFU) than A/Hamburg/05/09 (logMLD(50) = 5.2 PFU) in C57BL/6J mice. In contrast, the H5N1 influenza virus was more virulent in BALB/c mice (logMLD(50) = 0.3 PFU) than in C57BL/6J mice (logMLD(50) = 1.8 PFU). Seasonal H1N1 influenza revealed marginal pathogenicity in BALB/c or C57BL/6J mice (logMLD(50) >6 PFU). Enhanced susceptibility of C57BL/6J mice to pandemic H1N1 correlated with a depressed cytokine response. In contrast, enhanced H5N1 virulence in BALB/c mice correlated with an elevated proinflammatory cytokine response. These findings highlight that host determinants responsible for the pathogenesis of 2009 pandemic H1N1 influenza viruses are different from those contributing to H5N1 pathogenesis. Our results show, for the first time to our knowledge, that the C57BL/6J mouse strain is more appropriate for the evaluation and identification of intrinsic pathogenicity markers of 2009 pandemic H1N1 influenza viruses that are "masked" in BALB/c mice. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Immune protection induced on day 10 following administration of the 2009 A/H1N1 pandemic influenza vaccine.

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    Yizhuo Sun

    Full Text Available BACKGROUND: The 2009 swine-origin influenza virus (S-OIV H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. METHODOLOGY/PRINCIPAL FINDINGS: 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose. The sera were collected before Day 0 (pre-vaccination and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI assay and enzyme-linked immunosorbent assay (ELISA. After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%. This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21. However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1 more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2. The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21 than that in Group 2 (geometric mean titer: 70 on Day 21. CONCLUSIONS/SIGNIFICANCE: Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a

  5. Risk factors and immunity in a nationally representative population following the 2009 influenza A(H1N1 pandemic.

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    Don Bandaranayake

    Full Text Available BACKGROUND: Understanding immunity, incidence and risk factors of the 2009 influenza A(H1N1 pandemic (2009 H1N1 through a national seroprevalence study is necessary for informing public health interventions and disease modelling. METHODS AND FINDINGS: We collected 1687 serum samples and individual risk factor data between November-2009 to March-2010, three months after the end of the 2009 H1N1 wave in New Zealand. Participants were randomly sampled from selected general practices countrywide and hospitals in the Auckland region. Baseline immunity was measured from 521 sera collected during 2004 to April-2009. Haemagglutination inhibition (HI antibody titres of ≥1:40 against 2009 H1N1 were considered seroprotective as well as seropositive. The overall community seroprevalence was 26.7% (CI:22.6-29.4. The seroprevalence varied across age and ethnicity. Children aged 5-19 years had the highest seroprevalence (46.7%;CI:38.3-55.0, a significant increase from the baseline (14%;CI:7.2-20.8. Older adults aged ≥60 had no significant difference in seroprevalence between the serosurvey (24.8%;CI:18.7-30.9 and baseline (22.6%;CI:15.3-30.0. Pacific peoples had the highest seroprevalence (49.5%;CI:35.1-64.0. There was no significant difference in seroprevalence between both primary (29.6%;CI:22.6-36.5 and secondary healthcare workers (25.3%;CI:20.8-29.8 and community participants. No significant regional variation was observed. Multivariate analysis indicated age as the most important risk factor followed by ethnicity. Previous seasonal influenza vaccination was associated with higher HI titres. Approximately 45.2% of seropositive individuals reported no symptoms. CONCLUSIONS: Based on age and ethnicity standardisation to the New Zealand Population, about 29.5% of New Zealanders had antibody titers at a level consistent with immunity to 2009 H1N1. Around 18.3% of New Zealanders were infected with the virus during the first wave including about one child

  6. Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1) virus in influenza-like illness patients in Peru.

    Science.gov (United States)

    Laguna-Torres, Victor Alberto; Gómez, Jorge; Aguilar, Patricia V; Ampuero, Julia S; Munayco, Cesar; Ocaña, Víctor; Pérez, Juan; Gamero, María E; Arrasco, Juan Carlos; Paz, Irmia; Chávez, Edward; Cruz, Rollin; Chavez, Jaime; Mendocilla, Silvia; Gomez, Elizabeth; Antigoni, Juana; Gonzalez, Sofía; Tejada, Cesar; Chowell, Gerardo; Kochel, Tadeusz J

    2010-07-27

    We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009. At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR). We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case. The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

  7. Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1 virus in influenza-like illness patients in Peru.

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    Victor Alberto Laguna-Torres

    Full Text Available BACKGROUND: We describe the temporal variation in viral agents detected in influenza like illness (ILI patients before and after the appearance of the ongoing pandemic influenza A (H1N1 (pH1N1 in Peru between 4-January and 13-July 2009. METHODS: At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR. RESULTS: We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5% from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle cities during our study period. The city of Iquitos (Jungle had the highest number of influenza B cases and only one pH1N1 case. CONCLUSIONS: The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

  8. Epidemiological characteristics of the influenza A(H1N1 2009 pandemic in the Western Pacific Region

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    Lisa McCallum

    2010-12-01

    Full Text Available The first laboratory-confirmed cases of infection with pandemic influenza A(H1N1 2009 in the Western Pacific Region were reported on 28 April 2009. By 11 June 2009, the day the pandemic was declared by the World Health Organization, nine Western Pacific Region countries and areas had reported laboratory-confirmed pandemic influenza A(H1N1 2009 cases. From April 2009 to July 2010, more than 250 000 cases and 1800 deaths from laboratory-confirmed pandemic influenza A(H1N1 2009 were reported from 34 countries and areas in the Region. By age group region-wide, 8.6%, 41.9%, 48.3%, and 1.2% of cases were in the < 5 years, 5–14 years, 15–64 years, and 65+ years age groups, respectively; the overall crude case fatality ratio in the Western Pacific Region was 0.5%. The pandemic demonstrated that region-wide disease reporting was possible. Countries and areas of the Western Pacific Region should take this opportunity to strengthen the systems established during the pandemic to develop routine disease reporting.

  9. H-1 chemical shift imaging characterization of human brain tumor and edema

    NARCIS (Netherlands)

    Sijens, PE; Oudkerk, M

    Longitudinal (T1) and transverse (T2) relaxation times of metabolites in human brain tumor, peritumoral edema, and unaffected brain tissue were assessed from point resolved spectroscopy (PRESS) H-1 chemical shift imaging results at different repetition times (TR = 1500 and 5000 ms; T1: n = 19) and

  10. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: summary of an ecological study.

    Science.gov (United States)

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2013-09-01

    When the influenza A (H1N1) pandemic spread across the globe from April 2009 to August 2010, many WHO Member States used antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Antivirals have been found to be effective in reducing severity and duration of influenza illness, and likely reduce morbidity; however, it is unclear whether NAIs used during the pandemic reduced H1N1 mortality. To assess the association between antivirals and influenza mortality, at an ecologic level, country-level data on supply of oseltamivir and zanamivir were compared to laboratory-confirmed H1N1 deaths (per 100 000 people) from July 2009 to August 2010 in 42 WHO Member States. From this analysis, it was found that each 10% increase in kilograms of oseltamivir, per 100 000 people, was associated with a 1·6% reduction in H1N1 mortality over the pandemic period [relative rate (RR) = 0·84 per log increase in oseltamivir supply]. Each 10% increase in kilogram of active zanamivir, per 100 000, was associated with a 0·3% reduction in H1N1 mortality (RR = 0·97 per log increase). While limitations exist in the inference that can be drawn from an ecologic evaluation, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. This article summarises the original study described previously, which can be accessed through the following citation: Miller PE, Rambachan A, Hubbard RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An Ecological Study. PLoS ONE 7(9): e43491. © 2013 Blackwell Publishing Ltd.

  11. Serological evidence for avian H9N2 influenza virus infections among Romanian agriculture workers.

    Science.gov (United States)

    Coman, Alexandru; Maftei, Daniel N; Krueger, Whitney S; Heil, Gary L; Friary, John A; Chereches, Razvan M; Sirlincan, Emanuela; Bria, Paul; Dragnea, Claudiu; Kasler, Iosif; Gray, Gregory C

    2013-12-01

    In recent years, wild birds have introduced multiple highly pathogenic avian influenza (HPAI) H5N1 virus infections in Romanian poultry. In 2005 HPAI infections were widespread among domestic poultry and anecdotal reports suggested domestic pigs may also have been exposed. We sought to examine evidence for zoonotic influenza infections among Romanian agriculture workers. Between 2009 and 2010, 363 adult participants were enrolled in a cross-sectional, seroepidemiological study. Confined animal feeding operation (CAFO) swine workers in Tulcea and small, traditional backyard farmers in Cluj-Napoca were enrolled, as well as a non-animal exposed control group from Cluj-Napoca. Enrollment sera were examined for serological evidence of previous infection with 9 avian and 3 human influenza virus strains. Serologic assays showed no evidence of previous infection with 7 low pathogenic avian influenza viruses or with HPAI H5N1. However, 33 participants (9.1%) had elevated microneutralization antibody titers against avian-like A/Hong Kong/1073/1999(H9N2), 5 with titers ≥ 1:80 whom all reported exposure to poultry. Moderate poultry exposure was significantly associated with elevated titers after controlling for the subjects' age (adjusted OR = 3.6; 95% CI, 1.1-12.1). There was no evidence that previous infection with human H3N2 or H2N2 viruses were confounding the H9N2 seroreactivity. These data suggest that H9N2 virus may have circulated in Romanian poultry and occasionally infected man. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  12. Novel pandemic influenza A(H1N1 viruses are potently inhibited by DAS181, a sialidase fusion protein.

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    Gallen B Triana-Baltzer

    2009-11-01

    Full Text Available The recent emergence of a novel pandemic influenza A(H1N1 strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV. Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1. Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1 viruses.The activity of DAS181 against several pandemic influenza A(H1N1 virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1 strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1 strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus.The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1 viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y, DAS181 may be active against the antigenically novel pandemic influenza A(H1N1 virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for

  13. Human influenza A (H5N1): a brief review and recommendations for travelers.

    Science.gov (United States)

    Hurtado, Timothy R

    2006-01-01

    Although avian influenza A (H5N1) is common in birds worldwide, it has only recently led to disease in humans. Humans who are infected with the disease (referred to as human influenza A [H5N1]) have a greater than 50% mortality rate. Currently there has not been documented sustained human-to-human transmission; however, should the virus mutate and make this possible, the world could experience an influenza pandemic. Probable risk factors for infection include slaughtering, defeathering, and butchering fowl; close contact with wild birds or caged poultry; ingestion of undercooked poultry products; direct contact with surfaces contaminated with poultry feces; and close contact with infected humans. Possible risk factors include swimming in or ingesting water contaminated with bird feces or dead birds and the use of unprocessed poultry feces as fertilizer. Clinically, early human influenza A (H5N1) resembles typical influenza illnesses, with fever and a preponderance of lower respiratory tract symptoms. Often, patients develop rapidly progressive respiratory failure and require ventilatory support. Treatment is primarily supportive care with the addition of antiviral medications. Currently, travelers to countries with both human and avian influenza A (H5N1) have a low risk of developing the disease. There are no current recommended travel restrictions. Travelers are advised to avoid contact with all birds, especially poultry; avoid surfaces contaminated with poultry feces; and avoid undercooked poultry products. The use of prophylactic antiviral medications is not recommended.

  14. Spread of H1N1 within Households

    Centers for Disease Control (CDC) Podcasts

    This podcast describes an investigation into how H1N1 was spreading within households during the initial days of the pandemic in Texas. CDC's Dr. Oliver Morgan discusses what investigators learned about the role that children played in introducing the virus into households and spreading flu.

  15. Churg-Strauss Syndrome Following Vaccination Against 2010 Influenza A (H1N1): A Case Report.

    Science.gov (United States)

    Fu, Mu-Hui; Tsai, Wan-Chen; Lan, Jui; Lu, Cheng-Hsien; Lee, Lian-Hui; Huang, Chih-Cheng

    2014-09-01

    Churg-Strauss syndrome (CSS) is a systemic inflammatory disorder characterized by asthma, transient pulmonary infiltration, hyper-eosinophilia, and systemic vasculitis. Reported triggering factors include infections, drugs, allergic desensitization, and vaccinations, although cases involving the latter two are extremely rare. Herein, we describe a patient who developed CSS after receiving an H1N1 vaccination. A 55-year-old woman presented with fever, skin eruptions, and sensory impairment of her feet within one week after an H1N1 vaccine injection. A chest X-ray showed pulmonary infiltrations in both lower lung fields. Eosinophilia was noted in a hematological test, and an electrophysiological study revealed a pattern of mononeuritis multiplex. A skin biopsy was performed which revealed palisading necrotizing granuloma around a degenerated dermis and eosinophilic infiltration of the blood vessel walls. These findings combined with the hematological and electrophysiological findings met the criteria of CSS according to the American College of Rheumatology. The patient recovered well after steroid treatment. This case highlights the possibility that the H1N1 vaccination can trigger CSS. Due to the rarity of reported autoimmune events after vaccine administration and the obscure causal association between autoimmunity and a vaccine, further post-marketing surveillance and research are necessary to clarify the relationship and identify risk factors.

  16. Influenza A/H1N1/2009 virus - experience of the clinical microbiology laboratory of the “L. Sacco” University Hospital in Milan

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    Lisa Lucia Chenal

    2011-06-01

    Full Text Available In the spring of 2009, a new variant of influenza A/H1N1 virus that had never been isolated before, was identified. From April 27 to December 31, 2009 the respiratory samples of 974 patients, obtained from suspected cases of pandemic influenza A virus infection, were analyzed at the Clinical Microbiology Laboratory of the “L. Sacco” University Hospital in Milan. The diagnosis of influenza A/H1N1 infection was performed initially through the use of different molecular biological methods: Seeplex® RV12 ACE Detection (Seegene, NUCLISENS® EASYQ® INFLUENZA A/B (bioMérieux, Influenza A/B Q-PCR Alert (Nanogen running in parallel with rRT-PCR (CDC to confirm the positivity to the new influenza virus, then was used a single specific test, Fast set H1N1v (Arrow Diagnostics. Retrospective study of data showed that 293 (30.1% patients were positive for the new strain of influenza A/H1N1 virus and 8 (0.8% for influenza A other than H1N1 virus.The distribution of influenza A/H1N1 cases showed two peaks, one on July (62.9% and the other one on October (36%, moreover we observed that 155 patients (53% out of 293 positive for influenza A/H1N1 virus aged under 20 years old. The first positivity peak was found in travelers and the second one, occurred 2-3 months prior to the classic seasonal epidemic influenza, was attributed to autochthonous cases , by which the virus had spread worldwide. The highest proportion of cases were among subjects aged from 0 to 20 years and, over this age the positivity rate decreased proportionally with increasing age, in agreement with data reported in other countries.

  17. Emergence of influenza A (H1N1 PDM09 in the remote Islands of India - A molecular approach

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    N Muruganandam

    2015-01-01

    Full Text Available Background: A disease outbreak of A (H1N1 PDM09 was reported in Andaman and Nicobar islands in 2009 with an attack rate of 33.5% among settler population and 26.3% among the aboriginal Nicobarese tribe. During the ongoing outbreak of A (H1N1 PDM09 disease in different parts of the world, a subject working in Dubai city of Saudi Arabia, came to Port Blair, following which the pandemic triggered for the first time in these Islands. Materials and Methods: During the period August 2009 to January 2011, 30 confirmed cases of Influenza A (H1N1 PDM09 virus infection was detected. To understand the genetic relationship, the NA gene sequences of the viruses were phylogenetically analysed together along with the virus sequence isolated from other parts of the world. Result: Formation of multiple clusters were observed, with the sequences of Andaman Islands, mainland India, Mexico, Saudi Arabia and few other counties clustering together. The sequence analysis data revealed that there was no specific mutation conferring resistance to oseltamivir among the Andaman A (H1N1 PDM09 virus isolates. The result of phylogenetic analysis have also revealed that the A (H1N1 PDM09 virus might have spread in these remote Islands of India via the subject from Saudi Arabia/Dubai. Conclusion: A (H1N1 PDM09 Influenza outbreak have highlighted the need to strengthen the region-specific pandemic preparedness plans and surveillance strategies.

  18. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo.

    Science.gov (United States)

    Chan, Michael C W; Kuok, Denise I T; Leung, Connie Y H; Hui, Kenrie P Y; Valkenburg, Sophie A; Lau, Eric H Y; Nicholls, John M; Fang, Xiaohui; Guan, Yi; Lee, Jae W; Chan, Renee W Y; Webster, Robert G; Matthay, Michael A; Peiris, J S Malik

    2016-03-29

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

  19. Unique Infectious Strategy of H5N1 Avian Influenza Virus Is Governed by the Acid-Destabilized Property of Hemagglutinin.

    Science.gov (United States)

    Daidoji, Tomo; Watanabe, Yohei; Arai, Yasuha; Kajikawa, Junichi; Hirose, Ryohei; Nakaya, Takaaki

    Highly pathogenic avian influenza (HPAI) H5N1 virus emerged in 1997 as a zoonotic disease in Hong Kong. It has since spread to Asia and Europe and is a serious threat to both the poultry industry and human health. For effective surveillance and possible prevention/control of HPAI H5N1 viruses, it is necessary to understand the molecular mechanism underlying HPAI H5N1 pathogenesis. The hemagglutinin (HA) protein of influenza A viruses (IAVs) is one of the major determinants of host adaptation, transmissibility, and viral virulence. The main function of the HA protein is to facilitate viral entry and viral genome release within host cells before infection. To achieve viral infection, IAVs belonging to different subtypes or strains induce viral-cell membrane fusion at different endosomal pH levels after internalization through endocytosis. However, host-specific endosomal pH also affects induction of membrane fusion followed by infection. The HA protein of HPAI H5N1 has a higher pH threshold for membrane fusion than the HA protein of classical avian influenza viruses. Although this particular property of HA (which governs viral infection) is prone to deactivation in the avian intestine or in an ambient environment, it facilitates efficient infection of host cells, resulting in a broad host tropism, regardless of the pH in the host endosome. Accumulated knowledge, together with further research, about the HA-governed mechanism underlying HPAI H5N1 virulence (i.e., receptor tropism and pH-dependent viral-cell membrane fusion) will be helpful for developing effective surveillance strategies and for prevention/control of HPAI H5N1 infection.

  20. Immune influence of pregnancy on human H7N9 infection: a case report

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    G. Cui

    2015-05-01

    Full Text Available Introduction: H7N9 infection has raised serious concerns worldwide. Pregnant women were considered to be at a high risk of influenza infection. Normal pregnancy was dependent on T helper (Th 2 deviation. However, whether pregnancy influences the immune status of influenza H7N9 patients has not been reported. Case report: Here, we reported a case of pregnant woman in the first trimester with H7N9 infection compared with the two non-pregnant female H7N9 patients for clinical features and relevant immunological changes. We found that there were no differences in plasma levels of Th1 and Th2 cytokines between the pregnant and non-pregnant patients, and there was no Th2 deviation in the acute phase. However, the Th2 deviation was recurrent along with the clearance of infection in the H7N9 pregnant patient. Conclusion: These cases highlighted that the pregnant patient infected with H7N9 could induce an effective Th1 immune response equal to that of non-pregnant patients with H7N9 virus infection, although the pregnancy itself could lead to a Th2 deviation. These data suggested that pregnant patients could acquire a similar antiviral response for H7N9 infection versus non-pregnant patients. Keywords: Influenza, H7N9, Pregnancy, Immunologic characteristics, Cytokines

  1. Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

    Science.gov (United States)

    Meijer, Adam; Swaan, Corien M; Voerknecht, Martin; Jusic, Edin; van den Brink, Sharon; Wijsman, Lisa A; Voordouw, Bettie Cg; Donker, Gé A; Sleven, Jacqueline; Dorigo-Zetsma, Wendelien W; Svraka, Sanela; van Boven, Michiel; Haverkate, Manon R; Timen, Aura; van Dissel, Jaap T; Koopmans, Marion Pg; Bestebroer, Theo M; Fouchier, Ron Am

    2018-04-01

    A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general practitioner participating in the routine sentinel surveillance of ILI in the Netherlands. The patient recovered fully. Further epidemiological and virological investigation did not reveal additional cases.

  2. Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico

    Science.gov (United States)

    Comas‐García, Andreu; García‐Sepúlveda, Christian A.; Méndez‐de Lira, José J.; Aranda‐Romo, Saray; Hernández‐Salinas, Alba E.; Noyola, Daniel E.

    2010-01-01

    Please cite this paper as: Comas‐García et al. (2011) Mortality attributable to pandemic influenza A (H1N1) 2009 in San Luis Potosí, Mexico. Influenza and Other Respiratory Viruses 5(2), 76–82. Background  Acute respiratory infections are a leading cause of morbidity and mortality worldwide. Starting in 2009, pandemic influenza A(H1N1) 2009 virus has become one of the leading respiratory pathogens worldwide. However, the overall impact of this virus as a cause of mortality has not been clearly defined. Objectives  To determine the impact of pandemic influenza A(H1N1) 2009 on mortality in a Mexican population. Methods  We assessed the impact of pandemic influenza virus on mortality during the first and second outbreaks in San Luis Potosí, Mexico, and compared it to mortality associated with seasonal influenza and respiratory syncytial virus (RSV) during the previous winter seasons. Results  We estimated that, on average, 8·1% of all deaths that occurred during the 2003–2009 seasons were attributable to influenza and RSV. During the first pandemic influenza A(H1N1) 2009 outbreak, there was an increase in mortality in persons 5–59 years of age, but not during the second outbreak (Fall of 2009). Overall, pandemic influenza A (H1N1) 2009 outbreaks had similar effects on mortality to those associated with seasonal influenza virus epidemics. Conclusions  The impact of influenza A(H1N1) 2009 virus on mortality during the first year of the pandemic was similar to that observed for seasonal influenza. The establishment of real‐time surveillance systems capable of integrating virological, morbidity, and mortality data may result in the timely identification of outbreaks so as to allow for the institution of appropriate control measures to reduce the impact of emerging pathogens on the population. PMID:21306570

  3. Pathogenesis of infection with 2009 pandemic H1N1 influenza virus in isogenic guinea pigs after intranasal or intratracheal inoculation.

    Science.gov (United States)

    Wiersma, Lidewij C M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; van Run, Peter; Nieuwkoop, Nella J; Ladwig, Mechtild; Banneke, Stefanie; Schaefer, Hubert; Kuiken, Thijs; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2015-03-01

    To elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. To investigate protective immune responses, the use of inbred mouse strains has proven invaluable. Here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. Strain 2 isogenic guinea pigs were inoculated with H1N1pdm09 influenza virus A/Netherlands/602/09 by the intranasal or intratracheal route. Viral replication kinetics were assessed by determining virus titers in nasal swabs and respiratory tissues, which were also used to assess histopathologic changes and the number of infected cells. In all guinea pigs, virus titers peaked in nasal secretions at day 2 after inoculation. Intranasal inoculation resulted in higher virus excretion via the nose and higher virus titers in the nasal turbinates than intratracheal inoculation. After intranasal inoculation, infectious virus was recovered only from nasal epithelium; after intratracheal inoculation, it was recovered also from trachea, lung, and cerebrum. Histopathologic changes corresponded with virus antigen distribution, being largely limited to nasal epithelium for intranasally infected guinea pigs and more widespread in the respiratory tract for intratracheally infected guinea pigs. In summary, isogenic guinea pigs show promise as a model to investigate the role of humoral and cell-mediated immunities to influenza and their effect on virus transmission. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Divergent genetic evolution of hemagglutinin in influenza A H1N1 and A H1N2 subtypes isolated in the south-France since the winter of 2001-2002.

    Science.gov (United States)

    Al Faress, Shaker; Cartet, Gaëlle; Ferraris, Olivier; Norder, Helene; Valette, Martine; Lina, Bruno

    2005-07-01

    Influenza A viruses are divided into subtypes based on their hemagglutinin (H1 to H15) and neuraminidase (N1 to N9) glycoproteins. Of these, three A subtypes H1N1, H3N2 and H1N2 circulate in the human population. Influenza A viruses display a high antigenic variability called "antigenic drift" which allows the virus to escape antibody neutralization. Evaluate the mutations apparition that might predict a divergent antigenic evolution of hemagglutinin in influenza A H1N1 and A H1N2 viruses. During the three winters of 2001-2002 to 2003-2004, 58 A H1N1 and 23 A H1N2 subtypes have been isolated from patients with influenza-like illness in the south of France. The HA1 region was analyzed by RT-PCR and subsequently sequenced to compare the HA1 genetic evolution of influenza A H1N1 and A H1N2 subtypes. Our results showed that 28 amino acid substitutions have accumulated in the HA1 region since the circulation of A/New Caledonia/20/99-like viruses in France. Of these, fifteen were located in four antigenic sites (B, C, D and E). Six of them were observed only in the A H1N2 isolates, six only in the A H1N1 isolates and three in both subtypes. Furthermore, nine of twenty two A H1N2 isolates from the winter of 2002-2003 shared a T90A amino acid change which has not been observed in any A H1N1 isolate; resulting in the introduction of a new glycosylation site close to the antigenic site E. This might mask some antigenic E determinants and therefore, modify the A H1N2 antigenicity. The divergent genetic evolution of hemagglutinin may ultimately lead to a significant different antigenicity between A H1N1 and A H1N2 subtypes that would require the introduction of a new subtype in the vaccine batches.

  5. Caveolin-1 influences human influenza A virus (H1N1 multiplication in cell culture

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    Hemgård Gun-Viol

    2010-05-01

    Full Text Available Abstract Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1 as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1 strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1 virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK, a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.

  6. Seasonal influenza A/H3N2 virus infection and IL-1Β, IL-10, IL-17, and IL-28 polymorphisms in Iranian population.

    Science.gov (United States)

    Rogo, Lawal Dahiru; Rezaei, Farhad; Marashi, Seyed Mahdi; Yekaninejad, Mir Saeed; Naseri, Maryam; Ghavami, Nastaran; Mokhtari-Azad, Talat

    2016-12-01

    Increased blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A/H3N2 virus infection. The study was aimed to investigate the polymorphisms of IL-1β, IL-10, IL-17, and IL-28 genes to find the possibility of their association with the clinical outcome of influenza A/H3N2 virus infection among the infected patients in Iran. This is a Case-Control study in which influenza A/H3N2 virus positive confirmed with real-time PCR were the cases. DNA samples from groups were genotyped for polymorphisms in rs16944 (IL-1β), rs1800872 (IL-10), rs2275913 (IL-17), and rs8099917 (IL-28). Confidence interval (95%CI) and Odds ratio (OR) were calculated. IL-17 rs2275913 (GG and AG) were associated with risk of infection with that were statistically significant (P rs16944) (GG) was associated with reduced risk of infection (P < 0.01, OR = 0.46). Genotype GG and GT of IL-10 (rs1800872) were associated with increased risk of infection with influenza A/H3N2 virus (P < 0.05, OR = 2.04-2.58). In addition, IL-28 (rs8099917) genotypes GG (P < 0.05, OR = 0.49) and TG (P < 0.05, OR = 0.59) were associated with reduced risk of ILI symptom while genotype TT (P < 0.01, OR = 4.31) was associated with increased risk of ILI symptom. The results of this study demonstrated that polymorphisms of genes involved in the inflammatory and anti-inflammatory process affect the outcome of disease caused by influenza A/H3N2 virus. Thorough insight on host immune response at the time of influenza A virus infection is required to ensure adequate patient care in the case of feature outbreaks. J. Med. Virol. 88:2078-2084, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential

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    José Esteban Muñoz-Medina

    2015-01-01

    Full Text Available The unpredictable, evolutionary nature of the influenza A virus (IAV is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2 in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2 and in one of the main aviary subtypes responsible for zoonosis (H5N1. For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.

  8. Influenza A aviária (H5N1: a gripe do frango Avian influenza A (H5N1: the bird flu

    Directory of Open Access Journals (Sweden)

    Cássio da Cunha Ibiapina

    2005-10-01

    conducted using the Medline, MD Consult, HighWire, Medscape and Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS, Latin American and Caribbean Health Sciences Literature databases, as well as through direct research, limiting the scope to articles published within the past 10 years. We selected 31 original articles addressing the recent outbreaks of infection with the H5N1 subtype of avian influenza A in domesticated birds in Asia, which have resulted in significant economic losses and repercussions for public health, as well as some cases of human infection presenting high lethality. In most cases, infection has been associated with direct exposure to infected birds or contact with surfaces infected with bird excrement. However, cases of human-to-human transmission have been confirmed. In those cases, the incubation period varied from 2 to 4 days. The clinical manifestations range from asymptomatic infection to mild upper airway disease, pneumonia and multiple organ failure. Chest X-rays may reveal bilateral interstitial infiltrate, lobar collapse, focal consolidation and air bronchogram without pleural effusion. Lymphopenia is indicative of a poor prognosis. Supportive care appears to be the only acceptable treatment. Risk factors for poor prognosis include advanced age, delayed hospitalization, lower airway involvement, low white blood cell count or lymphopenia upon admission. Controlling outbreaks in domestic fowl and limiting contact between humans and infected birds must be the priorities in the management of this disease at the public health level. In addition, techniques and knowledge regarding the disease should be widely disseminated.

  9. Prediction of clinical factors associated with pandemic influenza A (H1N1 2009 in Pakistan.

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    Nadia Nisar

    Full Text Available BACKGROUND: Influenza is a viral infection that can lead to serious complications and death(s in vulnerable groups if not diagnosed and managed in a timely manner. This study was conducted to improve the accuracy of predicting influenza through various clinical and statistical models. METHODOLOGY: A retrospective cross sectional analysis was done on demographic and epidemiological data collected from March 2009 to March 2010. Patients were classified as ILI or SARI using WHO case definitions. Respiratory specimens were tested by RT-PCR. Clinical symptoms and co-morbid conditions were analyzed using binary logistic regression models. RESULTS: In the first approach, analysis compared children (≤12 and adults (>12. Of 1,243 cases, 262 (21% tested positive for A(H1N1pdm09 and the proportion of children (≤12 and adults (>12 were 27% and 73% respectively. Four symptoms predicted influenza in children: fever (OR 2.849, 95% CI 1.931-8.722, cough (OR 1.99, 95% CI 1.512-3.643, diarrhea (OR 2.100, 95% CI 2.040-3.25 and respiratory disease (OR 3.269, 95% CI 2.128-12.624. In adults, the strongest clinical predictor was fever (OR 2.80, 95% CI 1.025-3.135 followed by cough (OR 1.431, 95% CI 1.032-2.815. In the second instance, patients were separated into two groups: SARI 326 (26% and ILI 917 (74% cases. Male to female ratio was 1.41∶1.12 for SARI and 2∶1.5 for ILI cases. Chi-square test showed that fever, cough and sore throat were significant factors for A(H1N1pdm09 infections (p = 0.008. CONCLUSION: Studies in a primary care setting should be encouraged focused on patients with influenza-like illness to develop sensitive clinical case definition that will help to improve accuracy of detecting influenza infections. Formulation of a standard "one size fits all" case definition that best correlates with influenza infections can help guide decisions for additional diagnostic testing and also discourage unjustified antibiotic prescription and usage

  10. Contextualizing ethics: ventilators, H1N1 and marginalized populations.

    Science.gov (United States)

    Silva, Diego S; Nie, Jason X; Rossiter, Kate; Sahni, Sachin; Upshur, Ross E G

    2010-01-01

    If the H1N1 pandemic worsens, there may not be enough ventilated beds to care for all persons with respiratory failure. To date, researchers who explicitly discuss the ethics of intensive care unit admission and the allocation of ventilators during an influenza pandemic have based criteria predominantly on the principles of utility and efficiency, that is, promoting actions that maximize the greatest good for the greatest number of people. However, haphazardly applying utility and efficiency potentially disadvantages marginalized populations who might be at increased risk of severe reactions to H1N1. In Canada, Aboriginals represent 3% of Canadians, yet 11% of H1N1 cases requiring hospitalization involve Aboriginal persons. Aboriginal persons suffer from high rates of obesity due to socio-economic inequalities. Obesity is also a risk factor for severe H1N1 reactions. Yet, since obesity is found to increase the duration of stay in ventilated beds and a long stay is not considered an optimal use of ventilators, applying the principles of utility and efficiency may magnify existing social inequalities. Although promoting utility and efficiency is important, other ethical principles, such as equity and need, require thoughtful consideration and implementation. Furthermore, since public resources are being used to address a public health hazard, the viewpoints of the public, and specifically stakeholders who will be disproportionately affected, should inform decision-makers. Finally, giving attention to the needs and rights of marginalized populations means that ventilators should not be allocated based on criteria that exacerbate the social injustices faced by these groups of people.

  11. Incidence and Epidemiology of Hospitalized Influenza Cases in Rural Thailand during the Influenza A (H1N1)pdm09 Pandemic, 2009–2010

    Science.gov (United States)

    Baggett, Henry C.; Chittaganpitch, Malinee; Thamthitiwat, Somsak; Prapasiri, Prabda; Naorat, Sathapana; Sawatwong, Pongpun; Ditsungnoen, Darunee; Olsen, Sonja J.; Simmerman, James M.; Srisaengchai, Prasong; Chantra, Somrak; Peruski, Leonard F.; Sawanpanyalert, Pathom; Maloney, Susan A.; Akarasewi, Pasakorn

    2012-01-01

    Background Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009–2010. Methods We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1∶2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. Results Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged incidence of hospitalized influenza cases was 136 per 100,000, highest in ages 75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). Conclusions Influenza-associated hospitalization rates in Thailand during 2009–10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children. PMID:23139802

  12. IN VITRO INTERACTION OF INFLUENZA VIRUS A(H1N1pdm09 WITH MONOCYTIC MACROPHAGES: INDIVIDUAL RESPONSES OF TLR7 AND RIG1 RECEPTOR GENES

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    T. M. Sokolova

    2017-01-01

    Full Text Available In vitro differentiation of donor blood monocytes to macrophages (Mph following GM-CSF treatment was accompanied by a significant increase in the levels of gene transcription signaling receptors TLR7 or RIG1. The levels of intracellular viral RNA (M1 gene in Mph remained high upon infection by influenza virus A H1N1pdm (Moscow 2009 for 24-96 hours. The innate immunity reactions caused by influenza virus show individual features: they are decreased in Mph from donor 1 which had initially high level of endosomal TLR7 gene activity, and it increased by influenza virus in MPh from donor 2 who had a very low level of TLR7 gene expression. The influenza H1N1pdm virus weakly stimulated expression of gene RIG1 and production of inflammatory cytokines in Mf in donor 1. The differences may be connected with individual sensitivity of the donors to influenza infection.

  13. H1N1 Swine Influenza Viruses Differ from Avian Precursors by a Higher pH Optimum of Membrane Fusion.

    Science.gov (United States)

    Baumann, Jan; Kouassi, Nancy Mounogou; Foni, Emanuela; Klenk, Hans-Dieter; Matrosovich, Mikhail

    2016-02-01

    The H1N1 Eurasian avian-like swine (EAsw) influenza viruses originated from an avian H1N1 virus. To characterize potential changes in the membrane fusion activity of the hemagglutinin (HA) during avian-to-swine adaptation of the virus, we studied EAsw viruses isolated in the first years of their circulation in pigs and closely related contemporary H1N1 viruses of wild aquatic birds. Compared to the avian viruses, the swine viruses were less sensitive to neutralization by lysosomotropic agent NH4Cl in MDCK cells, had a higher pH optimum of hemolytic activity, and were less stable at acidic pH. Eight amino acid substitutions in the HA were found to separate the EAsw viruses from their putative avian precursor; four substitutions-T492S, N722D, R752K, and S1132F-were located in the structural regions of the HA2 subunit known to play a role in acid-induced conformational transition of the HA. We also studied low-pH-induced syncytium formation by cell-expressed HA proteins and found that the HAs of the 1918, 1957, 1968, and 2009 pandemic viruses required a lower pH for fusion induction than did the HA of a representative EAsw virus. Our data show that transmission of an avian H1N1 virus to pigs was accompanied by changes in conformational stability and fusion promotion activity of the HA. We conclude that distinctive host-determined fusion characteristics of the HA may represent a barrier for avian-to-swine and swine-to-human transmission of influenza viruses. Continuing cases of human infections with zoonotic influenza viruses highlight the necessity to understand which viral properties contribute to interspecies transmission. Efficient binding of the HA to cellular receptors in a new host species is known to be essential for the transmission. Less is known about required adaptive changes in the membrane fusion activity of the HA. Here we show that adaptation of an avian influenza virus to pigs in Europe in 1980s was accompanied by mutations in the HA, which decreased

  14. Rapid and highly informative diagnostic assay for H5N1 influenza viruses.

    Directory of Open Access Journals (Sweden)

    Nader Pourmand

    Full Text Available A highly discriminative and information-rich diagnostic assay for H5N1 avian influenza would meet immediate patient care needs and provide valuable information for public health interventions, e.g., tracking of new and more dangerous variants by geographic area as well as avian-to-human or human-to-human transmission. In the present study, we have designed a rapid assay based on multilocus nucleic acid sequencing that focuses on the biologically significant regions of the H5N1 hemagglutinin gene. This allows the prediction of viral strain, clade, receptor binding properties, low- or high-pathogenicity cleavage site and glycosylation status. H5 HA genes were selected from nine known high-pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in biologically significant regions of hemagglutinin and/or their ability to cause infection in humans. We devised a consensus pre-programmed pyrosequencing strategy, which may be used as a faster, more accurate alternative to de novo sequencing. The available data suggest that the assay described here is a reliable, rapid, information-rich and cost-effective approach for definitive diagnosis of H5N1 avian influenza. Knowledge of the predicted functional sequences of the HA will enhance H5N1 avian influenza surveillance efforts.

  15. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1 disease.

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    Oliver W Morgan

    Full Text Available BACKGROUND: Severe illness due to 2009 pandemic A(H1N1 infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1, independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP to increase the risk of influenza-related complications. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1 influenza occurring between April-July, 2009, with a cohort of the U.S. population estimated from the 2003-2006 National Health and Nutrition Examination Survey (NHANES; pregnant women and children or=20 year olds, hospitalization was associated with being morbidly obese (BMI>or=40 for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4-9.9 and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3-17.2. Among 2-19 year olds, hospitalization was associated with being underweight (BMIor=20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5-6.6 and morbid obesity (OR = 7.6, 95%CI 2.1-27.9. CONCLUSIONS/SIGNIFICANCE: Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination.

  16. Novel triple reassortant H1N2 influenza viruses bearing six internal genes of the pandemic 2009/H1N1 influenza virus were detected in pigs in China.

    Science.gov (United States)

    Qiao, Chuanling; Liu, Liping; Yang, Huanliang; Chen, Yan; Xu, Huiyang; Chen, Hualan

    2014-12-01

    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. Transmissions of the pandemic 2009/H1N1 virus from humans to poultry and other species of mammals were reported from several continents during the course of the 2009 H1N1 pandemic. Reassortant H1N1, H1N2, and H3N2 viruses containing genes of the pandemic 2009/H1N1 viruses appeared in pigs in some countries. In winter of 2012, a total of 2600 nasal swabs were collected from healthy pigs in slaughterhouses located throughout 10 provinces in China. The isolated viruses were subjected to genetic and antigenic analysis. Two novel triple-reassortant H1N2 influenza viruses were isolated from swine in China in 2012, with the HA gene derived from Eurasian avian-like swine H1N1, the NA gene from North American swine H1N2, and the six internal genes from the pandemic 2009/H1N1 viruses. The two viruses had similar antigenic features and some significant changes in antigenic characteristics emerged when compared to the previously identified isolates. We inferred that the novel reassortant viruses in China may have arisen from the accumulation of the three types of influenza viruses, which further indicates that swine herds serve as "mixing vessels" for influenza viruses. Influenza virus reassortment is an ongoing process, and our findings highlight the urgent need for continued influenza surveillance among swine herds. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Purification of neuraminidase from Influenza virus subtype H5N1

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    Simson Tariga

    2009-03-01

    Full Text Available Influenza-virus neuraminidase plays vital role in the survival of the organisms. Vaccination of animals with this glycoprotein confers immune responses so that enable it to protect the animals from incoming infection. Supplementation of conventional vaccines with this glycoprotein increases the protection and longevity of the vaccine. Purified neuraminidase can also be used to develop serological tests for differentiation of serologically positive animals due to infection or to vaccination. In this study purification of neuraminidase from influenza virus subtype H5N1 was described. Triton x-100 and Octyl β-D-glucopyranoside were used to extract and diluted the glycoprotein membrane. The enzymatic activity of the neuraminidase was assayed using a fluorochrome substrate, 4-methylumbelliferyl-a-D-N-acetyl neuraminic acid, which was found to be simple, sensitive and suitable for the purification purpose. The neuraminidase was absorbed selectively on an oxamic-acid agarose column. The purity of neuraminidase eluted from this affinity column was high. A higher purity of the neuraminidase was obtained by further separation with gel filtration on Superdex-200. The purified neuraminidase was enzymatically active and did not contain any detectable haemagglutinin, either by haemagglutination assay or by monospecific antibodies raised against H5N1 hemagglutinin. The purified neuraminidase was recognized strongly by antibodies raised against an internal but only weakly by that against C-terminal regions of the neuraminidase protein of H5N1-influenza virus. The purified neuraminidase was in tetrameric forms but dissociated into monomeric form on reducing condition, or mostly dimeric form on non-reducing SDS-PAGE.

  18. Differences in the detection of highly pathogenic avian influenza H5N1 virus in feather samples from 4-week-old and 24-week-old infected Pekin ducks (Anas platyrhynchos var. domestica).

    Science.gov (United States)

    Aiello, Roberta; Beato, Maria Serena; Mancin, Marzia; Rigoni, Michela; Tejeda, Aurora Romero; Maniero, Silvia; Capua, Ilaria; Terregino, Calogero

    2013-08-30

    Previous studies have reported the detection of H5N1 HPAI virus in feathers from ducks naturally and experimentally infected and suggested that feather calami (FC) could be used as diagnostic samples for the early detection of H5N1 HPAI infections. Ducks are readily infected with H5N1 HPAI viruses although the development of clinical signs and deaths were reported as age-related with younger birds being more susceptible. The correlation between age and virus localisation in FC of infected ducks has not been studied to date. In the present study juvenile (4-week-old) and adult (24-week-old) Pekin ducks (Anas platyrhynchos var. domestica) were infected experimentally with a clade 2.2 H5N1 HPAI virus (A/duck/Nigeria/1071-23/2007). Tracheal (Tr) and cloacal (Cl) swabs and FC were collected at 3, 5, 7 and 10 days post infection and tested by RRT-PCR and a double antibody sandwich-ELISA (DAS-ELISA) developed in house. Virus was detected in swabs and FC of challenged ducks with a higher rate of detection in juvenile ducks. In this age group virus was detected over a longer period of time in FC compared to swabs. Our study showed that FC samples collected from young ducks are a valid diagnostic specimen for H5N1 HPAI virus detection. The DAS-ELISA on FC proved to be a suitable alternative diagnostic test when molecular and/or virus isolation techniques are not available therefore it could be useful in the diagnosis of H5N1 HPAI infections in under-resourced countries. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. FDG uptake in axillary lymph nodes after vaccination against pandemic (H1N1)

    International Nuclear Information System (INIS)

    Panagiotidis, Emmanouil; Exarhos, Demetrios; Housianakou, Irene; Bournazos, Apostolos; Datseris, Ioannis

    2010-01-01

    To alert the imaging community to potential false positive findings related to current immunization programmes against H1N1 influenza virus. We reviewed 10 patients referred for positron emission tomography/computed tomography (PET/CT) who had undergone recent vaccination. All studies showed 18 F-fluorodeoxyglucose (FDG) uptake in the draining axillary lymph nodes close to the vaccination site, while low-dose CT revealed lymph nodes ranged between 0.5 cm and 1.2 cm at the same site. This potential pitfall in PET/CT should be borne in mind during current vaccination programmes. (orig.)

  20. Safety of pandemic H1N1 vaccines in children and adolescents

    NARCIS (Netherlands)

    E.G. Wijnans (Leonoor); S. de Bie (Sandra); J.P. Dieleman (Jeanne); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2011-01-01

    textabstractDuring the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of

  1. Influenza A/H1N1 septic shock in a patient with systemic lupus erythematosus. A case report

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    Tselios Konstantinos

    2011-12-01

    Full Text Available Abstract Background Immunocompromised patients, such as systemic lupus erythematosus (SLE sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. Case Presentation In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU discharge. Conclusions To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement.

  2. Cross-protection against lethal H5N1 challenge ferrets with an adjuvanted pandemic influenza vaccine

    NARCIS (Netherlands)

    B. Baras (Benoît); K.J. Stittelaar (Koert); J.H. Simon (James); R.J.M.M. Thoolen (Robert); S.P. Mossman (Sally); F.H. Pistoor (Frank); G. van Amerongen (Geert); M.A. Wettendorff (Martine); E. Hanon (Emmanuel); A.D.M.E. Osterhaus (Albert)

    2008-01-01

    textabstractBackground. Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be

  3. Mutations in polymerase genes enhanced the virulence of 2009 pandemic H1N1 influenza virus in mice.

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    Wenfei Zhu

    Full Text Available Influenza A virus can infect a wide variety of animal species with illness ranging from mild to severe, and is a continual cause for concern. Genetic mutations that occur either naturally or during viral adaptation in a poorly susceptible host are key mechanisms underlying the evolution and virulence of influenza A virus. Here, the variants containing PA-A36T or PB2-H357N observed in the mouse-adapted descendants of 2009 pandemic H1N1 virus (pH1N1, A/Sichuan/1/2009 (SC, were characterized. Both mutations enhanced polymerase activity in mammalian cells. These effects were confirmed using recombinant SC virus containing polymerase genes with wild type (WT or mutant PA or PB2. The PA-A36T mutant showed enhanced growth property compared to the WT in both human A549 cells and porcine PK15 cells in vitro, without significant effect on viral propagation in murine LA-4 cells and pathogenicity in mice; however, it did enhance the lung virus titer. PB2-H357N variant demonstrated growth ability comparable to the WT in A549 cells, but replicated well in PK15, LA-4 cells and in mice with an enhanced pathogenic phenotype. Despite such mutations are rare in nature, they could be observed in avian H5 and H7 subtype viruses which were currently recognized to pose potential threat to human. Our findings indicated that pH1N1 may adapt well in mammals when acquiring these mutations. Therefore, future molecular epidemiological surveillance should include scrutiny of both markers because of their potential impact on pathogenesis.

  4. Hemagglutinin 222D/G polymorphism facilitates fast intra-host evolution of pandemic (H1N1 2009 influenza A viruses.

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    Nora Seidel

    Full Text Available The amino acid substitution of aspartic acid to glycine in hemagglutinin (HA in position 222 (HA-D222G as well as HA-222D/G polymorphism of pandemic (H1N1 2009 influenza viruses (A(H1N1pdm09 were frequently reported in severe influenza in humans and mice. Their impact on viral pathogenicity and the course of influenza has been discussed controversially and the underlying mechanism remained unclarified. In the present study, BALB/c mice, infected with the once mouse lung- and cell-passaged A(H1N1pdm09 isolate A/Jena/5258/09 (mpJena/5258, developed severe pneumonia. From day 2 to 3 or 4 post infection (p.i. symptoms (body weight loss and clinical score continuously worsened. After a short disease stagnation or even recovery phase in most mice, severity of disease further increased on days 6 and 7 p.i. Thereafter, surviving mice recovered. A 45 times higher virus titer maximum in the lung than in the trachea on day 2 p.i. and significantly higher tracheal virus titers compared to lung on day 6 p.i. indicated changes in the organ tropism during infection. Sequence analysis revealed an HA-222D/G polymorphism. HA-D222 and HA-G222 variants co-circulated in lung and trachea. Whereas, HA-D222 variant predominated in the lung, HA-G222 became the major variant in the trachea after day 4 p.i. This was accompanied by lower neutralizing antibody titers and broader receptor recognition including terminal sialic acid α-2,3-linked galactose, which is abundant on mouse trachea epithelial cells. Plaque-purified HA-G222-mpJena/5258 virus induced severe influenza with maximum symptom on day 6 p.i. These results demonstrated for the first time that HA-222D/G quasispecies of A(H1N1pdm09 caused severe biphasic influenza because of fast viral intra-host evolution, which enabled partial antibody escape and minor changes in receptor binding.

  5. Detection and Characterization of Clade 1 Reassortant H5N1 Viruses Isolated from Human Cases in Vietnam during 2013.

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    Sharmi W Thor

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 is endemic in Vietnamese poultry and has caused sporadic human infection in Vietnam since 2003. Human infections with HPAI H5N1 are of concern due to a high mortality rate and the potential for the emergence of pandemic viruses with sustained human-to-human transmission. Viruses isolated from humans in southern Vietnam have been classified as clade 1 with a single genome constellation (VN3 since their earliest detection in 2003. This is consistent with detection of this clade/genotype in poultry viruses endemic to the Mekong River Delta and surrounding regions. Comparison of H5N1 viruses detected in humans from southern Vietnamese provinces during 2012 and 2013 revealed the emergence of a 2013 reassortant virus with clade 1.1.2 hemagglutinin (HA and neuraminidase (NA surface protein genes but internal genes derived from clade 2.3.2.1a viruses (A/Hubei/1/2010-like; VN12. Closer analysis revealed mutations in multiple genes of this novel genotype (referred to as VN49 previously associated with increased virulence in animal models and other markers of adaptation to mammalian hosts. Despite the changes identified between the 2012 and 2013 genotypes analyzed, their virulence in a ferret model was similar. Antigenically, the 2013 viruses were less cross-reactive with ferret antiserum produced to the clade 1 progenitor virus, A/Vietnam/1203/2004, but reacted with antiserum produced against a new clade 1.1.2 WHO candidate vaccine virus (A/Cambodia/W0526301/2012 with comparable hemagglutination inhibition titers as the homologous antigen. Together, these results indicate changes to both surface and internal protein genes of H5N1 viruses circulating in southern Vietnam compared to 2012 and earlier viruses.

  6. The Influenza Virus and the 2009 H1N1 Outbreak

    Science.gov (United States)

    2016-04-08

    MDW/SGVU SUBJECT: Professional Presentation Approval 8 APR 2016 1. Your paper, entitled The Influenza Virus and the 2009 HlNl Outbreak presented at...L TO BE PUBLISHED OR PRESENTED The Influenza Virus and the 2009 H1N1 Outbreak 2. FUNDING RECEIVED FOR THIS STUDY? DYES [g] NO FUNDING SOURCE: I I...336:!. ~~ 2 C-; MARKE. COON. :vtajor. USAF Acting Chic!’. Civil I.aw The Influenza Virus and the 2009 H 1 N 1 Outbreak Thomas. F. Gibbons, Ph.D

  7. Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice

    DEFF Research Database (Denmark)

    Moser, C; Johansen, H K; Song, Z

    1997-01-01

    model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p ... was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p BALB/c mice (p ... from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed....

  8. Evaluating the control of HPAIV H5N1 in Vietnam: virus transmission within infected flocks reported before and after vaccination

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    Pfeiffer Dirk U

    2010-06-01

    Full Text Available Abstract Background Currently, the highly pathogenic avian influenza virus (HPAIV of the subtype H5N1 is believed to have reached an endemic cycle in Vietnam. We used routine surveillance data on HPAIV H5N1 poultry outbreaks in Vietnam to estimate and compare the within-flock reproductive number of infection (R0 for periods before (second epidemic wave, 2004-5; depopulation-based disease control and during (fourth epidemic wave, beginning 2007; vaccination-based disease control vaccination. Results Our results show that infected premises (IPs in the initial (exponential phases of outbreak periods have the highest R0 estimates. The IPs reported during the outbreak period when depopulation-based disease control was implemented had higher R0 estimates than IPs reported during the outbreak period when vaccination-based disease control was used. In the latter period, in some flocks of a defined size and species composition, within-flock transmission estimates were not significantly below the threshold for transmission (R0 Conclusions Our results indicate that the current control policy based on depopulation plus vaccination has protected the majority of poultry flocks against infection. However, in some flocks the determinants associated with suboptimal protection need to be further investigated as these may explain the current pattern of infection in animal and human populations.

  9. Progress toward a universal H5N1 vaccine: a recombinant modified vaccinia virus Ankara-expressing trivalent hemagglutinin vaccine.

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    Mookkan Prabakaran

    Full Text Available The rapid evolution of new sublineages of H5N1 influenza poses the greatest challenge in control of H5N1 infection by currently existing vaccines. To overcome this, an MVAtor vector expressing three H5HA antigens A/Vietnam/1203/04, A/Indonesia/669/06 and A/Anhui/01/05 (MVAtor-tri-HA vector was developed to elicit broad cross-protection against diverse clades by covering amino acid variations in the major neutralizing epitopes of HA among H5N1 subtypes.BALB/c mice and guinea pigs were immunized i.m. with 8×107 TCID50/animal of MVAtor-tri-HA vector. The immunogenicity and cross-protective immunity of the MVAtor-tri-HA vector was evaluated against diverse clades of H5N1 strains.The results showed that mice immunized with MVAtor-tri-HA vector induced robust cross-neutralizing immunity to diverse H5N1 clades. In addition, the MVAtor-tri-HA vector completely protected against 10 MLD50 of a divergent clade of H5N1 infection (clade 7. Importantly, the serological surveillance of post-vaccinated guinea pig sera demonstrated that MVAtor-tri-HA vector was able to elicit strong cross-clade neutralizing immunity against twenty different H5N1 strains from six clades that emerged between 1997 and 2012.The present findings revealed that incorporation of carefully selected HA genes from divergent H5N1 strains within a single vector could be an effective approach in developing a vaccine with broad coverage to prevent infection during a pandemic situation.

  10. Cholinergic PET imaging in infections and inflammation using "1"1C-donepezil and "1"8F-FEOBV

    International Nuclear Information System (INIS)

    Joergensen, Nis Pedersen; Hoegsberg Schleimann, Mariane; Alstrup, Aage K.O.; Knudsen, Karoline; Jakobsen, Steen; Bender, Dirk; Gormsen, Lars C.; Borghammer, Per; Mortensen, Frank V.; Madsen, Line Bille; Breining, Peter; Petersen, Mikkel Steen; Dagnaes-Hansen, Frederik

    2017-01-01

    Immune cells utilize acetylcholine as a paracrine-signaling molecule. Many white blood cells express components of the cholinergic signaling pathway, and these are up-regulated when immune cells are activated. However, in vivo molecular imaging of cholinergic signaling in the context of inflammation has not previously been investigated. We performed positron emission tomography (PET) using the glucose analogue 18F-FDG, and 11C-donepezil and 18F-FEOBV, markers of acetylcholinesterase and the vesicular acetylcholine transporter, respectively. Mice were inoculated subcutaneously with Staphylococcus aureus, and PET scanned at 24, 72, 120, and 144 h post-inoculation. Four pigs with post-operative abscesses were also imaged. Finally, we present initial data from human patients with infections, inflammation, and renal and lung cancer. In mice, the FDG uptake in abscesses peaked at 24 h and remained stable. The 11C-donepezil and 18F-FEOBV uptake displayed progressive increase, and at 120-144 h was nearly at the FDG level. Moderate 11C-donepezil and slightly lower 18F-FEOBV uptake were seen in pig abscesses. PCR analyses suggested that the 11C-donepezil signal in inflammatory cells is derived from both acetylcholinesterase and sigma-1 receptors. In humans, very high 11C-donepezil uptake was seen in a lobar pneumonia and in peri-tumoral inflammation surrounding a non-small cell lung carcinoma, markedly superseding the 18F-FDG uptake in the inflammation. In a renal clear cell carcinoma no 11C-donepezil uptake was seen. The time course of cholinergic tracer accumulation in murine abscesses was considerably different from 18F-FDG, demonstrating in the 11C-donepezil and 18F-FEOBV image distinct aspects of immune modulation. Preliminary data in humans strongly suggest that 11C-donepezil can exhibit more intense accumulation than 18F-FDG at sites of chronic inflammation. Cholinergic PET imaging may therefore have potential applications for basic research into cholinergic

  11. Global patterns in seasonal activity of influenza A/H3N2, A/H1N1, and B from 1997 to 2005: viral coexistence and latitudinal gradients.

    Directory of Open Access Journals (Sweden)

    Brian S Finkelman

    Full Text Available Despite a mass of research on the epidemiology of seasonal influenza, overall patterns of infection have not been fully described on broad geographic scales and for specific types and subtypes of the influenza virus. Here we provide a descriptive analysis of laboratory-confirmed influenza surveillance data by type and subtype (A/H3N2, A/H1N1, and B for 19 temperate countries in the Northern and Southern hemispheres from 1997 to 2005, compiled from a public database maintained by WHO (FluNet. Key findings include patterns of large scale co-occurrence of influenza type A and B, interhemispheric synchrony for subtype A/H3N2, and latitudinal gradients in epidemic timing for type A. These findings highlight the need for more countries to conduct year-round viral surveillance and report reliable incidence data at the type and subtype level, especially in the Tropics.

  12. Evolution and adaptation of the pandemic A/H1N1 2009 influenza virus

    Directory of Open Access Journals (Sweden)

    Ducatez MF

    2011-07-01

    Full Text Available Mariette F Ducatez, Thomas P Fabrizio, Richard J WebbyDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USAAbstract: The emergence of the 2009 H1N1 pandemic influenza virus [A(H1N1pdm09] has provided the public health community with many challenges, but also the scientific community with an opportunity to monitor closely its evolution through the processes of drift and shift. To date, and despite having circulated in humans for nearly two years, little antigenic variation has been observed in the A(H1N1pdm09 viruses. However, as the A(H1N1pdm09 virus continues to circulate and the immunologic pressure within the human population increases, future antigenic change is almost a certainty. Several coinfections of A(H1N1pdm09 and seasonal A(H1N1 or A(H3N2 viruses have been observed, but no reassortant viruses have been described in humans, suggesting a lack of fitness of reassortant viruses or a lack of opportunities for interaction of different viral lineages. In contrast, multiple reassortment events have been detected in swine populations between A(H1N1 pdm09 and other endemic swine viruses. Somewhat surprisingly, many of the well characterized influenza virus virulence markers appear to have limited impact on the phenotype of the A(H1N1pdm09 viruses when they have been introduced into mutant viruses in laboratory settings. As such, it is unclear what the evolutionary path of the pandemic virus will be, but the monitoring of any changes in the circulating viruses will remain a global public and animal health priority.Keywords: influenza, pandemic, evolution, adaptation

  13. Reasons for Low Pandemic H1N1 2009 Vaccine Acceptance within a College Sample

    Directory of Open Access Journals (Sweden)

    Russell D. Ravert

    2012-01-01

    Full Text Available This study examined health beliefs associated with novel influenza A (H1N1 immunization among US college undergraduates during the 2009-2010 pandemic. Undergraduates (ages 18–24 years from a large Midwestern University were invited to complete an online survey during March, 2010, five months after H1N1 vaccines became available. Survey items measured H1N1 vaccine history and H1N1-related attitudes based on the health belief literature. Logistic regression was used to identify attitudes associated with having received an H1N1 vaccine, and thematic analysis of student comments was conducted to further understand influences on vaccine decisions. Among the 296 students who participated in the survey, 15.2% reported having received an H1N1 vaccine. In regression analysis, H1N1 immunization was associated with seasonal flu vaccine history, perceived vaccine effectiveness, perceived obstacles to vaccination, and vaccine safety concerns. Qualitative results illustrate the relationship of beliefs to vaccine decisions, particularly in demonstrating that students often held concerns that vaccine could cause H1N1 or side effects. Vaccine safety, efficacy, and obstacles to immunization were major considerations in deciding whether to accept the H1N1 pandemic vaccine. Therefore, focusing on those aspects might be especially useful in future vaccine efforts within the college population.

  14. Avian influenza virus (H5N1): a threat to human health

    NARCIS (Netherlands)

    Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

    2007-01-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes.

  15. Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.

    Directory of Open Access Journals (Sweden)

    Mai T Q Le

    2008-10-01

    Full Text Available Prior to 2007, highly pathogenic avian influenza (HPAI H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses.Respiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found.In 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.

  16. A monoclonal antibody-based ELISA for differential diagnosis of 2009 pandemic H1N1

    Science.gov (United States)

    The swine-origin 2009 pandemic H1N1 virus (pdmH1N1) is genetically related to North American swine H1 influenza viruses and unrelated to human seasonal H1 viruses. Currently, specific diagnosis of pdmH1N1 relies on RT-PCR. In order to develop an assay that does not rely in amplification of the viral...

  17. Factors associated with household transmission of pandemic (H1N1 2009 among self-quarantined patients in Beijing, China.

    Directory of Open Access Journals (Sweden)

    Daitao Zhang

    Full Text Available As the pandemic (H1N1 2009 progressed, the Ministry of Health of China advised cases with mild symptoms to remain home for isolation and observation, which may have increased the risk for infection among other household members. Describing the transmission characteristics of this novel virus is indispensable to effectively controlling the spread of disease; thus, the aim of this study was to assess risk factors associated with household transmission of pandemic H1N1 from self-quarantined patients in Beijing, the capital city of China. A 1:2 case-control study with 54 case households and 108 control households was conducted between August 1 and September 30, 2009 in Beijing. Cases were households with a self-quarantined index patient and a secondary case, while controls were households with a self-quarantined index patient and a close contact. Controls were also matched to cases for sex and age of index case-patient. A structured interview guide was used to collect the data. Conditional logistical models were employed to estimate Odds Ratios (OR with 95% confidence intervals (95% CI. Results indicated that higher education level (OR 0.42; 95% CI 0.22-0.83, sharing room with an index case-patient (OR 3.29; 95%CI 1.23-8.78, daily room ventilation (OR 0.28; 95%CI 0.08-0.93, and hand washing ≥ 3/d (OR 0.71; 95%CI 0.48-0.94 were related to the household transmission of pandemic H1N1 from self-quarantined patients. These results highlight that health education, as well as the quarantine of the index case-patient immediately after infection, frequent hand hygiene, and ventilation are critical to mitigating household spread of pandemic H1N1 virus and minimizing its impact. Household contacts should be educated to promote these in-home practices to contain transmission, particularly when household members are quarantined at home.

  18. Characterizing wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents.

    Science.gov (United States)

    Reed, Carrie; Bruden, Dana; Byrd, Kathy K; Veguilla, Vic; Bruce, Michael; Hurlburt, Debby; Wang, David; Holiday, Crystal; Hancock, Kathy; Ortiz, Justin R; Klejka, Joe; Katz, Jacqueline M; Uyeki, Timothy M

    2014-09-01

    Highly pathogenic avian influenza A (HPAI) H5N1 viruses have infected poultry and wild birds on three continents with more than 600 reported human cases (59% mortality) since 2003. Wild aquatic birds are the natural reservoir for avian influenza A viruses, and migratory birds have been documented with HPAI H5N1 virus infection. Since 2005, clade 2.2 HPAI H5N1 viruses have spread from Asia to many countries. We conducted a cross-sectional seroepidemiological survey in Anchorage and western Alaska to identify possible behaviors associated with migratory bird exposure and measure seropositivity to HPAI H5N1. We enrolled rural subsistence bird hunters and their families, urban sport hunters, wildlife biologists, and a comparison group without bird contact. We interviewed participants regarding their exposures to wild birds and collected blood to perform serologic testing for antibodies against a clade 2.2 HPAI H5N1 virus strain. Hunters and wildlife biologists reported exposures to wild migratory birds that may confer risk of infection with avian influenza A viruses, although none of the 916 participants had evidence of seropositivity to HPAI H5N1. We characterized wild bird contact among Alaskans and behaviors that may influence risk of infection with avian influenza A viruses. Such knowledge can inform surveillance and risk communication surrounding HPAI H5N1 and other influenza viruses in a population with exposure to wild birds at a crossroads of intercontinental migratory flyways. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  19. Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model▿

    OpenAIRE

    Yen, Hui-Ling; Lipatov, Aleksandr S.; Ilyushina, Natalia A.; Govorkova, Elena A.; Franks, John; Yilmaz, Neziha; Douglas, Alan; Hay, Alan; Krauss, Scott; Rehg, Jerold E.; Hoffmann, Erich; Webster, Robert G.

    2007-01-01

    The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synth...

  20. US school morbidity and mortality, mandatory vaccination, institution closure, and interventions implemented during the 2009 influenza A H1N1 pandemic.

    Science.gov (United States)

    Rebmann, Terri; Elliott, Michael B; Swick, Zachary; Reddick, David

    2013-03-01

    The 2009 H1N1 pandemic disproportionately affected school-aged children, but only school-based outbreak case studies have been conducted. The purposes of this study were to evaluate US academic institutions' experiences during the 2009 H1N1 pandemic in terms of infection prevention interventions implemented and to examine factors associated with school closure during the pandemic. An online survey was sent to school nurses in May through July 2011. Hierarchical logistic regressions were used to determine predictive models for having a mandatory H1N1 vaccination policy for school nurses and school closure. In all, 1,997 nurses from 26 states participated. Very few nurses (3.3%, n=65) reported having a mandatory H1N1 influenza vaccination policy; nurses were more likely than all other school employees (pnurse employed by a public health agency or hospital, and being a private school. The most commonly implemented interventions included encouraging staff and students to exercise hand hygiene and increasing classroom cleaning; least commonly implemented interventions included discouraging face-to-face meetings, training staff on H1N1 influenza and/or respiratory hygiene, and discouraging handshaking. Schools should develop and continue to improve their pandemic plans, including collaborating with community response agencies.

  1. Projected [1H,15N]-HMQC-[1H,1H]-NOESY for large molecular systems: application to a 121 kDa protein-DNA complex

    International Nuclear Information System (INIS)

    Galius, Veniamin; Leontiou, Chrysoula; Richmond, Timothy; Wider, Gerhard

    2008-01-01

    We present a projected [ 1 H, 15 N]-HMQC-[ 1 H, 1 H]-NOESY experiment for observation of NOE interactions between amide protons with degenerate 15 N chemical shifts in large molecular systems. The projection is achieved by simultaneous evolution of the multiple quantum coherence of the nitrogen spin and the attached proton spin. In this way NOE signals can be separated from direct-correlation peaks also in spectra with low resolution by fully exploiting both 1 H and 15 N frequency differences, such that sensitivity can be increased by using short maximum evolution times. The sensitivity of the experiment is not dependent on the projection angle for projections up to 45 deg. and no additional pulses or delays are required as compared to the conventional 2D [ 1 H, 15 N]-HMQC-NOESY. The experiment provides two distinct 2D spectra corresponding to the positive and negative angle projections, respectively. With a linear combination of 1D cross-sections from the two projections the unavoidable sensitivity loss in projection spectra can be compensated for each particular NOE interaction. We demonstrate the application of the novel projection experiment for the observation of an NOE interaction between two sequential glycines with degenerate 15 N chemical shifts in a 121.3 kDa complex of the linker H1 histone protein with a 152 bp linear DNA

  2. Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam

    NARCIS (Netherlands)

    Le, Mai T. Q.; Wertheim, Heiman F. L.; Nguyen, Hien D.; Taylor, Walter; Hoang, Phuong V. M.; Vuong, Cuong D.; Nguyen, Hang L. K.; Nguyen, Ha H.; Nguyen, Thai Q.; Nguyen, Trung V.; van, Trang D.; Ngoc, Bich T.; Bui, Thinh N.; Nguyen, Binh G.; Nguyen, Liem T.; Luong, San T.; Phan, Phuc H.; Pham, Hung V.; Nguyen, Tung; Fox, Annette; Nguyen, Cam V.; Do, Ha Q.; Crusat, Martin; Farrar, Jeremy; Nguyen, Hien T.; de Jong, Menno D.; Horby, Peter

    2008-01-01

    BACKGROUND: Prior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections

  3. Integrative study of pandemic A/H1N1 influenza infections: design and methods of the CoPanFlu-France cohort

    Directory of Open Access Journals (Sweden)

    Lapidus Nathanael

    2012-06-01

    Full Text Available Abstract Background The risk of influenza infection depends on biological characteristics, individual or collective behaviors and the environmental context. The Cohorts for Pandemic Influenza (CoPanFlu France study was set up in 2009 after the identification of the novel swine-origin A/H1N1 pandemic influenza virus. This cohort of 601 households (1450 subjects representative for the general population aims at using an integrative approach to study the risk and characteristics of influenza infection as a complex combination of data collected from questionnaires regarding sociodemographic, medical, behavioral characteristics of subjects and indoor environment, using biological samples or environmental databases. Methods/Design Households were included between December 2009 and July 2010. The design of this study relies on systematic follow-up visits between influenza seasons and additional visits during influenza seasons, when an influenza-like illness is detected in a household via an active surveillance system. During systematic visits, a nurse collects individual and environmental data on questionnaires and obtains blood samples from all members of the household. When an influenza-like-illness is detected, a nurse visits the household three times during the 12 following days, and collects data on questionnaires regarding exposure and symptoms, and biological samples (including nasal swabs from all subjects in the household. The end of the follow-up period is expected in fall 2012. Discussion The large amount of data collected throughout the follow-up will permit a multidisciplinary study of influenza infections. Additional data is being collected and analyzed in this ongoing cohort. The longitudinal analysis of these households will permit integrative analyses of complex phenomena such as individual, collective and environmental risk factors of infection, routes of transmission, or determinants of the immune response to infection or vaccination.

  4. Spread of H1N1 within Households

    Centers for Disease Control (CDC) Podcasts

    2010-03-29

    This podcast describes an investigation into how H1N1 was spreading within households during the initial days of the pandemic in Texas. CDC's Dr. Oliver Morgan discusses what investigators learned about the role that children played in introducing the virus into households and spreading flu.  Created: 3/29/2010 by Emerging Infectious Diseases.   Date Released: 3/29/2010.

  5. Transmission characteristics of the 2009 H1N1 influenza pandemic: comparison of 8 Southern hemisphere countries.

    Directory of Open Access Journals (Sweden)

    Lulla Opatowski

    2011-09-01

    Full Text Available While in Northern hemisphere countries, the pandemic H1N1 virus (H1N1pdm was introduced outside of the typical influenza season, Southern hemisphere countries experienced a single wave of transmission during their 2009 winter season. This provides a unique opportunity to compare the spread of a single virus in different countries and study the factors influencing its transmission. Here, we estimate and compare transmission characteristics of H1N1pdm for eight Southern hemisphere countries/states: Argentina, Australia, Bolivia, Brazil, Chile, New Zealand, South Africa and Victoria (Australia. Weekly incidence of cases and age-distribution of cumulative cases were extracted from public reports of countries' surveillance systems. Estimates of the reproduction numbers, R(0, empirically derived from the country-epidemics' early exponential phase, were positively associated with the proportion of children in the populations (p = 0.004. To explore the role of demography in explaining differences in transmission intensity, we then fitted a dynamic age-structured model of influenza transmission to available incidence data for each country independently, and for all the countries simultaneously. Posterior median estimates of R₀ ranged 1.2-1.8 for the country-specific fits, and 1.29-1.47 for the global fits. Corresponding estimates for overall attack-rate were in the range 20-50%. All model fits indicated a significant decrease in susceptibility to infection with age. These results confirm the transmissibility of the 2009 H1N1 pandemic virus was relatively low compared with past pandemics. The pattern of age-dependent susceptibility found confirms that older populations had substantial--though partial--pre-existing immunity, presumably due to exposure to heterologous influenza strains. Our analysis indicates that between-country-differences in transmission were at least partly due to differences in population demography.

  6. Stability and infectivity of novel pandemic influenza A (H1N1) virus in blood-derived matrices under different storage conditions.

    Science.gov (United States)

    Wang, Xue; Zoueva, Olga; Zhao, Jiangqin; Ye, Zhiping; Hewlett, Indira

    2011-12-22

    Influenza A virus has been detected in the blood of some infected individuals, and may pose a safety concern for collection, handling and transport of specimens for epidemiological and public health investigations if infectious virus is present in samples. Furthermore the effect of storage on virus stability and infectivity has not been well studied. We examined the stability of novel pandemic influenza A (H1N1) virus RNA when the virus was stored in phosphate buffered saline (PBS), plasma, or buffy coated blood at either room temperature or 4°C using a sensitive Taqman RT-PCR assay. We also investigated virus infectivity using the EID(50) assay when virus was stored in PBS, plasma, or buffy coats isolated from blood at 4°C. Viral RNA stability was affected by the matrix used for storage. The recovery of viral RNA was highest when virus was stored in PBS with lower amounts being recovered from plasma and buffy coats at either room temperature or 4°C. Incubation time did not appear to be a major factor for viral RNA stability, although there was gradual decline after longer periods post-incubation. Both sample matrix and incubation time affected virus infectivity. The decay in virus infectivity was greatest in PBS followed by buffy coats and plasma. Virus infectivity was abolished in buffy coats at day 20 post-incubation when virus concentrations were low. These data indicate that encapsidated viral RNA was stable overall in all three liquid matrices at room temperature or 4°C although it was most stable in PBS; virus infectivity in buffy coats at 4°C decayed in a time dependent manner while it remained unchanged in plasma. These findings have implications for storage, handling and transport of blood derived samples from influenza patients for epidemiological and laboratory investigations. It should be noted that there is little known about influenza viremia, and whether influenza viruses can be transmitted by blood or blood derived samples.

  7. Stability and infectivity of novel pandemic influenza A (H1N1 virus in blood-derived matrices under different storage conditions

    Directory of Open Access Journals (Sweden)

    Wang Xue

    2011-12-01

    Full Text Available Abstract Background Influenza A virus has been detected in the blood of some infected individuals, and may pose a safety concern for collection, handling and transport of specimens for epidemiological and public health investigations if infectious virus is present in samples. Furthermore the effect of storage on virus stability and infectivity has not been well studied. Methods We examined the stability of novel pandemic influenza A (H1N1 virus RNA when the virus was stored in phosphate buffered saline (PBS, plasma, or buffy coated blood at either room temperature or 4°C using a sensitive Taqman RT-PCR assay. We also investigated virus infectivity using the EID50 assay when virus was stored in PBS, plasma, or buffy coats isolated from blood at 4°C. Results Viral RNA stability was affected by the matrix used for storage. The recovery of viral RNA was highest when virus was stored in PBS with lower amounts being recovered from plasma and buffy coats at either room temperature or 4°C. Incubation time did not appear to be a major factor for viral RNA stability, although there was gradual decline after longer periods post-incubation. Both sample matrix and incubation time affected virus infectivity. The decay in virus infectivity was greatest in PBS followed by buffy coats and plasma. Virus infectivity was abolished in buffy coats at day 20 post-incubation when virus concentrations were low. Conclusion These data indicate that encapsidated viral RNA was stable overall in all three liquid matrices at room temperature or 4°C although it was most stable in PBS; virus infectivity in buffy coats at 4°C decayed in a time dependent manner while it remained unchanged in plasma. These findings have implications for storage, handling and transport of blood derived samples from influenza patients for epidemiological and laboratory investigations. It should be noted that there is little known about influenza viremia, and whether influenza viruses can be

  8. A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

    Science.gov (United States)

    This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

  9. Humoral and cell-mediated immunity to pandemic H1N1 influenza in a Canadian cohort one year post-pandemic: implications for vaccination.

    Directory of Open Access Journals (Sweden)

    Lisa E Wagar

    Full Text Available We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1 at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105 of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity.

  10. Affective language during the H1N1 influenza health crisis

    Directory of Open Access Journals (Sweden)

    Morant Marco, Ricard

    2010-12-01

    Full Text Available In this article we analyze the effects that, as seen through the written press, the arrival of H1N1 had on certain affective behaviors in society. After the spread of H1N1, health authorities recommended maintaining physical distance in social settings and, among other measures, advised against kissing. At first, this show of affection became a victim of the pandemic, especially in certain activities and rituals. However, once the media impact of swine flu had subsided, kissing recovered its habitual place and frequency, demonstrating that customs which are socially and culturally entrenched are resistant to change.

    El presente artículo analiza los efectos que según la prensa escrita tuvo la llegada de la gripe A en ciertos comportamientos afectivos de la población. Las autoridades sanitarias, tras la expansión del virus H1N1, recomendaron aumentar la distancia social y aconsejaron, entre otras medidas, evitar los besos. Esta manifestación afectiva, en un primer momento, notó los efectos de la pandemia, sobre todo en ciertas actividades y rituales. Sin embargo, una vez pasado el impacto mediático de la gripe A, recuperó su uso y frecuencia habitual, demostrando que las costumbres fuertemente enraizadas se resisten a cambiar.

  11. Induction of long-term protective immune responses by influenza H5N1 virus-like particles.

    Directory of Open Access Journals (Sweden)

    Sang-Moo Kang

    Full Text Available Recurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.Influenza virus-like particles (VLPs produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1 hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.These results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.

  12. Spatial and temporal characteristics of the 2009 A/H1N1 influenza pandemic in Peru.

    Science.gov (United States)

    Chowell, Gerardo; Viboud, Cécile; Munayco, Cesar V; Gómez, Jorge; Simonsen, Lone; Miller, Mark A; Tamerius, James; Fiestas, Victor; Halsey, Eric S; Laguna-Torres, Victor A

    2011-01-01

    Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6-2.2 for the Lima metropolitan area and 1.3-1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school-age children, the age group most affected

  13. Spatial and Temporal Characteristics of the 2009 A/H1N1 Influenza Pandemic in Peru

    Science.gov (United States)

    Chowell, Gerardo; Viboud, Cécile; Munayco, Cesar V.; Gómez, Jorge; Simonsen, Lone; Miller, Mark A.; Tamerius, James; Fiestas, Victor; Halsey, Eric S.; Laguna-Torres, Victor A.

    2011-01-01

    Background Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age-specific morbidity pandemic patterns across administrative areas of Peru. Methods We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases. Results The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6–2.2 for the Lima metropolitan area and 1.3–1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity. Conclusions Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school

  14. National surveillance of pandemic influenza A(H1N1) infection-related admissions to intensive care units during the 2009-10 winter peak in Denmark: two complementary approaches

    DEFF Research Database (Denmark)

    Gubbels, S; Perner, A; Valentiner-Branth, Palle

    2010-01-01

    close contact with a laboratory-confirmed case. Aggregate numbers of cases were reported weekly: during weeks 48-51 (the peak), reporting was daily. The case-based reports contained demographic and clinical information. The aggregate surveillance registered 93 new cases, the case-based surveillance 61......Surveillance of 2009 pandemic influenza A(H1N1) in Denmark was enhanced during the 2009–10 winter season with a system monitoring the burden of the pandemic on intensive care units (ICUs), in order to inform policymakers and detect shortages in ICUs in a timely manner. Between week 46 of 2009...... and week 11 of 2010, all 36 relevant Danish ICUs reported in two ways: aggregate data were reported online and case-based data on paper. Cases to be reported were defined as patients admitted to an ICU with laboratory-confirmed 2009 pandemic influenza A(H1N1) infection or clinically suspected illness after...

  15. Spreading patterns of the influenza A (H1N1 pandemic.

    Directory of Open Access Journals (Sweden)

    Sergio de Picoli Junior

    Full Text Available We investigate the dynamics of the 2009 influenza A (H1N1/S-OIV pandemic by analyzing data obtained from World Health Organization containing the total number of laboratory-confirmed cases of infections--by country--in a period of 69 days, from 26 April to 3 July, 2009. Specifically, we find evidence of exponential growth in the total number of confirmed cases and linear growth in the number of countries with confirmed cases. We also find that, i at early stages, the cumulative distribution of cases among countries exhibits linear behavior on log-log scale, being well approximated by a power law decay; ii for larger times, the cumulative distribution presents a systematic curvature on log-log scale, indicating a gradual change to lognormal behavior. Finally, we compare these empirical findings with the predictions of a simple stochastic model. Our results could help to select more realistic models of the dynamics of influenza-type pandemics.

  16. Cost-effective strategies for mitigating a future influenza pandemic with H1N1 2009 characteristics.

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    Nilimesh Halder

    Full Text Available BACKGROUND: We performed an analysis of the cost-effectiveness of pandemic intervention strategies using a detailed, individual-based simulation model of a community in Australia together with health outcome data of infected individuals gathered during 2009-2010. The aim was to examine the cost-effectiveness of a range of interventions to determine the most cost-effective strategies suitable for a future pandemic with H1N1 2009 characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Using transmissibility, age-stratified attack rates and health outcomes determined from H1N1 2009 data, we determined that the most cost-effective strategies involved treatment and household prophylaxis using antiviral drugs combined with limited duration school closure, with costs ranging from $632 to $777 per case prevented. When school closure was used as a sole intervention we found the use of limited duration school closure to be significantly more cost-effective compared to continuous school closure, a result with applicability to countries with limited access to antiviral drugs. Other social distancing strategies, such as reduced workplace attendance, were found to be costly due to productivity losses. CONCLUSION: The mild severity (low hospitalisation and case fatality rates and low transmissibility of H1N1 2009 meant that health treatment costs were dominated by the higher productivity losses arising from workplace absence due to illness and childcare requirements following school closure. Further analysis for higher transmissibility but with the same, mild severity had no effect on the overall findings.

  17. Proton magnetic resonance chemical shift imaging (1H CSI)-directed stereotactic biopsy

    International Nuclear Information System (INIS)

    Son, B.-C.; Kim, B.-C.; Kang, J.-K.; Choi, B.-G.; Kim, E.-N.; Baik, H.-M.; Choe, B.-Y.; Naruse, S.

    2001-01-01

    Introduction. To add metabolic information during stereotactic biopsy target selection, the authors adopted proton chemical shift imaging ( 1 H CSI)-directed stereotactic biopsy. Currently, proton single voxel spectroscopy (SVS) technique has been reported in stereotactic biopsy. We performed 1 H CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, and evaluated the pathological results. Patients and Method. The 1 H CSI-directed stereotactic biopsy was performed in four patients. 1 H CSI and conventional Gd-enhancement stereotactic MRI were performed simultaneously after the fitting of a stereotactic frame. After reconstructing the metabolic maps of N-acetylaspartate (NAA)/phosphocreatine (Cr), phosphocholine (Cho)/Cr, and Lactate/Cr ratios, focal areas of increased Cho/Cr ratio and Lac/Cr ratios were selected as target sites in the stereotactic MR images. Result. 1 H CSI is possible with the stereotactic headframe in place. No difficulty was experienced performing 1 H CSI or making a diagnosis. Pathological samples taken from areas of increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon increased cellularity, mitoses and cellular atypism, and facilitated diagnosis. Pathological samples taken from areas of increased Lac/ Cr ratio snowed predominant feature of necrosis. Conclusion. 1 H CSI was feasible with the stereotactic headframe in place. The final pathological results obtained were concordant with the local metabolic information from 1 H CSI. We believe that 1 H CSI-directed stereotactic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting. (author)

  18. Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

    LENUS (Irish Health Repository)

    Das, J P

    2012-02-01

    Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.

  19. Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

    LENUS (Irish Health Repository)

    Das, J P

    2011-03-01

    Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.

  20. Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

    Science.gov (United States)

    Ghaderi, Sara; Gunnes, Nina; Bakken, Inger Johanne; Magnus, Per; Trogstad, Lill; Håberg, Siri Eldevik

    2016-01-01

    Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009-2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47% of the population and the vaccination coverage was 39.25%. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95% confidence interval (CI) 1.08-1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95% CI 1.17-20.36). After pandemic vaccination the adjusted HR was 1.11 (95% CI 0.51-2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings.

  1. Evolution of highly pathogenic H5N1 avian influenza viruses in Vietnam between 2001 and 2007.

    Directory of Open Access Journals (Sweden)

    Xiu-Feng Wan

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses have caused dramatic economic losses to the poultry industry of Vietnam and continue to pose a serious threat to public health. As of June 2008, Vietnam had reported nearly one third of worldwide laboratory confirmed human H5N1 infections. To better understand the emergence, spread and evolution of H5N1 in Vietnam we studied over 300 H5N1 avian influenza viruses isolated from Vietnam since their first detection in 2001. Our phylogenetic analyses indicated that six genetically distinct H5N1 viruses were introduced into Vietnam during the past seven years. The H5N1 lineage that evolved following the introduction in 2003 of the A/duck/Hong Kong/821/2002-like viruses, with clade 1 hemagglutinin (HA, continued to predominate in southern Vietnam as of May 2007. A virus with a clade 2.3.4 HA newly introduced into northern Vietnam in 2007, reassorted with pre-existing clade 1 viruses, resulting in the emergence of novel genotypes with neuraminidase (NA and/or internal gene segments from clade 1 viruses. A total of nine distinct genotypes have been present in Vietnam since 2001, including five that were circulating in 2007. At least four of these genotypes appear to have originated in Vietnam and represent novel H5N1 viruses not reported elsewhere. Geographic and temporal analyses of H5N1 infection dynamics in poultry suggest that the majority of viruses containing new genes were first detected in northern Vietnam and subsequently spread to southern Vietnam after reassorting with pre-existing local viruses in northern Vietnam. Although the routes of entry and spread of H5N1 in Vietnam remain speculative, enhanced poultry import controls and virologic surveillance efforts may help curb the entry and spread of new HPAI viral genes.

  2. Segregation of virulent influenza A(H1N1 variants in the lower respiratory tract of critically ill patients during the 2010-2011 seasonal epidemic.

    Directory of Open Access Journals (Sweden)

    Antonio Piralla

    Full Text Available BACKGROUND: Since its appearance in 2009, the pandemic influenza A(H1N1 virus circulated worldwide causing several severe infections. METHODS: Respiratory samples from patients with 2009 influenza A(H1N1 and acute respiratory distress attending 24 intensive care units (ICUs as well as from patients with lower respiratory tract infections not requiring ICU admission and community upper respiratory tract infections in the Lombardy region (10 million inhabitants of Italy during the 2010-2011 winter-spring season, were analyzed. RESULTS: In patients with severe ILI, the viral load was higher in bronchoalveolar lavage (BAL with respect to nasal swab (NS, (p<0.001 suggesting a higher virus replication in the lower respiratory tract. Four distinct virus clusters (referred to as cluster A to D circulated simultaneously. Most (72.7%, n = 48 of the 66 patients infected with viruses belonging to cluster A had a severe (n = 26 or moderate ILI (n = 22. Amino acid mutations (V26I, I116M, A186T, D187Y, D222G/N, M257I, S263F, I286L/M, and N473D were observed only in patients with severe ILI. D222G/N variants were detected exclusively in BAL samples. CONCLUSIONS: Multiple virus clusters co-circulated during the 2010-2011 winter-spring season. Severe or moderate ILI were associated with specific 2009 influenza A(H1N1 variants, which replicated preferentially in the lower respiratory tract.

  3. Factors Associated with the Emergence of Highly Pathogenic Avian Influenza A (H5N1) Poultry Outbreaks in China: Evidence from an Epidemiological Investigation in Ningxia, 2012.

    Science.gov (United States)

    Liu, H; Zhou, X; Zhao, Y; Zheng, D; Wang, J; Wang, X; Castellan, D; Huang, B; Wang, Z; Soares Magalhães, R J

    2017-06-01

    In April 2012, highly pathogenic avian influenza virus of the H5N1 subtype (HPAIV H5N1) emerged in poultry layers in Ningxia. A retrospective case-control study was conducted to identify possible risk factors associated with the emergence of H5N1 infection and describe and quantify the spatial variation in H5N1 infection. A multivariable logistic regression model was used to identify risk factors significantly associated with the presence of infection; residual spatial variation in H5N1 risk unaccounted by the factors included in the multivariable model was investigated using a semivariogram. Our results indicate that HPAIV H5N1-infected farms were three times more likely to improperly dispose farm waste [adjusted OR = 0.37; 95% CI: 0.12-0.82] and five times more likely to have had visitors in their farm within the past month [adjusted OR = 5.47; 95% CI: 1.97-15.64] compared to H5N1-non-infected farms. The variables included in the final multivariable model accounted only 20% for the spatial clustering of H5N1 infection. The average size of a H5N1 cluster was 660 m. Bio-exclusion practices should be strengthened on poultry farms to prevent further emergence of H5N1 infection. For future poultry depopulation, operations should consider H5N1 disease clusters to be as large as 700 m. © 2015 Blackwell Verlag GmbH.

  4. Populations at risk for severe or complicated Avian Influenza H5N1: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dominik Mertz

    Full Text Available BACKGROUND: Little is known about risk factors for severe outcomes in patients infected with H5N1 and no systematic review has been conducted. Understanding risk factors is an important step for prioritizing prophylaxis or treatment in the event of a pandemic. OBJECTIVES: To systematically evaluate risk factors for severe outcomes in patients with avian influenza H5N1 infection. DATA SOURCES: MEDLINE, EMBASE, CINAHL, GlobalHealth, and CENTRAL through March 2011. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies of any design published in English, French, Spanish, German or Korean that reported on risk factor-outcome combinations of interest in participants with confirmed H5N1 infections. Outcomes considered included death, ventilator support, hospital and ICU admission, pneumonia, and composite outcomes. STUDY APPRAISAL: Risk of bias was assessed using the Newcastle-Ottawa scale (NOS. RESULTS: We identified 20 studies reporting on 999 patients infected with H5N1. The majority of studies (n = 14, 70% were at intermediate risk of bias, i.e. 4-6 points on the NOS. Females were at increased risk of death (OR 1.75, 95% CI 1.27-2.44, while young age, in particular <5 years of age (OR 0.44, 95% CI 0.25-0.79 for death, was protective. Data on traditional risk factors was scarce and requires further studies. Another major limitation in the published literature was lack of adjustment for confounders. INTERPRETATION: Females were at increased risk for complications following H5N1 infection while young age protected against severe outcomes. Research on traditional risk factors was limited and is required.

  5. Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

    Science.gov (United States)

    Zeng, Hui; Goldsmith, Cynthia S.; Maines, Taronna R.; Belser, Jessica A.; Gustin, Kortney M.; Pekosz, Andrew; Zaki, Sherif R.; Katz, Jacqueline M.

    2013-01-01

    Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses. PMID:23255802

  6. Spatial and temporal association of outbreaks of H5N1 influenza virus infection in wild birds with the 0 degrees C isotherm.

    Directory of Open Access Journals (Sweden)

    Leslie A Reperant

    2010-04-01

    Full Text Available Wild bird movements and aggregations following spells of cold weather may have resulted in the spread of highly pathogenic avian influenza virus (HPAIV H5N1 in Europe during the winter of 2005-2006. Waterbirds are constrained in winter to areas where bodies of water remain unfrozen in order to feed. On the one hand, waterbirds may choose to winter as close as possible to their breeding grounds in order to conserve energy for subsequent reproduction, and may be displaced by cold fronts. On the other hand, waterbirds may choose to winter in regions where adverse weather conditions are rare, and may be slowed by cold fronts upon their journey back to the breeding grounds, which typically starts before the end of winter. Waterbirds will thus tend to aggregate along cold fronts close to the 0 degrees C isotherm during winter, creating conditions that favour HPAIV H5N1 transmission and spread. We determined that the occurrence of outbreaks of HPAIV H5N1 infection in waterbirds in Europe during the winter of 2005-2006 was associated with temperatures close to 0 degrees C. The analysis suggests a significant spatial and temporal association of outbreaks caused by HPAIV H5N1 in wild birds with maximum surface air temperatures of 0 degrees C-2 degrees C on the day of the outbreaks and the two preceding days. At locations where waterbird census data have been collected since 1990, maximum mallard counts occurred when average and maximum surface air temperatures were 0 degrees C and 3 degrees C, respectively. Overall, the abundance of mallards (Anas platyrhynchos and common pochards (Aythya ferina was highest when surface air temperatures were lower than the mean temperatures of the region investigated. The analysis implies that waterbird movements associated with cold weather, and congregation of waterbirds along the 0 degrees C isotherm likely contributed to the spread and geographical distribution of outbreaks of HPAIV H5N1 infection in wild birds in

  7. Low adherence to influenza vaccination campaigns: is the H1N1 virus pandemic to be blamed?

    Directory of Open Access Journals (Sweden)

    Trivellin Valeria

    2011-11-01

    Full Text Available Abstract Background Over the last few months, debates about the handling of the influenza virus A (H1N1 pandemic took place, in particular regarding the change of the WHO pandemic definition, economic interests, the dramatic communication style of mass media. The activation of plans to reduce the virus diffusion resulted in an important investment of resources. Were those investments proportionate to the risk? Was the pandemic overrated? The workload of the Pediatric Emergency Room (P.E.R. at a teaching hospital in Varese (Northern Italy was investigated in order to evaluate the local diffusion and severity of the new H1N1 influenza epidemic. Discussion A 100% increase of the number of P.E.R. visits, particularly for influenza-like illness, was recorded during weeks 42-46 of 2009 (October, 17 to November, 2; the low rate of hospitalization and the mild presentation of the infection gave rise to the conclusion that the pandemic risk was overrated. Mass media communications concerning the new virus created a disproportionate fear in the population that significantly enhanced the burden of cares at the hospital. In the absence of generally implemented measures for etiological diagnosis, the actual incidence of the H1N1 infection could not be estimated. Virus identification, in fact, was limited to children showing severe symptoms after consultancy with an infectious disease specialist. The alarming nature of the communication campaign and the choice to limit etiologic diagnosis to severe cases created a climate of uncertainty which significantly contributed to the massive admissions to the P.E.R.. Summary The communication strategy adopted by the mass media was an important element during the pandemic: the absence of clarity contributed to the spread of a pandemic phobia that appeared to result more from the sensationalism of the campaign than from infection with the novel influenza A variant of human, avian, swine origin virus. One relevant effect

  8. High-resolution computed tomography findings of swine-origin influenza A (H1N1) virus (S-OIV) infection: comparison with scrub typhus

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Bang Sil; Lee, In Jae; Lee, Kwanseop [Dept. of Radiology, Hallym Univ. College of Medicine, Seoul (Korea, Republic of)], E-mail: ijlee2003@medimail.co.kr; Im, Hyoung June [Dept. of Occupational Medicine, Hallym Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-07-15

    Background. Swine-origin influenza A (H1N1) virus (S-OIV) infection and scrub typhus, also known as tsutsugamushi disease can manifest as acute respiratory illnesses, particularly during the late fall or early winter, with similar radiographic findings, such as a predominance of ground-glass opacity (GGO). Purpose. To differentiate S-OIV infection from scrub typhus using high-resolution computed tomography (HRCT). Material and Methods. We retrospectively reviewed the HRCT findings of 14 patients with S-OIV infection and 10 patients with scrub typhus. We assessed the location, cross-sectional distribution, and the presence of a peribronchovascular distribution of GGO and consolidations on HRCT. We also assessed the presence of interlobular septal thickening, bronchial wall thickening, pneumothorax, pneumomediastinum, pleural effusion, and mediastinal or axillary lymph node enlargement. Results. Scrub typhus was more common than S-OIV in elderly patients (P < 0.001). The monthly incidences of S-OIV and scrub typhus infection reached a peak between October and November. About 86% of S-OIV patients and 80% of scrub typhus patients presented with GGO. About 67% of the GGO lesions in S-OIV had a peribronchovascular distribution, but this was absent in scrub typhus (P = 0.005). Consolidation (93% vs. 10%, P < 0.001) and bronchial wall thickening (43% vs. 0%, P = 0.024) were more frequent in S-OIV infection than scrub typhus. Interlobular septal thickening (90% vs. 36%, P = 0.013) and axillary lymphadenopathy (90% vs. 0%, P < 0.001) were more common in scrub typhus than S-OIV infection. Conclusion. There was considerable overlap in HRCT findings between S-OIV infection and scrub typhus. However, S-OIV showed a distinctive peribronchovascular distribution of GGO lesions. Consolidation and bronchial wall thickening were seen more frequently in S-OIV infection, whereas interlobular septal thickening and axillary lymphadenopathy were more common in scrub typhus. Thus, CT could

  9. High-resolution computed tomography findings of swine-origin influenza A (H1N1) virus (S-OIV) infection: comparison with scrub typhus

    International Nuclear Information System (INIS)

    Jo, Bang Sil; Lee, In Jae; Lee, Kwanseop; Im, Hyoung June

    2012-01-01

    Background. Swine-origin influenza A (H1N1) virus (S-OIV) infection and scrub typhus, also known as tsutsugamushi disease can manifest as acute respiratory illnesses, particularly during the late fall or early winter, with similar radiographic findings, such as a predominance of ground-glass opacity (GGO). Purpose. To differentiate S-OIV infection from scrub typhus using high-resolution computed tomography (HRCT). Material and Methods. We retrospectively reviewed the HRCT findings of 14 patients with S-OIV infection and 10 patients with scrub typhus. We assessed the location, cross-sectional distribution, and the presence of a peribronchovascular distribution of GGO and consolidations on HRCT. We also assessed the presence of interlobular septal thickening, bronchial wall thickening, pneumothorax, pneumomediastinum, pleural effusion, and mediastinal or axillary lymph node enlargement. Results. Scrub typhus was more common than S-OIV in elderly patients (P < 0.001). The monthly incidences of S-OIV and scrub typhus infection reached a peak between October and November. About 86% of S-OIV patients and 80% of scrub typhus patients presented with GGO. About 67% of the GGO lesions in S-OIV had a peribronchovascular distribution, but this was absent in scrub typhus (P = 0.005). Consolidation (93% vs. 10%, P < 0.001) and bronchial wall thickening (43% vs. 0%, P = 0.024) were more frequent in S-OIV infection than scrub typhus. Interlobular septal thickening (90% vs. 36%, P = 0.013) and axillary lymphadenopathy (90% vs. 0%, P < 0.001) were more common in scrub typhus than S-OIV infection. Conclusion. There was considerable overlap in HRCT findings between S-OIV infection and scrub typhus. However, S-OIV showed a distinctive peribronchovascular distribution of GGO lesions. Consolidation and bronchial wall thickening were seen more frequently in S-OIV infection, whereas interlobular septal thickening and axillary lymphadenopathy were more common in scrub typhus. Thus, CT could

  10. Design and performance of the CDC real-time reverse transcriptase PCR swine flu panel for detection of 2009 A (H1N1) pandemic influenza virus.

    Science.gov (United States)

    Shu, Bo; Wu, Kai-Hui; Emery, Shannon; Villanueva, Julie; Johnson, Roy; Guthrie, Erica; Berman, LaShondra; Warnes, Christine; Barnes, Nathelia; Klimov, Alexander; Lindstrom, Stephen

    2011-07-01

    Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10(-1.3 - -0.7) 50% infectious doses (ID(50)) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.

  11. Pathology of natural infections by H5N1 highly pathogenic avian influenza virus in mute (Cygnus olor) and whooper (Cygnus cygnus) swans.

    Science.gov (United States)

    Teifke, J P; Klopfleisch, R; Globig, A; Starick, E; Hoffmann, B; Wolf, P U; Beer, M; Mettenleiter, T C; Harder, T C

    2007-03-01

    Mortality in wild aquatic birds due to infection with highly pathogenic avian influenza viruses (HPAIV) is a rare event. During the recent outbreak of highly pathogenic avian influenza in Germany, mortality due to H5N1 HPAIV was observed among mute and whooper swans as part of a rapid spread of this virus. In contrast to earlier reports, swans appeared to be highly susceptible and represented the mainly affected species. We report gross and histopathology and distribution of influenza virus antigen in mute and whooper swans that died after natural infection with H5N1 HPAIV. At necropsy, the most reliable lesions were multifocal hemorrhagic necrosis in the pancreas, pulmonary congestion and edema, and subepicardial hemorrhages. Major histologic lesions were acute pancreatic necrosis, multifocal necrotizing hepatitis, and lymphoplasmacytic encephalitis with neuronal necrosis. Adrenals displayed consistently scattered cortical and medullary necrosis. In spleen and Peyer's patches, mild lymphocyte necrosis was present. Immunohistochemical demonstration of HPAIV nucleoprotein in pancreas, adrenals, liver, and brain was strongly consistent with histologic lesions. In the brain, a large number of neurons and glial cells, especially Purkinje cells, showed immunostaining. Occasionally, ependymal cells of the spinal cord were also positive. In the lungs, influenza virus antigen was identified in a few endothelial cells but not within pneumocytes. The infection of the central nervous system supports the view that the neurotropism of H5N1 HPAIV leads to nervous disturbances with loss of orientation. More investigations are necessary to clarify the mechanisms of the final circulatory failure, lung edema, and rapid death of the swans.

  12. Airway Mucosal Immune-suppression in Neonates of Mothers Receiving A(H1N1)pnd09 Vaccination During Pregnancy

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Bischoff, Anne L.; Folsgaard, Nilofar V.

    2015-01-01

    , IL-5, IL-13, eotaxin-1, eotaxin-3, TARC, MDC, IL-17, IL-1 beta, IL-8, transforming growth factor beta (TGF)-beta 1, IL-10 and IL-2. Infections were monitored the first year of life by daily diary cards and clinical controls. Results: Neonates of mothers vaccinated during pregnancy had significant up...... significant and positive association to up-regulation of TGF-beta 1 levels (P = 0.0003) and significant negative association to other mediators. The study was not powered to study differences in the incidence of infections in early infancy which did not differ between the study groups. Conclusion: Influenza A......(H1N1) pnd09 vaccination during pregnancy up-regulates TGF-beta 1 and down-regulates key mediators of the protective immunity....

  13. Severe Pneumonia Caused by Influenza A (H1N1 Virus Successfully Managed with Extracorporeal Life Support in a Comorbid Former Preterm Infant

    Directory of Open Access Journals (Sweden)

    Genny Raffaeli

    2017-03-01

    Full Text Available Influenza A (H1N1 virus infection is a global health burden, leading to significant pediatric morbidity and mortality. Prematurity, young age and comorbidities are important risk factors for unfavorable outcomes. Preventive strategies, such as healthcare workers and household contacts vaccination as well as the implementation of infection control practices during the epidemic season, are crucial to protect the most vulnerable populations. Early diagnosis, timely administration of antiviral drugs and supportive therapy are crucial to lead to a complete recovery. When conventional treatment fails, extracorporeal life support (ECLS may be employed. In neonates and young infants, this high-tech support is burdened by specific technical complexity. Despite the potential risks related to this aggressive approach, ECLS is a life-saving procedure in 65% of pediatric viral pneumonia and in 73% of sepsis cases. Here, we report the successful outcome of a 51-day formerly preterm infant, suffering from a surgical necrotizing enterocolitis (NEC, complicated with hospital-acquired pneumonia due to influenza A (H1N1 virus. She developed a severe respiratory failure, unresponsive to conventional therapy, and successfully treated with ECLS. To our knowledge, this is the first report on the use of ECLS in a formerly preterm infant, suffering from NEC complicated by influenza A (H1N1 virus infection.

  14. Costo-efectividad en la detección de influenza H1N1: datos clínicos versus pruebas rápidas Cost-effectiveness in the detection of influenza H1N1: clinical data versus rapid tests

    Directory of Open Access Journals (Sweden)

    Jorge González-Canudas

    2011-01-01

    conducted in a reference laboratory and blinded to the results of the RIDT. An economic evaluation also was conducted to estimate the budgetary impact of using the RIDT. RESULTS: The study included 78 patients, 39 of whom tested positive for influenza H1N1 and 6 tested positive for seasonal influenza A, according to the results of the rRT-PCR. The ILI clinical data yielded a sensitivity of 96% and specificity of 21%; the RIDT yielded a sensitivity of 76% and specificity of 82%; and the ILI clinical data and RIDT together yielded a sensitivity of 96% and specificity of 100%. The positive likelihood quotient for ILI-headaches was 31.5 and that of ILI-odynophagia, 330. The use of RIDT yielded savings of US$12.6 per each suspected case. CONCLUSIONS: Use of the RIDT to aid in the diagnosis of influenza H1N1 increases certainty and lowers the average cost per suspected and infected patient.

  15. NS1 of H7N9 Influenza A Virus Induces NO-Mediated Cellular Senescence in Neuro2a Cells

    OpenAIRE

    Yinxia Yan; Yongming Du; Huali Zheng; Gefei Wang; Rui Li; Jieling Chen; Kangsheng Li

    2017-01-01

    Background/Aims: The novel avian H7N9 influenza A virus has been detected in brain tissues and associated with central nervous system (CNS) symptoms in infected human and mice. Roles of its virulence factor, NS1 protein in influenza virus infected neuron has yet to be explored. Methods: Nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in H7N9/NS1-expressed Neuro2a cells were detected by Griess test and western blotting. Cell proliferation rate of H7N9/NS1-expres...

  16. Bis(1-benzyl-1H-benzimidazole-κN3dichloridozinc

    Directory of Open Access Journals (Sweden)

    Rachid Bouhfid

    2014-03-01

    Full Text Available In the title compound, [ZnCl2(C14H12N22], the ZnII atom exhibits a distorted tetrahedral coordination geometry involving two chloride anions and two N-atom donors from 1-benzyl-1H-benzimidazole ligands. In both ligands, the benzyl and benzimidazole rings are nearly perpendicular [dihedral angles = 81.7 (2 and 81.5 (2°]. The two benzimidazole systems are essentially planar [maximum deviations = 0.015 (3 and 0.020 (2 Å] and form a dihedral angle of 78.09 (8°. In the crystal, centrosymmetrically related molecules are linked by pairs of C—H...Cl hydrogen bonds into chains parallel to the a axis.

  17. Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

    NARCIS (Netherlands)

    Lee, Laurel Yong-Hwa; Anh, Ha Do Lien; Simmons, Cameron; de Jong, Menno D.; Chau, Nguyen Van Vinh; Schumacher, Reto; Peng, Yan Chun; McMichael, Andrew J.; Farrar, Jeremy J.; Smith, Geoffrey L.; Townsend, Alain R. M.; Askonas, Brigitte A.; Rowland-Jones, Sarah; Dong, Tao

    2008-01-01

    The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to

  18. Core Histones H2B and H4 Are Mobilized during Infection with Herpes Simplex Virus 1

    Science.gov (United States)

    Conn, Kristen L.; Hendzel, Michael J.; Schang, Luis M.

    2011-01-01

    The infecting genomes of herpes simplex virus 1 (HSV-1) are assembled into unstable nucleosomes soon after nuclear entry. The source of the histones that bind to these genomes has yet to be addressed. However, infection inhibits histone synthesis. The histones that bind to HSV-1 genomes are therefore most likely those previously bound in cellular chromatin. In order for preexisting cellular histones to associate with HSV-1 genomes, however, they must first disassociate from cellular chromatin. Consistently, we have shown that linker histones are mobilized during HSV-1 infection. Chromatinization of HSV-1 genomes would also require the association of core histones. We therefore evaluated the mobility of the core histones H2B and H4 as measures of the mobilization of H2A-H2B dimers and the more stable H3-H4 core tetramer. H2B and H4 were mobilized during infection. Their mobilization increased the levels of H2B and H4 in the free pools and decreased the rate of H2B fast chromatin exchange. The histones in the free pools would then be available to bind to HSV-1 genomes. The mobilization of H2B occurred independently from HSV-1 protein expression or DNA replication although expression of HSV-1 immediate-early (IE) or early (E) proteins enhanced it. The mobilization of core histones H2B and H4 supports a model in which the histones that associate with HSV-1 genomes are those that were previously bound in cellular chromatin. Moreover, this mobilization is consistent with the assembly of H2A-H2B and H3-H4 dimers into unstable nucleosomes with HSV-1 genomes. PMID:21994445

  19. Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic - China, October 1, 2016-August 7, 2017.

    Science.gov (United States)

    Kile, James C; Ren, Ruiqi; Liu, Liqi; Greene, Carolyn M; Roguski, Katherine; Iuliano, A Danielle; Jang, Yunho; Jones, Joyce; Thor, Sharmi; Song, Ying; Zhou, Suizan; Trock, Susan C; Dugan, Vivien; Wentworth, David E; Levine, Min Z; Uyeki, Timothy M; Katz, Jacqueline M; Jernigan, Daniel B; Olsen, Sonja J; Fry, Alicia M; Azziz-Baumgartner, Eduardo; Davis, C Todd

    2017-09-08

    Among all influenza viruses assessed using CDC's Influenza Risk Assessment Tool (IRAT), the Asian lineage avian influenza A(H7N9) virus (Asian H7N9), first reported in China in March 2013,* is ranked as the influenza virus with the highest potential pandemic risk (1). During October 1, 2016-August 7, 2017, the National Health and Family Planning Commission of China; CDC, Taiwan; the Hong Kong Centre for Health Protection; and the Macao CDC reported 759 human infections with Asian H7N9 viruses, including 281 deaths, to the World Health Organization (WHO), making this the largest of the five epidemics of Asian H7N9 infections that have occurred since 2013 (Figure 1). This report summarizes new viral and epidemiologic features identified during the fifth epidemic of Asian H7N9 in China and summarizes ongoing measures to enhance pandemic preparedness. Infections in humans and poultry were reported from most areas of China, including provinces bordering other countries, indicating extensive, ongoing geographic spread. The risk to the general public is very low and most human infections were, and continue to be, associated with poultry exposure, especially at live bird markets in mainland China. Throughout the first four epidemics of Asian H7N9 infections, only low pathogenic avian influenza (LPAI) viruses were detected among human, poultry, and environmental specimens and samples. During the fifth epidemic, mutations were detected among some Asian H7N9 viruses, identifying the emergence of high pathogenic avian influenza (HPAI) viruses as well as viruses with reduced susceptibility to influenza antiviral medications recommended for treatment. Furthermore, the fifth-epidemic viruses diverged genetically into two separate lineages (Pearl River Delta lineage and Yangtze River Delta lineage), with Yangtze River Delta lineage viruses emerging as antigenically different compared with those from earlier epidemics. Because of its pandemic potential, candidate vaccine viruses

  20. Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1 virus infection during pregnancy.

    Directory of Open Access Journals (Sweden)

    Miloje Savic

    Full Text Available Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI responses in pandemic influenza A(H1N1pdm09 (pdm09 virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu. The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC. Infected cases (N = 75 were defined by having a serum hemagglutination inhibition (HI titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75 were randomly selected among non-infected pregnant women (HI titer <10. In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7- and naive (CD45RA+CCR7+ CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+ CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design.