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Sample records for confirmed influenza infection

  1. 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

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

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    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.

  3. Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

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    Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

    2018-05-31

    New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

  4. The effectiveness of seasonal trivalent inactivated influenza vaccine in preventing laboratory confirmed influenza hospitalisations in Auckland, New Zealand in 2012

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    Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael; Widdowson, Marc-Alain; Kelly, Heath

    2015-01-01

    Background Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). Methods A case test-negative study was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalization with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in Central, South and East Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season Results The propensity and season adjusted vaccine effectiveness (VE) was estimated as 37% (95% CI 18;51). The VE point estimate against influenza A (H1N1) was higher than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 51% (95% CI 28;67) in patients aged 18-64 years but only 6% (95% CI -51;42) in those aged 65 years and above. Conclusion Prospective surveillance for SARI has been successfully established in NZ . This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against hospitalisation for laboratory-confirmed influenza. PMID:24768730

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

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    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

  6. Avian Influenza A Virus Infections in Humans

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    ... people has ranged from mild to severe. Avian Influenza Transmission Avian Influenza Transmission Infographic [555 KB, 2 pages] Spanish [ ... important for public health. Signs and Symptoms of Avian Influenza A Virus Infections in Humans The reported signs ...

  7. The effectiveness of seasonal trivalent inactivated influenza vaccine in preventing laboratory confirmed influenza hospitalisations in Auckland, New Zealand in 2012.

    Science.gov (United States)

    Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael G; Widdowson, Marc-Alain; Kelly, Heath

    2014-06-17

    Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). A case test-negative design was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalisation with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in South and Central Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season. The propensity and season adjusted vaccine effectiveness (VE) was estimated as 39% (95% CI 16;56). The VE point estimate against influenza A (H1N1) was lower than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 59% (95% CI 26;77) in patients aged 45-64 years but only 8% (-78;53) in those aged 65 years and above. Prospective surveillance for SARI has been successfully established in NZ. This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against influenza positive hospitalisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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    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

  9. Influenza Virus Infection in Nonhuman Primates

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    Karlsson, Erik A.; Engel, Gregory A.; Feeroz, M.M.; San, Sorn; Rompis, Aida; Lee, Benjamin P. Y.-H.; Shaw, Eric; Oh, Gunwha; Schillaci, Michael A.; Grant, Richard; Heidrich, John; Schultz-Cherry, Stacey

    2012-01-01

    To determine whether nonhuman primates are infected with influenza viruses in nature, we conducted serologic and swab studies among macaques from several parts of the world. Our detection of influenza virus and antibodies to influenza virus raises questions about the role of nonhuman primates in the ecology of influenza. PMID:23017256

  10. Secondary Bacterial Infections Associated with Influenza Pandemics

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    Morris, Denise E.; Cleary, David W.; Clarke, Stuart C.

    2017-01-01

    Lower and upper respiratory infections are the fourth highest cause of global mortality (Lozano et al., 2012). Epidemic and pandemic outbreaks of respiratory infection are a major medical concern, often causing considerable disease and a high death toll, typically over a relatively short period of time. Influenza is a major cause of epidemic and pandemic infection. Bacterial co/secondary infection further increases morbidity and mortality of influenza infection, with Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus reported as the most common causes. With increased antibiotic resistance and vaccine evasion it is important to monitor the epidemiology of pathogens in circulation to inform clinical treatment and development, particularly in the setting of an influenza epidemic/pandemic. PMID:28690590

  11. Secondary Bacterial Infections Associated with Influenza Pandemics

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    Denise E. Morris

    2017-06-01

    Full Text Available Lower and upper respiratory infections are the fourth highest cause of global mortality (Lozano et al., 2012. Epidemic and pandemic outbreaks of respiratory infection are a major medical concern, often causing considerable disease and a high death toll, typically over a relatively short period of time. Influenza is a major cause of epidemic and pandemic infection. Bacterial co/secondary infection further increases morbidity and mortality of influenza infection, with Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus reported as the most common causes. With increased antibiotic resistance and vaccine evasion it is important to monitor the epidemiology of pathogens in circulation to inform clinical treatment and development, particularly in the setting of an influenza epidemic/pandemic.

  12. Human Infection with Avian Influenza A(H7N9) Virus - China

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    ... response operations Diseases Biorisk reduction Disease outbreak news Human infection with avian influenza A(H7N9) virus – China ... Region (SAR) notified WHO of a laboratory-confirmed human infection with avian influenza A(H7N9) virus and ...

  13. Vaccine effectiveness against medically attended laboratory-confirmed influenza in Japan, 2011-2012 Season.

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    Motoi Suzuki

    Full Text Available The objective of this study was to estimate influenza vaccine effectiveness (VE against medically attended, laboratory-confirmed influenza during the 2011-2012 season in Japan using a test-negative case-control study design. The effect of co-circulating non-influenza respiratory viruses (NIRVs on VE estimates was also explored. Nasopharyngeal swab samples were collected from outpatients with influenza-like illnesses (ILIs in a community hospital in Nagasaki, Japan. Thirteen respiratory viruses (RVs, including influenza A and B, were identified from the samples using a multiplex polymerase chain reaction. The difference in VE point estimates was assessed using three different controls: ILI patients that tested negative for influenza, those that tested negative for all RVs, and those that tested positive for NIRVs. The adjusted VE against medically attended, laboratory-confirmed influenza using all influenza-negative controls was 5.3% (95% confidence interval [CI], -60.5 to 44.1. The adjusted VEs using RV-negative and NIRV-positive controls were -1.5% (95% CI, -74.7 to 41 and 50% (95% CI, -43.2 to 82.5, respectively. Influenza VE was limited in Japan during the 2011-2012 season. Although the evidence is not conclusive, co-circulating NIRVs may affect influenza VE estimates in test-negative case-control studies.

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

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    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

  15. Elementary School-Based Influenza Vaccination: Evaluating Impact on Respiratory Illness Absenteeism and Laboratory-Confirmed Influenza

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    Kjos, Sonia A.; Irving, Stephanie A.; Meece, Jennifer K.; Belongia, Edward A.

    2013-01-01

    Background Studies of influenza vaccine effectiveness in schools have assessed all-cause absenteeism rather than laboratory-confirmed influenza. We conducted an observational pilot study to identify absences due to respiratory illness and laboratory-confirmed influenza in schools with and without school-based vaccination. Methods A local public health agency initiated school-based influenza vaccination in two Wisconsin elementary schools during October 2010 (exposed schools); two nearby schools served as a comparison group (non-exposed schools). Absences due to fever or cough illness were monitored for 12 weeks. During the 4 weeks of peak influenza activity, parents of absent children with fever/cough illness were contacted and offered influenza testing. Results Parental consent for sharing absenteeism data was obtained for 937 (57%) of 1,640 students. Fifty-two percent and 28%, respectively, of all students in exposed and non-exposed schools were vaccinated. Absences due to fever or cough illness were significantly lower in the exposed schools during seven of 12 surveillance weeks. Twenty-seven percent of students at exposed schools and 39% at unexposed schools had one or more days of absence due to fever/cough illness (pabsenteeism due to fever or cough illness, but not absenteeism for other reasons. Although nonspecific, absence due to fever or cough illness may be a useful surrogate endpoint in school-based studies if identification of laboratory confirmed influenza is not feasible. PMID:23991071

  16. [Contemporary threat of influenza virus infection].

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    Płusa, Tadeusz

    2010-01-01

    Swine-origine H1N1 influenza virus (S-OIV) caused a great mobilization of health medical service over the world. Now it is well known that a vaccine against novel virus is expected as a key point in that battle. In the situation when recommended treatment with neuraminidase inhibitors is not sufficient to control influenza A/H1N1 viral infection the quick and precisely diagnostic procedures should be applied to save and protect our patients.

  17. Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage.

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    Merani, Shahzma; Kuchel, George A; Kleppinger, Alison; McElhaney, Janet E

    2018-07-01

    Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear. The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection. Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection. HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose. This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in

  18. Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

    International Nuclear Information System (INIS)

    Sato, Yoshiko; Yoshioka, Kenichi; Suzuki, Chie; Awashima, Satoshi; Hosaka, Yasuhiro; Yewdell, Jonathan; Kuroda, Kazumichi

    2003-01-01

    We studied influenza virus M1 protein by generating HeLa and MDCK cell lines that express M1 genetically fused to green fluorescent protein (GFP). GFP-M1 was incorporated into virions produced by influenza virus infected MDCK cells expressing the fusion protein indicating that the fusion protein is at least partially functional. Following infection of either HeLa or MDCK cells with influenza A virus (but not influenza B virus), GFP-M1 redistributes from its cytosolic/nuclear location and accumulates in nuclear dots. Immunofluorescence revealed that the nuclear dots represent nuclear dot 10 (ND10) structures. The colocalization of authentic M1, as well as NS1 and NS2 protein, with ND10 was confirmed by immunofluorescence following in situ isolation of ND10. These findings demonstrate a previously unappreciated involvement of influenza virus with ND10, a structure involved in cellular responses to immune cytokines as well as the replication of a rapidly increasing list of viruses

  19. INFLUENZA IMMUNISATION IN HIV-INFECTED PERSONS

    African Journals Online (AJOL)

    in 1997' (surpassing the 6O'lb vaccine coverage goal for the country's Healthy People 2000 Project). ... (i) are HIV-infected persons at special risk for influenza complications and is annual immunisation .... virus type' 1 rep :cation can be increased in peripheral 0100d of sero- positive patiems aher influenrc. vacdnation.

  20. Influenza virus infection among pediatric patients reporting diarrhea and influenza-like illness

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    Uyeki Timothy M

    2010-01-01

    Full Text Available Abstract Background Influenza is a major cause of morbidity and hospitalization among children. While less often reported in adults, gastrointestinal symptoms have been associated with influenza in children, including abdominal pain, nausea, vomiting, and diarrhea. Methods From September 2005 and April 2008, pediatric patients in Indonesia presenting with concurrent diarrhea and influenza-like illness were enrolled in a study to determine the frequency of influenza virus infection in young patients presenting with symptoms less commonly associated with an upper respiratory tract infection (URTI. Stool specimens and upper respiratory swabs were assayed for the presence of influenza virus. Results Seasonal influenza A or influenza B viral RNA was detected in 85 (11.6% upper respiratory specimens and 21 (2.9% of stool specimens. Viable influenza B virus was isolated from the stool specimen of one case. During the time of this study, human infections with highly pathogenic avian influenza A (H5N1 virus were common in the survey area. However, among 733 enrolled subjects, none had evidence of H5N1 virus infection. Conclusions The detection of influenza viral RNA and viable influenza virus from stool suggests that influenza virus may be localized in the gastrointestinal tract of children, may be associated with pediatric diarrhea and may serve as a potential mode of transmission during seasonal and epidemic influenza outbreaks.

  1. Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

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    Asher Maroof

    2014-01-01

    Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

  2. Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention

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    Smallwood, Heather S.; Duan, Susu; Morfouace, Marie; Rezinciuc, Svetlana; Shulkin, Barry L.; Shelat, Anang; Zink, Erika E.; Milasta, Sandra; Bajracharya, Resha; Oluwaseum, Ajayi J.; Roussel, Martine F.; Green, Douglas R.; Pasa-Tolic, Ljiljana; Thomas, Paul G.

    2017-05-01

    Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention.

  3. Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention

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    Heather S. Smallwood

    2017-05-01

    Full Text Available Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on the early stages of viral replication. BEZ235 significantly increased survival in mice, while reducing viral titer. We show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention.

  4. DAMPs and influenza virus infection in ageing.

    Science.gov (United States)

    Samy, Ramar Perumal; Lim, Lina H K

    2015-11-01

    Influenza A virus (IAV) is a serious global health problem worldwide due to frequent and severe outbreaks. IAV causes significant morbidity and mortality in the elderly population, due to the ineffectiveness of the vaccine and the alteration of T cell immunity with ageing. The cellular and molecular link between ageing and virus infection is unclear and it is possible that damage associated molecular patterns (DAMPs) may play a role in the raised severity and susceptibility of virus infections in the elderly. DAMPs which are released from damaged cells following activation, injury or cell death can activate the immune response through the stimulation of the inflammasome through several types of receptors found on the plasma membrane, inside endosomes after endocytosis as well as in the cytosol. In this review, the detriment in the immune system during ageing and the links between influenza virus infection and ageing will be discussed. In addition, the role of DAMPs such as HMGB1 and S100/Annexin in ageing, and the enhanced morbidity and mortality to severe influenza infection in ageing will be highlighted. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

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    Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

    2012-01-01

    Please cite this paper as: Hall et al. (2012) Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00358.x. Background  Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are l...

  6. Incidence of influenza-like illness and severe acute respiratory infection during three influenza seasons in Bangladesh, 2008–2010

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    Alamgir, ASM; Rahman, Mustafizur; Homaira, Nusrat; Sohel, Badrul Munir; Sharker, MA Yushuf; Zaman, Rashid Uz; Dee, Jacob; Gurley, Emily S; Al Mamun, Abdullah; Mah-E-Muneer, Syeda; Fry, Alicia M; Widdowson, Marc-Alain; Bresee, Joseph; Lindstrom, Stephen; Azim, Tasnim; Brooks, Abdullah; Podder, Goutam; Hossain, M Jahangir; Rahman, Mahmudur; Luby, Stephen P

    2012-01-01

    Abstract Objective To determine how much influenza contributes to severe acute respiratory illness (SARI), a leading cause of death in children, among people of all ages in Bangladesh. Methods Physicians obtained nasal and throat swabs to test for influenza virus from patients who were hospitalized within 7 days of the onset of severe acute respiratory infection (SARI) or who consulted as outpatients for influenza-like illness (ILI). A community health care utilization survey was conducted to determine the proportion of hospital catchment area residents who sought care at study hospitals and calculate the incidence of influenza using this denominator. Findings The estimated incidence of SARI associated with influenza in children < 5 years old was 6.7 (95% confidence interval, CI: 0–18.3); 4.4 (95% CI: 0–13.4) and 6.5 per 1000 person–years (95% CI: 0–8.3/1000) during the 2008, 2009 and 2010 influenza seasons, respectively. The incidence of SARI in people aged ≥ 5 years was 1.1 (95% CI: 0.4–2.0) and 1.3 (95% CI: 0.5–2.2) per 10 000 person–years during 2009 and 2010, respectively. The incidence of medically attended, laboratory-confirmed seasonal influenza in outpatients with ILI was 10 (95% CI: 8–14), 6.6 (95% CI: 5–9) and 17 per 100 person–years (95% CI: 13–22) during the 2008, 2009 and 2010 influenza seasons, respectively. Conclusion Influenza-like illness is a frequent cause of consultation in the outpatient setting in Bangladesh. Children aged less than 5 years are hospitalized for influenza in greater proportions than children in other age groups. PMID:22271960

  7. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

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    Jong Seok Lee

    2014-01-01

    Full Text Available Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8 probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

  8. Mortality Attributable to Seasonal Influenza A and B Infections in Thailand, 2005–2009: A Longitudinal Study

    Science.gov (United States)

    Cooper, Ben S.; Kotirum, Surachai; Kulpeng, Wantanee; Praditsitthikorn, Naiyana; Chittaganpitch, Malinee; Limmathurotsakul, Direk; Day, Nicholas P. J.; Coker, Richard; Teerawattananon, Yot; Meeyai, Aronrag

    2015-01-01

    Influenza epidemiology differs substantially in tropical and temperate zones, but estimates of seasonal influenza mortality in developing countries in the tropics are lacking. We aimed to quantify mortality due to seasonal influenza in Thailand, a tropical middle-income country. Time series of polymerase chain reaction–confirmed influenza infections between 2005 and 2009 were constructed from a sentinel surveillance network. These were combined with influenza-like illness data to derive measures of influenza activity and relationships to mortality by using a Bayesian regression framework. We estimated 6.1 (95% credible interval: 0.5, 12.4) annual deaths per 100,000 population attributable to influenza A and B, predominantly in those aged ≥60 years, with the largest contribution from influenza A(H1N1) in 3 out of 4 years. For A(H3N2), the relationship between influenza activity and mortality varied over time. Influenza was associated with increases in deaths classified as resulting from respiratory disease (posterior probability of positive association, 99.8%), cancer (98.6%), renal disease (98.0%), and liver disease (99.2%). No association with circulatory disease mortality was found. Seasonal influenza infections are associated with substantial mortality in Thailand, but evidence for the strong relationship between influenza activity and circulatory disease mortality reported in temperate countries is lacking. PMID:25899091

  9. CXCR1/2 Antagonism Is Protective during Influenza and Post-Influenza Pneumococcal Infection

    Directory of Open Access Journals (Sweden)

    Luciana P. Tavares

    2017-12-01

    Full Text Available RationaleInfluenza A infections are a leading cause of morbidity and mortality worldwide especially when associated with secondary pneumococcal infections. Inflammation is important to control pathogen proliferation but may also cause tissue injury and death. CXCR1/2 are chemokine receptors relevant for the recruitment of neutrophils. We investigated the role of CXCR1/2 during influenza, pneumococcal, and post-influenza pneumococcal infections.MethodsMice were infected with influenza A virus (IAV or Streptococcus pneumoniae and then treated daily with the CXCR1/2 antagonist DF2162. To study secondary pneumococcal infection, mice were infected with a sublethal inoculum of IAV then infected with S. pneumoniae 14 days later. DF2162 was given in a therapeutic schedule from days 3 to 6 after influenza infection. Lethality, weight loss, inflammation, virus/bacteria counts, and lung injury were assessed.ResultsCXCL1 and CXCL2 were produced at high levels during IAV infection. DF2162 treatment decreased morbidity and this was associated with decreased infiltration of neutrophils in the lungs and reduced pulmonary damage and viral titers. During S. pneumoniae infection, DF2162 treatment decreased neutrophil recruitment, pulmonary damage, and lethality rates, without affecting bacteria burden. Therapeutic treatment with DF2162 during sublethal IAV infection reduced the morbidity associated with virus infection and also decreased the magnitude of inflammation, lung damage, and number of bacteria in the blood of mice subsequently infected with S. pneumoniae.ConclusionModulation of the inflammatory response by blocking CXCR1/2 improves disease outcome during respiratory influenza and pneumococcal infections, without compromising the ability of the murine host to deal with infection. Altogether, inhibition of CXCR1/2 may be a valid therapeutic strategy for treating lung infections caused by these pathogens, especially controlling secondary bacterial

  10. [Two cases of invasive Haemophilus influenzae type f infection

    DEFF Research Database (Denmark)

    Nielsen, J.D.; Lind, J.W.; Bruun, B.

    2009-01-01

    Two cases of invasive Haemophilus influenzae type f infection are presented: a three-week-old boy with meningitis and a 62-year-old woman with arthritis and bacteremia. Since 1993 vaccination against H. influenzae type b (Hib) has been offered to Danish children. The result has been a remarkable...... decrease in invasive Hib disease. However, physicians need to be aware of the existence of non-type b invasive H. influenzae disease Udgivelsesdato: 2009/1/19...

  11. Clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in Jingzhou, China.

    Science.gov (United States)

    Huai, Yang; Guan, Xuhua; Liu, Shali; Uyeki, Timothy M; Jiang, Hui; Klena, John; Huang, Jigui; Chen, Maoyi; Peng, Youxing; Yang, Hui; Luo, Jun; Zheng, Jiandong; Peng, Zhibin; Huo, Xixiang; Xiao, Lin; Chen, Hui; Zhang, Yuzhi; Xing, Xuesen; Feng, Luzhao; Hu, Dale J; Yu, Hongjie; Zhan, Faxian; Varma, Jay K

    2017-03-01

    Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in China. We conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza. During the study period, 15 354 children aged acute respiratory infection patients aged 5-15 years with confirmed influenza (H3N2) infection were more likely than children without influenza to have radiographic diagnosis of pneumonia (11/31, 36% vs 15/105, 14%. Pacute respiratory infection cases aged 5-15 years diagnosed with influenza were also more likely to have a household member who smoked cigarettes compared with SARI cases without a smoking household member (54/208, 26% vs 158/960, 16%, Pinfection was an important contributor to pneumonia requiring hospitalization. Our results highlight the importance of surveillance in identifying factors for influenza hospitalization, monitoring adherence to influenza prevention and treatment strategies, and evaluating the disease burden among hospitalized pediatric SARI patients. Influenza vaccination promotion should target children. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  12. Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period

    DEFF Research Database (Denmark)

    Dwyer, Dominic E; Lynfield, Ruth; Losso, Marcelo H

    2017-01-01

    Background: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited. Methods: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infect...

  13. Demographic and ecological risk factors for human influenza A virus infections in rural Indonesia.

    Science.gov (United States)

    Root, Elisabeth Dowling; Agustian, Dwi; Kartasasmita, Cissy; Uyeki, Timothy M; Simões, Eric A F

    2017-09-01

    Indonesia has the world's highest reported mortality for human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus. Indonesia is an agriculturally driven country where human-animal mixing is common and provides a unique environment for zoonotic influenza A virus transmission. To identify potential demographic and ecological risk factors for human infection with seasonal influenza A viruses in rural Indonesia, a population-based study was conducted in Cileunyi and Soreang subdistricts near Bandung in western Java from 2008 to 2011. Passive influenza surveillance with RT-PCR confirmation of influenza A viral RNA in respiratory specimens was utilized for case ascertainment. A population census and mapping were utilized for population data collection. The presence of influenza A(H3N2) and A(H1N1)pdm09 virus infections in a household was modeled using Generalized Estimating Equations. Each additional child aged <5 years in a household increased the odds of H3N2 approximately 5 times (OR=4.59, 95%CI: 3.30-6.24) and H1N1pdm09 by 3.5 times (OR=3.53, 95%CI: 2.51-4.96). In addition, the presence of 16-30 birds in the house was associated with an increased odds of H3N2 (OR=5.08, 95%CI: 2.00-12.92) and H1N1pdm09 (OR=12.51 95%CI: 6.23-25.13). Our findings suggest an increase in influenza A virus infections in rural Indonesian households with young children and poultry. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  14. 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.

  15. Challenges for molecular and serological ZIKV infection confirmation.

    Science.gov (United States)

    de Vasconcelos, Zilton Farias Meira; Azevedo, Renata Campos; Thompson, Nathália; Gomes, Leonardo; Guida, Letícia; Moreira, Maria Elisabeth Lopes

    2018-01-01

    Zika Virus (ZIKV), member of Flaviviridae family and Flavivirus genus, has recently emerged as international public health emergency after its association with neonatal microcephaly cases. Clinical diagnosis hindrance involves symptom similarities produced by other arbovirus infections, therefore laboratory confirmation is of paramount importance. The most reliable test available is based on ZIKV RNA detection from body fluid samples. However, short viremia window periods and asymptomatic infections diminish the success rate for RT-PCR positivity. Beyond molecular detection, all serology tests in areas where other Flavivirus circulates proved to be a difficult task due to the broad range of cross-reactivity, especially with dengue pre-exposed individuals. Altogether, lack of serological diagnostic tools brings limitations to any retrospective evaluation. Those studies are central in the context of congenital infection that could occur asymptomatically and mask prevalence and risk rates.

  16. Increasing laboratory confirmed cases of influenza in Europe, particularly cases of influenza B in the south west.

    NARCIS (Netherlands)

    Paget, J.

    2003-01-01

    Eleven networks in Europe reported no influenza activity to the European Influenza Surveillance Scheme (EISS, http://www.eiss.org/) in the week ending 29 December 2002 (week 52). Four networks reported sporadic activity (Belgium, Portugal, Spain and Switzerland), and one network (France) reported

  17. Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

    Science.gov (United States)

    Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    Background: Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are lacking. The ruddy turnstone (Arenaria interpres) is the shorebird species with the highest prevalence of influenza virus at Delaware Bay. Objectives: The primary objective of this study was to experimentally assess the patterns of influenza virus excretion, minimal infectious doses, and clinical outcome in ruddy turnstones. Methods: We experimentally challenged ruddy turnstones using a common LPAIV shorebird isolate, an LPAIV waterfowl isolate, or a highly pathogenic H5N1 avian influenza virus. Cloacal and oral swabs and sera were analyzed from each bird. Results: Most ruddy turnstones had pre-existing antibodies to avian influenza virus, and many were infected at the time of capture. The infectious doses for each challenge virus were similar (103·6–104·16 EID50), regardless of exposure history. All infected birds excreted similar amounts of virus and showed no clinical signs of disease or mortality. Influenza A-specific antibodies remained detectable for at least 2 months after inoculation. Conclusions: These results provide a reference for interpretation of surveillance data, modeling, and predicting the risks of avian influenza transmission and movement in these important hosts.

  18. Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011–2012 season in Spain, among population targeted for vaccination

    Science.gov (United States)

    2013-01-01

    Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed 4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. PMID:24053661

  19. Radiologic findings of childhood lower respiratory tract infection by influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Taek; Park, Choong Ki; Shin, Hee Jung; Choi, Yo Won; Jeon, Seok Chol; Hahm, Chang Kok; Hern, Ahn You [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2002-08-01

    After the RS (respiratory syncytial) virus, the influenza virus is the most common cause of childhood lower respiratory tract infection. We assessed the radiologic findings of childhood lower respiratory tract infection by the influenza virus. A total of 105 pediatric patients (76 males and 29 females; mean age, 2.4 years) with symptoms of respiratory tract infection were examined between March 1997 and April 2000. Nasopharyngeal aspirates were obtained and influenza virus infection was confirmed by direct or indirect immunofluorescent assays. Peribronchial infiltration, hyperinflation, atelectasis, pulmonary consolidation, and hilar lymphadenopathy were evaluated retrospectively at simple chest radiography. Bilateral perihiler peribronchial infiltration was noted in 78.1% of patients (n=82), hyperinflation in 63.8% (n=67), atelectasis in 3.8% (n=4, segmental 50%, lobar 50%), and pulmonary consolidation in 16.2% [n=17; segmental 70.6% (n=12), lobar 29.4% (n=5)]. Hilar lymphadenopathy was noted in one patient in whom there was no pleural effusion, and subglottic airway narrowing in 12 of 14 in whom the croup symptom complex was present. The major radiologic findings of influenza virus infection were bilateral perihilar peribronchial infiltration and hyperinflation. In some patients, upper respiratory tract infection was combined with subgolttic airway narrowing. Atelectasis or pleural effusion was rare.

  20. Underdiagnosis of Influenza Virus Infection in Hospitalized Older Adults.

    Science.gov (United States)

    Hartman, Lauren; Zhu, Yuwei; Edwards, Kathryn M; Griffin, Marie R; Talbot, H Keipp

    2018-03-01

    To describe factors associated with provider-ordered influenza testing in hospitalized older adults. Information on participant demographics, symptoms, and provider-ordered influenza testing were collected by questionnaire and chart review. We conducted prospective laboratory-based surveillance using reverse-transcriptase polymerase chain reaction (RT-PCR), the criterion standard for diagnosis of influenza, to determine how participant characteristics and provider-ordered testing affected accurate influenza diagnosis. One academic and three community hospitals in Davidson County, Tennessee. Adults aged 18 and older with acute respiratory illness or nonlocalizing fever (N=1,422). We compared characteristics of participants with and without provider-ordered testing for influenza using the Wilcoxon test and Pearson chi-square test. Multivariable logistic regression models were used to identify factors predictive of provider-ordered influenza testing. Twenty-eight percent (399/1,422) of participants had provider-ordered influenza testing. Participants who were tested were younger than those not tested (58 ± 18 vs 66 ± 15, p<.001) and more likely to have influenza-like illness (ILI) (71% vs 49%, p<.001). ILI decreased with increasing age (aged 18-49, 63%; aged 50-64, 60%; aged ≥65, 48%). ILI and younger age were independent predictors of provider-ordered testing. Of the 136 participants with influenza confirmed using RT-PCR, ILI was the only significant predictor of provider-ordered testing (adjusted odds ratio=3.43, 95% confidence interval=1.22-9.70). Adults aged 65 and older hospitalized with fever or respiratory symptoms during influenza season are less likely to undergo a provider-ordered influenza test than younger adults. Some, but not all, of this disparity is due to a lower likelihood of ILI. Further strategies are needed to increase clinician awareness and testing in this vulnerable group. © 2018, Copyright the Authors Journal compilation © 2018

  1. Executive summary. Management of influenza infection in solid-organ transplant recipients: consensus statement of the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI).

    Science.gov (United States)

    López-Medrano, Francisco; Cordero, Elisa; Gavaldá, Joan; Cruzado, Josep M; Marcos, M Ángeles; Pérez-Romero, Pilar; Sabé, Nuria; Gómez-Bravo, Miguel Ángel; Delgado, Juan Francisco; Cabral, Evelyn; Carratalá, Jordi

    2013-10-01

    Solid organ transplant (SOT) recipients are at greater risk than the general population for complications and mortality from influenza infection. We have conducted a systematic review to assess the management and prevention of influenza infection in SOT recipients. Recommendations are provided about the procurement of organs from donors with influenza infection. We highlight the importance of the possibility of influenza infection in any SOT recipient presenting upper or lower respiratory symptoms, including pneumonia. The importance of early antiviral treatment of SOT recipients with suspected or confirmed influenza infection and the necessity of annual influenza vaccination are emphasized. The microbiological techniques for diagnosis of influenza infection are reviewed. Guidelines for the use of antiviral prophylaxis are provided. Recommendations for household contacts of SOT recipients with influenza infection and health care workers are also included. Antiviral dose adjustment guidelines are presented for cases of impaired renal function and for pediatric populations. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  2. [Severe Haemophilus influenzae b infection in healthy male adult

    DEFF Research Database (Denmark)

    Vilmar, A.C.; Gjorup, I.; David, Kim Peter

    2008-01-01

    Haemophilus influenzae b (Hib) can be the cause of serious infections, and is mainly observed affecting children and immuno-compromised patients. We report a case of a healthy 49-year old male with a severe Hib infection complicated by septicaemia, meningitis and anuria. The risk of invasive Hib...

  3. Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

    Directory of Open Access Journals (Sweden)

    Steven Rockman

    2017-05-01

    Full Text Available Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1 or highly pathogenic avian influenza (H5N1. IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

  4. Prospective study of avian influenza virus infections among rural Thai villagers.

    Directory of Open Access Journals (Sweden)

    Whitney S Krueger

    Full Text Available In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV infections with H9N2 and H5N1 viruses.After enrollment, participants were contacted weekly for 24 mos for acute influenza-like illnesses (ILI. Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses.Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38% were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14% reported ILIs, and 11 (92% of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2 virus: 21 subjects (2.7% at 12-months and 40 subjects (5.1% at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1:80. While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04-5.2 at the 24-month encounter. One subject had an elevated titer (1:20 against H5N1 during follow-up.From 2008-10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in

  5. Prospective study of avian influenza virus infections among rural Thai villagers.

    Science.gov (United States)

    Krueger, Whitney S; Khuntirat, Benjawan; Yoon, In-Kyu; Blair, Patrick J; Chittagarnpitch, Malinee; Putnam, Shannon D; Supawat, Krongkaew; Gibbons, Robert V; Bhuddari, Darunee; Pattamadilok, Sirima; Sawanpanyalert, Pathom; Heil, Gary L; Gray, Gregory C

    2013-01-01

    In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV) infections with H9N2 and H5N1 viruses. After enrollment, participants were contacted weekly for 24 mos for acute influenza-like illnesses (ILI). Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses. Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38%) were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14%) reported ILIs, and 11 (92%) of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2) virus: 21 subjects (2.7%) at 12-months and 40 subjects (5.1%) at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1:80). While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04-5.2) at the 24-month encounter. One subject had an elevated titer (1:20) against H5N1 during follow-up. From 2008-10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in humans.

  6. Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia

    OpenAIRE

    Mangiri, Amalya; Iuliano, A. Danielle; Wahyuningrum, Yunita; Praptiningsih, Catharina Y.; Lafond, Kathryn E.; Storms, Aaron D.; Samaan, Gina; Ariawan, Iwan; Soeharno, Nugroho; Kreslake, Jennifer M.; Storey, J. Douglas; Uyeki, Timothy M.

    2016-01-01

    Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 vir...

  7. Avian Influenza A Viruses: Evolution and Zoonotic Infection.

    Science.gov (United States)

    Kim, Se Mi; Kim, Young-Il; Pascua, Philippe Noriel Q; Choi, Young Ki

    2016-08-01

    Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Serological Evidence of Human Infection with Avian Influenza A H7virus in Egyptian Poultry Growers.

    Science.gov (United States)

    Gomaa, Mokhtar R; Kandeil, Ahmed; Kayed, Ahmed S; Elabd, Mona A; Zaki, Shaimaa A; Abu Zeid, Dina; El Rifay, Amira S; Mousa, Adel A; Farag, Mohamed M; McKenzie, Pamela P; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

    2016-01-01

    Avian influenza viruses circulate widely in birds, with occasional human infections. Poultry-exposed individuals are considered to be at high risk of infection with avian influenza viruses due to frequent exposure to poultry. Some avian H7 viruses have occasionally been found to infect humans. Seroprevalence of neutralizing antibodies against influenza A/H7N7 virus among poultry-exposed and unexposed individuals in Egypt were assessed during a three-years prospective cohort study. The seroprevalence of antibodies (titer, ≥80) among exposed individuals was 0%, 1.9%, and 2.1% annually while the seroprevalence among the control group remained 0% as measured by virus microneutralization assay. We then confirmed our results using western blot and immunofluorescence assays. Although human infection with H7 in Egypt has not been reported yet, our results suggested that Egyptian poultry growers are exposed to avian H7 viruses. These findings highlight the need for surveillance in the people exposed to poultry to monitor the risk of zoonotic transmission of avian influenza viruses.

  9. Serological Evidence of Human Infection with Avian Influenza A H7virus in Egyptian Poultry Growers.

    Directory of Open Access Journals (Sweden)

    Mokhtar R Gomaa

    Full Text Available Avian influenza viruses circulate widely in birds, with occasional human infections. Poultry-exposed individuals are considered to be at high risk of infection with avian influenza viruses due to frequent exposure to poultry. Some avian H7 viruses have occasionally been found to infect humans. Seroprevalence of neutralizing antibodies against influenza A/H7N7 virus among poultry-exposed and unexposed individuals in Egypt were assessed during a three-years prospective cohort study. The seroprevalence of antibodies (titer, ≥80 among exposed individuals was 0%, 1.9%, and 2.1% annually while the seroprevalence among the control group remained 0% as measured by virus microneutralization assay. We then confirmed our results using western blot and immunofluorescence assays. Although human infection with H7 in Egypt has not been reported yet, our results suggested that Egyptian poultry growers are exposed to avian H7 viruses. These findings highlight the need for surveillance in the people exposed to poultry to monitor the risk of zoonotic transmission of avian influenza viruses.

  10. 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.

  11. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Kohio, Hinissan P.; Adamson, Amy L., E-mail: aladamso@uncg.edu

    2013-09-15

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

  12. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    International Nuclear Information System (INIS)

    Kohio, Hinissan P.; Adamson, Amy L.

    2013-01-01

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells

  13. Infection and Replication of Influenza Virus at the Ocular Surface.

    Science.gov (United States)

    Creager, Hannah M; Kumar, Amrita; Zeng, Hui; Maines, Taronna R; Tumpey, Terrence M; Belser, Jessica A

    2018-04-01

    Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subjected to aerosol inoculation. The temperature at which cells were cultured postinoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33°C relative to that at 37°C, and this effect was slightly greater for the conjunctivitis isolates than for the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multilayer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited the hemagglutination of both ocular and nonocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of nonocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells but that this is more likely for ocular-tropic viruses, as they are better able to maintain their infectivity during passage through the tear film. IMPORTANCE The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza virus tropism have yet to be fully

  14. Avian influenza infection alters fecal odor in mallards.

    Directory of Open Access Journals (Sweden)

    Bruce A Kimball

    Full Text Available Changes in body odor are known to be a consequence of many diseases. Much of the published work on disease-related and body odor changes has involved parasites and certain cancers. Much less studied have been viral diseases, possibly due to an absence of good animal model systems. Here we studied possible alteration of fecal odors in animals infected with avian influenza viruses (AIV. In a behavioral study, inbred C57BL/6 mice were trained in a standard Y-maze to discriminate odors emanating from feces collected from mallard ducks (Anas platyrhynchos infected with low-pathogenic avian influenza virus compared to fecal odors from non-infected controls. Mice could discriminate odors from non-infected compared to infected individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Prompted by this indication of odor change, fecal samples were subjected to dynamic headspace and solvent extraction analyses employing gas chromatography/mass spectrometry to identify chemical markers indicative of AIV infection. Chemical analyses indicated that AIV infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone in feces. These experiments demonstrate that information regarding viral infection exists via volatile metabolites present in feces. Further, they suggest that odor changes following virus infection could play a role in regulating behavior of conspecifics exposed to infected individuals.

  15. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    Science.gov (United States)

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  16. Protective effect of dietary xylitol on influenza A virus infection.

    Directory of Open Access Journals (Sweden)

    Sun Young Yin

    Full Text Available Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1. We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases.

  17. Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection

    Science.gov (United States)

    Epidemiologic evidence suggests that cigarette smoking is a risk factor for infection with influenza, but the mechanisms underlying this susceptibility remain unknown. To ascertain if airway epithelial cells from smokers demonstrate a decreased ability to orchestrate an influenza...

  18. Effect of Influenza Vaccination of Children on Infection Rate in Hutterite Communities: Follow-Up Study of a Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Biao Wang

    Full Text Available An earlier cluster randomized controlled trial (RCT of Hutterite colonies had shown that if more than 80% of children and adolescents were immunized with influenza vaccine there was a statistically significant reduction in laboratory-confirmed influenza among all unimmunized community members. We assessed the impact of this intervention for two additional influenza seasonal periods.Follow-up data for two influenza seasonal periods of a cluster randomized trial involving 1053 Canadian children and adolescents aged 36 months to 15 years in Season 2 and 1014 in Season 3 who received the study vaccine, and 2805 community members in Season 2 and 2840 in Season 3 who did not receive the study vaccine. Follow-up for Season 2 began November 18, 2009 and ended April 25, 2010 while Season 3 extended from December 6, 2010 and ended May 27, 2011. Children were randomly assigned in a blinded manner according to community membership to receive either inactivated trivalent influenza vaccine or hepatitis A. The primary outcome was confirmed influenza A and B infection using RT-PCR assay. Due to the outbreak of 2009 H1N1 pandemic, data in Season 2 were excluded for analysis.For an analysis of the combined Season 1 and Season 3 data, among non-recipients (i.e., participants who did not receive study vaccines, 66 of the 2794 (2.4% participants in the influenza vaccine colonies and 121 of the 2301 (5.3% participants in the hepatitis A colonies had influenza confirmed by RT-PCR, for a protective effectiveness of 60% (95% CI, 6% to 83%; P = 0.04; among all study participants (i.e., including both those who received study vaccine and those who did not, 125 of the 3806 (3.3% in the influenza vaccine colonies and 239 of the 3243 (7.4% in the hepatitis A colonies had influenza confirmed by RT-PCR, for a protective effectiveness of 63% (95% CI, 5% to 85%; P = 0.04.Immunizing children and adolescents with inactivated influenza vaccine can offer a protective effect among

  19. Reduction of Influenza Virus Titer and Protection against Influenza Virus Infection in Infant Mice Fed Lactobacillus casei Shirota

    OpenAIRE

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

    2004-01-01

    We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P < 0.05) lower than that in infant mice administered saline (control group) (102.48 ± 100.31...

  20. Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures.

    Science.gov (United States)

    Khurelbaatar, Nyamdavaa; Krueger, Whitney S; Heil, Gary L; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D; Gray, Gregory C

    2013-11-01

    In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2·1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population-based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine influenza virus strains. Seroreactivity was sparse among participants suggesting little human risk of zoonotic influenza infection. © 2013 John Wiley & Sons Ltd.

  1. 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.

  2. 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.

  3. 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.

  4. Host Cell Restriction Factors that Limit Influenza A Infection

    Directory of Open Access Journals (Sweden)

    Fernando Villalón-Letelier

    2017-12-01

    Full Text Available Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors” can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

  5. [Urinary tract infections : What has been confirmed in therapy?

    Science.gov (United States)

    Marcon, J; Stief, C G; Magistro, G

    2017-12-01

    Urinary tract infections (UTIs) affect approximately 150 million people worldwide per year, causing annual health costs of over three billion dollars just in the USA. Every second woman experiences at least one UTI in her lifetime, with every one in four experiencing recurrence. Uncomplicated infections like single or recurrent cystitis and pyelonephritis can be distinguished from complicated disease. UTIs in men can spread to the male glands, causing prostatitis and epididymitis. Antibiotic therapy is the standard procedure for UTIs. However, the extensive and sometimes irrational use of antibiotics for the treatment of infections has led to an increase in the incidence of multiresistant pathogens in recent years. Therefore, preventive nonantibiotic approaches are of great interest. This article provides an overview of the current management of urological infections as well as an outline of nonantibiotic preventive treatment modalities.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Global Emerging Infection Surveillance and Response (GEIS)- Avian Influenza Pandemic Influenza (AI/PI) Program

    Science.gov (United States)

    2014-10-01

    KEMRI operated reference laboratories for this work in Nairobi, Kericho, and Kisumu, including the arbovirus reference laboratory, the antimalarial ...in military and civilian populations, and monitor the pattern of antimalarial resistance across Kenya. 15. SUBJECT TERMS NOTHING LISTED 16...confirms our earlier assertion that as we progress away from the H1N1 pandemic, we have noticed a decline in influenza activity suggesting that the high

  8. Differential lung NK cell responses in avian influenza virus infected chickens correlate with pathogenicity

    OpenAIRE

    Jansen, C.A.; de Geus, E.D.; van Haarlem, D.A.; van de Haar, P.M.; Löndt, B.Z; Graham, S.P.; Göbel, T.W.; van Eden, W.; Brookes, S.M.; Vervelde, L.

    2013-01-01

    Infection of chickens with low pathogenicity avian influenza (LPAI) virus results in mild clinical signs while infection with highly pathogenic avian influenza (HPAI) viruses causes death of the birds within 36–48 hours. Since natural killer (NK) cells have been shown to play an important role in influenza-specific immunity, we hypothesise that NK cells are involved in this difference in pathogenicity. To investigate this, the role of chicken NK-cells in LPAI virus infection was studied. Next...

  9. Case Report: Severe Imported Influenza Infections Developed during Travel in Reunion Island.

    Science.gov (United States)

    Allyn, Jérôme; Brottet, Elise; Antok, Emmanuel; Dangers, Laurence; Persichini, Romain; Coolen-Allou, Nathalie; Roquebert, Bénédicte; Allou, Nicolas; Vandroux, David

    2017-12-01

    We report two cases of severe influenza infection imported by tourist patients from their country of origin and developed during travel. While studies have reported cases of influenza infections acquired during travel, here we examine two cases of severe influenza infection contracted in the country of origin that led to diagnosis and therapeutic problems in the destination country. No international recommendation exists concerning influenza vaccination before travel, and few countries recommend it for all travelers. Our study suggests that travel should be canceled when infectious signs are observed before departure. Influenza is a very common infection that is often benign, but sometimes very severe. The most severe cases include shock, acute respiratory distress syndrome (ARDS), myocarditis, rhabdomyolysis, and multiple organ failure. Management can require exceptional therapies, such as extracorporeal membrane oxygenation. A number of studies have focused on influenza infection in travelers. Cases of influenza acquired during travel have been reported in this literature, but no study has examined cases of influenza imported from the country of origin and developed while abroad. The latter situation may lead to 1) diagnostic problems during the nonepidemic season or in places where diagnostic techniques are lacking and 2) therapeutic difficulties resulting from the unavailability of techniques for the management of severe influenza infection in tourist areas. Here, we report two cases of extremely severe influenza infection imported by tourists from their country of origin and developed during travel.

  10. Influenza infection in the intensive care unit: Four years after the 2009 pandemic.

    Science.gov (United States)

    Pérez-Carrasco, Marcos; Lagunes, Leonel; Antón, Andrés; Gattarello, Simone; Laborda, César; Pumarola, Tomás; Rello, Jordi

    2016-03-01

    The role of influenza viruses in severe acute respiratory infection (SARI) in Intensive Care Units (ICU) remains unknown. The post-pandemic influenza A(H1N1)pdm09 period, in particular, has been poorly studied. To identify influenza SARI patients in ICU, to assess the usefulness of the symptoms of influenza-like illness (ILI), and to compare the features of pandemic vs. post-pandemic influenza A(H1N1) pdm09 infection. A prospective observational study with SARI patients admitted to ICU during the first three post-pandemic seasons. Patient demographics, characteristics and outcomes were recorded. An influenza epidemic period (IEP) was defined as >100 cases/100,000 inhabitants per week. One hundred sixty-three patients were diagnosed with SARI. ILI was present in 65 (39.9%) patients. Influenza infection was documented in 41 patients, 27 (41.5%) ILI patients, and 14 (14.3%) non-ILI patients, 27 of them during an IEP. Influenza A viruses were mainly responsible. Only five patients had influenza B virus infection, which were non-ILI during an IEP. SARI overall mortality was 22.1%, and 15% in influenza infection patients. Pandemic and post-pandemic influenza infection patients shared similar clinical features. During influenza epidemic periods, influenza infection screening should be considered in all SARI patients. Influenza SARI was mainly caused by subtype A(H1N1)pdm09 and A(H3N2) in post-pandemic seasons, and no differences were observed in ILI and mortality rate compared with a pandemic season. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Environmental contaminant mixtures modulate in vitro influenza infection

    DEFF Research Database (Denmark)

    Desforges, Jean-Pierre; Bandoro, Christopher; Shehata, Laila

    2018-01-01

    Environmental chemicals, particularly organochlorinated contaminants (OCs), are associated with a ranged of adverse health effects, including impairment of the immune system and antiviral immunity. Influenza A virus (IAV) is an infectious disease of major global public health concern and exposure...... studies such as ours can shed light on the complex processes underlying host-pathogen-pollutant interactions....... to OCs can increase the susceptibility, morbidity, and mortality to disease. It is however unclear how pollutants are interacting and affecting the outcome of viral infections at the cellular level. In this study, we investigated the effects of a mixture of environmentally relevant OCs on IAV infectivity...

  12. Influenza infection and heart failure-vaccination may change heart failure prognosis?

    Science.gov (United States)

    Kadoglou, Nikolaos P E; Bracke, Frank; Simmers, Tim; Tsiodras, Sotirios; Parissis, John

    2017-05-01

    The interaction of influenza infection with the pathogenesis of acute heart failure (AHF) and the worsening of chronic heart failure (CHF) is rather complex. The deleterious effects of influenza infection on AHF/CHF can be attenuated by specific immunization. Our review aimed to summarize the efficacy, effectiveness, safety, and dosage of anti-influenza vaccination in HF. In this literature review, we searched MEDLINE and EMBASE from January 1st 1966 to December 31st, 2016, for studies examining the association between AHF/CHF, influenza infections, and anti-influenza immunizations. We used broad criteria to increase the sensitivity of the search. HF was a prerequisite for our search. The search fields used included "heart failure," "vaccination," "influenza," "immunization" along with variants of these terms. No restrictions on the type of study design were applied. The most common clinical scenario is exacerbation of pre-existing CHF by influenza infection. Scarce evidence supports a potential positive association of influenza infection with AHF. Vaccinated patients with pre-existing CHF have reduced all-cause morbidity and mortality, but effects are not consistently documented. Immunization with higher antigen quantity may confer additional protection, but such aggressive approach has not been generally advocated. Further studies are needed to delineate the role of influenza infection on AHF/CHF pathogenesis and maintenance. Annual anti-influenza vaccination appears to be an effective measure for secondary prevention in HF. Better immunization strategies and more efficacious vaccines are urgently necessary.

  13. [Clinical aspects of human infection by the avian influenza virus].

    Science.gov (United States)

    Goubau, P

    2009-01-01

    The species barrier is not perfect for Influenza A and numerous transmissions of the virus from pigs or poultry to humans have been described these years. Appearing in 1997 and becoming epidemic in 2003, influenza A/H5N1 provoked many deadly enzootics in poultry batteries (highly pathogenic avian influenza of HPAI). Starting in Asia, many countries throughout Africa and Europe were affected. Sporadic human cases were described in direct contact with diseased chicken or other poultry. Half of the cases are lethal, but human to human transmission occurs with difficulty. From January 2003 to August 11th 2009, 438 cases were declared worldwide with 262 deaths. Many countries declared cases, but recently most cases occurred in Egypt. Measures in hospital were taken which were copied from the measures for SARS (Severe Acute Respiratory Syndrome), but these were probably excessive in this case, considering the low rate of secondary cases with A/H5N1. In many human infections, signs of severe respiratory distress develop and multi organ failure. It was feared that this deadly virus could become easily transmitted between humans, leading to a new pandemic. This was not the case up to now. The strong pathogenicity of the virus is still not completely explained, but the deep location of infection in the lungs and the deregulation of cytokine production by the target cells, particularly macrophages, may be part of the explanation.

  14. Hospital-acquired influenza: a synthesis using the Outbreak Reports and Intervention Studies of Nosocomial Infection (ORION) statement.

    Science.gov (United States)

    Voirin, N; Barret, B; Metzger, M-H; Vanhems, P

    2009-01-01

    Nosocomial influenza outbreaks occur in almost all types of hospital wards, and their consequences for patients and hospitals in terms of morbidity, mortality and costs are considerable. The source of infection is often unknown, since any patient, healthcare worker (HCW) or visitor is capable of transmitting it to susceptible persons within hospitals. Nosocomial influenza outbreak investigations should help to identify the source of infection, prevent additional cases, and increase our knowledge of disease control to face future outbreaks. However, such outbreaks are probably underdetected and underreported, making routes of transmission difficult to track and describe with precision. In addition, the absence of standardised information in the literature limits comparison between studies and better understanding of disease dynamics. In this study, reports of nosocomial influenza outbreaks are synthesised according to the ORION guidelines to highlight existing knowledge in relation to the detection of influenza cases, evidence of transmission between patients and HCWs and measures of disease incidence. Although a body of evidence has confirmed that influenza spreads within hospitals, we should improve clinical and virological confirmation and initiate active surveillance and quantitative studies to determine incidence rates in order to assess the risk to patients.

  15. Influenza D Virus Infection in Feral Swine Populations, United States.

    Science.gov (United States)

    Ferguson, Lucas; Luo, Kaijian; Olivier, Alicia K; Cunningham, Fred L; Blackmon, Sherry; Hanson-Dorr, Katie; Sun, Hailiang; Baroch, John; Lutman, Mark W; Quade, Bianca; Epperson, William; Webby, Richard; DeLiberto, Thomas J; Wan, Xiu-Feng

    2018-06-01

    Influenza D virus (IDV) has been identified in domestic cattle, swine, camelid, and small ruminant populations across North America, Europe, Asia, South America, and Africa. Our study investigated seroprevalence and transmissibility of IDV in feral swine. During 2012-2013, we evaluated feral swine populations in 4 US states; of 256 swine tested, 57 (19.1%) were IDV seropositive. Among 96 archived influenza A virus-seropositive feral swine samples collected from 16 US states during 2010-2013, 41 (42.7%) were IDV seropositive. Infection studies demonstrated that IDV-inoculated feral swine shed virus 3-5 days postinoculation and seroconverted at 21 days postinoculation; 50% of in-contact naive feral swine shed virus, seroconverted, or both. Immunohistochemical staining showed viral antigen within epithelial cells of the respiratory tract, including trachea, soft palate, and lungs. Our findings suggest that feral swine might serve an important role in the ecology of IDV.

  16. 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.

  17. 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.

  18. Past Life and Future Effects—How Heterologous Infections Alter Immunity to Influenza Viruses

    Directory of Open Access Journals (Sweden)

    Aisha Souquette

    2018-05-01

    Full Text Available Influenza virus frequently mutates due to its error-prone polymerase. This feature contributes to influenza virus’s ability to evade pre-existing immunity, leading to annual epidemics and periodic pandemics. T cell memory plays a key protective role in the face of an antigenically distinct influenza virus strain because T cell targets are often derived from conserved internal proteins, whereas humoral immunity targets are often sites of increased mutation rates that are tolerated by the virus. Most studies of influenza T cell memory are conducted in naive, specific pathogen free mice and do not account for repetitive influenza infection throughout a lifetime, sequential acute heterologous infections between influenza infections, or heterologous chronic co-infections. By contrast to these mouse models, humans often experience numerous influenza infections, encounter heterologous acute infections between influenza infections, and are infected with at least one chronic virus. In this review, we discuss recent advances in understanding the effects of heterologous infections on the establishment and maintenance of CD8+ T cell immunological memory. Understanding the various factors that affect immune memory can provide insights into the development of more effective vaccines and increase reproducibility of translational studies between animal models and clinical results.

  19. Evidence for subclinical avian influenza virus infections among rural Thai villagers.

    Science.gov (United States)

    Khuntirat, Benjawan P; Yoon, In-Kyu; Blair, Patrick J; Krueger, Whitney S; Chittaganpitch, Malinee; Putnam, Shannon D; Supawat, Krongkaew; Gibbons, Robert V; Pattamadilok, Sirima; Sawanpanyalert, Pathom; Heil, Gary L; Friary, John A; Capuano, Ana W; Gray, Gregory C

    2011-10-01

    Regions of Thailand reported sporadic outbreaks of A/H5N1 highly pathogenic avian influenza (HPAI) among poultry between 2004 and 2008. Kamphaeng Phet Province, in north-central Thailand had over 50 HPAI poultry outbreaks in 2004 alone, and 1 confirmed and 2 likely other human HPAI infections between 2004 and 2006. In 2008, we enrolled a cohort of 800 rural Thai adults living in 8 sites within Kamphaeng Phet Province in a prospective study of zoonotic influenza transmission. We studied participants' sera with serologic assays against 16 avian, 2 swine, and 8 human influenza viruses. Among participants (mean age 49.6 years and 58% female) 65% reported lifetime poultry exposure of at least 30 consecutive minutes. Enrollees had elevated antibodies by microneutralization assay against 3 avian viruses: A/Hong Kong/1073/1999(H9N2), A/Thailand/676/2005(H5N1), and A/Thailand/384/2006(H5N1). Bivariate risk factor modeling demonstrated that male gender, lack of an indoor water source, and tobacco use were associated with elevated titers against avian H9N2 virus. Multivariate modeling suggested that increasing age, lack of an indoor water source, and chronic breathing problems were associated with infection with 1 or both HPAI H5N1 strains. Poultry exposure was not associated with positive serologic findings. These data suggest that people in rural central Thailand may have experienced subclinical avian influenza infections as a result of yet unidentified environmental exposures. Lack of an indoor water source may play a role in transmission.

  20. Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review.

    OpenAIRE

    Warren-Gash, C; Fragaszy, E; Hayward, AC

    2012-01-01

    : Please cite this paper as: Warren-Gash et al. (2012) Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12015. Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary an...

  1. Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures

    OpenAIRE

    Khurelbaatar, Nyamdavaa; Krueger, Whitney S.; Heil, Gary L.; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D.; Gray, Gregory C.

    2013-01-01

    In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2?1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population?based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine inf...

  2. Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.

    Science.gov (United States)

    Kedzierski, Lukasz; Tate, Michelle D; Hsu, Alan C; Kolesnik, Tatiana B; Linossi, Edmond M; Dagley, Laura; Dong, Zhaoguang; Freeman, Sarah; Infusini, Giuseppe; Starkey, Malcolm R; Bird, Nicola L; Chatfield, Simon M; Babon, Jeffrey J; Huntington, Nicholas; Belz, Gabrielle; Webb, Andrew; Wark, Peter Ab; Nicola, Nicos A; Xu, Jianqing; Kedzierska, Katherine; Hansbro, Philip M; Nicholson, Sandra E

    2017-02-14

    Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5 -deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.

  3. Influenza A virus infections in marine mammals and terrestrial carnivores.

    Science.gov (United States)

    Harder, Timm C; Siebert, Ursula; Wohlsein, Peter; Vahlenkamp, Thomas

    2013-01-01

    Influenza A viruses (IAV), members of the Orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. The viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. The mammalian-adapted IAVs originally arose by transspecies transmission from avian sources. In swine, horse and man, species-adapted IAV lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly variable severity. Sporadic outbreaks of IAV infections associated with pneumonic clinical signs have repeatedly occurred in marine mammals (harbour seals [Phoca vitulina]) off the New England coast of the U.S.A. due to episodic transmission of avian IAV. However, no indigenous marine mammal IAV lineages are described. In contrast to marine mammals, avian- and equine-derived IAVs have formed stable circulating lineages in terrestrial carnivores: IAVs of subtype H3N2 and H3N8 are found in canine populations in South Korea, China, and the U.S.A. Experimental infections revealed that dogs and cats can be infected with an even wider range of avian IAVs. Cats, in particular, also proved susceptible to native infection with human pandemic H1N1 viruses and, according to serological data, may be vulnerable to infection with further human-adapted IAVs. Ferrets are susceptible to a variety of avian and mammalian IAVs and are an established animal model of human IAV infection. Thus, a potential role of pet cats, dogs and ferrets as mediators of avian-derived viruses to the human population does exist. A closer observation for influenza virus infections and transmissions at this animal-human interface is indicated.

  4. Haemophilus influenzae type B genital infection and septicemia in pregnant woman: a case report

    Directory of Open Access Journals (Sweden)

    Hosuru Subramanya Supram

    2014-06-01

    Full Text Available Haemophilus influenzae (H. influenzae type B a non-motile, aerobic, gram negative cocobacillus is a commensal of upper respiratory tract. Genitourinary infection due to H. influenzae has been reported but bacteremia associated with such infection appears to be rare. We report a case of 19 years young primigravida with complaints of amenorrhea of 32 weeks and 5 days, pyrexia, abdominal pain and blood stained discharge per vaginum. H. influenzae type B was recovered from the genital tract as well as blood of the mother indicating maternal septicemia. Septicemia caused by H. influenzae type B in pregnant women following vaginal colonization and infection is rare. It has been reported in many parts of world over the years; to the best of our knowledge this is the first reported case from Nepal. H. influenzae should be considered as a potential maternal, fetal, and neonatal pathogen.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Control of mucosal virus infection by influenza nucleoprotein-specific CD8+ cytotoxic T lymphocytes

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    Couch Robert B

    2007-06-01

    Full Text Available Abstract Background MHC class I-restricted CD8+ cytotoxic T lymphocytes (CTL are thought to play a major role in clearing virus and promoting recovery from influenza infection and disease. This has been demonstrated for clearance of influenza virus from the lungs of infected mice. However, human influenza infection is primarily a respiratory mucosal infection involving the nasopharynx and tracheobronchial tree. The role of CD8+ CTL directed toward the influenza nucleoprotein (NP in defense against influenza virus infection at the respiratory mucosa was evaluated in two separate adoptive transfer experiments. Methods Influenza nucleoprotein (NP-specific CD8+ CTL were generated from splenocytes obtained from Balb/c mice previously primed with influenza A/Taiwan/1/86 (H1N1 infection or with influenza A/PR/8/34 (H1N1-derived NP plasmid DNA vaccine followed by infection with A/Hong Kong/68 (H3N2 virus. After in vitro expansion by exposure to an influenza NP-vaccinia recombinant, highly purified CD8+ T cells exhibited significant lysis in vitro of P815 target cells infected with A/Hong Kong/68 (H3N2 virus while the CD8- fraction (CD4+ T cells, B cells and macrophages had no CTL activity. Purified CD8+ and CD8- T cells (1 × 107 were injected intravenously or interperitoneally into naive mice four hours prior to intranasal challenge with A/HK/68 (H3N2 virus. Results The adoptively transferred NP-vaccinia-induced CD8+ T cells caused significant reduction of virus titers in both the lungs and nasal passages when compared to CD8- cells. Neither CD8+ nor CD8- T cells from cultures stimulated with HIV gp120-vaccinia recombinant reduced virus titers. Conclusion The present data demonstrate that influenza NP-specific CD8+ CTL can play a direct role in clearance of influenza virus from the upper respiratory mucosal surfaces.

  7. Swine-origin influenza A (H3N2) virus infection in two children--Indiana and Pennsylvania, July-August 2011.

    Science.gov (United States)

    2011-09-09

    Influenza A viruses are endemic in many animal species, including humans, swine, and wild birds, and sporadic cases of transmission of influenza A viruses between humans and animals do occur, including human infections with avian-origin influenza A viruses (i.e., H5N1 and H7N7) and swine-origin influenza A viruses (i.e., H1N1, H1N2, and H3N2). Genetic analysis can distinguish animal origin influenza viruses from the seasonal human influenza viruses that circulate widely and cause annual epidemics. This report describes two cases of febrile respiratory illness caused by swine-origin influenza A (H3N2) viruses identified on August 19 and August 26, 2011, and the current investigations. No epidemiologic link between the two cases has been identified, and although investigations are ongoing, no additional confirmed human infections with this virus have been detected. These viruses are similar to eight other swine-origin influenza A (H3N2) viruses identified from previous human infections over the past 2 years, but are unique in that one of the eight gene segments (matrix [M] gene) is from the 2009 influenza A (H1N1) virus. The acquisition of the M gene in these two swine-origin influenza A (H3N2) viruses indicates that they are "reassortants" because they contain genes of the swine-origin influenza A (H3N2) virus circulating in North American pigs since 1998 and the 2009 influenza A (H1N1) virus that might have been transmitted to pigs from humans during the 2009 H1N1 pandemic. However, reassortments of the 2009 influenza A (H1N1) virus with other swine influenza A viruses have been reported previously in swine. Clinicians who suspect influenza virus infection in humans with recent exposure to swine should obtain a nasopharyngeal swab from the patient for timely diagnosis at a state public health laboratory and consider empiric neuraminidase inhibitor antiviral treatment to quickly limit potential human transmission.

  8. Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period

    DEFF Research Database (Denmark)

    Dwyer, Dominic E; Lynfield, Ruth; Losso, Marcelo H

    2017-01-01

    Background: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited. Methods: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infect...... to be hospitalized than those with A(H3N2). Hospitalized patients infected with A(H1N1)pdm09 were younger and more likely to have severe disease at study entry (measured by ICU enrollment), but did not have worse 60-day outcomes.......Background: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited. Methods: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus...... infections were compared in 2 prospective cohorts enrolled globally from 2009 through 2015. Logistic regression was used to compare outcomes among influenza virus type/subtypes. Results: Of 3952 outpatients, 1290 (32.6%) had A(H1N1)pdm09 virus infection, 1857 (47.0%) had A(H3N2), and 805 (20.4%) had...

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies

    DEFF Research Database (Denmark)

    Horvath, A; Andersen, I; Junker, K

    2001-01-01

    . These studies were extended to comprise five mouse-adapted influenza A strains, two swine influenza A strains, a mink influenza A virus, a ferret influenza A reassortant virus, a influenza B virus and a parainfluenza 3 virus. The HA activity of all these viruses was inhibited by SAP. Western blotting showed......Serum amyloid P component (SAP) binds in vitro Ca(2+)-dependently to several ligands including oligosaccharides with terminal mannose and galactose. We have earlier reported that SAP binds to human influenza A virus strains, inhibiting hemagglutinin (HA) activity and virus infectivity in vitro...... that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and circulating...

  12. Influenza and Respiratory Syncytial viral infections in Malaysia: Demographic and Clinical perspective.

    Science.gov (United States)

    Rahman, M M; Wong, K K; Hanafiah, A; Isahak, I

    2014-01-01

    Respiratory infections represent a major public health problem worldwide. The study aimed to determine the prevalence of respiratory syncytial and influenza virus infections and analyzed in respect to demography and clinical perspective. Methods : The specimens were processed by cell culture and immunofluorescent assay (IFA) and real-time reverse transcriptase-PCR (rRT-PCR) for detection of respiratory viruses. Results : Out of 505 specimens 189 (37.8%) were positive, in which RSV was positive in 124(24.8%) cases and influenza A was positive in 65(13%) cases. Positive cases for influenza virus A and RSV were analyzed based on demography: age, gender, ethnicity and clinical symptoms. There were no significant differences among gender, ethnicity and clinical symptoms in both RSV and influenza A virus infections. It was observed that children below 3 years of ages were more prone to RSV infections. On the contrary, influenza virus A infected all age groups of humans. RSV infects mostly child below 3 years of age and influenza virus infects all age group. No specificity of RSV and influenza infection in relation to demography.

  13. Nontypeable Haemophilus influenzae biofilms: role in chronic airway infections

    Directory of Open Access Journals (Sweden)

    W Edward Swords

    2012-07-01

    Full Text Available Like many pathogens inhabiting mucosal surfaces, nontypeable Haemophilus influenzae (NTHi forms multicellular biofilm communities both in vitro and in various infection models. In the past 15 years much has been learned about determinants of biofilm formation by this organism and potential roles in bacterial virulence, especially in the context of chronic and recurrent infections. However, this concept has not been without some degree of controversy, and in the past some have expressed doubts about the relevance of NTHi biofilms to disease. In this review, I will summarize the present information on the composition and potential role(s of NTHi biofilms in different clinical contexts, as well as highlight potential areas for future work.

  14. Nontypeable Haemophilus influenzae biofilms: role in chronic airway infections.

    Science.gov (United States)

    Swords, W Edward

    2012-01-01

    Like many pathogens inhabiting mucosal surfaces, nontypeable Haemophilus influenzae (NTHi) forms multicellular biofilm communities both in vitro and in various infection models. In the past 15 years much has been learned about determinants of biofilm formation by this organism and potential roles in bacterial virulence, especially in the context of chronic and recurrent infections. However, this concept has not been without some degree of controversy, and in the past some have expressed doubts about the relevance of NTHi biofilms to disease. In this review, I will summarize the present information on the composition and potential role(s) of NTHi biofilms in different clinical contexts, as well as highlight potential areas for future work.

  15. Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota.

    Science.gov (United States)

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

    2004-07-01

    We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P survival rate of the L. casei Shirota group was significantly (P L. casei Shirota group were significantly greater than those of mice in the control group. These findings suggest that oral administration of L. casei Shirota activates the immature immune system of neonatal and infant mice and protects against IFV infection. Therefore, oral administration of L. casei Shirota may accelerate the innate immune response of the respiratory tract and protect against various respiratory infections in neonates, infants, and children, a high risk group for viral and bacterial infections.

  16. Influenza C infections in Western Australia and Victoria from 2008 to 2014.

    Science.gov (United States)

    Jelley, Lauren; Levy, Avram; Deng, Yi-Mo; Spirason, Natalie; Lang, Jurissa; Buettner, Iwona; Druce, Julian; Blyth, Chris; Effler, Paul; Smith, David; Barr, Ian G

    2016-11-01

    Influenza C is usually considered a minor cause of respiratory illness in humans with many infections being asymptomatic or clinically mild. Large outbreaks can occur periodically resulting in significant morbidity. This study aimed at analyzing the available influenza C clinical samples from two widely separated states of Australia, collected over a 7-year period and to compare them with influenza C viruses detected in other parts of the world in recent years. Between 2008 and 2014, 86 respiratory samples that were influenza C positive were collected from subjects with influenza-like illness living in the states of Victoria and Western Australia. A battery of other respiratory viruses were also tested for in these influenza C-positive samples. Virus isolation was attempted on all of these clinical samples, and gene sequencing was performed on all influenza C-positive cultures. Detections of influenza C in respiratory samples were sporadic in most years studied, but higher rates of infection occurred in 2012 and 2014. Many of the patients with influenza C had coinfections with other respiratory pathogens. Phylogenetic analysis of the full-length hemagglutinin-esterase-fusion (HE) gene found that most of the viruses grouped in the C/Sao Paulo/378/82 clade with the remainder grouping in the C/Kanagawa/1/76 clade. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  17. Social participation and risk of influenza infection in older adults: a cross-sectional study.

    Science.gov (United States)

    Shobugawa, Yugo; Fujiwara, Takeo; Tashiro, Atsushi; Saito, Reiko; Kondo, Katsunori

    2018-01-24

    Influenza infection can cause severe pneumonia, which is sometimes fatal, particularly in older adults. Influenza results in 3-5 million cases of severe illness and about 250 000 to 500 000 deaths annually worldwide. Social participation in the context of influenza infection is controversial because, although social participation is beneficial in maintaining physical function and mental health, it also increases the risk of contact with infected people. This study examined the association between social participation and influenza infection in Japanese adults aged 65 years or older. Cross-sectional study. Japanese functionally independent adults aged 65 years or older. Among the respondents to the Japan Gerontological Evaluation Study (JAGES) 2013 survey, which took place during the period from October to December 2013, 12 231 men and 14 091 women responded to questions on influenza vaccination and influenza infection. Using JAGES data for 12 231 men and 14 091 women aged ≥65 years, we examined the association between social participation and influenza infection. The association between influenza infection and number of groups in which respondents participated was investigated among adults aged≥65 years, stratified by vaccination status and sex. Unvaccinated women who participated in two or more social activities were 2.20 times (95% CI 1.47 to 3.29) as likely to report an influenza infection as those who reported no social participation. In contrast, vaccinated women who participated in two or more social groups had no additional risk of influenza infection as compared with female elders with no social participation. Among men, participation in social activities was not significantly associated with influenza infection, regardless of vaccination status. Social participation was associated with a higher risk of influenza infection among unvaccinated older women, which suggests a need for further efforts to promote influenza vaccination

  18. 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)

  19. Diagnosing avian influenza infection in vaccinated populations by systems for differentiating infected from vaccinated animals (DIVA).

    Science.gov (United States)

    Capua, I; Cattoli, G

    2007-01-01

    Vaccination against avian influenza is recommended as a tool to support control measures in countries affected by avian influenza. Vaccination is known to increase the resistance of susceptible birds to infection and also to reduce shedding; however, it does not always prevent infection. Vaccinated infected flocks can therefore be a source of infection and thus be responsible for the perpetuation of infection. To avoid the spread of infection in a vaccinated population, immunization strategies must allow differentiation of infected from vaccinated animals (DIVA), combined with an appropriate monitoring system. Vaccinated exposed flocks must be identified and managed by restriction policies that include controlled marketing and stamping-out. Several vaccines and diagnostic tests to detect infection in vaccinated populations are available, the tests having various properties and characteristics. In order to achieve eradication, the most appropriate DIVA vaccination strategy must be identified and an appropriate monitoring programme be designed, taking into account risk factors, the epidemiological situation and the socioeconomic implications of the policy.

  20. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    International Nuclear Information System (INIS)

    Zhirnov, O.P.; Manykin, A.A.; Rossman, J.S.; Klenk, H.D.

    2016-01-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  1. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  2. Infection by Streptococcus pneumoniae in children with or without radiologically confirmed pneumonia

    Directory of Open Access Journals (Sweden)

    Dafne C. Andrade

    2018-01-01

    Conclusions: Among children with clinical diagnosis of community‐acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph.

  3. tion and/or treatment of influenza virus infections

    African Journals Online (AJOL)

    Repro

    more frequent in children and more seri- ous in the elderly, ... The main option for the prevention of influenza and ... rapid development of influenza virus resistance ... drugs that affect the CNS, particu- .... include employees of hospitals, clinics ...

  4. Investigation of avian influenza infections in wild birds, poultry and humans in Eastern Dongting Lake, China.

    Science.gov (United States)

    Shi, Jinghong; Gao, Lidong; Zhu, Yun; Chen, Tao; Liu, Yunzhi; Dong, Libo; Liu, Fuqiang; Yang, Hao; Cai, Yahui; Yu, Mingdong; Yao, Yi; Xu, Cuilin; Xiao, Xiangming; Shu, Yuelong

    2014-01-01

    We investigated avian influenza infections in wild birds, poultry, and humans at Eastern Dongting Lake, China. We analyzed 6,621 environmental samples, including fresh fecal and water samples, from wild birds and domestic ducks that were collected from the Eastern Dongting Lake area from November 2011 to April 2012. We also conducted two cross-sectional serological studies in November 2011 and April 2012, with 1,050 serum samples collected from people exposed to wild birds and/or domestic ducks. Environmental samples were tested for the presence of avian influenza virus (AIV) using quantitative PCR assays and virus isolation techniques. Hemagglutination inhibition assays were used to detect antibodies against AIV H5N1, and microneutralization assays were used to confirm these results. Among the environmental samples from wild birds and domestic ducks, AIV prevalence was 5.19 and 5.32%, respectively. We isolated 39 and 5 AIVs from the fecal samples of wild birds and domestic ducks, respectively. Our analysis indicated 12 subtypes of AIV were present, suggesting that wild birds in the Eastern Dongting Lake area carried a diverse array of AIVs with low pathogenicity. We were unable to detect any antibodies against AIV H5N1 in humans, suggesting that human infection with H5N1 was rare in this region.

  5. A quantitative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection.

    Science.gov (United States)

    Johnson, D F; Druce, J D; Birch, C; Grayson, M L

    2009-07-15

    We assessed the in vivo efficacy of surgical and N95 (respirator) masks to filter reverse transcription-polymerase chain reaction (RT-PCR)-detectable virus when worn correctly by patients with laboratory-confirmed acute influenza. Of 26 patients with a clinical diagnosis of influenza, 19 had the diagnosis confirmed by RT-PCR, and 9 went on to complete the study. Surgical and N95 masks were equally effective in preventing the spread of PCR-detectable influenza.

  6. Direct medical cost of influenza-related hospitalizations among severe acute respiratory infections cases in three provinces in China.

    Directory of Open Access Journals (Sweden)

    Lei Zhou

    Full Text Available BACKGROUND: Influenza-related hospitalizations impose a considerable economic and social burden. This study aimed to better understand the economic burden of influenza-related hospitalizations among patients in China in different age and risk categories. METHODS: Laboratory-confirmed influenza-related hospitalizations between December 2009 and June 2011 from three hospitals participating in the Chinese Severe Acute Respiratory Infections (SARI sentinel surveillance system were included in this study. Hospital billing data were collected from each hospital's Hospital Information System (HIS and divided into five cost categories. Demographic and clinical information was collected from medical records. Mean (range and median (interquartile range [IQR] costs were calculated and compared among children (≤15 years, adults (16-64 years and elderly (≥65 years groups. Factors influencing cost were analyzed. RESULTS: A total of 106 laboratory-confirmed influenza-related hospitalizations were identified, 60% of which were children. The mean (range direct medical cost was $1,797 ($80-$27,545 for all hospitalizations, and the median (IQR direct medical cost was $231 ($164, $854 ($890, and $2,263 ($7,803 for children, adults, and elderly, respectively. Therapeutics and diagnostics were the two largest components of direct medical cost, comprising 57% and 23%, respectively. Cost of physician services was the lowest at less than 1%. CONCLUSION: Direct medical cost of influenza-related hospitalizations imposes a heavy burden on patients and their families in China. Further study is needed to provide more comprehensive evidence on the economic burden of influenza. Our study highlights the need to increase vaccination rate and develop targeted national preventive strategies.

  7. Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection

    Science.gov (United States)

    Qasmieh, Saba; Mounts, Anthony Wayne; Alexander, Burmaa; Besselaar, Terry; Briand, Sylvie; Brown, Caroline; Clark, Seth; Dueger, Erica; Gross, Diane; Hauge, Siri; Hirve, Siddhivinayak; Jorgensen, Pernille; Katz, Mark A; Mafi, Ali; Malik, Mamunur; McCarron, Margaret; Meerhoff, Tamara; Mori, Yuichiro; Mott, Joshua; Olivera, Maria Teresa da Costa; Ortiz, Justin R; Palekar, Rakhee; Rebelo-de-Andrade, Helena; Soetens, Loes; Yahaya, Ali Ahmed; Zhang, Wenqing; Vandemaele, Katelijn

    2018-01-01

    Abstract The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009–2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza – i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden. PMID:29403115

  8. Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season.

    Science.gov (United States)

    Zimmerman, Richard K; Rinaldo, Charles R; Nowalk, Mary Patricia; Gk, Balasubramani; Thompson, Mark G; Moehling, Krissy K; Bullotta, Arlene; Wisniewski, Stephen

    2014-07-01

    Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings. During January-April 2012, outpatients with acute respiratory illness (≤ 7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression. Among 662 participants (6 months-82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (κ = 0.83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15.4%), coronavirus (CoV, 10.4%), respiratory syncytial virus (RSV, 8.4%), human metapneumovirus (hMPV, 8.3%), and influenza (6%). Co-detections were infrequent (6.9%) and most commonly occurred among those infections (P = 0.008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0.001), and body mass index was higher among those with influenza (P = 0.036). Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  9. Risk factors for laboratory-confirmed bloodstream infection in neonates undergoing surgical procedures

    Directory of Open Access Journals (Sweden)

    Roberta Maia de Castro Romanelli

    2014-07-01

    Conclusions: Shortening time on parenteral nutrition whenever possible and preference for non-invasive ventilation in neonates undergoing surgery should be considered in the assistance of these patients, with the goal of reducing Healthcare Associated Infections, especially laboratory-confirmed bloodstream infection.

  10. Randomized controlled trials for influenza drugs and vaccines: a review of controlled human infection studies

    Directory of Open Access Journals (Sweden)

    Shobana Balasingam

    2016-08-01

    Conclusions: Controlled human infection studies are an important research tool in assessing promising influenza vaccines and antivirals. These studies are performed quickly and are cost-effective and safe, with a low incidence of serious adverse events.

  11. Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

    KAUST Repository

    Al-Garawi, A.; Husain, M.; Ilieva, D.; Humbles, A. A.; Kolbeck, R.; Stampfli, M. R.; O'Byrne, P. M.; Coyle, A. J.; Jordana, M.

    2011-01-01

    significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review

    Science.gov (United States)

    Warren‐Gash, Charlotte; Fragaszy, Ellen; Hayward, Andrew C.

    2012-01-01

    Please cite this paper as: Warren‐Gash et al. (2012) Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12015. Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary and secondary transmission of (i) influenza and (ii) acute respiratory tract infections in community settings. We searched Medline, Embase, Global Health and Cochrane databases up to 13 February 2012 for reports in any language of original research investigating the effect of hand hygiene on influenza or acute respiratory tract infection where aetiology was unspecified in community settings including institutions such as schools, and domestic residences. Data were presented and quality rated across outcomes according to the Grading of Recommendations Assessment, Development and Evaluation system. Sixteen articles met inclusion criteria. There was moderate to low‐quality evidence of a reduction in both influenza and respiratory tract infection with hand hygiene interventions in schools, greatest in a lower–middle‐income setting. There was high‐quality evidence of a small reduction in respiratory infection in childcare settings. There was high‐quality evidence for a large reduction in respiratory infection with a hand hygiene intervention in squatter settlements in a low‐income setting. There was moderate‐ to high‐quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case. While hand hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections, their effectiveness varies depending on setting, context and compliance. PMID:23043518

  15. 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.

  16. 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.

  17. Acute Respiratory Distress Syndrome Caused by Influenza B Virus Infection in a Patient with Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Silvio A. Ñamendys-Silva

    2011-01-01

    Full Text Available Influenza B virus infections are less common than infections caused by influenza A virus in critically ill patients, but similar mortality rates have been observed for both influenza types. Pneumonia caused by influenza B virus is uncommon and has been reported in pediatric patients and previously healthy adults. Critically ill patients with pneumonia caused by influenza virus may develop acute respiratory distress syndrome. We describe the clinical course of a critically ill patient with diffuse large B-cell lymphoma nongerminal center B-cell phenotype who developed acute respiratory distress syndrome caused by influenza B virus infection. This paper emphasizes the need to suspect influenza B virus infection in critically ill immunocompromised patients with progressive deterioration of cardiopulmonary function despite treatment with antibiotics. Early initiation of neuraminidase inhibitor and the implementation of guidelines for management of severe sepsis and septic shock should be considered.

  18. Skewing to the LFA-3 adhesion pathway by influenza infection of antigen-presenting cells

    NARCIS (Netherlands)

    van Kemenade, F. J.; Kuijpers, K. C.; de Waal-Malefijt, R.; van Lier, R. A.; Miedema, F.

    1993-01-01

    The effect of influenza (FLU) infection on heterotypic conjugate formation between antigen-presenting cells and T lymphocytes has been studied with FLU-specific T cell clones and FLU-infected B-lymphoblastoid cells (B-LCL). Conjugate formation between FLU-infected B-LCL (FLU+ B-LCL) and T cells was

  19. Effect of gargling with tea and ingredients of tea on the prevention of influenza infection: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Kazuki Ide

    2016-05-01

    % CI = 0.56–0.91. The fixed effects model had a better quality of fit than the random effects model (fixed effects model: AIC = 6.04, BIC = 5.65; random effects model: AIC = 8.74, BIC = 7.52. Conclusions Gargling with tea and its ingredients may have a preventative effect for influenza infection. However, additional large-scale studies in different populations and a pooled analysis of these studies are needed to confirm the effect.

  20. Influenza hospitalization epidemiology from a severe acute respiratory infection surveillance system in Jordan, January 2008-February 2014.

    Science.gov (United States)

    Al-Abdallat, Mohammad; Dawson, Patrick; Haddadin, Aktham Jeries; El-Shoubary, Waleed; Dueger, Erica; Al-Sanouri, Tarek; Said, Mayar M; Talaat, Maha

    2016-03-01

    Acute respiratory infections (ARIs) are a major cause of morbidity and mortality worldwide. Influenza typically contributes substantially to the burden of ARI, but only limited data are available on influenza activity and seasonality in Jordan. Syndromic case definitions were used to identify individuals with severe acute respiratory infections (SARI) admitted to four sentinel hospitals in Jordan. Demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real-time reverse transcription polymerase chain reaction and typed as influenza A or B, with influenza A further subtyped. From January 2008-February 2014, 2891 SARI cases were tested for influenza, and 257 (9%) were positive. While 73% of all SARI cases were under 5 years of age, only 57% of influenza-positive cases were under 5 years of age. Eight (3%) influenza-positive cases died. An annual seasonal pattern of influenza activity was observed. The proportion of influenza-positive cases peaked during November-January (14-42%) in the non-pandemic years. Influenza is associated with substantial morbidity and mortality in Jordan. The seasonal pattern of influenza aligns with known Northern Hemisphere seasonality. Further characterization of the clinical and financial burden of influenza in Jordan will be critical in supporting decisions regarding disease control activities. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  1. The effects of synoptic weather on influenza infection incidences: a retrospective study utilizing digital disease surveillance

    Science.gov (United States)

    Zhao, Naizhuo; Cao, Guofeng; Vanos, Jennifer K.; Vecellio, Daniel J.

    2018-01-01

    The environmental drivers and mechanisms of influenza dynamics remain unclear. The recent development of influenza surveillance-particularly the emergence of digital epidemiology-provides an opportunity to further understand this puzzle as an area within applied human biometeorology. This paper investigates the short-term weather effects on human influenza activity at a synoptic scale during cold seasons. Using 10 years (2005-2014) of municipal level influenza surveillance data (an adjustment of the Google Flu Trends estimation from the Centers for Disease Control's virologic surveillance data) and daily spatial synoptic classification weather types, we explore and compare the effects of weather exposure on the influenza infection incidences in 79 cities across the USA. We find that during the cold seasons the presence of the polar [i.e., dry polar (DP) and moist polar (MP)] weather types is significantly associated with increasing influenza likelihood in 62 and 68% of the studied cities, respectively, while the presence of tropical [i.e., dry tropical (DT) and moist tropical (MT)] weather types is associated with a significantly decreasing occurrence of influenza in 56 and 43% of the cities, respectively. The MP and the DP weather types exhibit similar close positive correlations with influenza infection incidences, indicating that both cold-dry and cold-moist air provide favorable conditions for the occurrence of influenza in the cold seasons. Additionally, when tropical weather types are present, the humid (MT) and the dry (DT) weather types have similar strong impacts to inhibit the occurrence of influenza. These findings suggest that temperature is a more dominating atmospheric factor than moisture that impacts the occurrences of influenza in cold seasons.

  2. Characteristics of patients with influenza-like illness, severe acture respiratory illness, and laboratory-confirmed influenza at a major children's hospital in Angola, 2009-2011.

    Science.gov (United States)

    Cardoso, Yolanda; Oliveira, Erika; Vasconcelos, Jocelyne; Cohen, Adam L; Francisco, Moises

    2012-12-15

    There are no published data on influenza trends in Angola, where pneumonia is a leading cause of death among young children. This study aims to describe the seasonal trends, types, and subtypes of influenza virus recovered from patients with respiratory illness who were admitted to the major children's hospital in Angola from May 2009 through April 2011. Nasal and oral swabs were collected from patients seen in the outpatient clinic with influenza-like illness (ILI) or hospitalized with severe acute respiratory illness (SARI) and tested for influenza virus by polymerase chain reaction assays. Of 691 samples collected, 334 (48%) were from case patients with ILI, and 357 (52%) were from case patients with SARI. Most (86%) of these children were Angola.

  3. Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection.

    Science.gov (United States)

    Merani, Shahzma; Pawelec, Graham; Kuchel, George A; McElhaney, Janet E

    2017-01-01

    The number of people over the age of 60 is expected to double by 2050 according to the WHO. This emphasizes the need to ensure optimized resilience to health stressors in late life. In older adults, influenza is one of the leading causes of catastrophic disability (defined as the loss of independence in daily living and self-care activities). Influenza vaccination is generally perceived to be less protective in older adults, with some studies suggesting that the humoral immune response to the vaccine is further impaired in cytomegalovirus (CMV)-seropositive older people. CMV is a β-herpes virus infection that is generally asymptomatic in healthy individuals. The majority of older adults possess serum antibodies against the virus indicating latent infection. Age-related changes in T-cell-mediated immunity are augmented by CMV infection and may be associated with more serious complications of influenza infection. This review focuses on the impact of aging and CMV on immune cell function, the response to influenza infection and vaccination, and how the current understanding of aging and CMV can be used to design a more effective influenza vaccine for older adults. It is anticipated that efforts in this field will address the public health need for improved protection against influenza in older adults, particularly with regard to the serious complications leading to loss of independence.

  4. Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection in mice.

    Science.gov (United States)

    Taylor, Andrew K; Cao, Weiping; Vora, Keyur P; De La Cruz, Juan; Shieh, Wun-Ju; Zaki, Sherif R; Katz, Jacqueline M; Sambhara, Suryaprakash; Gangappa, Shivaprakash

    2013-02-01

    Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. Very few studies have addressed the relevance of PEM as a risk factor for influenza. We investigated the influence of PEM on susceptibility to, and immune responses following, influenza virus infection using isocaloric diets providing either adequate protein (AP; 18%) or very low protein (VLP; 2%) in a mouse model. We found that mice maintained on the VLP diet, when compared to mice fed with the AP diet, exhibited more severe disease following influenza infection based on virus persistence, trafficking of inflammatory cell types to the lung tissue, and virus-induced mortality. Furthermore, groups of mice maintained on the VLP diet showed significantly lower virus-specific antibody response and a reduction in influenza nuclear protein-specific CD8(+) T cells compared with mice fed on the AP diet. Importantly, switching diets for the group maintained on the VLP diet to the AP diet improved virus clearance, as well as protective immunity to viral challenge. Our results highlight the impact of protein energy on immunity to influenza infection and suggest that balanced protein energy replenishment may be one strategy to boost immunity against influenza viral infections.

  5. Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

    Directory of Open Access Journals (Sweden)

    Shahzma Merani

    2017-07-01

    Full Text Available The number of people over the age of 60 is expected to double by 2050 according to the WHO. This emphasizes the need to ensure optimized resilience to health stressors in late life. In older adults, influenza is one of the leading causes of catastrophic disability (defined as the loss of independence in daily living and self-care activities. Influenza vaccination is generally perceived to be less protective in older adults, with some studies suggesting that the humoral immune response to the vaccine is further impaired in cytomegalovirus (CMV-seropositive older people. CMV is a β-herpes virus infection that is generally asymptomatic in healthy individuals. The majority of older adults possess serum antibodies against the virus indicating latent infection. Age-related changes in T-cell-mediated immunity are augmented by CMV infection and may be associated with more serious complications of influenza infection. This review focuses on the impact of aging and CMV on immune cell function, the response to influenza infection and vaccination, and how the current understanding of aging and CMV can be used to design a more effective influenza vaccine for older adults. It is anticipated that efforts in this field will address the public health need for improved protection against influenza in older adults, particularly with regard to the serious complications leading to loss of independence.

  6. [Status of acute upper respiratory infection, influenza-like illness, and influenza vaccination coverage among community residents in Jinan].

    Science.gov (United States)

    Liu, Ying; Song, Shaoxia; Wang, Wei; Geng, Xingyi; Liu, Wen; Han, Debiao; Liu, Ti; Wu, Julong; Li, Zhong; Wang, Xianjun; Bi, Zhenqiang

    2015-12-01

    To analyze the status of acute upper respiratory infection and influenza-like illness (ILI) among community residents in Jinan in 2015, and to make a understand of the patient's medical treatment behavior and influenza vaccination coverage status in 2014. Balloting method and convenient sampling method were used to launch a household survey. The residents who had been in Jinan for more than 3 months were selected, to investigate the residents' attack ratio of acute upper respiratory and influenza-like from Jan. 8 to Feb. 7, 2015. Totally, 1 300 persons from 410 families were involved in this survey which recovered 1 241 valid questionnaires with the efficiency of 95.5%. Based on the national age-urban demographic statistics in 2010, the attack rates of acute respiratory infections, influenza-like illness were estimated by the direct standardization method, and the influenza vaccination rates were also calculated in this study. χ(2)-test method was used to compare the different status of incidence and vaccination among residents with different features. The attack rate of acute upper respiratory infection and influenza-like illness in Jinan from January 8, 2015 to February 7, 2015 were 30.2% (375 cases), and 6.1% (76 cases), respectively, with a standardized rate of 29.1% and 5.4%. 5.3% (66 cases) of the residents have vaccinated with the influenza vaccine inoculation, with an adjusted rate of 3.8%. The attack rate difference of acute upper respiratory tract infections was statistically significant between each age group (χ(2)=17.121, P= 0.002). The 0-4 age group had a highest attack rate (45.4%) of acute respiratory infection, while the 15-24 age group got the lowest (26.5%). 38.9% (146 cases) of patients went for a treatment in hospital. Among them, 37.7% (55 cases) of them selected the county level hospitals for treatment, 37.7% (55 cases) selected the community level hospitals, and 24.6% (36 cases) selected the individual clinic. Significant differences of

  7. 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

  8. Iota-carrageenan is a potent inhibitor of influenza A virus infection.

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    Andreas Leibbrandt

    Full Text Available The 2009 flu pandemic and the appearance of oseltamivir-resistant H1N1 influenza strains highlight the need for treatment alternatives. One such option is the creation of a protective physical barrier in the nasal cavity. In vitro tests demonstrated that iota-carrageenan is a potent inhibitor of influenza A virus infection, most importantly also of pandemic H1N1/2009 in vitro. Consequently, we tested a commercially available nasal spray containing iota-carrageenan in an influenza A mouse infection model. Treatment of mice infected with a lethal dose of influenza A PR8/34 H1N1 virus with iota-carrageenan starting up to 48 hours post infection resulted in a strong protection of mice similar to mice treated with oseltamivir. Since alternative treatment options for influenza are rare, we conclude that the nasal spray containing iota-carrageenan is an alternative to neuraminidase inhibitors and should be tested for prevention and treatment of influenza A in clinical trials in humans.

  9. Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype.

    Science.gov (United States)

    Campbell, Gillian M; Nicol, Marlynne Q; Dransfield, Ian; Shaw, Darren J; Nash, Anthony A; Dutia, Bernadette M

    2015-10-01

    The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-α, and TNF-α expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-α was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of pro-inflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

  10. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R., E-mail: grw7@cornell.edu

    2014-07-25

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

  11. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    International Nuclear Information System (INIS)

    Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R.

    2014-01-01

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza

  12. Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection.

    Science.gov (United States)

    Randolph, Adrienne G; Yip, Wai-Ki; Allen, Emma Kaitlynn; Rosenberger, Carrie M; Agan, Anna A; Ash, Stephanie A; Zhang, Yu; Bhangale, Tushar R; Finkelstein, David; Cvijanovich, Natalie Z; Mourani, Peter M; Hall, Mark W; Su, Helen C; Thomas, Paul G

    2017-07-01

    Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site. © 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.

  13. 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

  14. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection

    Science.gov (United States)

    Perwitasari, Olivia; Johnson, Scott; Yan, Xiuzhen; Register, Emery; Crabtree, Jackelyn; Gabbard, Jon; Howerth, Elizabeth; Shacham, Sharon; Carlson, Robert; Tamir, Sharon; Tripp, Ralph A.

    2016-01-01

    Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection. PMID:27893810

  15. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Olivia Perwitasari

    Full Text Available Influenza A virus (IAV causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

  16. Investigating avian influenza infection hotspots in old-world shorebirds.

    Directory of Open Access Journals (Sweden)

    Nicolas Gaidet

    Full Text Available Heterogeneity in the transmission rates of pathogens across hosts or environments may produce disease hotspots, which are defined as specific sites, times or species associations in which the infection rate is consistently elevated. Hotspots for avian influenza virus (AIV in wild birds are largely unstudied and poorly understood. A striking feature is the existence of a unique but consistent AIV hotspot in shorebirds (Charadriiformes associated with a single species at a specific location and time (ruddy turnstone Arenaria interpres at Delaware Bay, USA, in May. This unique case, though a valuable reference, limits our capacity to explore and understand the general properties of AIV hotspots in shorebirds. Unfortunately, relatively few shorebirds have been sampled outside Delaware Bay and they belong to only a few shorebird families; there also has been a lack of consistent oropharyngeal sampling as a complement to cloacal sampling. In this study we looked for AIV hotspots associated with other shorebird species and/or with some of the larger congregation sites of shorebirds in the old world. We assembled and analysed a regionally extensive dataset of AIV prevalence from 69 shorebird species sampled in 25 countries across Africa and Western Eurasia. Despite this diverse and extensive coverage we did not detect any new shorebird AIV hotspots. Neither large shorebird congregation sites nor the ruddy turnstone were consistently associated with AIV hotspots. We did, however, find a low but widespread circulation of AIV in shorebirds that contrast with the absence of AIV previously reported in shorebirds in Europe. A very high AIV antibody prevalence coupled to a low infection rate was found in both first-year and adult birds of two migratory sandpiper species, suggesting the potential existence of an AIV hotspot along their migratory flyway that is yet to be discovered.

  17. [Intestinal disorder of anaerobic bacteria aggravates pulmonary immune pathological injury of mice infected with influenza virus].

    Science.gov (United States)

    Wu, Sha; Yan, Yuqi; Zhang, Mengyuan; Shi, Shanshan; Jiang, Zhenyou

    2016-04-01

    To investigate the relationship between the intestinal disorder of anaerobic bacteria and influenza virus infection, and the effect on pulmonary inflammatory cytokines in mice. Totally 36 mice were randomly divided into normal control group, virus-infected group and metronidazole treatment group (12 mice in each group). Mice in the metronidazole group were administrated orally with metronidazole sulfate for 8 days causing anaerobic bacteria flora imbalance; then all groups except the normal control group were treated transnasally with influenza virus (50 μL/d FM1) for 4 days to establish the influenza virus-infected models. Their mental state and lung index were observed, and the pathological morphological changes of lung tissues, caecum and intestinal mucosa were examined by HE staining. The levels of interleukin 4 (IL-4), interferon γ (IFN-γ), IL-10 and IL-17 in the lung homogenates were determined by ELISA. Compared with the virus control group, the metronidazole group showed obviously increased lung index and more serious pathological changes of the lung tissue and appendix inflammation performance. After infected by the FM1 influenza virus, IFN-γ and IL-17 of the metronidazole group decreased significantly and IL-4 and IL-10 levels were raised, but there was no statistically difference between the metronidazole and virus control groups. Intestinal anaerobic bacteria may inhibit the adaptive immune response in the lungs of mice infected with FM1 influenza virus through adjusting the lung inflammatory factors, affect the replication and clean-up time of the FM1 influenza virus, thus further aggravating pulmonary immune pathological injury caused by the influenza virus infection.

  18. Burden of medically attended influenza infection and cases averted by vaccination — United States, 2013/14 through 2015/16 influenza seasons

    Science.gov (United States)

    Jackson, Michael L.; Phillips, C. Hallie; Benoit, Joyce; Jackson, Lisa A.; Gaglani, Manjusha; Murthy, Kempapura; McLean, Huong Q.; Belongia, Edward A.; Malosh, Ryan; Zimmerman, Richard; Flannery, Brendan

    2018-01-01

    Background In addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons. Methods We defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination. Results Across the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1,000 population. Incidence was highest in children aged 6 months to 9 years (33 to 70 per 1,000) and lowest in adults aged 18-49 years (21 to 27 per 1,000). Cases averted ranged from 9 per 1,000 vaccinees (Washington, 2014/15) to 28 per 1,000 (Wisconsin, 2013/14). Discussion Seasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain. PMID:29249545

  19. Hampered foraging and migratory performance in swans infected with low-pathogenic avian influenza A virus.

    Directory of Open Access Journals (Sweden)

    Jan A van Gils

    Full Text Available It is increasingly acknowledged that migratory birds, notably waterfowl, play a critical role in the maintenance and spread of influenza A viruses. In order to elucidate the epidemiology of influenza A viruses in their natural hosts, a better understanding of the pathological effects in these hosts is required. Here we report on the feeding and migratory performance of wild migratory Bewick's swans (Cygnus columbianus bewickii Yarrell naturally infected with low-pathogenic avian influenza (LPAI A viruses of subtypes H6N2 and H6N8. Using information on geolocation data collected from Global Positioning Systems fitted to neck-collars, we show that infected swans experienced delayed migration, leaving their wintering site more than a month after uninfected animals. This was correlated with infected birds travelling shorter distances and fuelling and feeding at reduced rates. The data suggest that LPAI virus infections in wild migratory birds may have higher clinical and ecological impacts than previously recognised.

  20. Management of influenza infection in solid-organ transplant recipients: consensus statement of the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI).

    Science.gov (United States)

    López-Medrano, Francisco; Cordero, Elisa; Gavaldá, Joan; Cruzado, Josep M; Marcos, M Ángeles; Pérez-Romero, Pilar; Sabé, Nuria; Gómez-Bravo, Miguel Ángel; Delgado, Juan Francisco; Cabral, Evelyn; Carratalá, Jordi

    2013-10-01

    Solid organ transplant (SOT) recipients are at greater risk than the general population for complications and mortality from influenza infection. Researchers and clinicians with experience in SOT infections have developed this consensus document in collaboration with several Spanish scientific societies and study networks related to transplant management. We conducted a systematic review to assess the management and prevention of influenza infection in SOT recipients. Evidence levels based on the available literature are given for each recommendation. This article was written in accordance with international recommendations on consensus statements and the recommendations of the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Recommendations are provided on the procurement of organs from donors with suspected or confirmed influenza infection. We highlight the importance of the possibility of influenza infection in any SOT recipient presenting upper or lower respiratory symptoms, including pneumonia. The importance of early antiviral treatment of SOT recipients with suspected or confirmed influenza infection and the necessity of annual influenza vaccination are emphasized. The microbiological techniques for diagnosis of influenza infection are reviewed. Guidelines for the use of antiviral prophylaxis in inpatients and outpatients are provided. Recommendations for household contacts of SOT recipients with influenza infection and health care workers in close contact with transplant patients are also included. Finally antiviral dose adjustment guidelines are presented for cases of impaired renal function and for pediatric populations. The latest scientific information available regarding influenza infection in the context of SOT is incorporated into this document. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

    Directory of Open Access Journals (Sweden)

    Ryuta Ueda

    Full Text Available BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA, a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1 the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins than the membranes of cells in S/G2/M-phase; 2 the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3 S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

  2. Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Bresser, P.; Out, T. A.; van Alphen, L.; Jansen, H. M.; Lutter, R.

    2000-01-01

    Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and

  3. INFLUENZA AND ACUTE VIRAL RESPIRATORY INFECTIONS IN THE PRACTICE OF THE EMERGENCY CREWS OF MOSCOW

    Directory of Open Access Journals (Sweden)

    N. F. Plavunov

    2016-01-01

    Full Text Available Influenza and acute viral respiratory infections have a great social significance during epidemic rise of morbidity and demand differential diagnosis of pneumonia with bacterial etiology and consultation with an infectious disease doctor in case of seeing patients in non-core hospitals. This article highlights the problem of influenza and acute respiratory viral infections’ early diagnosis. Clinical manifestations of influenza and other respiratory extremely similar. The differential diagnosis must take into account the presence of mixed infection in the same patient. According to the results of consultative infectious ambulance teams in 2014-2016, quality of diagnostics of this infectious pathology was examined. Observed deaths in persons later seeking medical treatment, not receiving timely antiviral therapy and related to high-risk groups: patients with obesity, chronic alcohol intoxication, diabetes, pregnant women. Influenza and acute viral respiratory infections, more complicated by pneumonia, people in the older age group, indicating the need for timely medical evacuation of patients older than 60 years. In some cases, in the diagnosis of influenza was helped by the results of laboratory studies (especially the trend to leukopenia and a positive rapid test. It should be noted that a negative rapid test for influenza was not a reason for exclusion of the diagnosis “influenza”.

  4. Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

    KAUST Repository

    Al-Garawi, A.

    2011-12-14

    Respiratory viral infections have been associated with an increased incidence of allergic asthma. However, the mechanisms by which respiratory infections facilitate allergic airway disease are incompletely understood.We previously showed that exposure to a low dose of house dust mite (HDM) resulted in enhanced HDM-mediated allergic airway inflammation, and, importantly, marked airway hyperreactivity only when allergen exposure occurred during an acute influenza A infection. In this study, we evaluated the impact of concurrent influenza infection and allergen exposure at the genomic level, using whole-genome micro-array. Our data showed that, in contrast to exposure to a low dose of HDM, influenza A infection led to a dramatic increase in gene expression, particularly of TLRs, C-type lectin receptors, several complement components, as well as FcεR1. Additionally, we observed increased expression of a number of genes encoding chemokines and cytokines associated with the recruitment of proinflammatory cells. Moreover, HDM exposure in the context of an influenza A infection resulted in the induction of unique genes, including calgranulin A (S100a8), an endogenous damage-associated molecular pattern and TLR4 agonist. In addition, we observed significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying the ensuing immune-inflammatory response. We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype. Copyright © 2012 by The American Association of Immunologists, Inc.

  5. Haemophilus influenzae pneumonia in human immunodeficiency virus-infected patients. The Grupo Andaluz para el Estudio de las Enfermedades Infecciosas.

    Science.gov (United States)

    Cordero, E; Pachón, J; Rivero, A; Girón, J A; Gómez-Mateos, J; Merino, M D; Torres-Tortosa, M; González-Serrano, M; Aliaga, L; Collado, A; Hernández-Quero, J; Barrera, A; Nuño, E

    2000-03-01

    Although Haemophilus influenzae is a common etiologic agent of pneumonia in patients infected with human immunodeficiency virus (HIV), the characteristics of this pneumonia have not been adequately assessed. We have prospectively studied features of H. influenzae pneumonia in 26 consecutive HIV-infected inpatients. Most of these patients were severely immunosuppressed; 73.1% had a CD4+ cell count caused by H. influenzae affects mainly patients with advanced HIV disease, and since its clinical and radiological features may be diverse, this etiology should be considered when pneumonia occurs in patients with advanced HIV infection. The mortality rate associated with H. influenzae pneumonia is not higher than that occurring in the general population.

  6. Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein.

    Science.gov (United States)

    Cheah, Esther Y; Mann, Tracy S; Burcham, Philip C; Henry, Peter J

    2015-02-15

    The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n=14, pacrolein and SP were reduced in VIRUS segments (>35% reduction, n=6, pacrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. 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.

  8. Comparative epidemiology of influenza A and B viral infection in a subtropical region: a 7-year surveillance in Okinawa, Japan

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    Yoshikazu Iha

    2016-11-01

    Full Text Available Abstract Background The epidemic patterns of influenza B infection and their association with climate conditions are not well understood. Influenza surveillance in Okinawa is important for clarifying transmission patterns in both temperate and tropical regions. Using surveillance data, collected over 7 years in the subtropical region of Japan, this study aims to characterize the epidemic patterns of influenza B infection and its association with ambient temperature and relative humidity, in a parallel comparison with influenza A. Methods From January 2007 until March 2014, two individual influenza surveillance datasets were collected from external sources. The first dataset, included weekly rapid antigen test (RAT results from four representative general hospitals, located in the capital city of Okinawa. A nation-wide surveillance of influenza, diagnosed by RAT results and/or influenza-like illness symptoms, included the age distribution of affected patients and was used as the second dataset. To analyze the association between infection and local climate conditions, ambient temperature and relative humidity during the study period were retrieved from the Japanese Meteorological Agency website. Results Although influenza A maintained high number of infections from December through March, epidemics of influenza B infection were observed annually from March through July. The only observed exception was 2010, when the pandemic strain of 2009 dominated. During influenza B outbreaks, influenza patients aged 5 to 9 years old and 10 to 14 years old more frequently visited sentinel sites. Although both ambient temperature and relative humidity are inversely associated with influenza A infection, influenza B infection was found to be directly associated with high relative humidity. Conclusion Further studies are needed to elucidate the complex epidemiology of influenza B and its relationship with influenza A. In the subtropical setting of Okinawa

  9. Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011.

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    Sharon K Greene

    Full Text Available Guillain-Barré Syndrome (GBS can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1 pandemic in the United States, monovalent inactivated influenza vaccine (MIV availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited.We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009-10 MIV, 2010-11 trivalent inactivated influenza vaccine (TIV, and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls.Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009-10 MIV recipients and 2.80 million 2010-11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009-10 MIV/2010-11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI, 0.59-3.99; risk difference = 0.93 per million doses, 95% CI, -0.71-5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60-16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49-26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior

  10. Estimated incidence of influenza-associated severe acute respiratory infections in Indonesia, 2013-2016.

    Science.gov (United States)

    Susilarini, Ni K; Haryanto, Edy; Praptiningsih, Catharina Y; Mangiri, Amalya; Kipuw, Natalie; Tarya, Irmawati; Rusli, Roselinda; Sumardi, Gestafiana; Widuri, Endang; Sembiring, Masri M; Noviyanti, Widya; Widaningrum, Christina; Lafond, Kathryn E; Samaan, Gina; Setiawaty, Vivi

    2018-01-01

    Indonesia's hospital-based Severe Acute Respiratory Infection (SARI) surveillance system, Surveilans Infeksi Saluran Pernafasan Akut Berat Indonesia (SIBI), was established in 2013. While respiratory illnesses such as SARI pose a significant problem, there are limited incidence-based data on influenza disease burden in Indonesia. This study aimed to estimate the incidence of influenza-associated SARI in Indonesia during 2013-2016 at three existing SIBI surveillance sites. From May 2013 to April 2016, inpatients from sentinel hospitals in three districts of Indonesia (Gunung Kidul, Balikpapan, Deli Serdang) were screened for SARI. Respiratory specimens were collected from eligible inpatients and screened for influenza viruses. Annual incidence rates were calculated using these SIBI-enrolled influenza-positive SARI cases as a numerator, with a denominator catchment population defined through hospital admission survey (HAS) to identify respiratory-coded admissions by age to hospitals in the sentinel site districts. From May 2013 to April 2016, there were 1527 SARI cases enrolled, of whom 1392 (91%) had specimens tested and 199 (14%) were influenza-positive. The overall estimated annual incidence of influenza-associated SARI ranged from 13 to 19 per 100 000 population. Incidence was highest in children aged 0-4 years (82-114 per 100 000 population), followed by children 5-14 years (22-36 per 100 000 population). Incidence rates of influenza-associated SARI in these districts indicate a substantial burden of influenza hospitalizations in young children in Indonesia. Further studies are needed to examine the influenza burden in other potential risk groups such as pregnant women and the elderly. © 2017 The Authors. Influenza and Other Respiratory Viruses. Published by John Wiley & Sons Ltd.

  11. 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.

  12. Infective endocarditis caused by Neisseria elongata on a native tricuspid valve and confirmed by DNA sequencing.

    Science.gov (United States)

    Yoo, Yeon Pyo; Kang, Ki-Woon; Yoon, Hyeon Soo; Yoo, Seungmin; Lee, Myung-Shin

    2014-04-01

    Neisseria elongata, a common oral bacterium, has been recognized as a cause of infections such as infective endocarditis, septicemia, and osteomyelitis. Neisseria-induced infective endocarditis, although infrequently reported, typically arises after dental procedures. Without antibiotic therapy, its complications can be severe. We report the case of a 27-year-old man who presented with fever, severe dyspnea, and a leg abscess from cellulitis. An echocardiogram showed a vegetation-like echogenic structure on the septal leaflet of the patient's native tricuspid valve, and an insignificant Gerbode defect. Three blood cultures grew gram-negative, antibiotic-susceptible coccobacilli that were confirmed to be N. elongata. Subsequent DNA sequencing conclusively isolated N. elongata subsp nitroreducens as the organism responsible for the infective endocarditis. The patient recovered after 21 days of antibiotic therapy. In addition to the patient's unusual case, we discuss the nature and isolation of N. elongata and its subspecies.

  13. Avian Influenza.

    Science.gov (United States)

    Zeitlin, Gary Adam; Maslow, Melanie Jane

    2005-05-01

    The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia raises serious concerns that genetic reassortment will result in the next influenza pandemic. There have been 164 confirmed cases of human infection with avian influenza since 1996. In 2004, there were 45 cases of human H5N1 in Vietnam and Thailand, with a mortality rate more than 70%. In addition to the potential public health hazard, the current zoonotic epidemic has caused severe economic losses. Efforts must be concentrated on early detection of bird outbreaks with aggressive culling, quarantining, and disinfection. To prepare for and prevent an increase in human cases, it is essential to improve detection methods and stockpile effective antivirals. Novel therapeutic modalities, including short-interfering RNAs and new vaccine strategies that use plasmid-based genetic systems, offer promise should a pandemic occur.

  14. Burden of pediatric influenza A virus infection post swine-flu H1N1 pandemic in Egypt.

    Science.gov (United States)

    Khattab, Adel; Shaheen, Malak; Kamel, Terez; El Faramay, Amel; El Rahman, Safaa Abd; Nabil, Dalia; Gouda, Mohamed

    2013-09-01

    To screen children with influenza like illness or with symptoms of acute respiratory tract infections for influenza A virus infection - post swine flu pandemic era - using rapid influenza diagnostic tests. During two years (2010 & 2011), 1 200 children with influenza like illness or acute respiratory tract infections (according to World Health Organization criteria) were recruited. Their ages ranged from 2-60 months. Nasopharyngeal aspirates specimens were collected from all children for rapid influenza A diagnostic test. Influenza A virus rapid test was positive in 47.5% of the children; the majority (89.6%) were presented with lower respiratory tract infections. Respiratory rate and temperature were significantly higher among positive rapid influenza test patients. Influenza A virus infection is still a major cause of respiratory tract infections in Egyptian children. It should be considered in all cases with cough and febrile episodes and influenza like symptoms even post swine flu pandemic. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  15. Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review.

    Science.gov (United States)

    Warren-Gash, Charlotte; Fragaszy, Ellen; Hayward, Andrew C

    2013-09-01

    Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary and secondary transmission of (i) influenza and (ii) acute respiratory tract infections in community settings. We searched Medline, Embase, Global Health and Cochrane databases up to 13 February 2012 for reports in any language of original research investigating the effect of hand hygiene on influenza or acute respiratory tract infection where aetiology was unspecified in community settings including institutions such as schools, and domestic residences. Data were presented and quality rated across outcomes according to the Grading of Recommendations Assessment, Development and Evaluation system. Sixteen articles met inclusion criteria. There was moderate to low-quality evidence of a reduction in both influenza and respiratory tract infection with hand hygiene interventions in schools, greatest in a lower-middle-income setting. There was high-quality evidence of a small reduction in respiratory infection in childcare settings. There was high-quality evidence for a large reduction in respiratory infection with a hand hygiene intervention in squatter settlements in a low-income setting. There was moderate- to high-quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case. While hand hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections, their effectiveness varies depending on setting, context and compliance. © 2012 John Wiley & Sons Ltd.

  16. Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.

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    Cristian Cillóniz

    2009-10-01

    Full Text Available The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.

  17. Pretreatment of Mice with Oligonucleotide prop5 Protects Them from Influenza Virus Infections

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    Kang Li

    2014-02-01

    Full Text Available Influenza A virus is a successful parasite and requires host factors to complete its life cycle. Prop5 is an antisense oligonucleotide, targeting programmed cell death protein 5 (PDCD5. In this study, we tested the antiviral activity of prop5 against mouse-adapted A/FM/1/47 strain of influenza A virus in a mouse model. Prop5 intranasally administered the mice at dosages of 10 and 20 mg/kg/d at 24 h and 30 min before infection, provided 80% and 100% survival rates and prolonged mean survival days in comparison with influenza virus-infected mice (both p < 0.01. Moreover, viral titres in mice pretreated with prop5, at dose of 10 and 20 mg/kg/d, had declined significantly on day two, four, and six post-infection compared with the yields in infected mice (p < 0.05 or p < 0.01; lung index in mice pretreated with prop5 (20 mg/kg/d had been inhibited on day six post-infection (p < 0.05. Western blotting and immunohistochemistry showed that prop5 could down-regulate the PDCD5 protein expression levels in lung tissues of infected mice. These data indicate that antisense oligonucleotide prop5 is a promising drug for prophylaxis and control influenza virus infections and provides an insight into the host-pathogen interaction.

  18. 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.

  19. Evidence for avian H9N2 influenza virus infections among rural villagers in Cambodia.

    Science.gov (United States)

    Blair, Patrick J; Putnam, Shannon D; Krueger, Whitney S; Chum, Channimol; Wierzba, Thomas F; Heil, Gary L; Yasuda, Chadwick Y; Williams, Maya; Kasper, Matthew R; Friary, John A; Capuano, Ana W; Saphonn, Vonthanak; Peiris, Malik; Shao, Hongxia; Perez, Daniel R; Gray, Gregory C

    2013-04-01

    Southeast Asia remains a critical region for the emergence of novel and/or zoonotic influenza, underscoring the importance of extensive sampling in rural areas where early transmission is most likely to occur. In 2008, 800 adult participants from eight sites were enrolled in a prospective population-based study of avian influenza (AI) virus transmission where highly pathogenic avian influenza (HPAI) H5N1 virus had been reported in humans and poultry from 2006 to 2008. From their enrollment sera and questionnaires, we report risk factor findings for serologic evidence of previous infection with 18 AI virus strains. Serologic assays revealed no evidence of previous infection with 13 different low-pathogenic AI viruses or with HPAI avian-like A/Cambodia/R0404050/2007(H5N1). However, 21 participants had elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2), validated with a monoclonal antibody blocking ELISA assay specific for avian H9. Although cross-reaction from antibodies against human influenza viruses cannot be completely excluded, the study data suggest that a number of participants were previously infected with the avian-like A/Hong Kong/1073/1999(H9N2) virus, likely due to as yet unidentified environmental exposures. Prospective data from this cohort will help us better understand the serology of zoonotic influenza infection in a rural cohort in SE Asia. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.

  20. Confirmation of eradication of Helicobacter pylori infection by 14C-urea breath test

    International Nuclear Information System (INIS)

    Pathak, C.M.; Bhasin, D.K.; Sharma, B.C.; Roy, P.; Vaiphei, K.

    1998-01-01

    Helicobacter pylori (H. pylori) is a potent urease producer, a characteristic that has been exploited in the development of the 14 C-urea breath test (UBT). 14 C-UBT is being used as a highly reliable test for the diagnosis of H. pylori infection. There is paucity of reports on the utility of this test to confirm the H. pylori eradication after its treatment. The study was conducted to determine the utility of 14 C-UBT in confirming the eradication of H. pylori

  1. 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)

  2. Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus.

    Science.gov (United States)

    Samarasinghe, Amali E; Melo, Rossana C N; Duan, Susu; LeMessurier, Kim S; Liedmann, Swantje; Surman, Sherri L; Lee, James J; Hurwitz, Julia L; Thomas, Paul G; McCullers, Jonathan A

    2017-04-15

    Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus-infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8 + T cell numbers in the airways. In vitro assays with primary or bone marrow-derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide-exposed eosinophils induced CD8 + T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Optic neuritis and acute anterior uveitis associated with influenza A infection: a case report

    Directory of Open Access Journals (Sweden)

    Nakagawa H

    2017-01-01

    Full Text Available Hayate Nakagawa, Hidetaka Noma, Osamu Kotake, Ryosuke Motohashi, Kanako Yasuda, Masahiko Shimura Department of Ophthalmology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan Background: A few reports have described ocular complications of influenza A infection, such as impaired ocular movement, parasympathetic ocular nerve, keratitis, macular lesion, and frosted branch angiitis. We encountered a rare case of acute anterior uveitis and optic neuritis associated with influenza A infection. Case presentation: A 70-year-old man presented with symptoms of upper respiratory tract infection. A rapid diagnostic test showed a positive result for influenza A. At the same time, he developed ocular symptoms including blurred vision with optic disk edema and hemorrhage in the left eye, and bilateral red eyes. Multiplex polymerase chain reaction performed on aqueous humor sample detected no viral infection. Visual field testing with a Goldmann perimeter showed central and paracentral scotomas in the left eye. In addition to antiviral agent (oseltamivir phosphate 75 mg, the patient was prescribed topical prednisolone acetate ophthalmic suspension eye drops every 5 hours and high-dose intravenous methylprednisolone 1,000 mg daily for 3 days. Two months later, his best-corrected visual acuity improved to 20/50 with regression of visual field defects in his left eye. Conclusion: We report a case of bilateral acute anterior uveitis and unilateral optic neuritis concomitant with influenza A infection. Topical and systemic corticosteroids were effective to resolve acute anterior uveitis and neuritis. Analysis of aqueous humor sample suggested that acute anterior uveitis and optic neuritis in this case were not caused by influenza A virus infection per se but by autoimmune mechanism. Keywords: optic neuritis, anterior uveitis, influenza virus, multiplex polymerase chain reaction

  4. Serious systemic infection caused by non-encapsulated Haemophilus influenzae biotype III in an adult

    DEFF Research Database (Denmark)

    Lester, Anne; Pedersen, P B

    1991-01-01

    Haemophilus influenzae is the aetiological agent in less than 1% of septic arthritis cases in adults and most often serotype b is involved. We report here a case of severe systemic infection due to non-encapsulated H. influenzae biotype III in a 40-year-old man, previously healthy although alcohol...... abuser. Cholangitis and acute alcoholic hepatitis were diagnosed simultaneously. The organism was grown from blood and from synovial fluid of the left knee, but several other joints were also affected. The close relationship between H. influenzae biotype III and H. aegyptius is mentioned in view...... of recent reports of fatal childhood illness caused by a special clone of H. aegyptius and the importance of reporting both serotype and biotype in severe H. influenzae induced disease is emphasized....

  5. 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.

  6. Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.

    Directory of Open Access Journals (Sweden)

    Alan C-Y Hsu

    Full Text Available Innate antiviral responses in bronchial epithelial cells (BECs provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs. However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.

  7. Little evidence of subclinical avian influenza virus infections among rural villagers in Cambodia.

    Directory of Open Access Journals (Sweden)

    Gregory C Gray

    Full Text Available In 2008, 800 adults living within rural Kampong Cham Province, Cambodia were enrolled in a prospective cohort study of zoonotic influenza transmission. After enrollment, participants were contacted weekly for 24 months to identify acute influenza-like illnesses (ILI. Follow-up sera were collected at 12 and 24 months. A transmission substudy was also conducted among the family contacts of cohort members reporting ILI who were influenza A positive. Samples were assessed using serological or molecular techniques looking for evidence of infection with human and avian influenza viruses. Over 24 months, 438 ILI investigations among 284 cohort members were conducted. One cohort member was hospitalized with a H5N1 highly pathogenic avian influenza (HPAI virus infection and withdrew from the study. Ninety-seven ILI cases (22.1% were identified as influenza A virus infections by real-time RT-PCR; none yielded evidence for AIV. During the 2 years of follow-up, 21 participants (3.0% had detectable antibody titers (≥ 1:10 against the studied AIVs: 1 against an avian-like A/Migratory duck/Hong Kong/MPS180/2003(H4N6, 3 against an avian-like A/Teal/Hong Kong/w312/97(H6N1, 9 (3 of which had detectible antibody titers at both 12- and 24-month follow-up against an avian-like A/Hong Kong/1073/1999(H9N2, 6 (1 detected at both 12- and 24-month follow-up against an avian-like A/Duck/Memphis/546/74(H11N9, and 2 against an avian-like A/Duck/Alberta/60/76(H12N5. With the exception of the one hospitalized cohort member with H5N1 infection, no other symptomatic avian influenza infections were detected among the cohort. Serological evidence for subclinical infections was sparse with only one subject showing a 4-fold rise in microneutralization titer over time against AvH12N5. In summary, despite conducting this closely monitored cohort study in a region enzootic for H5N1 HPAI, we were unable to detect subclinical avian influenza infections, suggesting either that these

  8. Estimating burden of influenza-associated influenza-like illness and severe acute respiratory infection at public healthcare facilities in Romania during the 2011/12-2015/16 influenza seasons.

    Science.gov (United States)

    Gefenaite, Giedre; Pistol, Adriana; Popescu, Rodica; Popovici, Odette; Ciurea, Daniel; Dolk, Christiaan; Jit, Mark; Gross, Diane

    2018-01-01

    Influenza is responsible for substantial morbidity and mortality, but there is limited information on reliable disease burden estimates, especially from middle-income countries in the WHO European Region. To estimate the incidence of medically attended influenza-associated influenza-like illness (ILI) and hospitalizations due to severe acute respiratory infection (SARI) presenting to public healthcare facilities in Romania. Sentinel influenza surveillance data for ILI and SARI from 2011/12-2015/16, including virological data, were used to estimate influenza-associated ILI and SARI incidence/100 000 and their 95% confidence intervals (95% CI). The overall annual incidence of ILI and influenza-associated ILI per 100 000 persons in Romania varied between 68 (95% CI: 61-76) and 318 (95% CI: 298-338) and between 23 (95% CI: 19-29) and 189 (95% CI: 149-240), respectively. The highest ILI and influenza incidence was among children aged 0-4 years. We estimated that SARI incidence per 100 000 persons was 6 (95% CI: 5-7) to 9 (95% CI: 8-10), of which 2 (95% CI: 1-2) to 3 (95% CI: 2-4) were due to influenza. Up to 0.3% of the Romanian population were annually reported with ILI, and 0.01% was hospitalized with SARI, of which as much as one-third could be explained by influenza. This evaluation was the first study estimating influenza burden in Romania. We found that during each influenza season, a substantial number of persons in Romania suffer from influenza-related ILI or are hospitalized due to influenza-associated SARI. © 2017 The World Health Organization. Influenza and Other Respiratory Viruses. Published by John Wiley & Sons Ltd.

  9. Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice.

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    Michelle A Carey

    Full Text Available BACKGROUND: We previously demonstrated that cyclooxygenase (COX-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560, a COX-2 inhibitor (celecoxib or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

  10. Effects of closing and reopening live poultry markets on the epidemic of human infection with avian influenza A virus

    OpenAIRE

    Lu, Jian; Liu, Wendong; Xia, Rui; Dai, Qigang; Bao, Changjun; Tang, Fenyang; Zhu, yefei; Wang, Qiao

    2015-01-01

    Abstract Live poultry markets (LPMs) are crucial places for human infection of influenza A (H7N9 virus). In Yangtze River Delta, LPMs were closed after the outbreak of human infection with avian influenza A (H7N9) virus, and then reopened when no case was found. Our purpose was to quantify the effect of LPMs? operations in this region on the transmission of influenza A (H7N9) virus. We obtained information about dates of symptom onset and locations for all human influenza A (H7N9) cases repor...

  11. Influenza A virus alters pneumococcal nasal colonization and middle ear infection independently of phase variation.

    Science.gov (United States)

    Wren, John T; Blevins, Lance K; Pang, Bing; King, Lauren B; Perez, Antonia C; Murrah, Kyle A; Reimche, Jennifer L; Alexander-Miller, Martha A; Swords, W Edward

    2014-11-01

    Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. Epidemiological and molecular surveillance of influenza and respiratory syncytial viruses in children with acute respiratory infections (2004/2005 season

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    Alessandra Zappa

    2008-03-01

    Full Text Available Objective. During the 2004/2005 influenza season an active virological surveillance of influenza viruses and respiratory syncytial virus (RSV was carried out to monitor the epidemiologic trend of acute respiratory infections (ARI in the paediatric community. Materials and methods. 100 patients (51 males, 49 females; mean age: 19 months, either treated at the Emergency Unit or hospitalized in the Pediatric Unit of “San Carlo Borromeo Hospital” (Milan, reporting symptoms related to ARI were enrolled. Pharyngeal swabs were collected for virological investigation by: 1 multiplexnested- PCR for the simultaneous identification of both influenza A and B viruses and RSV; 2 multiplex-nested- PCR for the subtyping of influenza A viruses (H1 and H3. Results. 12% (12/100 subjects were infected with influenza A virus, 4% (4/100 with influenza B virus and 14 (14% with RSV. Of all the 12 influenza A positive samples 4 (33.3% belonged to subtype H1 and 8 (66.7% to subtype H3. Bronchiolitis and bronchitis episodes were significantly higher among RSV-infected subjects than among influenza- infected subjects (42.8% vs 6.2%; p<0.05 and 35.7% vs 6.2%; p<0.05, respectively. Pneumonia episodes occurred similarly both in influenza-infected children and in RSV-infected ones. Conclusions. During the 2004/2005 influenza season, influenza viruses and RSV were liable for high morbidity among paediatric subjects.The present study underlies the importance of planning an active surveillance of respiratory viral infections among paediatric cases requiring hospitalization due to ARI.A thorough analysis of target population features, of viruses antigenic properties and seasonality will be decisive in the evaluation of each clinical event.

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

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    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

  14. 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

  15. Hemato-biochemical and pathological changes on avian influenza in naturally infected domestic ducks in Egypt

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    Essam A. Mahmoud

    2015-10-01

    Full Text Available Aim: Few studies have been made in regard to avian influenza (AI in ducks, thus the aim of this work was planned to investigate the hematological, biochemical, and pathological changes in domestic Egyptian ducks naturally infected with AI. Materials and Methods: 30 duck from private backyards 3-month-old 15 were clinically healthy (Group 1 and the other fifteen (Group 2 were naturally diseased with AI (H5N1. The disease was diagnosed by polymerase chain reaction as H5N1. Results: Duck showed cyanosis, subcutaneous edema of head and neck with nervous signs (torticollis. Hematological studies revealed a microcytic hypochromic anemia. Biochemical studies revealed a significant decrease in total protein, albumin and globulin concentration with significant increase of activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, Υ-glutamyl transpeptidase, lactic acid dehydrogenase and creatine phsphokinase. Prominent increase in creatinine and uric acid in addition to hypocalcemia and hyperphosphatemia were significantly detected in the infected ducks. Histopathological finding confirm these investigations. Conclusion: The highly pathogenic AIV (A/H5N1 became more severe infectious to ducks than before and causes nervous manifestations and blindness which were uncommon in ducks. Besides the significant increases of hepatic enzymes, brain, heart, and renal markers as a response to virus damage to these organs.

  16. Fluorescent dye labeled influenza virus mainly infects innate immune cells and activated lymphocytes and can be used in cell-mediated immune response assay

    OpenAIRE

    Xie, Dongxu

    2009-01-01

    Early results have recognized that influenza virus infects the innate and adaptive immune cells. The data presented in this paper demonstrated that influenza virus labeled with fluorescent dye not only retained the ability to infect and replicate in host cells, but also stimulated a similar human immune response as did unlabeled virus. Influenza virus largely infected the innate and activated adaptive immune cells. Influenza B type virus was different from that of A type virus. B type virus w...

  17. Effect of influenza infection on the phagocytic and bactericidal activities of pulmonary macrophages

    International Nuclear Information System (INIS)

    Nugent, K.M.; Pesanti, E.L.

    1979-01-01

    The effect of mouse-adapted influenza A/PR/8/34 virus on pulmonary macrophage function was evaluated by using an in vitro system which allowed direct virus interaction with macrophages and then separate analysis of the steps required for bacterial clearance by macrophages. Infection of macrophages with this virus resulted in the appearance of a hemagglutinating activity on the macrophage surface; expression of this activity was inhibited by amantadine, 2-deoxyglucose, and cycloheximide and by pretreatment of the virus inoculum with with ultraviolet light and specific antiserum. After influenza infection, net ingestion of viable Staphylococcus aureus by macrophage monolayers was unaltered and there was no change in the fraction of the monolayer which ingested cocci over a wide range of bacterial inputs. Influenza-infected microphages also inactivated intracellular S. aureus at a rate indistinguishable from controls. Therefore, these in vitro studies do not support the hypothesis that the defect in pulmonary antibacterial mechanisms associated with influenza infections results from a direct effect of virus infection on either the phagocytic or bactericidal activity of resistant pulmonary macarophages

  18. Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

    DEFF Research Database (Denmark)

    Kristensen, Anne B; Lay, William N; Ana-Sosa-Batiz, Fernanda

    2016-01-01

    to immunize this at-risk group. IMPORTANCE: Infection with HIV is associated with increasing disease severity following influenza infections, and annual influenza vaccinations are recommended for this target group. However, HIV-infected individuals respond relatively poorly to vaccination compared to healthy......This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV......-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV...

  19. Epidemiology of human infections with highly pathogenic avian influenza A(H7N9) virus in Guangdong, 2016 to 2017.

    Science.gov (United States)

    Kang, Min; Lau, Eric H Y; Guan, Wenda; Yang, Yuwei; Song, Tie; Cowling, Benjamin J; Wu, Jie; Peiris, Malik; He, Jianfeng; Mok, Chris Ka Pun

    2017-07-06

    We describe the epidemiology of highly pathogenic avian influenza (HPAI) A(H7N9) based on poultry market environmental surveillance and laboratory-confirmed human cases (n = 9) in Guangdong, China. We also compare the epidemiology between human cases of high- and low-pathogenic avian influenza A(H7N9) (n = 51) in Guangdong. Case fatality and severity were similar. Touching sick or dead poultry was the most important risk factor for HPAI A(H7N9) infections and should be highlighted for the control of future influenza A(H7N9) epidemics. This article is copyright of The Authors, 2017.

  20. A prospective study of Romanian agriculture workers for zoonotic influenza infections.

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    Alexandru Coman

    Full Text Available In this prospective study we sought to examine seroepidemiological evidence for acute zoonotic influenza virus infection among Romanian agricultural workers.Sera were drawn upon enrollment (2009 and again at 12 and 24 months from 312 adult agriculture workers and 51 age-group matched controls. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI. Cohort members meeting ILI criteria permitted respiratory swab collections as well as acute and convalescent serum collection. Serologic assays were performed against 9 avian, 3 swine, and 3 human influenza viruses.During the two-year follow-up, a total of 23 ILI events were reported. Two subjects' specimens were identified as influenza A by rRT-PCR. During the follow-up period, three individuals experienced elevated microneutralization antibody titers ≥1∶80 against three (one each avian influenza viruses: A/Teal/Hong Kong/w312/97(H6N1, A/Hong Kong/1073/1999(H9N2, or A/Duck/Alberta/60/1976(H12N5. However, none of these participants met the criteria for poultry exposure. A number of subjects demonstrated four-fold increases over time in hemagglutination inhibition (HI assay titers for at least one of the three swine influenza viruses (SIVs; however, it seems likely that two of these three responses were due to cross-reacting antibody against human influenza. Only elevated antibody titers against A/Swine/Flanders/1/1998(H3N2 lacked evidence for such confounding. In examining risk factors for elevated antibody against this SIV with multiple logistic regression, swine exposure (adjusted OR = 1.8, 95% CI 1.1-2.8 and tobacco use (adjusted OR = 1.8; 95% CI 1.1-2.9 were important predictors.While Romania has recently experienced multiple incursions of highly pathogenic avian influenza among domestic poultry, this cohort of Romanian agriculture workers had sparse evidence of avian influenza virus infections. In contrast, there was

  1. Further investigation of confirmed urinary tract infection (UTI in children under five years: a systematic review

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    Cooper Julie

    2005-03-01

    Full Text Available Abstract Background Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. Methods We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI in children under five years of age. Results 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68 and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8. None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR, as an alternative to micturating cystourethrography (MCUG (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29; these techniques have the advantage of not requiring exposure to ionising radiation. Conclusion There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required.

  2. In Vivo Imaging of Influenza Virus Infection in Immunized Mice

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    Rita Czakó

    2017-05-01

    Full Text Available Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titers in the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support preclinical evaluation of candidate medical countermeasures for influenza in mice.

  3. Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy.

    Science.gov (United States)

    Bartley, Jenna M; Pan, Sarah J; Keilich, Spencer R; Hopkins, Jacob W; Al-Naggar, Iman M; Kuchel, George A; Haynes, Laura

    2016-04-01

    Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly.

  4. New methods and reagents to improve the ferret model for human influenza infections

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Kirkeby, Svend; Aasted, Bent

    The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, ...... improvements of the model will aim at establishing a reliable RT-PCR for ferret cytokines, as well as investigating the location of influenza receptors and viral particles in the upper and lower respiratory tract via immunohistochemistry......The ferret has been extensively used to study human influenza infections. However, its value as a model has suffered from the limited set of reagents and methods available for this animal. We have recently tested a large number of monoclonal antibodies cross-reacting with ferret CD markers (CD8, CD...

  5. 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.)

  6. Evidence of infection with avian, human, and swine influenza viruses in pigs in Cairo, Egypt.

    Science.gov (United States)

    Gomaa, Mokhtar R; Kandeil, Ahmed; El-Shesheny, Rabeh; Shehata, Mahmoud M; McKenzie, Pamela P; Webby, Richard J; Ali, Mohamed A; Kayali, Ghazi

    2018-02-01

    The majority of the Egyptian swine population was culled in the aftermath of the 2009 H1N1 pandemic, but small-scale growing remains. We sampled pigs from piggeries and an abattoir in Cairo. We found virological evidence of infection with avian H9N2 and H5N1 viruses as well as human pandemic H1N1 influenza virus. Serological evidence suggested previous exposure to avian H5N1 and H9N2, human pandemic H1N1, and swine avian-like and human-like viruses. This raises concern about potential reassortment of influenza viruses in pigs and highlights the need for better control and prevention of influenza virus infection in pigs.

  7. Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies

    DEFF Research Database (Denmark)

    Horvath, A; Andersen, I; Junker, K

    2001-01-01

    Serum amyloid P component (SAP) binds in vitro Ca(2+)-dependently to several ligands including oligosaccharides with terminal mannose and galactose. We have earlier reported that SAP binds to human influenza A virus strains, inhibiting hemagglutinin (HA) activity and virus infectivity in vitro...... that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and circulating...... on day 10 and these mice approached normal body weight, whereas control mice (one out of five surviving on day 10) died. The data provide evidence of the potential of intranasally administered SAP for prophylactic treatment of influenza A virus infections in humans....

  8. Flow cytometric monitoring of influenza A virus infection in MDCK cells during vaccine production

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    Reichl Udo

    2008-04-01

    Full Text Available Abstract Background In cell culture-based influenza vaccine production the monitoring of virus titres and cell physiology during infection is of great importance for process characterisation and optimisation. While conventional virus quantification methods give only virus titres in the culture broth, data obtained by fluorescence labelling of intracellular virus proteins provide additional information on infection dynamics. Flow cytometry represents a valuable tool to investigate the influences of cultivation conditions and process variations on virus replication and virus yields. Results In this study, fluorescein-labelled monoclonal antibodies against influenza A virus matrix protein 1 and nucleoprotein were used for monitoring the infection status of adherent Madin-Darby canine kidney cells from bioreactor samples. Monoclonal antibody binding was shown for influenza A virus strains of different subtypes (H1N1, H1N2, H3N8 and host specificity (human, equine, swine. At high multiplicity of infection in a bioreactor, the onset of viral protein accumulation in adherent cells on microcarriers was detected at about 2 to 4 h post infection by flow cytometry. In contrast, a significant increase in titre by hemagglutination assay was detected at the earliest 4 to 6 h post infection. Conclusion It is shown that flow cytometry is a sensitive and robust method for the monitoring of viral infection in fixed cells from bioreactor samples. Therefore, it is a valuable addition to other detection methods of influenza virus infection such as immunotitration and RNA hybridisation. Thousands of individual cells are measured per sample. Thus, the presented method is believed to be quite independent of the concentration of infected cells (multiplicity of infection and total cell concentration in bioreactors. This allows to perform detailed studies on factors relevant for optimization of virus yields in cell cultures. The method could also be used for process

  9. H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

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    M Anthony Moody

    Full Text Available BACKGROUND: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection. METHODS AND FINDINGS: To study hemagglutinin (HA antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV and compared them to the plasma cell repertoires of subjects experimentally infected (EI with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject. CONCLUSION: The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.

  10. Evidence for avian H9N2 influenza virus infections among rural villagers in Cambodia

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    Patrick J. Blair

    2013-04-01

    Full Text Available Summary: Background: Southeast Asia remains a critical region for the emergence of novel and/or zoonotic influenza, underscoring the importance of extensive sampling in rural areas where early transmission is most likely to occur. Methods: In 2008, 800 adult participants from eight sites were enrolled in a prospective population-based study of avian influenza (AI virus transmission where highly pathogenic avian influenza (HPAI H5N1 virus had been reported in humans and poultry from 2006 to 2008. From their enrollment sera and questionnaires, we report risk factor findings for serologic evidence of previous infection with 18 AI virus strains. Results: Serologic assays revealed no evidence of previous infection with 13 different low-pathogenic AI viruses or with HPAI avian-like A/Cambodia/R0404050/2007(H5N1. However, 21 participants had elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2, validated with a monoclonal antibody blocking ELISA assay specific for avian H9. Conclusions: Although cross-reaction from antibodies against human influenza viruses cannot be completely excluded, the study data suggest that a number of participants were previously infected with the avian-like A/Hong Kong/1073/1999(H9N2 virus, likely due to as yet unidentified environmental exposures. Prospective data from this cohort will help us better understand the serology of zoonotic influenza infection in a rural cohort in SE Asia. Keywords: Influenza A virus, Avian, Zoonoses, Occupational exposure, Communicable diseases, Emerging, Cohort studies

  11. Influenza

    OpenAIRE

    Solórzano-Santos, Fortino; Miranda-Novales, Ma. Guadalupe

    2009-01-01

    La influenza es una infección viral aguda de las vías respiratorias, altamente contagiosa. Es causada por el virus de la influenza A, B y C. Puede afectar a todos los grupos etarios durante epidemias, aunque tiene mayor morbilidad en los extremos de la vida. La enfermedad frecuentemente requiere de atención médica y hospitalización, contribuyendo sustancialmente a pérdidas económicas, exceso en el número de días/cama-hospital y muertes. Considerando la epidemia reciente en México del virus de...

  12. Influenza

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    Forleo-Neto Eduardo

    2003-01-01

    Full Text Available A influenza (gripe é doença infecciosa aguda de origem viral que acomete o trato respiratório e a cada inverno atinge mais de 100 milhões de pessoas na Europa, Japão e Estados Unidos, causando anualmente a morte de cerca de 20 a 40 mil pessoas somente neste último país. O agente etiológico é o Myxovirus influenzae, ou vírus da gripe. Este subdivide-se nos tipos A, B e C, sendo que apenas os do tipo A e B apresentam relevância clínica em humanos. O vírus influenza apresenta altas taxas de mutação, o que resulta freqüentemente na inserção de novas variantes virais na comunidade, para as quais a população não apresenta imunidade. São poucas as opções disponíveis para o controle da influenza. Dentre essas, a vacinação constitui a forma mais eficaz para o controle da doença e de suas complicações. Em função das mutações que ocorrem naturalmente no vírus influenza, recomenda-se que a vacinação seja realizada anualmente. No Brasil, segundo dados obtidos pelo Projeto VigiGripe - ligado à Universidade Federal de São Paulo -, verifica-se que a influenza apresenta pico de atividade entre os meses de maio e setembro. Assim, a época mais indicada para a vacinação corresponde aos meses de março e abril. Para o tratamento específico da influenza estão disponíveis quatro medicamentos antivirais: os fármacos clássicos amantadina e rimantidina e os antivirais de segunda geração oseltamivir e zanamivir. Os últimos, acrescentam alternativas para o tratamento da influenza e ampliam as opções disponíveis para o seu controle.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.

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    Yongsheng Huang

    2011-08-01

    Full Text Available Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.

  15. Avian influenza (H7N9) virus infection in Chinese tourist in Malaysia, 2014.

    Science.gov (United States)

    William, Timothy; Thevarajah, Bharathan; Lee, Shiu Fee; Suleiman, Maria; Jeffree, Mohamad Saffree; Menon, Jayaram; Saat, Zainah; Thayan, Ravindran; Tambyah, Paul Anantharajah; Yeo, Tsin Wen

    2015-01-01

    Of the ≈400 cases of avian influenza (H7N9) diagnosed in China since 2003, the only travel-related cases have been in Hong Kong and Taiwan. Detection of a case in a Chinese tourist in Sabah, Malaysia, highlights the ease with which emerging viral respiratory infections can travel globally.

  16. Infectivity, transmission and pathogenicity of avian influenza viruses for domestic and wild birds

    Science.gov (United States)

    Individual avian influenza (AI) virus strains vary in their ability to infect, transmit and cause disease and death in different bird species. Low pathogenicity AI (LPAI) viruses are maintained in wild birds, and must be adapted to pass to domestic poultry, where they replicate in respiratory and in...

  17. MODERN OPPORTUNITIES OF INTERFERON THERAPY AT INFLUENZA AND ACUTE RESPIRATORY INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    T. A. Chebotareva

    2013-01-01

    Full Text Available The new dosing scheme for the preparation VIFERON®, rectal suppositories for infants of II, III and IV groups of health was suggested. The application of the scheme has resulted in a more pronounced clinical and immunological effects at treatment of influenza and acute respiratory infections compared to the previously used sc heme. 

  18. Reduced incorporation of the influenza B virus BM2 protein in virus particles decreases infectivity

    International Nuclear Information System (INIS)

    Jackson, David; Zuercher, Thomas; Barclay, Wendy

    2004-01-01

    BM2 is the fourth integral membrane protein encoded by the influenza B virus genome. It is synthesized late in infection and transported to the plasma membrane from where it is subsequently incorporated into progeny virus particles. It has recently been reported that BM2 has ion channel activity and may be the functional homologue of the influenza A virus M2 protein acting as an ion channel involved in viral entry. Using a reverse genetic approach it was not possible to recover virus which lacked BM2. A recombinant influenza B virus was generated in which the BM2 AUG initiation codon was mutated to GUG. This decreased the efficiency of translation of BM2 protein such that progeny virions contained only 1/8 the amount of BM2 seen in wild-type virus. The reduction in BM2 incorporation resulted in a reduction in infectivity although there was no concomitant decrease in the numbers of virions released from the infected cells. These data imply that the incorporation of sufficient BM2 protein into influenza B virions is required for infectivity of the virus particles

  19. 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

  20. Avian Influenza (H7N9) Virus Infection in Chinese Tourist in Malaysia, 2014

    OpenAIRE

    William, Timothy; Thevarajah, Bharathan; Lee, Shiu Fee; Suleiman, Maria; Jeffree, Mohamad Saffree; Menon, Jayaram; Saat, Zainah; Thayan, Ravindran; Tambyah, Paul Anantharajah; Yeo, Tsin Wen

    2015-01-01

    Of the ?400 cases of avian influenza (H7N9) diagnosed in China since 2003, the only travel-related cases have been in Hong Kong and Taiwan. Detection of a case in a Chinese tourist in Sabah, Malaysia, highlights the ease with which emerging viral respiratory infections can travel globally.

  1. Mouse Model for Aerosol Infection of Influenza (Postprint)

    Science.gov (United States)

    2011-12-01

    quantified by cell culture end- point–dilution assays performed using Madin–Darby canine kidney (MDCK) cells and calculated using the Spearman–Kärber...viduals with underlying conditions such as obesity and or diabetes (Jhung et al. 2011). Influenza A (H1N1) virus selected for this study was chosen based on

  2. Viral etiologies of influenza-like illness and severe acute respiratory infections in Thailand.

    Science.gov (United States)

    Chittaganpitch, Malinee; Waicharoen, Sunthareeya; Yingyong, Thitipong; Praphasiri, Prabda; Sangkitporn, Somchai; Olsen, Sonja J; Lindblade, Kim A

    2018-07-01

    Information on the burden, characteristics and seasonality of non-influenza respiratory viruses is limited in tropical countries. Describe the epidemiology of selected non-influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. Patients with influenza-like illness (ILI; history of fever or documented temperature ≥38°C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature ≥38°C, cough, onset respiratory syncytial virus (RSV), metapneumovirus (MPV), parainfluenza viruses (PIV) 1-3, and adenoviruses by polymerase chain reaction (PCR) or real-time reverse transcriptase-PCR. We screened 15 369 persons with acute respiratory infections and enrolled 8106 cases of ILI (5069 cases respiratory viruses tested, while for SARI cases respiratory viruses, particularly seasonality, although adjustments to case definitions may be required. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  3. 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

  4. Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand

    Directory of Open Access Journals (Sweden)

    Q Sue Huang

    2014-05-01

    Full Text Available Background: Recent experience with pandemic influenza A(H1N1pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition. Methods/Design: All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources. Discussion: Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9 virus infections and seasonal influenza prevention and control.

  5. Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.

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    Michael A Pazos

    Full Text Available Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.

  6. Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.

    Science.gov (United States)

    Pazos, Michael A; Kraus, Thomas A; Muñoz-Fontela, César; Moran, Thomas M

    2012-01-01

    Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.

  7. Little evidence of avian or equine influenza virus infection among a cohort of Mongolian adults with animal exposures, 2010-2011.

    Directory of Open Access Journals (Sweden)

    Nyamdavaa Khurelbaatar

    Full Text Available Avian (AIV and equine influenza virus (EIV have been repeatedly shown to circulate among Mongolia's migrating birds or domestic horses. In 2009, 439 Mongolian adults, many with occupational exposure to animals, were enrolled in a prospective cohort study of zoonotic influenza transmission. Sera were drawn upon enrollment and again at 12 and 24 months. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI. Cohort members confirmed to have acute influenza A infections, permitted respiratory swab collections which were studied with rRT-PCR for influenza A. Serologic assays were performed against equine, avian, and human influenza viruses. Over the 2 yrs of follow-up, 100 ILI investigations in the cohort were conducted. Thirty-six ILI cases (36% were identified as influenza A infections by rRT-PCR; none yielded evidence for AIV or EIV. Serological examination of 12 mo and 24 mo annual sera revealed 37 participants had detectable antibody titers (≥1∶10 against studied viruses during the course of study follow-up: 21 against A/Equine/Mongolia/01/2008(H3N8; 4 against an avian A/Teal/Hong Kong/w3129(H6N1, 11 against an avian-like A/Hong Kong/1073/1999(H9N2, and 1 against an avian A/Migrating duck/Hong Kong/MPD268/2007(H10N4 virus. However, all such titers were <1∶80 and none were statistically associated with avian or horse exposures. A number of subjects had evidence of seroconversion to zoonotic viruses, but the 4-fold titer changes were again not associated with avian or horse exposures. As elevated antibodies against seasonal influenza viruses were high during the study period, it seems likely that cross-reacting antibodies against seasonal human influenza viruses were a cause of the low-level seroreactivity against AIV or EIV. Despite the presence of AIV and EIV circulating among wild birds and horses in Mongolia, there was little evidence of AIV or EIV infection in this

  8. Little Evidence of Avian or Equine Influenza Virus Infection among a Cohort of Mongolian Adults with Animal Exposures, 2010–2011

    Science.gov (United States)

    Khurelbaatar, Nyamdavaa; Krueger, Whitney S.; Heil, Gary L.; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D.; Gray, Gregory C.

    2014-01-01

    Avian (AIV) and equine influenza virus (EIV) have been repeatedly shown to circulate among Mongolia’s migrating birds or domestic horses. In 2009, 439 Mongolian adults, many with occupational exposure to animals, were enrolled in a prospective cohort study of zoonotic influenza transmission. Sera were drawn upon enrollment and again at 12 and 24 months. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI). Cohort members confirmed to have acute influenza A infections, permitted respiratory swab collections which were studied with rRT-PCR for influenza A. Serologic assays were performed against equine, avian, and human influenza viruses. Over the 2 yrs of follow-up, 100 ILI investigations in the cohort were conducted. Thirty-six ILI cases (36%) were identified as influenza A infections by rRT-PCR; none yielded evidence for AIV or EIV. Serological examination of 12 mo and 24 mo annual sera revealed 37 participants had detectable antibody titers (≥1∶10) against studied viruses during the course of study follow-up: 21 against A/Equine/Mongolia/01/2008(H3N8); 4 against an avian A/Teal/Hong Kong/w3129(H6N1), 11 against an avian-like A/Hong Kong/1073/1999(H9N2), and 1 against an avian A/Migrating duck/Hong Kong/MPD268/2007(H10N4) virus. However, all such titers were avian or horse exposures. A number of subjects had evidence of seroconversion to zoonotic viruses, but the 4-fold titer changes were again not associated with avian or horse exposures. As elevated antibodies against seasonal influenza viruses were high during the study period, it seems likely that cross-reacting antibodies against seasonal human influenza viruses were a cause of the low-level seroreactivity against AIV or EIV. Despite the presence of AIV and EIV circulating among wild birds and horses in Mongolia, there was little evidence of AIV or EIV infection in this prospective study of Mongolians with animal exposures. PMID

  9. Little evidence of avian or equine influenza virus infection among a cohort of Mongolian adults with animal exposures, 2010-2011.

    Science.gov (United States)

    Khurelbaatar, Nyamdavaa; Krueger, Whitney S; Heil, Gary L; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D; Gray, Gregory C

    2014-01-01

    Avian (AIV) and equine influenza virus (EIV) have been repeatedly shown to circulate among Mongolia's migrating birds or domestic horses. In 2009, 439 Mongolian adults, many with occupational exposure to animals, were enrolled in a prospective cohort study of zoonotic influenza transmission. Sera were drawn upon enrollment and again at 12 and 24 months. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI). Cohort members confirmed to have acute influenza A infections, permitted respiratory swab collections which were studied with rRT-PCR for influenza A. Serologic assays were performed against equine, avian, and human influenza viruses. Over the 2 yrs of follow-up, 100 ILI investigations in the cohort were conducted. Thirty-six ILI cases (36%) were identified as influenza A infections by rRT-PCR; none yielded evidence for AIV or EIV. Serological examination of 12 mo and 24 mo annual sera revealed 37 participants had detectable antibody titers (≥1∶10) against studied viruses during the course of study follow-up: 21 against A/Equine/Mongolia/01/2008(H3N8); 4 against an avian A/Teal/Hong Kong/w3129(H6N1), 11 against an avian-like A/Hong Kong/1073/1999(H9N2), and 1 against an avian A/Migrating duck/Hong Kong/MPD268/2007(H10N4) virus. However, all such titers were avian or horse exposures. A number of subjects had evidence of seroconversion to zoonotic viruses, but the 4-fold titer changes were again not associated with avian or horse exposures. As elevated antibodies against seasonal influenza viruses were high during the study period, it seems likely that cross-reacting antibodies against seasonal human influenza viruses were a cause of the low-level seroreactivity against AIV or EIV. Despite the presence of AIV and EIV circulating among wild birds and horses in Mongolia, there was little evidence of AIV or EIV infection in this prospective study of Mongolians with animal exposures.

  10. 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.

  11. Airborne Transmission of Highly Pathogenic Influenza Virus during Processing of Infected Poultry.

    Science.gov (United States)

    Bertran, Kateri; Balzli, Charles; Kwon, Yong-Kuk; Tumpey, Terrence M; Clark, Andrew; Swayne, David E

    2017-11-01

    Exposure to infected poultry is a suspected cause of avian influenza (H5N1) virus infections in humans. We detected infectious droplets and aerosols during laboratory-simulated processing of asymptomatic chickens infected with human- (clades 1 and 2.2.1) and avian- (clades 1.1, 2.2, and 2.1) origin H5N1 viruses. We detected fewer airborne infectious particles in simulated processing of infected ducks. Influenza virus-naive chickens and ferrets exposed to the air space in which virus-infected chickens were processed became infected and died, suggesting that the slaughter of infected chickens is an efficient source of airborne virus that can infect birds and mammals. We did not detect consistent infections in ducks and ferrets exposed to the air space in which virus-infected ducks were processed. Our results support the hypothesis that airborne transmission of HPAI viruses can occur among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry.

  12. Rapid and quantitative detection of zoonotic influenza A virus infection utilizing coumarin-derived dendrimer-based fluorescent immunochromatographic strip test (FICT).

    Science.gov (United States)

    Yeo, Seon-Ju; Huong, Dinh Thi; Hong, Nguyen Ngoc; Li, Chun-Ying; Choi, Kyunghan; Yu, Kyoungsik; Choi, Du-Young; Chong, Chom-Kyu; Choi, Hak Soo; Mallik, Shyam Kumar; Kim, Hak Sung; Sung, Haan Woo; Park, Hyun

    2014-01-01

    Great efforts have been made to develop robust signal-generating fluorescence materials which will help in improving the rapid diagnostic test (RDT) in terms of sensitivity and quantification. In this study, we developed coumarin-derived dendrimer-based fluorescent immunochromatographic strip test (FICT) assay with enhanced sensitivity as a quantitative diagnostic tool in typical RDT environments. The accuracy of the proposed FICT was compared with that of dot blot immunoassay techniques and conventional RDTs. Through conjugation of coumarin-derived dendrimers with latex beads, fluorescent emission covering broad output spectral ranges was obtained which provided a distinct advantage of easy discrimination of the fluorescent emission of the latex beads with a simple insertion of a long-pass optical filter away from the excitation wavelength. The newly developed FICT assay was able to detect 100 ng/10 μL of influenza A nucleoprotein (NP) antigen within 5 minutes, which corresponded to 2.5-fold higher sensitivity than that of the dot blot immunoassay or conventional RDTs. Moreover, the FICT assay was confirmed to detect at least four avian influenza A subtypes (H5N3, H7N1, H7N7, and H9N2). On applying the FICT to the clinical swab samples infected with respiratory viruses, our FICT assay was confirmed to differentiate influenza H1N1 infection from other respiratory viral diseases. These data demonstrate that the proposed FICT assay is able to detect zoonotic influenza A viruses with a high sensitivity, and it enables the quantitation of the infection intensity by providing the numerical diagnostic values; thus demonstrating enhanced detectability of influenza A viruses.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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...

  15. Influenza A virus infection dynamics in swine farms in Belgium, France, Italy and Spain 2006-2008

    NARCIS (Netherlands)

    Kyriakis, C.S.; Rose, N.; Foni, E.; Maldonado, J.; Loeffen, W.L.A.; Madec, F.; Simon, G.; Reeth, K.

    2013-01-01

    Avian-like H1N1 and reassortant H3N2 and H1N2 influenza A viruses with a human-like haemagglutinin have been co-circulating in swine in Europe for more than a decade. We aimed to examine the infection dynamics of the three swine influenza virus (SIV) lineages at the farm level, and to identify

  16. A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors

    NARCIS (Netherlands)

    Zhang, Heng; de Vries, Robert P; Tzarum, Netanel; Zhu, Xueyong; Yu, Wenli; McBride, Ryan; Paulson, James C; Wilson, Ian A

    2015-01-01

    Recent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8

  17. Expression of urease by Haemophilus influenzae during human respiratory tract infection and role in survival in an acid environment

    Science.gov (United States)

    2011-01-01

    Background Nontypeable Haemophilus influenzae is a common cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Prior studies have shown that H. influenzae expresses abundant urease during growth in the middle ear of the chinchilla and in pooled human sputum, suggesting that expression of urease is important for colonization and infection in the hostile environments of the middle ear and in the airways in adults. Virtually nothing else is known about the urease of H. influenzae, which was characterized in the present study. Results Analysis by reverse transcriptase PCR revealed that the ure gene cluster is expressed as a single transcript. Knockout mutants of a urease structural gene (ureC) and of the entire ure operon demonstrated no detectable urease activity indicating that this operon is the only one encoding an active urease. The ure operon is present in all strains tested, including clinical isolates from otitis media and COPD. Urease activity decreased as nitrogen availability increased. To test the hypothesis that urease is expressed during human infection, purified recombinant urease C was used in ELISA with pre acquisition and post infection serum from adults with COPD who experienced infections caused by H. influenzae. A total of 28% of patients developed new antibodies following infection indicating that H. influenzae expresses urease during airway infection. Bacterial viability assays performed at varying pH indicate that urease mediates survival of H. influenzae in an acid environment. Conclusions The H. influenzae genome contains a single urease operon that mediates urease expression and that is present in all clinical isolates tested. Nitrogen availability is a determinant of urease expression. H. influenzae expresses urease during human respiratory tract infection and urease is a target of the human antibody response. Expression of urease enhances viability in an acid

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

    Directory of Open Access Journals (Sweden)

    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.

  19. The innate immunity of guinea pigs against highly pathogenic avian influenza virus infection.

    Science.gov (United States)

    Zhang, Kun; Xu, Wei Wei; Zhang, Zhaowei; Liu, Jing; Li, Jing; Sun, Lijuan; Sun, Weiyang; Jiao, Peirong; Sang, Xiaoyu; Ren, Zhiguang; Yu, Zhijun; Li, Yuanguo; Feng, Na; Wang, Tiecheng; Wang, Hualei; Yang, Songtao; Zhao, Yongkun; Zhang, Xuemei; Wilker, Peter R; Liu, WenJun; Liao, Ming; Chen, Hualan; Gao, Yuwei; Xia, Xianzhu

    2017-05-02

    H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was required for RIG-I mediated inhibition of viral replication upstream of the activity of MAVS. Furthermore, we show that guinea pig complement is involved in viral clearance, the regulation of inflammation, and cellular apoptosis during influenza virus infection of guinea pigs. This work uncovers features of the guinea pig innate immune response to influenza that may render guinea pigs resistant to highly pathogenic influenza viruses.

  20. Serological characterization of guinea pigs infected with H3N2 human influenza or immunized with hemagglutinin protein

    Directory of Open Access Journals (Sweden)

    Bushnell Ruth V

    2010-08-01

    Full Text Available Abstract Background Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. To more fully characterize the model, antibody responses following either infection/re-infection with human influenza A/Wyoming/03/2003 H3N2 or immunization with its homologous recombinant hemagglutinin (HA protein were studied. Results Serological samples were collected and tested for anti-HA immunoglobulin by ELISA, antiviral antibodies by hemagglutination inhibition (HI, and recognition of linear epitopes by peptide scanning (PepScan. Animals inoculated with infectious virus demonstrated pronounced viral replication and subsequent serological conversion. Animals either immunized with the homologous HA antigen or infected, showed a relatively rapid rise in antibody titers to the HA glycoprotein in ELISA assays. Antiviral antibodies, measured by HI assay, were detectable after the second inoculation. PepScan data identified both previously recognized and newly defined linear epitopes. Conclusions Infection and/or recombinant HA immunization of guinea pigs with H3N2 Wyoming influenza virus resulted in a relatively rapid production of viral-specific antibody thus demonstrating the strong immunogenicity of the major viral structural proteins in this animal model for influenza infection. The sensitivity of the immune response supports the utility of the guinea pig as a useful animal model of influenza infection and immunization.

  1. 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.

  2. Pathobiology of avian influenza virus infection in minor gallinaceous species: a review.

    Science.gov (United States)

    Bertran, Kateri; Dolz, Roser; Majó, Natàlia

    2014-01-01

    Susceptibility to avian influenza viruses (AIVs) can vary greatly among bird species. Chickens and turkeys are major avian species that, like ducks, have been extensively studied for avian influenza. To a lesser extent, minor avian species such as quail, partridges, and pheasants have also been investigated for avian influenza. Usually, such game fowl species are highly susceptible to highly pathogenic AIVs and may consistently spread both highly pathogenic AIVs and low-pathogenic AIVs. These findings, together with the fact that game birds are considered bridge species in the poultry-wildlife interface, highlight their interest from the transmission and biosecurity points of view. Here, the general pathobiological features of low-pathogenic AIV and highly pathogenic AIV infections in this group of avian species have been covered.

  3. Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection.

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    Matthew J Kesic

    Full Text Available Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs human airway trypsin-like protease (HAT and transmembrane protease, serine 2 (TMPRSS2, whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI. Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility.

  4. Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

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    Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

    2018-02-15

    Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

  5. Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung.

    Science.gov (United States)

    Talker, Stephanie C; Stadler, Maria; Koinig, Hanna C; Mair, Kerstin H; Rodríguez-Gómez, Irene M; Graage, Robert; Zell, Roland; Dürrwald, Ralf; Starick, Elke; Harder, Timm; Weissenböck, Herbert; Lamp, Benjamin; Hammer, Sabine E; Ladinig, Andrea; Saalmüller, Armin; Gerner, Wilhelm

    2016-10-15

    Pigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67(+)) CD8(+) T cells with an early effector phenotype (perforin(+) CD27(+)) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4(+) and CD8(+) T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4(+) and CD8(+) T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4(+) and CD8(+) memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs. Pigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we

  6. 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

  7. Avian influenza A (H7N9) virus infection in humans: epidemiology, evolution, and pathogenesis.

    Science.gov (United States)

    Husain, Matloob

    2014-12-01

    New human influenza A virus strains regularly emerge causing seasonal epidemics and occasional pandemics. Lately, several zoonotic avian influenza A strains have been reported to directly infect humans. In early 2013, a novel avian influenza A virus (H7N9) strain was discovered in China to cause severe respiratory disease in humans. Since then, over 450 human cases of H7N9 infection have been discovered and 165 of them have died. Multiple epidemiological, phylogenetic, in vivo, and in vitro studies have been done to determine the origin and pathogenesis of novel H7N9 strain. This article reviews the literature related to the epidemiology, evolution, and pathogenesis of the H7N9 strain since its discovery in February 2013 till August 2014. The data available so far indicate that H7N9 was originated by a two-step reassortment process in birds and transmitted to humans through direct contact with live-bird markets. H7N9 is a low-pathogenic avian virus and contains several molecular signatures for adaptation in mammals. The severity of the respiratory disease caused by novel H7N9 virus in humans can be partly attributed to the age, sex, and underlying medical conditions of the patients. A universal influenza vaccine is not available, though several strain-specific H7N9 candidate vaccine viruses have been developed. Further, novel H7N9 virus is resistant to antiviral drug amantadine and some H7N9 isolates have acquired the resistance to neuraminidase-inhibitors. Therefore, constant surveillance and prompt control measures combined with novel research approaches to develop alternative and effective anti-influenza strategies are needed to overcome influenza A virus. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection

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    Deborah M. Brown

    2016-03-01

    Full Text Available CD4 T cells that recognize peptide antigen in the context of Class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL play a role in chronic, as well as, acute infections such as influenza A virus (IAV infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections such as HIV, mouse pox, murine gamma herpes virus, CMV, EBV and influenza among others. We now appreciate a greater role for CD4 CTL as direct effectors in viral infections and anti-tumor immunity through their ability to acquire perforin mediated cytolytic activity and contribution to lysis of virally infected targets or tumors. As early as the 1980s, CD4 T cell clones with cytolytic potential were identified after influenza virus infection, yet much of this early work was dependent on in vitro culture and little was known about the physiological relevance of CD4 CTL. Here, we discuss the direct role CD4 CTL play in protection against lethal IAV infection and the factors that drive the generation of perforin mediated lytic activity in CD4 cells in vivo during IAV infection. While focusing on CD4 CTL generated during IAV infection, we pull comparisons from the literature in other anti-viral and anti-tumor systems. Further, we highlight what is currently known about CD4 CTL secondary and memory responses, as well as vaccination strategies to induce these potent killer cells that provide an extra layer of cell mediated immune protection against heterosubtypic IAV infection.

  9. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

    Science.gov (United States)

    Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

  10. Viruses Associated With Acute Respiratory Infections and Influenza-like Illness Among Outpatients From the Influenza Incidence Surveillance Project, 2010–2011

    Science.gov (United States)

    Fowlkes, Ashley; Giorgi, Andrea; Erdman, Dean; Temte, Jon; Goodin, Kate; Di Lonardo, Steve; Sun, Yumei; Martin, Karen; Feist, Michelle; Linz, Rachel; Boulton, Rachelle; Bancroft, Elizabeth; McHugh, Lisa; Lojo, Jose; Filbert, Kimberly; Finelli, Lyn

    2017-01-01

    Background The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. Methods From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. Results The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2–17 years, whereas other viruses had varied patterns among age groups. Conclusions The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children. PMID:24338352

  11. Viruses associated with acute respiratory infections and influenza-like illness among outpatients from the Influenza Incidence Surveillance Project, 2010-2011.

    Science.gov (United States)

    Fowlkes, Ashley; Giorgi, Andrea; Erdman, Dean; Temte, Jon; Goodin, Kate; Di Lonardo, Steve; Sun, Yumei; Martin, Karen; Feist, Michelle; Linz, Rachel; Boulton, Rachelle; Bancroft, Elizabeth; McHugh, Lisa; Lojo, Jose; Filbert, Kimberly; Finelli, Lyn

    2014-06-01

    The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥ 2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2-17 years, whereas other viruses had varied patterns among age groups. The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.

  12. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

    Energy Technology Data Exchange (ETDEWEB)

    Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaeelle [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Frobert, Emilie [Laboratoire de Virologie, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 59 boulevard Pinel, F-69677 Bron Cedex, Lyon (France); Yver, Matthieu; Traversier, Aurelien [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Wolff, Thorsten [Division of Influenza/Respiratory Viruses, Robert Koch Institute, Nordufer 20, D-13353 Berlin (Germany); Riteau, Beatrice [Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Naffakh, Nadia [Institut Pasteur, Unite de Genetique Moleculaire des Virus Respiratoires, URA CNRS 3015, EA302 Universite Paris Diderot, Paris (France); and others

    2012-10-10

    Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

  13. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

    International Nuclear Information System (INIS)

    Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaëlle; Frobert, Emilie; Yver, Matthieu; Traversier, Aurelien; Wolff, Thorsten; Riteau, Beatrice; Naffakh, Nadia

    2012-01-01

    Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus–host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

  14. Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

    Science.gov (United States)

    Abdeldaim, Guma M K; Strålin, Kristoffer; Korsgaard, Jens; Blomberg, Jonas; Welinder-Olsson, Christina; Herrmann, Björn

    2010-12-03

    Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 10⁵ genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively.In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. The PCR provides increased

  15. Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Welinder-Olsson Christina

    2010-12-01

    Full Text Available Abstract Background Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR for detection of S. pneumoniae (9802 gene fragment, H. influenzae (omp P6 gene and N. meningitidis (ctrA gene. The method was evaluated on bronchoalveolar lavage (BAL samples from 156 adults with lower respiratory tract infection (LRTI and 31 controls, and on 87 cerebrospinal fluid (CSF samples from meningitis patients. Results The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively. In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both

  16. Avian influenza: a review.

    Science.gov (United States)

    Thomas, Jennifer K; Noppenberger, Jennifer

    2007-01-15

    A review of the avian influenza A/H5N1 virus, including human cases, viral transmission, clinical features, vaccines and antivirals, surveillance plans, infection control, and emergency response plans, is presented. The World Health Organization (WHO) considers the avian influenza A/H5N1 virus a public health risk with pandemic potential. The next human influenza pandemic, if caused by the avian influenza A/H5N1 virus, is estimated to have a potential mortality rate of more than a hundred million. Outbreaks in poultry have been associated with human transmission. WHO has documented 258 confirmed human infections with a mortality rate greater than 50%. Bird-to-human transmission of the avian influenza virus is likely by the oral-fecal route. The most effective defense against an influenza pandemic would be a directed vaccine to elicit a specific immune response toward the strain or strains of the influenza virus. However, until there is an influenza pandemic, there is no evidence that vaccines or antivirals used in the treatment or prevention of such an outbreak would decrease morbidity or mortality. Surveillance of the bird and human populations for the highly pathogenic H5N1 is being conducted. Infection-control measures and an emergency response plan are discussed. Avian influenza virus A/H5N1 is a public health threat that has the potential to cause serious illness and death in humans. Understanding its pathology, transmission, clinical features, and pharmacologic treatments and preparing for the prevention and management of its outbreak will help avoid its potentially devastating consequences.

  17. 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.

  18. Protective Effect of Panax notoginseng Root Water Extract against Influenza A Virus Infection by Enhancing Antiviral Interferon-Mediated Immune Responses and Natural Killer Cell Activity

    Directory of Open Access Journals (Sweden)

    Jang-Gi Choi

    2017-11-01

    Full Text Available Influenza is an acute respiratory illness caused by the influenza A virus, which causes economic losses and social disruption mainly by increasing hospitalization and mortality rates among the elderly and people with chronic diseases. Influenza vaccines are the most effective means of preventing seasonal influenza, but can be completely ineffective if there is an antigenic mismatch between the seasonal vaccine virus and the virus circulating in the community. In addition, influenza viruses resistant to antiviral drugs are emerging worldwide. Thus, there is an urgent need to develop new vaccines and antiviral drugs against these viruses. In this study, we conducted in vitro and in vivo analyses of the antiviral effect of Panax notoginseng root (PNR, which is used as an herbal medicine and nutritional supplement in Korea and China. We confirmed that PNR significantly prevented influenza virus infection in a concentration-dependent manner in mouse macrophages. In addition, PNR pretreatment inhibited viral protein (PB1, PB2, HA, NA, M1, PA, M2, and NP and viral mRNA (NS1, HA, PB2, PA, NP, M1, and M2 expression. PNR pretreatment also increased the secretion of pro-inflammatory cytokines [tumor necrosis factor alpha and interleukin 6] and interferon (IFN-beta and the phosphorylation of type-I IFN-related proteins (TANK-binding kinase 1, STAT1, and IRF3 in vitro. In mice exposed to the influenza A H1N1 virus, PNR treatment decreased mortality by 90% and prevented weight loss (by approximately 10% compared with the findings in untreated animals. In addition, splenocytes from PNR-administered mice displayed significantly enhanced natural killer (NK cell activity against YAC-1 cells. Taking these findings together, PNR stimulates an antiviral response in murine macrophages and mice that protects against viral infection, which may be attributable to its ability to stimulate NK cell activity. Further investigations are needed to reveal the molecular

  19. 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.

  20. Influenza hospitalization epidemiology from a severe acute respiratory infection surveillance system in Jordan, January 2008?February 2014

    OpenAIRE

    Al?Abdallat, Mohammad; Dawson, Patrick; Haddadin, Aktham Jeries; El?Shoubary, Waleed; Dueger, Erica; Al?Sanouri, Tarek; Said, Mayar M.; Talaat, Maha

    2016-01-01

    Background Acute respiratory infections (ARIs) are a major cause of morbidity and mortality worldwide. Influenza typically contributes substantially to the burden of ARI, but only limited data are available on influenza activity and seasonality in Jordan. Methods Syndromic case definitions were used to identify individuals with severe acute respiratory infections (SARI) admitted to four sentinel hospitals in Jordan. Demographic and clinical data were collected. Nasopharyngeal and oropharyngea...

  1. Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses

    OpenAIRE

    Jenna M. Bartley; Jenna M. Bartley; Xin Zhou; Xin Zhou; George A. Kuchel; George A. Kuchel; George M. Weinstock; George M. Weinstock; Laura Haynes; Laura Haynes

    2017-01-01

    Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu). Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection t...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Intranasal administration of live Lactobacillus species facilitates protection against influenza virus infection in mice.

    Science.gov (United States)

    Youn, Ha-Na; Lee, Dong-Hun; Lee, Yu-Na; Park, Jae-Keun; Yuk, Seong-Su; Yang, Si-Yong; Lee, Hyun-Jeong; Woo, Seo-Hyung; Kim, Hyoung-Moon; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Song, Chang-Seon

    2012-01-01

    Influenza virus infections continue to be a significant public health problem. For improved therapies and preventive measures against influenza, there has been an increased tendency in modern medicine involving the use of probiotics. In this study, we compared the protective efficacy of various live and dead Lactobacillus species against challenge with influenza virus in mice according to the administration route and dose. In addition, to understand the underlying mechanism behind this clinical protective effect, we performed immunologic assays including examination of IgA levels and cytokine profiles in the lung. The survival rate of mice receiving intranasal administration of Lactobacillus was higher than after oral administration, and administration of live bacteria was more protective than of dead bacteria. The lung levels of interleukin (IL)-12 and IgA were significantly increased (PLactobacillus strains on influenza virus infection. Therefore, for clinical applications, selection of effective strains could be critical and individually optimized application regimens of the selected strains are required. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine.

    Science.gov (United States)

    Solórzano, Alicia; Foni, Emanuela; Córdoba, Lorena; Baratelli, Massimiliano; Razzuoli, Elisabetta; Bilato, Dania; Martín del Burgo, María Ángeles; Perlin, David S; Martínez, Jorge; Martínez-Orellana, Pamela; Fraile, Lorenzo; Chiapponi, Chiara; Amadori, Massimo; del Real, Gustavo; Montoya, María

    2015-11-01

    Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed thus far in this host. To gain insight into the possibility of H3N8 avian IAVs to cross the species barrier into pigs, in vitro experiments and an experimental infection in pigs with four H3N8 viruses from different origins (equine, canine, avian, and seal) were performed. As a positive control, an H3N2 swine influenza virus A was used. Although equine and canine viruses hardly replicated in the respiratory systems of pigs, avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Interestingly, antibodies against hemagglutinin could not be detected after infection by hemagglutination inhibition (HAI) test with avian and seal viruses. This phenomenon was observed not only in pigs but also in mice immunized with the same virus strains. Our data indicated that H3N8 IAVs from wild aquatic birds have the potential to cross the species barrier and establish successful infections in pigs that might spread unnoticed using the HAI test as diagnostic tool. Although natural infection of humans with an avian H3N8 influenza A virus has not yet been reported, this influenza A virus subtype has already crossed the species barrier. Therefore, we have examined the potential of H3N8 from canine, equine, avian, and seal origin to productively infect pigs. Our results demonstrated that avian and seal viruses replicated substantially and caused detectable lesions in inoculated pigs without previous adaptation. Surprisingly, we

  5. Mechanism of aftered cytoskeleton organization in influenza virus infection

    International Nuclear Information System (INIS)

    Krizanova, O.; Ciampor, F.; Zavodska, E.; Matis, J.; Stancek, D.; Krivjanska, M.

    1989-01-01

    The autophosphorylation was followed of cytoskeleton (CS) isolated from control chick embryo cell membranes (CS-C) and from these membranes after influenza virus adsorption (CS-V) under conditions allowing to determine the activity of a single type proteinkinase. The Ca 2+ dependent calmodulin (CaM) kinase used different substrates from CS-V than did the c'AMP dependent proteinkinase. The catalytic subunit (c-subunit) of the c'AMP dependent proteinkinase added from outside phosphorylated the same polypeptides than the endogeneous c'AMP dependent proteinkinase, the further being more active than the latter. The purified influenza virus incorporated 32 P in the presence of the c-subunit only. Incubation of influenza virus with the c-subunit caused morphological changes visible by electron microscopy. The pleomorphy of the particles as well as their electron transmissibility were enhanced in the result of structural alterations and rarefaction of surface spikes of the haemagglutinin and neuraminidase. The contractibility of CS isolated from normal CEC and of the CS from CEC by 15 min postinfection (p.i.) was determined according to the actomyosin ATPase activity. The ATPase activity of the cytoskeleton in the presence of the Ca 2+ /CaM and that in the presence of c'AMP were used as controls. The virus as well as the Ca 2+ /CaM increased the ATPase activity. EGTA had no effect but did not interfere with virus stimulation, while c'AMP blocked the virus-induced enhancement of the ATPase activity. (author). 3 figs., 1 tab., 36 refs

  6. 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)

  7. DNA microarray global gene expression analysis of influenza virus-infected chicken and duck cells

    Directory of Open Access Journals (Sweden)

    Suresh V. Kuchipudi

    2015-06-01

    Full Text Available The data described in this article pertain to the article by Kuchipudi et al. (2014 titled “Highly Pathogenic Avian Influenza Virus Infection in Chickens But Not Ducks Is Associated with Elevated Host Immune and Pro-inflammatory Responses” [1]. While infection of chickens with highly pathogenic avian influenza (HPAI H5N1 virus subtypes often leads to 100% mortality within 1 to 2 days, infection of ducks in contrast causes mild or no clinical signs. The rapid onset of fatal disease in chickens, but with no evidence of severe clinical symptoms in ducks, suggests underlying differences in their innate immune mechanisms. We used Chicken Genechip microarrays (Affymetrix to analyse the gene expression profiles of primary chicken and duck lung cells infected with a low pathogenic avian influenza (LPAI H2N3 virus and two HPAI H5N1 virus subtypes to understand the molecular basis of host susceptibility and resistance in chickens and ducks. Here, we described the experimental design, quality control and analysis that were performed on the data set. The data are publicly available through the Gene Expression Omnibus (GEOdatabase with accession number GSE33389, and the analysis and interpretation of these data are included in Kuchipudi et al. (2014 [1].

  8. Nanostructured glycan architecture is important in the inhibition of influenza A virus infection

    Science.gov (United States)

    Kwon, Seok-Joon; Na, Dong Hee; Kwak, Jong Hwan; Douaisi, Marc; Zhang, Fuming; Park, Eun Ji; Park, Jong-Hwan; Youn, Hana; Song, Chang-Seon; Kane, Ravi S.; Dordick, Jonathan S.; Lee, Kyung Bok; Linhardt, Robert J.

    2017-01-01

    Rapid change and zoonotic transmission to humans have enhanced the virulence of the influenza A virus (IAV). Neutralizing antibodies fail to provide lasting protection from seasonal epidemics. Furthermore, the effectiveness of anti-influenza neuraminidase inhibitors has declined because of drug resistance. Drugs that can block viral attachment and cell entry independent of antigenic evolution or drug resistance might address these problems. We show that multivalent 6‧-sialyllactose-polyamidoamine (6SL-PAMAM) conjugates, when designed to have well-defined ligand valencies and spacings, can effectively inhibit IAV infection. Generation 4 (G4) 6SL-PAMAM conjugates with a spacing of around 3 nm between 6SL ligands (S3-G4) showed the strongest binding to a hemagglutinin trimer (dissociation constant of 1.6 × 10-7 M) and afforded the best inhibition of H1N1 infection. S3-G4 conjugates were resistant to hydrolysis by H1N1 neuraminidase. These conjugates protected 75% of mice from a lethal challenge with H1N1 and prevented weight loss in infected animals. The structure-based design of multivalent nanomaterials, involving modulation of nanoscale backbone structures and number and spacing between ligands, resulted in optimal inhibition of IAV infection. This approach may be broadly applicable for designing effective and enduring therapeutic protection against human or avian influenza viruses.

  9. Nonencapsulated Streptococcus pneumoniae causes otitis media during single-species infection and during polymicrobial infection with nontypeable Haemophilus influenzae.

    Science.gov (United States)

    Murrah, Kyle A; Pang, Bing; Richardson, Stephen; Perez, Antonia; Reimche, Jennifer; King, Lauren; Wren, John; Swords, W Edward

    2015-07-01

    Streptococcus pneumoniae strains lacking capsular polysaccharide have been increasingly reported in carriage and disease contexts. Since most cases of otitis media involve more than one bacterial species, we aimed to determine the capacity of a nonencapsulated S. pneumoniae clinical isolate to induce disease in the context of a single-species infection and as a polymicrobial infection with nontypeable Haemophilus influenzae. Using the chinchilla model of otitis media, we found that nonencapsulated S. pneumoniae colonizes the nasopharynx following intranasal inoculation, but does not readily ascend into the middle ear. However, when we inoculated nonencapsulated S. pneumoniae directly into the middle ear, the bacteria persisted for two weeks post-inoculation and induced symptoms consistent with chronic otitis media. During coinfection with nontypeable H. influenzae, both species persisted for one week and induced polymicrobial otitis media. We also observed that nontypeable H. influenzae conferred passive protection from killing by amoxicillin upon S. pneumoniae from within polymicrobial biofilms in vitro. Therefore, based on these results, we conclude that nonencapsulated pneumococci are a potential causative agent of chronic/recurrent otitis media, and can also cause mutualistic infection with other opportunists, which could complicate treatment outcomes. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    International Nuclear Information System (INIS)

    Pan, Yang; Sasaki, Tadahiro; Kubota-Koketsu, Ritsuko; Inoue, Yuji; Yasugi, Mayo; Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha; Du, Anariwa; Boonsathorn, Naphatsawan; Ibrahim, Madiha S.

    2014-01-01

    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses

  11. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Yang [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Sasaki, Tadahiro [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Kubota-Koketsu, Ritsuko [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Inoue, Yuji [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yasugi, Mayo [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Yamashita, Akifumi; Ramadhany, Ririn; Arai, Yasuha [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Du, Anariwa [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Boonsathorn, Naphatsawan [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Medical Sciences, Ministry of Public Health, Muang, Nonthaburi (Thailand); JST/JICA, Science and Technology Research Partnership for Sustainable Development (SATREPS), Tokyo (Japan); Ibrahim, Madiha S. [Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour (Egypt); and others

    2014-07-18

    Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

  12. A quantitative comet infection assay for influenza virus

    Science.gov (United States)

    Lindsay, Stephen M.; Timm, Andrea; Yin, John

    2011-01-01

    Summary The virus comet assay is a cell-based virulence assay used to evaluate an antiviral drug or antibody against a target virus. The comet assay differs from the plaque assay in allowing spontaneous flows in 6-well plates to spread virus. When implemented quantitatively the comet assay has been shown to have an order-of-magnitude greater sensitivity to antivirals than the plaque assay. In this study, a quantitative comet assay for influenza virus is demonstrated, and is shown to have a 13-fold increase in sensitivity to ribavirin. AX4 cells (MDCK cells with increased surface concentration of α2–6 sialic acid, the influenza virus receptor) have reduced the comet size variability relative to MDCK cells, making them a better host cell for use in this assay. Because of enhanced antiviral sensitivity in flow-based assays, less drug is required, which could lead to lower reagent costs, reduced cytotoxicity, and fewer false-negative drug screen results. The comet assay also serves as a readout of flow conditions in the well. Observations from comets formed at varying humidity levels indicate a role for evaporation in the mechanism of spontaneous fluid flow in wells. PMID:22155578

  13. Neurological manifestations of influenza infection in children and adults: results of a National British Surveillance Study.

    Science.gov (United States)

    Goenka, Anu; Michael, Benedict D; Ledger, Elizabeth; Hart, Ian J; Absoud, Michael; Chow, Gabriel; Lilleker, James; Lunn, Michael; McKee, David; Peake, Deirdre; Pysden, Karen; Roberts, Mark; Carrol, Enitan D; Lim, Ming; Avula, Shivaram; Solomon, Tom; Kneen, Rachel

    2014-03-01

    The emergence of influenza A(H1N1) 2009 was met with increased reports of associated neurological manifestations. We aimed to describe neurological manifestations of influenza in adults and children in the United Kingdom that presented at this time. A 2-year surveillance study was undertaken through the British adult and pediatric neurological surveillance units from February 2011. Patients were included if they met clinical case definitions within 1 month of proven influenza infection. Twenty-five cases were identified: 21 (84%) in children and 4 (16%) in adults. Six (29%) children had preexisting neurological disorders. Polymerase chain reaction of respiratory secretions identified influenza A in 21 (81%; 20 of which [95%] were H1N1) and influenza B in 4 (15%). Twelve children had encephalopathy (1 with movement disorder), 8 had encephalitis, and 1 had meningoencephalitis. Two adults had encephalopathy with movement disorder, 1 had encephalitis, and 1 had Guillain-Barré syndrome. Seven individuals (6 children) had specific acute encephalopathy syndromes (4 acute necrotizing encephalopathy, 1 acute infantile encephalopathy predominantly affecting the frontal lobes, 1 hemorrhagic shock and encephalopathy, 1 acute hemorrhagic leukoencephalopathy). Twenty (80%) required intensive care, 17 (68%) had poor outcome, and 4 (16%) died. This surveillance study described a cohort of adults and children with neurological manifestations of influenza. The majority were due to H1N1. More children than adults were identified; many children had specific encephalopathy syndromes with poor outcomes. None had been vaccinated, although 8 (32%) had indications for this. A modified classification system is proposed based on our data and the increasing spectrum of recognized acute encephalopathy syndromes.

  14. 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)

  15. A Perfect Storm: Increased Colonization and Failure of Vaccination Leads to Severe Secondary Bacterial Infection in Influenza Virus-Infected Obese Mice

    Directory of Open Access Journals (Sweden)

    Erik A. Karlsson

    2017-09-01

    Full Text Available Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Streptococcus pneumoniae. Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection. This result was unexpected, given that most influenza virus strains, especially seasonal human A and B viruses, are nonlethal in this model. Both viral and bacterial titers were increased in the upper respiratory tract and lungs of obese animals as early as days 1 and 2 post-bacterial infection, leading to a significant decrease in lung function. This increased bacterial load correlated with extensive cellular damage and upregulation of platelet-activating factor receptor, a host receptor central to pneumococcal invasion. Importantly, while vaccination of obese mice against either influenza virus or pneumococcus failed to confer protection, antibiotic treatment was able to resolve secondary bacterial infection-associated mortality. Overall, secondary bacterial pneumonia could be a widespread, unaddressed public health problem in an increasingly obese population.

  16. Maintenance of influenza virus infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings.

    Science.gov (United States)

    Sakaguchi, Hiroko; Wada, Koji; Kajioka, Jitsuo; Watanabe, Mayumi; Nakano, Ryuichi; Hirose, Tatsuko; Ohta, Hiroshi; Aizawa, Yoshiharu

    2010-11-01

    The maintenance of infectivity of influenza viruses on the surfaces of personal protective equipment and clothing is an important factor in terms of controlling viral cross-infection in the environment and preventing contact infection. The aim of this study was to determine if laboratory-grown influenza A (H1N1) virus maintained infectivity on the surfaces of personal protective equipment and clothing used in healthcare settings. Influenza A virus (0.5 mL) was deposited on the surface of a rubber glove, an N95 particulate respirator, a surgical mask made of non-woven fabric, a gown made of Dupont Tyvek, a coated wooden desk, and stainless steel. Each sample was left for 1, 8, and 24 h, and hemagglutination (HA) and 50% tissue culture infective dose (TCID(50))/mL were measured. The HA titer of this influenza A virus did not decrease in any of the materials tested even after 24 h. The infectivity of influenza A virus measured by TCID(50) was maintained for 8 h on the surface of all materials, with the exception of the rubber glove for which virus infectivity was maintained for 24 h. Our results indicate that the replacement/renewal of personal protective equipment and clothing by healthcare professionals in cases of exposure to secretions and droplets containing viruses spread by patients is an appropriate procedure to prevent cross-infection.

  17. 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.

  18. Virions and intracellular nucleocapsids produced during mixed heterotypic influenza infection of MDCK cells

    International Nuclear Information System (INIS)

    Sklyanskaya, E.I.; Varich, N.L.; Amvrosieva, T.V.; Kaverin, N.V.

    1985-01-01

    Phenotypically mixed virus yields, obtained by coinfection of MDCK cells with influenza A/WSN/33 and B/Lee/40 viruses, contained both A/WSN/33 and B/Lee/40 NP proteins, as revealed by polyacrylamide gel electrophoresis of the purified 14 C-amino acids-labeled virus. Virions were lysed with 0.6 M KCl-Triton X-100 buffer, and nucleocapsids were immunoprecipitated with antibodies against NP protein of influenza A virus. Polyacrylamide gel electrophoresis of the immunoprecipitate revealed NP protein of A/WSN/33 but not of B/Lee/40 virus. However, in similar experiments with the lysates of doubly infected cells, the band of B/Lee/40 NP protein was revealed in the polyacrylamide gel electrophoresis patterns of the immunoprecipitates. In an attempt to analyze the RNA content of the immune complexes, the authors absorbed the lysates of doubly infected [ 3 H]uridine-labeled cells with protein A-containing Staphylococcus aureus covered with antibodies against the NP protein of influenza A virus. RNA extracted from the immune complexes contained genomic RNA segments of both A/WSN/33 and B/Lee/40 viruses. In control samples containing an artificial mixture of cell lysates separately infected with each virus, the analysis revealed homologous components (i.e., A/WSN/33 NP protein or RNA segments) in the immune complexes. The results suggest the presence of phenotypically mixed nucleocapsids in the cells doubly infected with influenza A and B viruses; in the course of the virion formation, the nucleocapsids lacking the heterologous NP protein are selected

  19. Swine influenza virus infection dynamics in two pig farms; results of a longitudinal assessment

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    Simon-Grifé Meritxell

    2012-03-01

    Full Text Available Abstract In order to assess the dynamics of influenza virus infection in pigs, serological and virological follow-ups were conducted in two whole batches of pigs from two different farms (F1 and F2, from 3 weeks of age until market age. Anti-swine influenza virus (SIV antibodies (measured by ELISA and hemagglutination inhibition and nasal virus shedding (measured by RRT-PCR and isolation in embryonated chicken eggs and MDCK cells were carried out periodically. SIV isolates were subtyped and hemagglutinin and neuraminidase genes were partially sequenced and analyzed phylogenetically. In F1, four waves of viral circulation were detected, and globally, 62/121 pigs (51.2% were positive by RRT-PCR at least once. All F1 isolates corresponded to H1N1 subtype although hemagglutination inhibition results also revealed the presence of antibodies against H3N2. The first viral wave took place in the presence of colostral-derived antibodies. Nine pigs were positive in two non-consecutive sampling weeks, with two of the animals being positive with the same isolate. Phylogenetic analyses showed that different H1N1 variants circulated in that farm. In F2, only one isolate, H1N2, was detected and all infections were concentrated in a very short period of time, as assumed for a classic influenza outbreak. These findings led us to propose that influenza virus infection in pigs might present different patterns, from an epidemic outbreak to an endemic form with different waves of infections with a lower incidence.

  20. 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.

  1. Infection with human H1N1 influenza virus affects the expression of sialic acids of metaplastic mucous cells in the ferret airways

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Martel, Cyril Jean-Marie; Aasted, Bent

    2009-01-01

    Glycans terminating in sialic acids serve as receptors for influenza viruses. In this study ferrets were infected with influenza virus A/New Caledonia/20/99, and the in situ localization of sialic acids linked a2-3 and a2-6 in the airways was investigated in infected and non-infected animals by use...

  2. Health-seeking behavior and transmission dynamics in the control of influenza infection among different age groups.

    Science.gov (United States)

    You, Shu-Han; Chen, Szu-Chieh; Liao, Chung-Min

    2018-01-01

    It has been found that health-seeking behavior has a certain impact on influenza infection. However, behaviors with/without risk perception on the control of influenza transmission among age groups have not been well quantified. The purpose of this study was to assess to what extent, under scenarios of with/without control and preventive/protective behaviors, the age-specific network-driven risk perception influences influenza infection. A behavior-influenza model was used to estimate the spread rate of age-specific risk perception in response to an influenza outbreak. A network-based information model was used to assess the effect of network-driven risk perception information transmission on influenza infection. A probabilistic risk model was used to assess the infection risk effect of risk perception with a health behavior change. The age-specific overlapping percentage was estimated to be 40%-43%, 55%-60%, and 19%-35% for child, teenage and adult, and elderly age groups, respectively. Individuals perceive the preventive behavior to improve risk perception information transmission among teenage and adult and elderly age groups, but not in the child age group. The population with perceived health behaviors could not effectively decrease the percentage of infection risk in the child age group, whereas for the elderly age group, the percentage of decrease in infection risk was more significant, with a 97.5th percentile estimate of 97%. The present integrated behavior-infection model can help health authorities in communicating health messages for an intertwined belief network in which health-seeking behavior plays a key role in controlling influenza infection.

  3. The evaluation of a nucleoprotein ELISA for the detection of equine influenza antibodies and the differentiation of infected from vaccinated horses (DIVA).

    Science.gov (United States)

    Galvin, Pamela; Gildea, Sarah; Arkins, Sean; Walsh, Cathal; Cullinane, Ann

    2013-12-01

    Antibodies against equine influenza virus (EIV) are traditionally quantified by haemagglutination inhibition (HI) or single radial haemolysis (SRH). To evaluate an ELISA for the detection of antibodies against influenza nucleoprotein in the diagnosis and surveillance of equine influenza (EI). The ELISA was compared with the SRH and HI tests. Serial serum samples from 203 naturally and 14 experimentally infected horses, from 60 weanlings following primary vaccination with five different vaccines (two whole inactivated vaccines, two ISCOM-based subunit vaccines and a recombinant canarypox virus vaccine) and from 44 adult horses following annual booster vaccination with six different vaccines were analysed. Fewer seroconversions were detected in clinical samples by ELISA than by SRH or HI but ELISA was more sensitive than SRH in naïve foals post-experimental infection. The ELISA did not detect the antibody response to vaccination with the recombinant canarypox virus vaccine confirming the usefulness of the combination of this kit and vaccine to differentiate between naturally infected and vaccinated horses, that is, DIVA. No DIVA capacity was evident with the other vaccines. The results suggest that this ELISA is a useful supplementary test for the diagnosis of EI although less sensitive than HI or SRH. It is an appropriate test for EI surveillance in a naïve population and may be combined with the recombinant canarypox virus vaccine but not with other commercially available subunit vaccines, in a DIVA strategy. © 2013 Blackwell Publishing Ltd.

  4. NADPH oxidases as novel pharmacologic targets against influenza A virus infection.

    Science.gov (United States)

    Vlahos, Ross; Selemidis, Stavros

    2014-12-01

    Influenza A viruses represent a major global health care challenge, with imminent pandemics, emerging antiviral resistance, and long lag times for vaccine development, raising a pressing need for novel pharmacologic strategies that ideally target the pathology irrespective of the infecting strain. Reactive oxygen species (ROS) pervade all facets of cell biology with both detrimental and protective properties. Indeed, there is compelling evidence that activation of the NADPH oxidase 2 (NOX2) isoform of the NADPH oxidase family of ROS-producing enzymes promotes lung oxidative stress, inflammation, injury, and dysfunction resulting from influenza A viruses of low to high pathogenicity, as well as impeding virus clearance. By contrast, the dual oxidase isoforms produce ROS that provide vital protective antiviral effects for the host. In this review, we propose that inhibitors of NOX2 are better alternatives than broad-spectrum antioxidant approaches for treatment of influenza pathologies, for which clinical efficacy may have been limited owing to poor bioavailability and inadvertent removal of beneficial ROS. Finally, we briefly describe the current suite of NADPH oxidase inhibitors and the molecular features of the NADPH oxidase enzymes that could be exploited by drug discovery for development of more specific and novel inhibitors to prevent or treat disease caused by influenza. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children : a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko

    2008-01-01

    OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with

  6. Seventeen years of subcutaneous infection by Aspergillus flavus; eumycetoma confirmed by immunohistochemistry.

    Science.gov (United States)

    Ahmed, Sarah A; Abbas, Manal A; Jouvion, Gregory; Al-Hatmi, Abdullah M S; de Hoog, G Sybren; Kolecka, Anna; Mahgoub, El Sheikh

    2015-12-01

    Chronic subcutaneous infections caused by Aspergillus species are considered to be extremely rare. Because these fungi are among the most common laboratory contaminants, their role as eumycetoma causative agents is difficult to ascertain. Here, we report the first case of A. flavus eumycetoma confirmed by isolation, molecular identification and immunohistochemical analysis. Patient was a 55-year-old male from Sudan suffering from eumycetoma on his left foot for a period of 17 years. He developed swelling, sinuses and white grain discharge was observed. He has been operated nine times and was treated with several regimens of ketoconazole and itraconazole without improvement. Initial diagnosis based on histology and radiology was Scedosporium eumycetoma. However, examination of the biopsy revealed A. flavus, which was identified by molecular analysis and MALDI-TOF MS. Immunohistochemistry using antibody directed against Aspergillus species was positive. Because of the earlier treatment failures with ketoconazole and itraconazole, therapy with voriconazole was initiated. However, in vitro susceptibility testing yielded a lower Minimum Inhibitory Concentration (MIC) value for itraconazole (0.25 μg ml(-1) ) than for voriconazole (1 μg ml(-1) ). Based on the presented results, A. flavus can be considered as one of the agents of white-grain eumycetoma. © 2015 Blackwell Verlag GmbH.

  7. 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

  8. 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

  9. Surface localization of the nuclear receptor CAR in influenza A virus-infected cells

    International Nuclear Information System (INIS)

    Takahashi, Tadanobu; Moriyama, Yusuke; Ikari, Akira; Sugatani, Junko; Suzuki, Takashi; Miwa, Masao

    2008-01-01

    Constitutive active/androstane receptor CAR is a member of the nuclear receptors which regulate transcription of xenobiotic metabolism enzymes. CAR is usually localized in the cytosol and nucleus. Here, we found that CAR was localized at the cell surface of influenza A virus (IAV)-infected cells. Additionally, we demonstrated that expression of a viral envelope glycoprotein, either hemagglutinin (HA) or neuraminidase (NA), but not viral nucleoprotein (NP), was responsible for this localization. This report is the first demonstration of CAR at the surface of tissue culture cells, and suggests that CAR may exert the IAV infection mechanism

  10. ATP catabolism by tissue nonspecific alkaline phosphatase contributes to development of ARDS in influenza-infected mice.

    Science.gov (United States)

    Woods, Parker S; Doolittle, Lauren M; Hickman-Davis, Judy M; Davis, Ian C

    2018-01-01

    Influenza A viruses are highly contagious respiratory pathogens that are responsible for significant morbidity and mortality worldwide on an annual basis. We have shown previously that influenza infection of mice leads to increased ATP and adenosine accumulation in the airway lumen. Moreover, we demonstrated that A 1 -adenosine receptor activation contributes significantly to influenza-induced acute respiratory distress syndrome (ARDS). However, we found that development of ARDS in influenza-infected mice does not require catabolism of ATP to adenosine by ecto-5'-nucleotidase (CD73). Hence, we hypothesized that increased adenosine generation in response to infection is mediated by tissue nonspecific alkaline phosphatase (TNAP), which is a low-affinity, high-capacity enzyme that catabolizes nucleotides in a nonspecific manner. In the current study, we found that whole lung and BALF TNAP expression and alkaline phosphatase enzymatic activity increased as early as 2 days postinfection (dpi) of C57BL/6 mice with 10,000 pfu/mouse of influenza A/WSN/33 (H1N1). Treatment at 2 and 4 dpi with a highly specific quinolinyl-benzenesulfonamide TNAP inhibitor (TNAPi) significantly reduced whole lung alkaline phosphatase activity at 6 dpi but did not alter TNAP gene or protein expression. TNAPi treatment attenuated hypoxemia, lung dysfunction, histopathology, and pulmonary edema at 6 dpi without impacting viral replication or BALF adenosine. Treatment also improved epithelial barrier function and attenuated cellular and humoral immune responses to influenza infection. These data indicate that TNAP inhibition can attenuate influenza-induced ARDS by reducing inflammation and fluid accumulation within the lung. They also further emphasize the importance of adenosine generation for development of ARDS in influenza-infected mice.

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. No evidence of increasing Haemophilus influenzae non-b infection in Australian Aboriginal children

    Directory of Open Access Journals (Sweden)

    Robert I. Menzies

    2013-08-01

    Full Text Available Background. High, or increasing, rates of invasive Haemophilus influenzae (Hi type a disease have been reported from North American native children from circumpolar regions, raising the question of serotype replacement being driven by vaccination against Hi type b (Hib. Indigenous Australians from remote areas had high rates of invasive Hib disease in the past, comparable to those in North American Indigenous populations. Objective. Evaluate incidence rates of invasive Hi (overall and by serotype in Indigenous Australian children over time. Design. Descriptive study of Hi incidence rates by serotype, in the Northern Territory (NT and South Australia (SA from 2001 to 2011. Comparison of NT data with a study that was conducted in the NT in 1985–1988, before Hib vaccine was introduced. Results. The average annual rate of invasive Hi type a (Hia disease in Indigenous children aged <5 years was 11/100,000 population. Although the incidence of Hi infection in Indigenous children in 2001–2003 was lower than during 2004–2011, this may be due to changes in surveillance. No other trend over time in individual serotypes or total invasive Hi disease, in Indigenous or non-Indigenous people, was identified. Compared to 1985–1988, rates in 2001–2011 were lower in all serotype groupings, by 98% for Hib, 75% for Hia, 79% for other serotypes and 67% for non-typeable Hi. Conclusions. There is no evidence of increases in invasive disease due to Hia, other specific non-b types, or non-typeable Hi in Australian Indigenous children. These data suggest that the increase in Hia some time after the introduction of Hib vaccine, as seen in the North American Arctic Region, is not common to all populations with high pre-vaccine rates of invasive Hib disease. However, small case numbers and the lack of molecular subtyping and PCR confirmation of pre-vaccine results complicate comparisons with North American epidemiology.

  14. Modeling genome-wide dynamic regulatory network in mouse lungs with influenza infection using high-dimensional ordinary differential equations.

    Science.gov (United States)

    Wu, Shuang; Liu, Zhi-Ping; Qiu, Xing; Wu, Hulin

    2014-01-01

    The immune response to viral infection is regulated by an intricate network of many genes and their products. The reverse engineering of gene regulatory networks (GRNs) using mathematical models from time course gene expression data collected after influenza infection is key to our understanding of the mechanisms involved in controlling influenza infection within a host. A five-step pipeline: detection of temporally differentially expressed genes, clustering genes into co-expressed modules, identification of network structure, parameter estimate refinement, and functional enrichment analysis, is developed for reconstructing high-dimensional dynamic GRNs from genome-wide time course gene expression data. Applying the pipeline to the time course gene expression data from influenza-infected mouse lungs, we have identified 20 distinct temporal expression patterns in the differentially expressed genes and constructed a module-based dynamic network using a linear ODE model. Both intra-module and inter-module annotations and regulatory relationships of our inferred network show some interesting findings and are highly consistent with existing knowledge about the immune response in mice after influenza infection. The proposed method is a computationally efficient, data-driven pipeline bridging experimental data, mathematical modeling, and statistical analysis. The application to the influenza infection data elucidates the potentials of our pipeline in providing valuable insights into systematic modeling of complicated biological processes.

  15. Distribution of sialic acid receptors and influenza A viruses of avian and swine origin and in experimentally infected pigs

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Larsen, Lars Erik; Viuff, Birgitte M.

    2011-01-01

    Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses...... in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. Methods: This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA) I...... and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated that the distribution of influenza A virus receptors in pigs are similar to that of humans and therefore challenge the theory that the pig...

  16. 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.

  17. Host behaviour and physiology underpin individual variation in avian influenza virus infection in migratory Bewick's swans.

    Science.gov (United States)

    Hoye, Bethany J; Fouchier, Ron A M; Klaassen, Marcel

    2012-02-07

    Individual variation in infection modulates both the dynamics of pathogens and their impact on host populations. It is therefore crucial to identify differential patterns of infection and understand the mechanisms responsible. Yet our understanding of infection heterogeneity in wildlife is limited, even for important zoonotic host-pathogen systems, owing to the intractability of host status prior to infection. Using novel applications of stable isotope ecology and eco-immunology, we distinguish antecedent behavioural and physiological traits associated with avian influenza virus (AIV) infection in free-living Bewick's swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher serum δ13C (-25.3±0.4) than their non-infected counterparts (-26.3±0.2). Thus, individuals preferentially foraging in aquatic rather than terrestrial habitats experienced a higher risk of infection, suggesting that the abiotic requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles were more likely to be infected (30.8% compared with 11.3% for adults), shed approximately 15-fold higher quantity of virus and exhibited a lower specific immune response than adults. Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness.

  18. Avian influenza viruses in humans.

    Science.gov (United States)

    Malik Peiris, J S

    2009-04-01

    Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.

  19. Identification of equine influenza virus infection in Asian wild horses (Equus przewalskii).

    Science.gov (United States)

    Yin, Xin; Lu, Gang; Guo, Wei; Qi, Ting; Ma, Jian; Zhu, Chao; Zhao, Shihua; Pan, Jialiang; Xiang, Wenhua

    2014-05-01

    An outbreak of equine influenza was observed in the Asian wild horse population in Xinjiang Province, China, in 2007. Nasal swabs were collected from wild horses and inoculated into 9-10-day SPF embryonated eggs. The complete genome of the isolate was sequenced. A comparison of the amino acid sequence revealed that the isolate was an equine influenza virus strain, which we named A/equine/Xinjiang/4/2007. Each gene of the virus was found to have greater than 99 % homology to equine influenza virus strains of the Florida-2 sublineage, which were circulating simultaneously in China, and a lesser amount of homology was found to the strain A/equine/Qinghai/1/1994 (European lineage), which was isolated during the last outbreak in China. These observations were confirmed by phylogenetic analysis. In addition, the deduced amino acid sequence of the neuraminidase of the A/equine/Xinjiang/4/2007 strain was identical to that of A/equine/California/8560/2002, an American isolate, and was found to be similar to those of Florida-2 strains found in other countries by comparing them with nine other field strains that were isolated in China from 2007 to 2008. It is suggested that the neuraminidase segment of A/equine/Xinjiang/4/2007 may have been obtained from equine influenza virus strains from other countries. We report for the first time an outbreak of equine influenza in the Asian wild horse population, and the complete genome of the virus is provided and analyzed.

  20. Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017.

    Science.gov (United States)

    Zhou, Lei; Tan, Yi; Kang, Min; Liu, Fuqiang; Ren, Ruiqi; Wang, Yali; Chen, Tao; Yang, Yiping; Li, Chao; Wu, Jie; Zhang, Hengjiao; Li, Dan; Greene, Carolyn M; Zhou, Suizan; Iuliano, A Danielle; Havers, Fiona; Ni, Daxin; Wang, Dayan; Feng, Zijian; Uyeki, Timothy M; Li, Qun

    2017-08-01

    We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients.

  1. 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.

  2. 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...

  3. Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis.

    Science.gov (United States)

    Rosales-Chilama, Mariana; Gongora, Rafael E; Valderrama, Liliana; Jojoa, Jimena; Alexander, Neal; Rubiano, Luisa C; Cossio, Alexandra; Adams, Emily R; Saravia, Nancy G; Gomez, María Adelaida

    2015-12-01

    The contribution of individuals with subclinical infection to the transmission and endemicity of cutaneous leishmaniasis (CL) is unknown. Immunological evidence of exposure to Leishmania in residents of endemic areas has been the basis for defining the human population with asymptomatic infection. However, parasitological confirmation of subclinical infection is lacking. We investigated the presence and viability of Leishmania in blood and non-invasive mucosal tissue samples from individuals with immunological evidence of subclinical infection in endemic areas for CL caused by Leishmania (Viannia) in Colombia. Detection of Leishmania kDNA was conducted by PCR-Southern Blot, and parasite viability was confirmed by amplification of parasite 7SLRNA gene transcripts. A molecular tool for genetic diversity analysis of parasite populations causing persistent subclinical infection based on PCR amplification and sequence analysis of an 82bp region between kDNA conserved blocks 1 and 2 was developed. Persistent Leishmania infection was demonstrated in 40% (46 of 114) of leishmanin skin test (LST) positive individuals without active disease; parasite viability was established in 59% of these (27 of 46; 24% of total). Parasite burden quantified from circulating blood monocytes, nasal, conjunctival or tonsil mucosal swab samples was comparable, and ranged between 0.2 to 22 parasites per reaction. kDNA sequences were obtained from samples from 2 individuals with asymptomatic infection and from 26 with history of CL, allowing genetic distance analysis that revealed diversity among sequences and clustering within the L. (Viannia) subgenus. Our results provide parasitological confirmation of persistent infection among residents of endemic areas of L. (Viannia) transmission who have experienced asymptomatic infection or recovered from CL, revealing a reservoir of infection that potentially contributes to the endemicity and transmission of disease. kDNA genotyping establishes proof

  4. Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis.

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    Mariana Rosales-Chilama

    2015-12-01

    Full Text Available The contribution of individuals with subclinical infection to the transmission and endemicity of cutaneous leishmaniasis (CL is unknown. Immunological evidence of exposure to Leishmania in residents of endemic areas has been the basis for defining the human population with asymptomatic infection. However, parasitological confirmation of subclinical infection is lacking.We investigated the presence and viability of Leishmania in blood and non-invasive mucosal tissue samples from individuals with immunological evidence of subclinical infection in endemic areas for CL caused by Leishmania (Viannia in Colombia. Detection of Leishmania kDNA was conducted by PCR-Southern Blot, and parasite viability was confirmed by amplification of parasite 7SLRNA gene transcripts. A molecular tool for genetic diversity analysis of parasite populations causing persistent subclinical infection based on PCR amplification and sequence analysis of an 82bp region between kDNA conserved blocks 1 and 2 was developed.Persistent Leishmania infection was demonstrated in 40% (46 of 114 of leishmanin skin test (LST positive individuals without active disease; parasite viability was established in 59% of these (27 of 46; 24% of total. Parasite burden quantified from circulating blood monocytes, nasal, conjunctival or tonsil mucosal swab samples was comparable, and ranged between 0.2 to 22 parasites per reaction. kDNA sequences were obtained from samples from 2 individuals with asymptomatic infection and from 26 with history of CL, allowing genetic distance analysis that revealed diversity among sequences and clustering within the L. (Viannia subgenus.Our results provide parasitological confirmation of persistent infection among residents of endemic areas of L. (Viannia transmission who have experienced asymptomatic infection or recovered from CL, revealing a reservoir of infection that potentially contributes to the endemicity and transmission of disease. kDNA genotyping

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

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    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. 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

  7. 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

  8. COMPARISON OF SUSCEPTIBILITY TO INFLUENZA INFECTION IN NASAL EPITHELIAL CELLS OBTAINED FROM SMOKERS AND NON-SMOKERS

    Science.gov (United States)

    Several studies have demonstrated that individuals who smoke have greater susceptibility to influenza infections, as well as other respiratory virus infections, than non-smokers, yet the role of airway epithelial cells in this response is not clear. To determine whether in vivo t...

  9. 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

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

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    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.

  12. 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.

  13. 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.

  14. Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection.

    Science.gov (United States)

    Tabynov, Kaissar; Sansyzbay, Abylai; Kydyrbayev, Zhailaubay; Yespembetov, Bolat; Ryskeldinova, Sholpan; Zinina, Nadezhda; Assanzhanova, Nurika; Sultankulova, Kulaisan; Sandybayev, Nurlan; Khairullin, Berik; Kuznetsova, Irina; Ferko, Boris; Egorov, Andrej

    2014-04-10

    We generated novel, effective candidate vaccine against Brucella abortus based on recombinant influenza viruses expressing the Brucella ribosomal protein L7/L12 or outer membrane protein (Omp)-16 from the NS1 open reading frame. The main purpose of this work was to evaluate the safety, immunogenicity and protectiveness of vaccine candidate in laboratory animals. Four recombinant influenza A viral constructs of the subtypes Н5N1 or H1N1 expressing the Brucella proteins L7/L12 or Omp16 were obtained by a reverse genetics method: Flu-NS1-124-L7/L12-H5N1, Flu-NS1-124-Omp16-H5N1, Flu-NS1-124-L7/L12-H1N1 and Flu-NS1-124-Omp16-H1N1. Despite of substantial modification of NS1 gene, all constructs replicated well and were retain their Brucella inserts over five passages in embryonated chicken eggs (CE). Administration of the mono- or bivalent vaccine formulation via prime-boost intranasal (i.n.), conjunctival (c.) or subcutaneous (s.c.) immunization was safe in mice; no deaths, body weight loss or pathomorphological changes were observed over 56 days. Moreover, guinea pigs vaccinated i.n. with vaccine vectors did not shed the vaccine viruses through their upper respiratory tract after the prime and booster vaccination. These findings confirmed the replication-deficient phenotype of viral vectors. The highest antibody response to Brucella antigen was obtained with constructs expressing L7/L12 (ELISA, GMT 242.5-735.0); whereas the highest T-cell immune response- with construct expressing Omp16 (ELISPOT, 337 ± 52-651 ± 45 spots/4×105cells), which was comparable (P > 0.05) to the response induced by the commercial vaccine B. abortus 19. Interestingly, c. immunization appeared to be optimal for eliciting T-cell immune response. In guinea pigs, the highest protective efficacy after challenge with B. abortus 544 was achieved with Omp16 expressing constructs in both monovalent or bivalent vaccine formulations; protective efficacy was comparable to those induced by

  15. Expression of innate immune genes, proteins and microRNAs in lung tissue of pigs infected experimentally with influenza virus (H1N2)

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Cirera, Susanna; Vasby, Ditte

    2013-01-01

    This study aimed at providing a better understanding of the involvement of innate immune factors, including miRNA, in the local host response to influenza virus infection. Twenty pigs were challenged by influenza A virus subtype H1N2. Expression of microRNA (miRNA), mRNA and proteins were...... results suggest that, in addition to a wide range of innate immune factors, miRNAs may also be involved in controlling acute influenza infection in pigs....

  16. Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

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    Young J. Lee

    2018-01-01

    Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

  17. [Epidemiology of human infection with avian influenza A(H7N9) virus in China, 2013-2017].

    Science.gov (United States)

    Han, D D; Han, C X; Li, L Y; Wang, M; Yang, J H; Li, M

    2018-01-10

    Objective: To understand the epidemiological characteristics of human infection with avian influenza A (H7N9) virus in China, and provide evidence for the prevention and control of human infection with H7N9 virus. Methods: The published incidence data of human infection with H7N9 virus in China from March 2013 to April 2017 were collected. Excel 2007 software was used to perform the analysis. The characteristics of distribution of the disease, exposure history, cluster of the disease were described. Results: By the end of April 2017, a total of 1 416 cases of human infection with H7N9 virus were confirmed in China, including 559 deaths, the case fatality rate was 39.5%. In 2016, the case number was lowest (127 cases), with the highest fatality rate (57.5%). The first three provinces with high case numbers were Zhejiang, Guangdong and Jiangsu. The median age of the cases was 55 years and the male to female ratio was 2.3∶1. Up to 66% of cases had clear live poultry exposure history before illness onset, 31% of cases had unknown exposure history and only 3% of the cases had no live poultry exposure history. There were 35 household clusters (5 in 2013, 9 in 2014, 6 in 2015, 5 in 2016, 10 in 2017), which involved 72 cases, accounting for 5% of the total cases. Conclusions: The epidemic of human infection with H7N9 virus in China during 2013-2017 had obvious seasonality and spatial distribution. There was limited family clustering. Infection cases were mostly related to poultry contact.

  18. Are Swine Workers in the United States at Increased Risk of Infection with Zoonotic Influenza Virus?

    Science.gov (United States)

    Myers, Kendall P.; Olsen, Christopher W.; Setterquist, Sharon F.; Capuano, Ana W.; Donham, Kelley J.; Thacker, Eileen L.; Merchant, James A.; Gray, Gregory C.

    2006-01-01

    Background Pandemic influenza strains originate in nonhuman species. Pigs have an important role in interspecies transmission of the virus. We examined multiple swine-exposed human populations in the nation's number 1 swine-producing state for evidence of previous swine influenza virus infection. Methods We performed controlled, cross-sectional seroprevalence studies among 111 farmers, 97 meat processing workers, 65 veterinarians, and 79 control subjects using serum samples collected during the period of 2002–2004. Serum samples were tested using a hemagglutination inhibition assay against the following 6 influenza A virus isolates collected recently from pigs and humans: A/Swine/WI/238/97 (H1N1), A/Swine/WI/R33F/01 (H1N2), A/Swine/Minnesota/593/99 (H3N2), A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and A/Nanchang/933/95 (H3N2). Results Using multivariable proportional odds modeling, all 3 exposed study groups demonstrated markedly elevated titers against the H1N1 and H1N2 swine influenza virus isolates, compared with control subjects. Farmers had the strongest indication of exposure to swine H1N1 virus infection (odds ratio [OR], 35.3; 95% confidence interval [CI], 7.7–161.8), followed by veterinarians (OR, 17.8; 95% CI, 3.8–82.7), and meat processing workers (OR, 6.5; 95% CI, 1.4–29.5). Similarly, farmers had the highest odds for exposure to swine H1N2 virus (OR, 13.8; 95% CI, 5.4–35.4), followed by veterinarians (OR, 9.5; 95% CI, 3.6–24.6) and meat processing workers (OR, 2.7; 95% CI, 1.1–6.7). Conclusions Occupational exposure to pigs greatly increases workers' risk of swine influenza virus infection. Swine workers should be included in pandemic surveillance and in antiviral and immunization strategies. PMID:16323086

  19. Laboratory experimental infection of sheep to Ornithobilharzia turkestanicum and its confirmation using post-mortem examination and histopathology

    Directory of Open Access Journals (Sweden)

    gholamreza karimi

    2014-11-01

    Full Text Available Ornithobilharzia turkestanicum from genus Ornithobilharzia genus and family Schistosomatidae is an important agent of parasitological infection in sheep. This parasite has been reported from Russia, China, Turkestan (Kazakhstan, Kyrgyzstan, Turkmenistan and Uzbekistan, Pakistan, Iraq, Turkey and Iran. Parasitological infection due to this agent could be one of the important factors of decreasing the production rate of livestock in Iran. The purpose of this study, was to experimentally infect sheep with this parasite and confirm the infection by post-mortem examination and Histopathology which was done successfully. Twenty five sheep were used in the study of which 10 sheep were experimentally infected by Ornithobilharzia turkestanikum using subcutaneous injection and 10 sheep by skin contact method and the other 5 sheep were kept as control. Result of post-mortem and Histopathology during a one year period confirmed that all of sheep were infected and adult worm, were seen in their mesentery. Mean number of cercaria used for inducing the infection was 6425 and 462 adult worms were collected post-mortem. There was no significant relationship between the number of cercaria and adult worms collected. Male sheep were more infected than female.

  20. Assessing the oseltamivir-induced resistance risk and implications for influenza infection control strategies

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    Hsieh NH

    2017-07-01

    Full Text Available Nan-Hung Hsieh,1 Yi-Jun Lin,2 Ying-Fei Yang,2 Chung-Min Liao2 1Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA; 2Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan Background: Oseltamivir-resistant mutants with higher drug resistance rates and low transmission fitness costs have not accounted for influenza (subtype viruses. Predicting the impacts of neuraminidase inhibitor therapy on infection rates and transmission of drug-resistant viral strains requires further investigation.Objectives: The purpose of this study was to assess the potential risk of oseltamivir-induced resistance for influenza A (H1N1 and A (H3N2 viruses.Materials and methods: An immune-response-based virus dynamic model was used to best fit the oseltamivir-resistant A (H1N1 and A (H3N2 infection data. A probabilistic risk assessment model was developed by incorporating branching process-derived probability distribution of resistance to estimate oseltamivir-induced resistance risk.Results: Mutation rate and sensitive strain number were key determinants in assessing resistance risk. By increasing immune response, antiviral efficacy, and fitness cost, the spread of resistant strains for A (H1N1 and A (H3N2 were greatly decreased. Probability of resistance depends most strongly on the sensitive strain number described by a Poisson model. Risk of oseltamivir-induced resistance increased with increasing the mutation rate for A (H1N1 only. The ≥50% of resistance risk induced by A (H1N1 and A (H3N2 sensitive infected cells were 0.4 (95% CI: 0.28–0.43 and 0.95 (95% CI 0.93–0.99 at a mutation rate of 10−6, respectively. Antiviral drugs must be administrated within 1–1.5 days for A (H1N1 and 2–2.5 days for A (H3N2 virus infections to limit viral production.Conclusion: Probabilistic risk assessment of antiviral drug

  1. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

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    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  2. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice

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    Reading Patrick C

    2008-08-01

    Full Text Available Abstract Background Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. Methods The anti-Gr-1 monoclonal antibody (mAb RB6-8C5 was used to (i identify neutrophils in the upper (nasal tissues and lower (lung respiratory tract of uninfected and influenza virus-infected mice, and (ii deplete neutrophils prior to and during influenza virus infection of mice. Results Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6 mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. Conclusion Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response.

  3. Association of history of allergies and influenza-like infections with laryngeal cancer in a case-control study.

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    Filippidis, Filippos T; Schwartz, Stephen M; Becker, Nikolaus; Dyckhoff, Gerhard; Kirschfink, Michael; Dietz, Andreas; Becher, Heiko; Ramroth, Heribert

    2015-08-01

    Prior studies suggest that history of allergy and infections early in life might be inversely associated with cancer. We explored the association between allergies, recent influenza infections and laryngeal cancer risk. We used data from a case-control study which included 229 cases of laryngeal cancer and 769 population controls matched for age and sex. History of a physician-diagnosed allergy, influenza-like infections in the past 5 years, smoking, alcohol consumption and occupational exposure to carcinogens were self-reported. Allergies were classified into two groups (Type I and Type IV), according to the underlying immunologic mechanism. Conditional logistic regression models were fitted using laryngeal cancer as the outcome, adjusting for smoking, alcohol consumption and occupational exposure and stratified for age and sex. Having any allergy was not associated significantly with laryngeal cancer. Although Type I and Type IV allergies were non-significantly associated with laryngeal cancer, Type IV allergies showed a strong inverse association after adjusting for smoking and alcohol (OR 0.50, 95 % CI 0.22-1.2). Participants who reported at least one influenza-like infection during the past 5 years were significantly less likely to have laryngeal cancer (OR 0.57, 95 % CI 0.39-0.81). After considering fever (≥38.5 °C) as a criterion for influenza infection, the association between influenza infection and laryngeal cancer was even stronger (OR 0.29, 95 % CI 0.13-0.63). We found no significant association between any allergy and laryngeal cancer, some indication of an inverse association between Type IV allergy and laryngeal cancer, whereas recent influenza infections were inversely associated with laryngeal cancer risk.

  4. Linezolid Decreases Susceptibility to Secondary Bacterial Pneumonia Post-Influenza Infection in Mice Through its Effects on Interferon-γ

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    Breslow-Deckman, Jessica M.; Mattingly, Cynthia M.; Birket, Susan E.; Hoskins, Samantha N.; Ho, Tam N.; Garvy, Beth A.; Feola, David J.

    2013-01-01

    Influenza infection predisposes patients to secondary bacterial pneumonia that contributes significantly to morbidity and mortality. While this association is well documented, the mechanisms that govern this synergism are poorly understood. A window of hyporesponsiveness following influenza infection has been associated with a substantial increase in local and systemic IFNγ concentrations. Recent data suggests that the oxazolidinone antibiotic linezolid decreases IFNγ and TNFα production in vitro from stimulated peripheral blood mononuclear cells. We therefore sought to determine whether linezolid would reverse immune hyporesponsiveness after influenza infection in mice through its effects on IFNγ. In vivo dose response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFNγ at day 7 post-influenza infection in a dose-dependent manner. The drug also decreased morbidity as measured by weight loss compared to vehicle-treated controls. When mice were challenged intranasally with S. pneumoniae 7 days after infection with influenza, linezolid pre-treatment led to decreased IFNγ and TNFα production, decreased weight loss, and lower bacterial burdens at 24 hours post bacterial infection in comparison to vehicle-treated controls. To determine whether these effects were due to suppression of IFNγ, linezolid-treated animals were given intranasal instillations of recombinant IFNγ before challenge with S. pneumoniae. This partially reversed the protective effects observed in the linezolid-treated mice, suggesting that the modulatory effects of linezolid are mediated partially by its ability to blunt IFNγ production. These results suggest that IFNγ, and potentially TNFα, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection. PMID:23833238

  5. Transcription factor regulation and cytokine expression following in vitro infection of primary chicken cell culture with low pathogenic avian influenza virus

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    Avian influenza virus (AIV) induced proinflammatory cytokine expression is believed to contribute to the disease pathogenesis following infection. However, there is limited information on the avian immune response to infection with low pathogenic avian influenza virus (LPAIV). To gain a better under...

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

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    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.

  7. Spatial assessment of the potential risk of avian influenza A virus infection in three raptor species in Japan

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    MORIGUCHI, Sachiko; ONUMA, Manabu; GOKA, Koichi

    2016-01-01

    Avian influenza A, a highly pathogenic avian influenza, is a lethal infection in certain species of wild birds, including some endangered species. Raptors are susceptible to avian influenza, and spatial risk assessment of such species may be valuable for conservation planning. We used the maximum entropy approach to generate potential distribution models of three raptor species from presence-only data for the mountain hawk-eagle Nisaetus nipalensis, northern goshawk Accipiter gentilis and peregrine falcon Falco peregrinus, surveyed during the winter from 1996 to 2001. These potential distribution maps for raptors were superimposed on avian influenza A risk maps of Japan, created from data on incidence of the virus in wild birds throughout Japan from October 2010 to March 2011. The avian influenza A risk map for the mountain hawk-eagle showed that most regions of Japan had a low risk for avian influenza A. In contrast, the maps for the northern goshawk and peregrine falcon showed that their high-risk areas were distributed on the plains along the Sea of Japan and Pacific coast. We recommend enhanced surveillance for each raptor species in high-risk areas and immediate establishment of inspection systems. At the same time, ecological risk assessments that determine factors, such as the composition of prey species, and differential sensitivity of avian influenza A virus between bird species should provide multifaceted insights into the total risk assessment of endangered species. PMID:26972333

  8. Influenza-Like Illness among University Students: Symptom Severity and Duration Due to Influenza Virus Infection Compared to Other Etiologies

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    Mullins, Jocelyn; Cook, Robert; Rinaldo, Charles; Yablonsky, Eric; Hess, Rachel; Piazza, Paolo

    2011-01-01

    Objective: University students with influenza-like illness (ILI) were assessed to determine whether symptom severity, duration, or missed days of school or work varied according to etiology. Participants: Sixty persons presenting to a university health clinic with ILI symptoms during 3 consecutive influenza seasons completed baseline survey and…

  9. Non-Type b Haemophilus influenzae Invasive Infections in North Dakota and South Dakota, 2013-2015.

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    Antony, Stephanie; Kaushik, Ashlesha; Mauriello, Clifford; Chatterjee, Archana

    2017-09-01

    Reports of children with non-type b Haemophilus influenzae infection in the United States in recent years have been limited. Here, we report the spectrum and severity of disease associated with invasive non-type b H influenzae infection in 17 patients at 2 tertiary-care children's hospitals over a 2-year period. Meningitis was the most common diagnosis. The majority of the patients had neurologic sequelae, and 1 patient died. The high proportions of hospitalization, intensive care utilization, and neurologic complications reveal that non-type b H influenzae infection was associated with significant morbidity in this pediatric population. © The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection.

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    Trevenan Walther

    2013-03-01

    Full Text Available The first step in influenza infection of the human respiratory tract is binding of the virus to sialic (Sia acid terminated receptors. The binding of different strains of virus for the receptor is determined by the α linkage of the sialic acid to galactose and the adjacent glycan structure. In this study the N- and O-glycan composition of the human lung, bronchus and nasopharynx was characterized by mass spectrometry. Analysis showed that there was a wide spectrum of both Sia α2-3 and α2-6 glycans in the lung and bronchus. This glycan structural data was then utilized in combination with binding data from 4 of the published glycan arrays to assess whether these current glycan arrays were able to predict replication of human, avian and swine viruses in human ex vivo respiratory tract tissues. The most comprehensive array from the Consortium for Functional Glycomics contained the greatest diversity of sialylated glycans, but was not predictive of productive replication in the bronchus and lung. Our findings indicate that more comprehensive but focused arrays need to be developed to investigate influenza virus binding in an assessment of newly emerging influenza viruses.

  11. Edible bird's nest modulate intracellular molecular pathways of influenza A virus infected cells.

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    Haghani, Amin; Mehrbod, Parvaneh; Safi, Nikoo; Kadir, Fadzilah A'ini Abd; Omar, Abdul Rahman; Ideris, Aini

    2017-01-05

    Edible Bird's Nest (EBN) as a popular traditional Chinese medicine is believed to have health enhancing and antiviral activities against influenza A virus (IAV); however, the molecular mechanism behind therapeutic effects of EBN is not well characterized. In this study, EBNs that underwent different enzymatic preparation were tested against IAV infected cells. 50% cytotoxic concentration (CC 50 ) and 50% inhibitory concentration (IC 50 ) of the EBNs against IAV strain A/Puerto Rico/8/1934(H1N1) were determined by HA and MTT assays. Subsequently, the sialic acid content of the used EBNs were analyzed by fluorometric HPLC. Western Blotting and immunofluorescent staining were used to investigate the effects of EBNs on early endosomal trafficking and autophagy process of influenza virus. This study showed that post inoculations of EBNs after enzymatic preparations have the highest efficacy to inhibit IAV. While CC50 of the tested EBNs ranged from 27.5-32 mg/ml, the IC50 of these compounds ranged between 2.5-4.9 mg/ml. EBNs could inhibit IAV as efficient as commercial antiviral agents, such as amantadine and oseltamivir with different mechanisms of action against IAV. The antiviral activity of these EBNs correlated with the content of N-acetyl neuraminic acid. EBNs could affect early endosomal trafficking of the virus by reducing Rab5 and RhoA GTPase proteins and also reoriented actin cytoskeleton of IAV infected cells. In addition, for the first time this study showed that EBNs can inhibit intracellular autophagy process of IAV life cycle as evidenced by reduction of LC3-II and increasing of lysosomal degradation. The results procured in this study support the potential of EBNs as supplementary medication or alternative to antiviral agents to inhibit influenza infections. Evidently, EBNs can be a promising antiviral agent; however, these natural compounds should be screened for their metabolites prior to usage as therapeutic approach.

  12. Impact of aging and HIV infection on serologic response to seasonal influenza vaccination.

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    Pallikkuth, Suresh; De Armas, Lesley R; Pahwa, Rajendra; Rinaldi, Stefano; George, Varghese K; Sanchez, Celeste M; Pan, Li; Dickinson, Gordon; Rodriguez, Allan; Fischl, Margaret; Alcaide, Maria; Pahwa, Savita

    2018-02-08

    To determine influence of age and HIV infection on influenza vaccine responses. Evaluate serologic response to seasonal trivalent influenza vaccine (TIV) as the immunologic outcome in HIV-infected (HIV) and age-matched HIV negative (HIV) adults. During 2013-2016, 151 virologically controlled HIV individuals on antiretroviral therapy and 164 HIV volunteers grouped by age as young (<40 years), middle aged (40-59 years) and old (≥60 years) were administered TIV and investigated for serum antibody response to vaccine antigens. At prevaccination (T0) titers were in seroprotective range in more than 90% of participants. Antibody titers increased in all participants postvaccination but frequency of classified vaccine responders to individual or all three vaccine antigens at 3-4 weeks was higher in HIV than HIV adults with the greatest differences manifesting in the young age group. Of the three vaccine strains in TIV, antibody responses at T2 were weakest against H3N2 with those to H1N1 and B antigens dominating. Among the age groups, the titers for H1N1 and B were lowest in old age, with evidence of an age-associated interaction in HIV persons with antibody to B antigen. Greater frequencies of vaccine nonresponders are seen in HIV young compared with HIV adults and the observed age-associated interaction for B antigen in HIV persons are supportive of the concept of premature immune senescence in controlled HIV infection. High-potency influenza vaccination recommended for healthy aging could be considered for HIV adults of all ages.

  13. Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection.

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    Zosky, Graeme R; Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D

    2009-11-01

    The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10(4.5) plaque-forming units of influenza A/Mem/1/71 in 50 microl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-alpha, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

  14. Viral RNA Degradation and Diffusion Act as a Bottleneck for the Influenza A Virus Infection Efficiency.

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    Max Schelker

    2016-10-01

    Full Text Available After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. There, the viral glycoprotein hemagglutinin (HA triggers fusion between endosomal and viral membrane, a critical step that leads to release of the viral segmented genome destined to reach the cell nucleus. Endosomal maturation is a complex process involving acidification of the endosomal lumen as well as endosome motility along microtubules. While the pH drop is clearly critical for the conformational change and membrane fusion activity of HA, the effect of intracellular transport dynamics on the progress of infection remains largely unclear. In this study, we developed a comprehensive mathematical model accounting for the first steps of influenza virus infection. We calibrated our model with experimental data and challenged its predictions using recombinant viruses with altered pH sensitivity of HA. We identified the time point of virus-endosome fusion and thereby the diffusion distance of the released viral genome to the nucleus as a critical bottleneck for efficient virus infection. Further, we concluded and supported experimentally that the viral RNA is subjected to cytosolic degradation strongly limiting the probability of a successful genome import into the nucleus.

  15. 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.

  16. Impaired immune responses in the lungs of aged mice following influenza infection

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    Toapanta Franklin R

    2009-11-01

    Full Text Available Abstract Background Each year, influenza virus infection causes severe morbidity and mortality, particularly in the most susceptible groups including children, the elderly (>65 years-old and people with chronic respiratory diseases. Among the several factors that contribute to the increased susceptibility in elderly populations are the higher prevalence of chronic diseases (e.g. diabetes and the senescence of the immune system. Methods In this study, aged and adult mice were infected with sublethal doses of influenza virus (A/Puerto Rico/8/1934. Differences in weight loss, morbidity, virus titer and the kinetics of lung infiltration with cells of the innate and adaptive immune responses were analyzed. Additionally, the main cytokines and chemokines produced by these cells were also assayed. Results Compared to adult mice, aged mice had higher morbidity, lost weight more rapidly, and recovered more slowly from infection. There was a delay in the accumulation of granulocytic cells and conventional dendritic cells (cDCs, but not macrophages in the lungs of aged mice compared to adult animals. The delayed infiltration kinetics of APCs in aged animals correlated with alteration in their activation (CD40 expression, which also correlated with a delayed detection of cytokines and chemokines in lung homogenates. This was associated with retarded lung infiltration by natural killer (NK, CD4+ and CD8+ T-cells. Furthermore, the percentage of activated (CD69+ influenza-specific and IL-2 producer CD8+ T-cells was higher in adult mice compared to aged ones. Additionally, activation (CD69+ of adult B-cells was earlier and correlated with a quicker development of neutralizing antibodies in adult animals. Conclusion Overall, alterations in APC priming and activation lead to delayed production of cytokines and chemokines in the lungs that ultimately affected the infiltration of immune cells following influenza infection. This resulted in delayed activation of the

  17. Incidence of medically attended influenza infection and cases averted by vaccination, 2011/12 and 2012/13 influenza seasons

    Science.gov (United States)

    Jackson, Michael L.; Jackson, Lisa A.; Kieke, Burney; McClure, David; Gaglani, Manjusha; Murthy, Kempapura; Malosh, Ryan; Monto, Arnold; Zimmerman, Richard K.; Foppa, Ivo M.; Flannery, Brendan; Thompson, Mark G.

    2018-01-01

    Background We estimated the burden of outpatient influenza and cases prevented by vaccination during the 2011/12 and 2012/13 influenza seasons using data from the United States Influenza Vaccine Effectiveness (US Flu VE) Network. Methods We defined source populations of persons who could seek care for acute respiratory illness (ARI) at each of the five US Flu VE Network sites. We identified all members of the source population who were tested for influenza during US Flu VE influenza surveillance. Each influenza-positive subject received a sampling weight based on the proportion of source population members who were tested for influenza, stratified by site, age, and other factors. We used the sampling weights to estimate the cumulative incidence of medically attended influenza in the source populations. We estimated cases averted by vaccination using estimates of cumulative incidence, vaccine coverage, and vaccine effectiveness. Results Cumulative incidence of medically attended influenza ranged from 0.8% to 2.8% across sites during 2011/12 and from 2.6% to 6.5% during the 2012/13 season. Stratified by age, incidence ranged from 1.2% among adults 50 years of age and older in 2011/12 to 10.9% among children 6 months to 8 years of age in 2012/13. Cases averted by vaccination ranged from 4 to 41 per 1,000 vaccinees, depending on the study site and year. Conclusions The incidence of medically attended influenza varies greatly by year and even by geographic region within the same year. The number of cases averted by vaccination varies greatly based on overall incidence and on vaccine coverage. PMID:26271827

  18. Low pathogenicity avian influenza viruses infect chicken layers by different routes of inoculation.

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    Pantin-Jackwood, Mary J; Smith, Diane M; Wasilenko, Jamie L; Spackman, Erica

    2012-06-01

    In order to develop better control measures against avian influenza, it is necessary to understand how the virus transmits in poultry. In a previous study in which the infectivity and transmissibility of the pandemic H1N1 influenza virus was examined in different poultry species, we found that no or minimal infection occurred in chicken and turkeys intranasally (IN) inoculated with the virus. However, we demonstrated that the virus can infect laying turkey hens by the intracloacal (IC) and intraoviduct (IO) routes, possibly explaining the drops in egg production observed in turkey breeder farms affected by the virus. Such novel routes of exposure have not been previously examined in chickens and could also explain outbreaks of low pathogenicity avian influenza (LPAI) that cause a decrease in egg production in chicken layers and breeders. In the present study, 46-wk-old specific-pathogen-free chicken layers were infected by the IN, IC, or IO routes with one of two LPAI viruses: a poultry origin virus, A/chicken/CA/1255/02 (H6N2), and a live bird market isolate, A/chicken/NJ/12220/97 (H9N2). Only hens IN inoculated with the H6N2 virus presented mild clinical signs consisting of depression and anorexia. However, a decrease in number of eggs laid was observed in all virus-inoculated groups when compared to control hens. Evidence of infection was found in all chickens inoculated with the H6N2 virus by any of the three routes and the virus transmitted to contact hens. On the other hand, only one or two hens from each of the groups inoculated with the H9N2 virus shed detectable levels of virus, or seroconverted and did not transmit the virus to contacts, regardless of the route of inoculation. In conclusion, LPAI viruses can also infect chickens through other routes besides the IN route, which is considered the natural route of exposure. However, as seen with the H9N2 virus, the infectivity of the virus did not increase when given by these alternate routes.

  19. Multi-level intervention to prevent influenza infections in older low income and minority adults.

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    Schensul, Jean J; Radda, Kim; Coman, Emil; Vazquez, Elsie

    2009-06-01

    In this paper we describe a successful multi-level participatory intervention grounded in principles of individual and group empowerment, and guided by social construction theory. The intervention addressed known and persistent inequities in influenza vaccination among African American and Latino older adults, and associated infections, hospitalizations and mortality. It was designed to increase resident ability to make informed decisions about vaccination, and to build internal and external infrastructure to support sustainability over time. The intervention brought a group of social scientists, vaccine researchers, geriatricians, public health nurses, elder services providers and advocates together with senior housing management and activist African American and Latino residents living in public senior housing in a small east coast city. Two buildings of equal size and similar ethnic composition were randomized as intervention and control buildings. Pre and post intervention surveys were conducted in both buildings, measuring knowledge, attitudes and peer norms. Processes and outcomes were documented at four levels: Influenza Strategic Alliance (macro and exo levels), building management (meso level), building resident committee (meso level) and individual residents. The Influenza Strategic Alliance (I.S.A.) provided ongoing resources, information and vaccine; the building management provided economic and other in-kind resources and supported residents to continue flu clinics in the building. The V.I.P. Resident Committee conducted flu campaigns with flu clinics in English and Spanish. The vaccination rate in the intervention building at post test exceeded the study goal of 70% and showed a significant improvement over the control building. The intervention achieved desired outcomes at all four levels and resulted in a significant increase in influenza vaccination, and improvements in pro-vaccination knowledge, beliefs, and understanding of health consequences.

  20. 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.

  1. A cell culture-derived whole virus influenza A vaccine based on magnetic sulfated cellulose particles confers protection in mice against lethal influenza A virus infection.

    Science.gov (United States)

    Pieler, Michael M; Frentzel, Sarah; Bruder, Dunja; Wolff, Michael W; Reichl, Udo

    2016-12-07

    Downstream processing and formulation of viral vaccines employs a large number of different unit operations to achieve the desired product qualities. The complexity of individual process steps involved, the need for time consuming studies towards the optimization of virus yields, and very high requirements regarding potency and safety of vaccines results typically in long lead times for the establishment of new processes. To overcome such obstacles, to enable fast screening of potential vaccine candidates, and to explore options for production of low cost veterinary vaccines a new platform for whole virus particle purification and formulation based on magnetic particles has been established. Proof of concept was carried out with influenza A virus particles produced in suspension Madin Darby canine kidney (MDCK) cells. The clarified, inactivated, concentrated, and diafiltered virus particles were bound to magnetic sulfated cellulose particles (MSCP), and directly injected into mice for immunization including positive and negative controls. We show here, that in contrast to the mock-immunized group, vaccination of mice with antigen-loaded MSCP (aMSCP) resulted in high anti-influenza A antibody responses and full protection against a lethal challenge with replication competent influenza A virus. Antiviral protection correlated with a 400-fold reduced number of influenza nucleoprotein gene copies in the lungs of aMSCP immunized mice compared to mock-treated animals, indicating the efficient induction of antiviral immunity by this novel approach. Thus, our data proved the use of MSCP for purification and formulation of the influenza vaccine to be fast and efficient, and to confer protection of mice against influenza A virus infection. Furthermore, the method proposed has the potential for fast purification of virus particles directly from bioreactor harvests with a minimum number of process steps towards formulation of low-cost veterinary vaccines, and for screening

  2. 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.

  3. Serial Head and Brain Imaging of 17 Fetuses With Confirmed Zika Virus Infection in Colombia, South America.

    Science.gov (United States)

    Parra-Saavedra, Miguel; Reefhuis, Jennita; Piraquive, Juan Pablo; Gilboa, Suzanne M; Badell, Martina L; Moore, Cynthia A; Mercado, Marcela; Valencia, Diana; Jamieson, Denise J; Beltran, Mauricio; Sanz-Cortes, Magda; Rivera-Casas, Ana Maria; Yepez, Mayel; Parra, Guido; Ospina Martinez, Martha; Honein, Margaret A

    2017-07-01

    To evaluate fetal ultrasound and magnetic resonance imaging findings among a series of pregnant women with confirmed Zika virus infection to evaluate the signs of congenital Zika syndrome with respect to timing of infection. We conducted a retrospective case series of pregnant women referred to two perinatal clinics in Barranquilla and Ibagué, Colombia, who had findings consistent with congenital Zika syndrome and Zika virus infection confirmed in maternal, fetal, or neonatal samples. Serial ultrasound measurements, fetal magnetic resonance imaging results, laboratory results, and perinatal outcomes were evaluated. We describe 17 cases of confirmed prenatal maternal Zika virus infection with adverse fetal outcomes. Among the 14 symptomatic women, the median gestational age for maternal Zika virus symptoms was 10 weeks (range 7-14 weeks of gestation). The median time between Zika virus symptom onset and microcephaly (head circumference less than 3 standard deviations below the mean) was 18 weeks (range 15-24 weeks). The earliest fetal head circumference measurement consistent with microcephaly diagnosis was at 24 weeks of gestation. The earliest sign of congenital Zika syndrome was talipes equinovarus, which in two patients was noted first at 19 weeks of gestation. Common findings on fetal magnetic resonance imaging were microcephaly, ventriculomegaly, polymicrogyria, and calcifications. Our analysis suggests a period of at least 15 weeks between maternal Zika virus infection in pregnancy and development of microcephaly and highlights the importance of serial and detailed neuroimaging.

  4. Early indication for a reduced burden of radiologically confirmed pneumonia in children following the introduction of routine vaccination against Haemophilus influenzae type b in Nha Trang, Vietnam.

    Science.gov (United States)

    Flasche, Stefan; Takahashi, Kensuke; Vu, Dinh Thiem; Suzuki, Motoi; Nguyen, Thi Hien-Anh; Le, HuuTho; Hashizume, Masahiro; Dang, Duc Anh; Edmond, Karen; Ariyoshi, Koya; Mulholland, E Kim; Edmunds, W John; Yoshida, Lay-Myint

    2014-12-05

    Despite the global success of Hib vaccination in reducing disease and mortality, uncertainty about the disease burden and the potential impact of Hib vaccination in Southeast Asia has delayed the introduction of vaccination in some countries in the region. Hib vaccination was introduced throughout Vietnam in July 2010 without catch-up. In an observational, population based surveillance study we estimated the impact of routine Hib vaccination on all cause radiologically confirmed childhood pneumonia in Nha Trang, Vietnam. In 2007 active hospital based surveillance was established in Khanh Hoa General Hospital, the only hospital in Nha Trang, Khanh Hoa province. Nasopharyngeal samples and chest radiographs are taken routinely from all children diagnosed with acute respiratory illness on admission. For admissions between 02/2007 and 03/2012 chest radiographs were interpreted for the presence of WHO primary endpoint pneumonia and nasopharyngeal swabs were analysed by PCR for the presence of Influenza A or B, RSV and rhinovirus. We employed Poisson regression to estimate the impact of Hib vaccination on radiologically confirmed pneumonia (RCP) while statistically accounting for potential differences in viral circulation in the post vaccination era which could have biased the estimate. Of 3151 cases admitted during the study period, 166 had RCP and major viruses were detected in 1601. The adjusted annual incidence of RCP in children younger than 5 years declined by 39% (12-58%) after introduction of Hib vaccination. This decline was most pronounced in children less than 2 years old, adjusted IRR: 0.52 (0.33-0.81), and no significant impact was observed in the 2-4 years old who were not eligible for vaccination, adjusted IRR: 0.96 (0.52-1.72). We present early evidence that the burden of Hib associated RCP in Nha Trang before vaccination was substantial and that shortly after introduction to the routine childhood immunisation scheme vaccination has substantially reduced

  5. 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

  6. 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

  7. 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

  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. Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

    Science.gov (United States)

    Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

    2015-01-01

    Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

  10. Seventeen years of subcutaneous infection by Aspergillus flavus; eumycetoma confirmed by immunohistochemistry

    NARCIS (Netherlands)

    Ahmed, Sarah A; Abbas, Manal A; Jouvion, Gregory; Al-Hatmi, Abdullah M S; de Hoog, G Sybren; Kolecka, Anna; Mahgoub, El Sheikh

    2015-01-01

    Chronic subcutaneous infections caused by Aspergillus species are considered to be extremely rare. Because these fungi are among the most common laboratory contaminants, their role as eumycetoma causative agents is difficult to ascertain. Here, we report the first case of A. flavus eumycetoma

  11. Endogenous Murine BST-2/Tetherin Is Not a Major Restriction Factor of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Sarah L Londrigan

    Full Text Available BST-2 (tetherin, CD317, HM1.24 restricts virus growth by tethering enveloped viruses to the cell surface. The role of BST-2 during influenza A virus infection (IAV is controversial. Here, we assessed the capacity of endogenous BST-2 to restrict IAV in primary murine cells. IAV infection increased BST-2 surface expression by primary macrophages, but not alveolar epithelial cells (AEC. BST-2-deficient AEC and macrophages displayed no difference in susceptibility to IAV infection relative to wild type cells. Furthermore, BST-2 played little role in infectious IAV release from either AEC or macrophages. To examine BST-2 during IAV infection in vivo, we infected BST-2-deficient mice. No difference in weight loss or in viral loads in the lungs and/or nasal tissues were detected between BST-2-deficient and wild type animals. This study rules out a major role for endogenous BST-2 in modulating IAV in the mouse model of infection.

  12. Can preening contribute to influenza A virus infection in wild waterbirds?

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    Mauro Delogu

    Full Text Available Wild aquatic birds in the Orders Anseriformes and Charadriiformes are the main reservoir hosts perpetuating the genetic pool of all influenza A viruses, including pandemic viruses. High viral loads in feces of infected birds permit a fecal-oral route of transmission. Numerous studies have reported the isolation of avian influenza viruses (AIVs from surface water at aquatic bird habitats. These isolations indicate aquatic environments have an important role in the transmission of AIV among wild aquatic birds. However, the progressive dilution of infectious feces in water could decrease the likelihood of virus/host interactions. To evaluate whether alternate mechanisms facilitate AIV transmission in aquatic bird populations, we investigated whether the preen oil gland secretions by which all aquatic birds make their feathers waterproof could support a natural mechanism that concentrates AIVs from water onto birds' bodies, thus, representing a possible source of infection by preening activity. We consistently detected both viral RNA and infectious AIVs on swabs of preened feathers of 345 wild mallards by using reverse transcription-polymerase chain reaction (RT-PCR and virus-isolation (VI assays. Additionally, in two laboratory experiments using a quantitative real-time (qR RT-PCR assay, we demonstrated that feather samples (n = 5 and cotton swabs (n = 24 experimentally impregnated with preen oil, when soaked in AIV-contaminated waters, attracted and concentrated AIVs on their surfaces. The data presented herein provide information that expands our understanding of AIV ecology in the wild bird reservoir system.

  13. Prion protein protects mice from lethal infection with influenza A viruses.

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    Junji Chida

    2018-05-01

    Full Text Available The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT mice, PrPC-null mice (Prnp0/0 were highly susceptible to influenza A viruses (IAVs, with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO, a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR region, Tg(PrPΔOR/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPΔOR/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics.

  14. Genetic Reassortment Among the Influenza Viruses (Avian Influenza, Human Influenza and Swine Influenza in Pigs

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    Dyah Ayu Hewajuli

    2012-12-01

    Full Text Available Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries for 80 years. In 1998, triple reassortant H3N2 swine influenza viruses that contains genes of human influenza A virus (H3N2, swine influenza virus (H1N1 and avian influenza are reported as cause an outbreaks in pigs in North America. Furthermore, the circulation of triple reassortant H3N2 swine influenza virus resulting reassortant H1N1 swine influenza and reassortant H1N2 swine influenza viruses cause infection in humans. Humans who were infected by triple reassortant swine influenza A virus (H1N1 usually made direct contact with pigs. Although without any clinical symptoms, pigs that are infected by triple reassortant swine influenza A (H1N1 can transmit infection to the humans around them. In June 2009, WHO declared that pandemic influenza of reassortant H1N1 influenza A virus (novel H1N1 has reached phase 6. In Indonesia until 2009, there were 1005 people were infected by H1N1 influenza A and 5 of them died. Novel H1N1 and H5N1 viruses have been circulated in humans and pigs in Indonesia. H5N1 reassortant and H1N1 viruses or the seasonal flu may could arise because of genetic reassortment between avian influenza and humans influenza viruses that infect pigs together.

  15. Effect of low-pathogenicity influenza virus H3N8 infection on Mycoplasma gallisepticum infection of chickens.

    Science.gov (United States)

    Stipkovits, Laszlo; Egyed, Laszlo; Palfi, Vilmos; Beres, Andrea; Pitlik, Ervin; Somogyi, Maria; Szathmary, Susan; Denes, Bela

    2012-01-01

    Mycoplasma infection is still very common in chicken and turkey flocks. Several low-pathogenicity avian influenza (LPAI) viruses are circulating in wild birds that can be easily transmitted to poultry flocks. However, the effect of LPAI on mycoplasma infection is not well understood. The aim of the present study was to investigate the infection of LPAI virus H3N8 (A/mallard/Hungary/19616/07) in chickens challenged with Mycoplasma gallisepticum. Two groups of chickens were aerosol challenged with M. gallisepticum. Later one of these groups and one mycoplasma-free group were aerosol challenged with the LPAI H3N8 virus. The birds were observed for clinical signs for 8 days, then euthanized, and examined for the presence of M. gallisepticum in the trachea, lung, air sac, liver, spleen, kidney and heart, and for developing anti-mycoplasma and anti-viral antibodies. The LPAI H3N8 virus did not cause any clinical signs but M. gallisepticum infection caused clinical signs, reduction of body weight gain and colonization of the inner organs. These parameters were more severe in the birds co-infected with M. gallisepticum and LPAI H3N8 virus than in the group challenged with M. gallisepticum alone. In addition, in the birds infected with both M. gallisepticum and LPAI H3N8 virus, the anti-mycoplasma antibody response was reduced significantly when compared with the group challenged with M. gallisepticum alone. Co-infection with LPAI H3N8 virus thus enhanced pathogenesis of M. gallisepticum infection significantly.

  16. Avian influenza A virus and Newcastle disease virus mono- and co-infections in birds

    Directory of Open Access Journals (Sweden)

    Iv. Zarkov

    2017-06-01

    Full Text Available The main features of avian influenza viruses (AIV and Newcastle disease virus (APMV-1, the possibilities for isolation and identification in laboratory conditions, methods of diagnostics, main hosts, clinical signs and virus shedding are reviewed in chronological order. The other part of the review explains the mechanisms and interactions in cases of co-infection of AIV and APMV-1, either between them or with other pathogens in various indicator systems – cell cultures, chick embryos or birds. The emphasis is placed on quantitative data on the virus present mainly in the first ten days following experimental infection of birds, the periods of virus carrier ship and shedding, clinical signs, pathological changes, diagnostic challenges

  17. Infection of the upper respiratory tract with seasonal influenza A(H3N2) virus induces protective immunity in ferrets against infection with A(H1N1)pdm09 virus after intranasal, but not intratracheal, inoculation

    NARCIS (Netherlands)

    R. Bodewes (Rogier); J.H.C.M. Kreijtz (Joost); G. van Amerongen (Geert); M.L.B. Hillaire (Marine); S.E. Vogelzang-van Trierum (Stella ); N. Nieuwkoop; P. van Run (Peter); T. Kuiken (Thijs); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); G.F. Rimmelzwaan (Guus)

    2013-01-01

    textabstractThe clinical symptoms caused by infection with influenza A virusvary widely and depend on the strain causing the infection, the dose and route of inoculation, and the presence of preexisting immunity. In most cases, seasonal influenza A viruses cause relatively mild upper respiratory

  18. Distribution of sialic acid receptors and influenza A virus of avian and swine origin in experimentally infected pigs

    Directory of Open Access Journals (Sweden)

    Viuff Birgitte M

    2011-09-01

    Full Text Available Abstract Background Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SA-alpha-2,3 and swine/human (SA-alpha-2,6 influenza viruses in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. Methods This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA I, and II, and Sambucus Nigra (SNA. Furthermore, the predilection sites of swine influenza virus (SIV subtypes H1N1 and H1N2 as well as avian influenza virus (AIV subtype H4N6 were investigated in the respiratory tract of experimentally infected pigs using immunohistochemical methods. Results SIV antigen was widely distributed in bronchi, but was also present in epithelial cells of the nose, trachea, bronchioles, and alveolar type I and II epithelial cells in severely affected animals. AIV was found in the lower respiratory tract, especially in alveolar type II epithelial cells and occasionally in bronchiolar epithelial cells. SA-alpha-2,6 was the predominant receptor in all areas of the respiratory tract with an average of 80-100% lining at the epithelial cells. On the contrary, the SA-alpha-2,3 was not present (0% at epithelial cells of nose, trachea, and most bronchi, but was found in small amounts in bronchioles, and in alveoli reaching an average of 20-40% at the epithelial cells. Interestingly, the receptor expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza infected areas compared to non-infected areas. Conclusions A difference in predilection sites between SIV and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated

  19. 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.

  20. Aryl Hydrocarbon Receptor Activation Reduces Dendritic Cell Function during Influenza Virus Infection

    Science.gov (United States)

    Jin, Guang-Bi; Moore, Amanda J.; Head, Jennifer L.; Neumiller, Joshua J.; Lawrence, B. Paige

    2010-01-01

    It has long been known that activation of the aryl hydrocarbon receptor (AhR) by ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses T cell–dependent immune responses; however, the underlying cellular targets and mechanism remain unclear. We have previously shown that AhR activation by TCDD reduces the proliferation and differentiation of influenza virus–specific CD8+ T cells through an indirect mechanism; suggesting that accessory cells are critical AhR targets during infection. Respiratory dendritic cells (DCs) capture antigen, migrate to lymph nodes, and play a key role in activating naive CD8+ T cells during respiratory virus infection. Herein, we report an examination of how AhR activation alters DCs in the lung and affects their trafficking to and function in the mediastinal lymph nodes (MLN) during infection with influenza virus. We show that AhR activation impairs lung DC migration and reduces the ability of DCs isolated from the MLN to activate naive CD8+ T cells. Using novel AhR mutant mice, in which the AhR protein lacks its DNA-binding domain, we show that the suppressive effects of TCDD require that the activated AhR complex binds to DNA. These new findings suggest that AhR activation by chemicals from our environment impacts DC function to stimulate naive CD8+ T cells and that immunoregulatory genes within DCs are critical targets of AhR. Moreover, our results reinforce the idea that environmental signals and AhR ligands may contribute to differential susceptibilities and responses to respiratory infection. PMID:20498003

  1. Oral intake of Lactobacillus rhamnosus M21 enhances the survival rate of mice lethally infected with influenza virus.

    Science.gov (United States)

    Song, Jeong Ah; Kim, Hee Joo; Hong, Seong Keun; Lee, Dong Hoon; Lee, Sang Won; Song, Chang Seon; Kim, Ki Taek; Choi, In Soo; Lee, Joong Bok; Park, Seung Yong

    2016-02-01

    Influenza viruses cause acute respiratory disease. Because of the high genetic variability of viruses, effective vaccines and antiviral agents are limited. Considering the fact that the site of influenza virus entry is the mucosa of the upper respiratory tract, probiotics that can enhance mucosal immunity as well as systemic immunity could be an important source of treatment against influenza infection. Mice were fed with Lactobacillus rhamnosus M21 or skim milk and were challenged with influenza virus. The resulting survival rate, lung inflammation, and changes in the cytokine and secretory immunoglobulin A (sIgA) levels were examined. Because of infection (influenza virus), all the mice in the control group and 60% of the mice in the L. rhamnosus M21 group died; however, the remaining 40% of the mice fed with L. rhamnosus M21 survived the infection. Pneumonia was severe in the control group but moderate in the group treated with L. rhamnosus M21. Although there were no significant changes in the proinflammatory cytokines in the lung lysates of mice collected from both groups, levels of interferon-γ and interleukin-2, which are representative cytokines of type I helper T cells, were significantly increased in the L. rhamnosus M21-treated group. An increase in sIgA as well as the diminution of inflammatory cells in bronchoalveolar lavage fluid was also observed in the L. rhamnosus M21-treated group. These results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection. Copyright © 2014. Published by Elsevier B.V.

  2. A20 (Tnfaip3 deficiency in myeloid cells protects against influenza A virus infection.

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    Jonathan Maelfait

    Full Text Available The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-κB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.

  3. Heterosubtypic immunity to influenza A virus infections in mallards may explain existence of multiple virus subtypes.

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    Neus Latorre-Margalef

    Full Text Available Wild birds, particularly duck species, are the main reservoir of influenza A virus (IAV in nature. However, knowledge of IAV infection dynamics in the wild bird reservoir, and the development of immune responses, are essentially absent. Importantly, a detailed understanding of how subtype diversity is generated and maintained is lacking. To address this, 18,679 samples from 7728 Mallard ducks captured between 2002 and 2009 at a single stopover site in Sweden were screened for IAV infections, and the resulting 1081 virus isolates were analyzed for patterns of immunity. We found support for development of homosubtypic hemagglutinin (HA immunity during the peak of IAV infections in the fall. Moreover, re-infections with the same HA subtype and related prevalent HA subtypes were uncommon, suggesting the development of natural homosubtypic and heterosubtypic immunity (p-value = 0.02. Heterosubtypic immunity followed phylogenetic relatedness of HA subtypes, both at the level of HA clades (p-value = 0.04 and the level of HA groups (p-value = 0.05. In contrast, infection patterns did not support specific immunity for neuraminidase (NA subtypes. For the H1 and H3 Clades, heterosubtypic immunity showed a clear temporal pattern and we estimated within-clade immunity to last at least 30 days. The strength and duration of heterosubtypic immunity has important implications for transmission dynamics of IAV in the natural reservoir, where immune escape and disruptive selection may increase HA antigenic variation and explain IAV subtype diversity.

  4. Analysis of nuclear accumulation of influenza NP antigen in von Magnus virus-infected cells.

    Science.gov (United States)

    Maeno, K; Aoki, H; Hamaguchi, M; Iinuma, M; Nagai, Y; Matsumoto, T; Takeura, S; Shibata, M

    1981-01-01

    When 1-5C-4 cells were infected with von Magnus virus derived from influenza A/RI/5+ virus by successive undiluted passages in chick embryos, virus-specific proteins were synthesized but production of infectious virus was inhibited. In these cells the synthesis of viral RNA was suppressed and the nucleoprotein (NP) antigen was found predominantly in the nucleus in contrast to standard virus-infected cells in which the antigen was distributed throughout the whole cell. The intracellular location and migration of NP were determined by isotope labeling and sucrose gradient centrifugation of subcellular fractions. In standard virus-infected cell NP polypeptide was present predominantly in the cytoplasm in the form of viral ribonucleoprotein (RNP) and intranuclear RNP was detected in reduced amounts. In contrast, in von Magnus virus-infected cells NP polypeptide was present predominantly in the nucleus in a nonassembled, soluble from and the amount of cytoplasmic RNP was considerably reduced. After short-pulse labeling NP was detected exclusively in the cytoplasm in a soluble form and after a chase a large proportion of such soluble NP was seen in the nucleus. It is suggested that a large proportion of the NP synthesized in von Magnus virus-infected cells in not assembled into cytoplasmic RNP because of the lack of available RNA and the NP migrated into the nucleus and remained there.

  5. The onset of virus shedding and clinical signs in chickens infected with high-pathogenicity and low-pathogenicity avian influenza viruses.

    Science.gov (United States)

    Spickler, Anna R; Trampel, Darrell W; Roth, James A

    2008-12-01

    Some avian influenza viruses may be transmissible to mammals by ingestion. Cats and dogs have been infected by H5N1 avian influenza viruses when they ate raw poultry, and two human H5N1 infections were linked to the ingestion of uncooked duck blood. The possibility of zoonotic influenza from exposure to raw poultry products raises concerns about flocks with unrecognized infections. The present review examines the onset of virus shedding and the development of clinical signs for a variety of avian influenza viruses in chickens. In experimentally infected birds, some high-pathogenicity avian influenza (HPAI) and low-pathogenicity avian influenza (LPAI) viruses can occur in faeces and respiratory secretions as early as 1 to 2 days after inoculation. Some HPAI viruses have also been found in meat 1 day after inoculation and in eggs after 3 days. There is no evidence that LPAI viruses can be found in meat, and the risk of their occurrence in eggs is poorly understood. Studies in experimentally infected birds suggest that clinical signs usually develop within a few days of virus shedding; however, some models and outbreak descriptions suggest that clinical signs may not become evident for a week or more in some H5 or H7 HPAI-infected flocks. During this time, avian influenza viruses might be found in poultry products. LPAI viruses can be shed in asymptomatically infected or minimally affected flocks, but these viruses are unlikely to cause significant human disease.

  6. Strategies for differentiating infection in vaccinated animals (DIVA) for foot-and-mouth disease, classical swine fever and avian influenza

    DEFF Research Database (Denmark)

    Uttenthal, Åse; Parida, Satya; Rasmussen, Thomas Bruun

    2010-01-01

    for the presence of infection. This literature review describes the current knowledge on the use of DIVA diagnostic strategies for three important transboundary animal diseases: foot-and-mouth disease in cloven-hoofed animals, classical swine fever in pigs and avian influenza in poultry....

  7. Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection

    International Nuclear Information System (INIS)

    Chapman, Timothy J.; Castrucci, Maria R.; Padrick, Ryan C.; Bradley, Linda M.; Topham, David J.

    2005-01-01

    To track epitope-specific CD4 + T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA 323-339 epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVA II , replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4 + T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4 + T cells were recruited to the infected lung both in the presence and absence of the OVA 323-339 epitope. These data show that, when primed, CD4 + T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection

  8. Distribution of sialic acid receptors and influenza A viruses of avian and swine origin and in experimentally infected pigs

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Larsen, Lars Erik; Viuff, Birgitte M.

    2011-01-01

    Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses in the up......Background: Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SAalpha- 2,3)) and swine/human (SA-alpha-2,6) influenza viruses...... and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated that the distribution of influenza A virus receptors in pigs are similar to that of humans and therefore challenge the theory that the pig...

  9. Primary cytomegalovirus infection in pregnant Egyptian women confirmed by cytomegalovirus IgG avidity testing.

    Science.gov (United States)

    Kamel, N; Metwally, L; Gomaa, N; Sayed Ahmed, W A; Lotfi, M; Younis, S

    2014-01-01

    To determine the frequency of primary cytomegalovirus (CMV) infection in pregnant Egyptian women using CMV IgG avidity testing. A cross-sectional study was conducted at Suez Canal University Hospital, Ismailia, Egypt. A total of 546 pregnant women, presenting for routine antenatal screening, were tested for CMV IgG and IgM using a commercially available enzyme-linked immunosorbent assay (ELISA). Sera from CMV IgM-positive women were tested by CMV IgG avidity assay. All the 546 pregnant women were seropositive for anti-CMV IgG. Of the 546 women, 40 (7.3%) were positive or equivocal for IgM antibodies. All sera from the 40 women (IgG+/IgM+) showed a high or intermediate CMV IgG avidity index. Of the 40 women, 23 (57.5%) were in the second or third trimesters of pregnancy and had their first-trimester blood retrieved, and the tested CMV IgG avidity assay showed a high avidity index. Women who were IgM positive had no primary CMV infection in the index pregnancy as evidenced by the high CMV IgG avidity testing. © 2013 S. Karger AG, Basel.

  10. Confirming Sterility of an Autoclaved Infected Femoral Component for Use in an Articulated Antibiotic Knee Spacer: A Pilot Study.

    Science.gov (United States)

    Lyons, Steven T; Wright, Coy A; Krute, Christina N; Rivera, Frances E; Carroll, Ronan K; Shaw, Lindsey N

    2016-01-01

    Antibiotic spacer designs have proven effective at eradicating infection during a two-stage revision arthroplasty. Temporary reuse of the steam-sterilized femoral component and a new all poly tibia component has been described as an effective articulating antibiotic spacer, but sterility concerns persist. Six explanted cobalt chrome femurs from patients with grossly infected TKA's and six stock femurs inoculated with different bacterial species were confirmed to be bacteria-free after autoclaving under a standard gravity-displacement cycle. The effect of steam sterilization on cobalt chrome fragments contaminated with MRSA biofilm was analyzed microscopically to quantify remaining biofilm. The autoclave significantly reduced the biofilm burden on the cobalt chrome fragments. This study confirmed sterility of the femur after a standard gravity-displacement cycle (132°C, 27 PSIG, 10 minutes). Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

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

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    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.

  13. Influenza A virus infection of healthy piglets in an abattoir in Brazil: animal-human interface and risk for interspecies transmission

    Directory of Open Access Journals (Sweden)

    Ariane Ribeiro Amorim

    2013-08-01

    Full Text Available Asymptomatic influenza virus infections in pigs are frequent and the lack of measures for controlling viral spread facilitates the circulation of different virus strains between pigs. The goal of this study was to demonstrate the circulation of influenza A virus strains among asymptomatic piglets in an abattoir in Brazil and discuss the potential public health impacts. Tracheal samples (n = 330 were collected from asymptomatic animals by a veterinarian that also performed visual lung tissue examinations. No slaughtered animals presented with any noticeable macroscopic signs of influenza infection following examination of lung tissues. Samples were then analysed by reverse transcription-polymerase chain reaction that resulted in the identification of 30 (9% influenza A positive samples. The presence of asymptomatic pig infections suggested that these animals could facilitate virus dissemination and act as a source of infection for the herd, thereby enabling the emergence of influenza outbreaks associated with significant economic losses. Furthermore, the continuous exposure of the farm and abattoir workers to the virus increases the risk for interspecies transmission. Monitoring measures of swine influenza virus infections and vaccination and monitoring of employees for influenza infection should also be considered. In addition regulatory agencies should consider the public health ramifications regarding the potential zoonotic viral transmission between humans and pigs.

  14. Retrospective multicenter matched case-control study on the risk factors for narcolepsy with special focus on vaccinations (including pandemic influenza vaccination) and infections in Germany.

    Science.gov (United States)

    Oberle, Doris; Pavel, Jutta; Mayer, Geert; Geisler, Peter; Keller-Stanislawski, Brigitte

    2017-06-01

    Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible. Case report forms were validated according to the criteria for narcolepsy defined by the Brighton Collaboration (BC). Confirmed cases of narcolepsy (BC level of diagnostic certainty 1-4a) were matched with population-based controls by year of birth, gender, and place of residence. A second control group was established including patients in whom narcolepsy was definitely excluded (test-negative controls). A total of 103 validated cases of narcolepsy were matched with 264 population-based controls. The second control group included 29 test-negative controls. A significantly increased odd ratio (OR) to develop narcolepsy (crude OR [cOR] = 3.9, 95% confidence interval [CI] = 1.8-8.5; adjusted OR [aOR] = 4.5, 95% CI = 2.0-9.9) was detected in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset as compared to nonvaccinated individuals. Using test-negative controls, in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset, a nonsignificantly increased OR of narcolepsy was detected when compared to nonvaccinated individuals (whole study population, BC levels 1-4a: cOR = 1.9, 95% CI = 0.5-6.9; aOR = 1.8, 95% CI = 0.3-10.1). The findings of this study support an increased risk for narcolepsy after immunization with pandemic influenza A/H1N1/v vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. CD151, a novel host factor of nuclear export signaling in influenza virus infection.

    Science.gov (United States)

    Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

    2018-05-01

    Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China.

    Science.gov (United States)

    Ke, Changwen; Mok, Chris Ka Pun; Zhu, Wenfei; Zhou, Haibo; He, Jianfeng; Guan, Wenda; Wu, Jie; Song, Wenjun; Wang, Dayan; Liu, Jiexiong; Lin, Qinhan; Chu, Daniel Ka Wing; Yang, Lei; Zhong, Nanshan; Yang, Zifeng; Shu, Yuelong; Peiris, Joseph Sriyal Malik

    2017-07-01

    The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient's adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.

  17. Club cells surviving influenza A virus infection induce temporary nonspecific antiviral immunity.

    Science.gov (United States)

    Hamilton, Jennifer R; Sachs, David; Lim, Jean K; Langlois, Ryan A; Palese, Peter; Heaton, Nicholas S

    2016-04-05

    A brief window of antigen-nonspecific protection has been observed after influenza A virus (IAV) infection. Although this temporary immunity has been assumed to be the result of residual nonspecific inflammation, this period of induced immunity has not been fully studied. Because IAV has long been characterized as a cytopathic virus (based on its ability to rapidly lyse most cell types in culture), it has been a forgone conclusion that directly infected cells could not be contributing to this effect. Using a Cre recombinase-expressing IAV, we have previously shown that club cells can survive direct viral infection. We show here not only that these cells can eliminate all traces of the virus and survive but also that they acquire a heightened antiviral response phenotype after surviving. Moreover, we experimentally demonstrate temporary nonspecific viral immunity after IAV infection and show that surviving cells are required for this phenotype. This work characterizes a virally induced modulation of the innate immune response that may represent a new mechanism to prevent viral diseases.

  18. Investigation of avian influenza infection in wild birds in Ismailia and Damietta cities, Egypt

    Science.gov (United States)

    Fadel, Hanaa Mohamed; Afifi, Rabab

    2017-01-01

    Aim: This study was carried out to monitor avian influenza (AI) infection in wild birds in Egypt. Materials and Methods: A total of 135 wild birds were examined for the presence of H5, H7, and H9 hemagglutination inhibition antibodies. Organs and swab samples of 75 birds were screened by multiplex real-time reverse transcriptase-polymerase chain reaction (RRT-PCR) to detect AI subtypes H5, H7, and H9 matrix genes. Results: The highest seropositive result was recorded in cattle egrets (90.9%) followed by crows (88.6%), semi-captive pigeons (44.8%), and moorhens (39.1%). In cattle egrets, semi-captive pigeons and moorhens, H5 antibodies predominated. In crows, H9 antibodies predominated. Multiple infections with two or three virus subtypes were highest in crows (6/39, 15.4%) followed by cattle egrets (3/30, 10%) and moorhens’ (1/9, 11.1%) positive samples. Multiplex RRT-PCR results revealed two positive samples in cattle egrets and moorhens. Conclusion: The results indicated high seropositive rates against AI virus subtypes H5 and H9 in the examined wild birds. Multiple infections with more than one AI virus (AIV) subtypes were detected in some birds. This requires a collaboration of efforts to monitor AIV infection in wild birds and implement suitable early intervention measures. PMID:28717324

  19. Serological response to the 2009 pandemic influenza A (H1N1 virus for disease diagnosis and estimating the infection rate in Thai population.

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    Hatairat Lerdsamran

    Full Text Available BACKGROUND: Individuals infected with the 2009 pandemic virus A(H1N1 developed serological response which can be measured by hemagglutination-inhibition (HI and microneutralization (microNT assays. METHODOLOGY/PRINCIPAL FINDINGS: MicroNT and HI assays for specific antibody to the 2009 pandemic virus were conducted in serum samples collected at the end of the first epidemic wave from various groups of Thai people: laboratory confirmed cases, blood donors and health care workers (HCW in Bangkok and neighboring province, general population in the North and the South, as well as archival sera collected at pre- and post-vaccination from vaccinees who received influenza vaccine of the 2006 season. This study demonstrated that goose erythrocytes yielded comparable HI antibody titer as compared to turkey erythrocytes. In contrast to the standard protocol, our investigation found out the necessity to eliminate nonspecific inhibitor present in the test sera by receptor destroying enzyme (RDE prior to performing microNT assay. The investigation in pre-pandemic serum samples showed that HI antibody was more specific to the 2009 pandemic virus than NT antibody. Based on data from pre-pandemic sera together with those from the laboratory confirmed cases, HI antibody titers ≥ 40 for adults and ≥ 20 for children could be used as the cut-off level to differentiate between the individuals with or without past infection by the 2009 pandemic virus. CONCLUSIONS/SIGNIFICANCE: Based on the cut-off criteria, the infection rates of 7 and 12.8% were estimated in blood donors and HCW, respectively after the first wave of the 2009 influenza pandemic. Among general population, the infection rate of 58.6% was found in children versus 3.1% in adults.

  20. Differential sensitivity of bat cells to infection by enveloped RNA viruses: coronaviruses, paramyxoviruses, filoviruses, and influenza viruses.

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    Markus Hoffmann

    Full Text Available Bats (Chiroptera host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat or Yangochiroptera (genera Carollia and Tadarida for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV, a porcine coronavirus, or to infection mediated by the Spike (S protein of SARS-coronavirus (SARS-CoV incorporated into pseudotypes based on vesicular stomatitis virus (VSV. The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3 were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.

  1. 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.

  2. 18S rRNA is a reliable normalisation gene for real time PCR based on influenza virus infected cells

    Directory of Open Access Journals (Sweden)

    Kuchipudi Suresh V

    2012-10-01

    Full Text Available Abstract Background One requisite of quantitative reverse transcription PCR (qRT-PCR is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses. To date no detailed study has been described that compares the suitability of commonly used housekeeping genes in influenza virus infections. The present study evaluated several commonly used housekeeping genes [ACTB, GAPDH, 18S ribosomal RNA (18S rRNA, ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9 (ATP5G1] to identify the most stably expressed gene in human, pig, chicken and duck cells infected with a range of influenza A virus subtypes. Results The relative expression stability of commonly used housekeeping genes were determined in primary human bronchial epithelial cells (HBECs, pig tracheal epithelial cells (PTECs, and chicken and duck primary lung-derived cells infected with five influenza A virus subtypes. Analysis of qRT-PCR data from virus and mock infected cells using NormFinder and BestKeeper software programmes found that 18S rRNA was the most stable gene in HBECs, PTECs and avian lung cells. Conclusions Based on the presented data from cell culture models (HBECs, PTECs, chicken and duck lung cells infected with a range of influenza viruses, we found that 18S rRNA is the most stable reference gene for normalising qRT-PCR data. Expression levels of the other housekeeping genes evaluated in this study (including ACTB and GPADH were highly affected by influenza virus infection and

  3. Reduction in the incidence of influenza A but not influenza B associated with use of hand sanitizer and cough hygiene in schools: a randomized controlled trial.

    Science.gov (United States)

    Stebbins, Samuel; Cummings, Derek A T; Stark, James H; Vukotich, Chuck; Mitruka, Kiren; Thompson, William; Rinaldo, Charles; Roth, Loren; Wagner, Michael; Wisniewski, Stephen R; Dato, Virginia; Eng, Heather; Burke, Donald S

    2011-11-01

    Laboratory-based evidence is lacking regarding the efficacy of nonpharmaceutical interventions (NPIs) such as alcohol-based hand sanitizer and respiratory hygiene to reduce the spread of influenza. The Pittsburgh Influenza Prevention Project was a cluster-randomized trial conducted in 10 elementary schools in Pittsburgh, PA, during the 2007 to 2008 influenza season. Children in 5 intervention schools received training in hand and respiratory hygiene, and were provided and encouraged to use hand sanitizer regularly. Children in 5 schools acted as controls. Children with influenza-like illness were tested for influenza A and B by reverse-transcriptase polymerase chain reaction. A total of 3360 children participated in this study. Using reverse-transcriptase polymerase chain reaction, 54 cases of influenza A and 50 cases of influenza B were detected. We found no significant effect of the intervention on the primary study outcome of all laboratory-confirmed influenza cases (incidence rate ratio [IRR]: 0.81; 95% confidence interval [CI]: 0.54, 1.23). However, we did find statistically significant differences in protocol-specified ancillary outcomes. Children in intervention schools had significantly fewer laboratory-confirmed influenza A infections than children in control schools, with an adjusted IRR of 0.48 (95% CI: 0.26, 0.87). Total absent episodes were also significantly lower among the intervention group than among the control group; adjusted IRR 0.74 (95% CI: 0.56, 0.97). NPIs (respiratory hygiene education and the regular use of hand sanitizer) did not reduce total laboratory-confirmed influenza. However, the interventions did reduce school total absence episodes by 26% and laboratory-confirmed influenza A infections by 52%. Our results suggest that NPIs can be an important adjunct to influenza vaccination programs to reduce the number of influenza A infections among children.

  4. Reduction in the Incidence of Influenza A but Not Influenza B Associated with Use of Hand Sanitizer and Cough Hygiene in Schools: A Randomized Controlled Trial

    Science.gov (United States)

    STEBBINS, SAMUEL; CUMMINGS, DEREK A.T.; STARK, JAMES H.; VUKOTICH, CHUCK; MITRUKA, KIREN; THOMPSON, WILLIAM; RINALDO, CHARLES; ROTH, LOREN; WAGNER, MICHAEL; WISNIEWSKI, STEPHEN R.; DATO, VIRGINIA; ENG, HEATHER; BURKE, DONALD S.

    2012-01-01

    Background Laboratory-based evidence is lacking regarding the efficacy of non-pharmaceutical interventions such as alcohol-based hand sanitizer and respiratory hygiene to reduce the spread of influenza. Methods The Pittsburgh Influenza Prevention Project was a cluster-randomized trial conducted in ten Pittsburgh, PA elementary schools during the 2007-2008 influenza season. Children in five intervention schools received training in hand and respiratory hygiene, and were provided and encouraged to use hand sanitizer regularly. Children in five schools acted as controls. Children with influenza-like illness were tested for influenza A and B by RT-PCR. Results 3360 children participated. Using RT-PCR, 54 cases of influenza A and 50 cases of influenza B were detected. We found no significant effect of the intervention on the primary study outcome of all laboratory confirmed influenza cases (IRR 0.81 95% CI 0.54, 1.23). However, we did find statistically significant differences in protocol-specified ancillary outcomes. Children in intervention schools had significantly fewer laboratory-confirmed influenza A infections than children in control schools, with an adjusted IRR of 0.48 (95% CI 0.26, 0.87). Total absent episodes were also significantly lower among the intervention group than among the control group; adjusted IRR 0.74 (95% CI 0.56, 0.97). Conclusions Non-pharmaceutical interventions (respiratory hygiene education and the regular use of hand sanitizer) did not reduce total laboratory confirmed influenza. However the interventions did reduce school total absence episodes by 26% and laboratory-confirmed influenza A infections by 52%. Our results suggest that NPIs can be an important adjunct to influenza vaccination programs to reduce the number of influenza A infections among children. PMID:21691245

  5. Detection of Influenza C Viruses Among Outpatients and Patients Hospitalized for Severe Acute Respiratory Infection, Minnesota, 2013-2016.

    Science.gov (United States)

    Thielen, Beth K; Friedlander, Hannah; Bistodeau, Sarah; Shu, Bo; Lynch, Brian; Martin, Karen; Bye, Erica; Como-Sabetti, Kathryn; Boxrud, David; Strain, Anna K; Chaves, Sandra S; Steffens, Andrea; Fowlkes, Ashley L; Lindstrom, Stephen; Lynfield, Ruth

    2018-03-19

    Existing literature suggests that influenza C typically causes mild respiratory tract disease. However, clinical and epidemiological data are limited. Four outpatient clinics and 3 hospitals submitted clinical data and respiratory specimens through a surveillance network for acute respiratory infection (ARI) from May 2013 through December 2016. Specimens were tested using multitarget nucleic acid amplification for 19-22 respiratory pathogens, including influenza C. Influenza C virus was detected among 59 of 10 202 (0.58%) hospitalized severe ARI cases and 11 of 2282 (0.48%) outpatients. Most detections occurred from December to March, 73% during the 2014-2015 season. Influenza C detections occurred among patients of all ages, with rates being similar between inpatients and outpatients. The highest rate of detection occurred among children aged 6-24 months (1.2%). Among hospitalized cases, 7 required intensive care. Medical comorbidities were reported in 58% of hospitalized cases and all who required intensive care. At least 1 other respiratory pathogen was detected in 40 (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial virus (20%). The hemagglutinin-esterase-fusion gene was sequenced in 37 specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in inpatients and outpatients. We found seasonal circulation of influenza C with year-to-year variability. Detection was most frequent among young children but occurred in all ages. Some cases that were positive for influenza C, particularly those with comorbid conditions, had severe disease, suggesting a need for further study of the role of influenza C virus in the pathogenesis of respiratory disease.

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

    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), 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)

  7. 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)

  8. Impact of respiratory infections by influenza viruses A and B in pediatrics patients from Federal University of Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    M.C. Coelho

    Full Text Available The objective of the present study was to determine the impact of influenza virus on pediatric hospitalized patients. We retrospectively reviewed records of children with laboratory diagnoses, by cell culture and/or indirect immunofluorescence assay, of influenza virus seen in a period of 6 years. A total of 1,033 samples were analyzed, 45 (4.3% of them being reactive to influenza virus. Thirty-one samples were positive to influenza A virus and 14 to influenza B. The frequency of hospitalization in intensive care and medical emergency was found to be high. Three (8.6% patients died, two of them due to respiratory failure. Low frequency of influenza virus infection was observed in the study. The data suggest the need of more efficient epidemiological surveillance measures in order to obtain reliable information to better assess the impact of the virus on our region and determine the need of preventive measures, such as immunization.

  9. Suppressor of cytokine signaling 4 (SOCS4 protects against severe cytokine storm and enhances viral clearance during influenza infection.

    Directory of Open Access Journals (Sweden)

    Lukasz Kedzierski

    2014-05-01

    Full Text Available Suppressor of cytokine signaling (SOCS proteins are key regulators of innate and adaptive immunity. There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8 and are hypersusceptible to infection with the less virulent H3N2 (X31 strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infection and linked to defects in T cell receptor activation. These results demonstrate that SOCS4 is a critical regulator of anti-viral immunity.

  10. Fatal H5N6 Avian Influenza Virus Infection in a Domestic Cat and Wild Birds in China.

    Science.gov (United States)

    Yu, Zhijun; Gao, Xiaolong; Wang, Tiecheng; Li, Yanbing; Li, Yongcheng; Xu, Yu; Chu, Dong; Sun, Heting; Wu, Changjiang; Li, Shengnan; Wang, Haijun; Li, Yuanguo; Xia, Zhiping; Lin, Weishi; Qian, Jun; Chen, Hualan; Xia, Xianzhu; Gao, Yuwei

    2015-06-02

    H5N6 avian influenza viruses (AIVs) may pose a potential human risk as suggested by the first documented naturally-acquired human H5N6 virus infection in 2014. Here, we report the first cases of fatal H5N6 avian influenza virus (AIV) infection in a domestic cat and wild birds. These cases followed human H5N6 infections in China and preceded an H5N6 outbreak in chickens. The extensive migration routes of wild birds may contribute to the geographic spread of H5N6 AIVs and pose a risk to humans and susceptible domesticated animals, and the H5N6 AIVs may spread from southern China to northern China by wild birds. Additional surveillance is required to better understand the threat of zoonotic transmission of AIVs.

  11. Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1 in experimentally infected chickens

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Histopathological and immunohistochemical findings of swine with spontaneous influenza A infection in Brazil, 2009-2010

    Directory of Open Access Journals (Sweden)

    Tatiane T.N. Watanabe

    2012-11-01

    Full Text Available Swine influenza (SI is caused by the type A swine influenza virus (SIV. It is a highly contagious disease with a rapid course and recovery. The major clinical signs and symptoms are cough, fever, anorexia and poor performance. The disease has been associated with other co-infections in many countries, but not in Brazil, where, however, the first outbreak has been reported in 2011. The main aim of this study was to characterize the histological features in association with the immunohistochemical (IHC results for influenza A (IA, porcine circovirus type 2 (PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV in lung samples from 60 pigs submitted to Setor de Patologia Veterinária at the Universidade Federal do Rio Grande do Sul (SPV-UFRGS, Brazil, during 2009-2010. All of these lung samples had changes characterized by interstitial pneumonia with necrotizing bronchiolitis, never observed previously in the evaluation of swine lungs in our laboratory routine. Pigs in this study had showed clinical signs of a respiratory infection. Swine samples originated from Rio Grande do Sul 31 (52%, Santa Catarina 14 (23%, Paraná 11 (18%, and Mato Grosso do Sul 4 (7%. Positive anti-IA IHC labelling was observed in 45% of the cases, which were associated with necrotizing bronchiolitis, atelectasis, purulent bronchopneumonia and hyperemia. Moreover, type II pneumocyte hyperplasia, alveolar and bronchiolar polyp-like structures, bronchus-associated lymphoid tissue (BALT hyperplasia and pleuritis were the significant features in negative anti-IA IHC, which were also associated with chronic lesions. There were only two cases with positive anti-PCV2 IHC and none to PRRSV. Therefore, SIV was the predominant infectious agent in the lung samples studied. The viral antigen is often absent due to the rapid progress of SI, which may explain the negative IHC results for IA (55%; therefore, IHC should be performed at the beginning of the disease. This study

  15. Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses.

    Science.gov (United States)

    Bajimaya, Shringkhala; Frankl, Tünde; Hayashi, Tsuyoshi; Takimoto, Toru

    2017-10-01

    Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In this study, we analyzed the role of cholesterol on influenza A virus (IAV) and respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human airway cells with the agents did not decrease virus particle production. However, the released virions were less homogeneous in density and unstable. Addition of exogenous cholesterol to the released virions restored virus stability and infectivity. Collectively, these data indicate a critical role of cholesterol in maintaining IAV and RSV membrane structure that is essential for sustaining viral stability and infectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 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...

  17. Expression of microRNAs and innate immune factor genes in lung tissue of pigs infected with influenza virus (H1N2)

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Cirera, S.; Vasby, D.

    A infection. The present work aimed of providing a better understanding of the involvement of innate immune factors including miRNA in the host response to establishment and progression of influenza virus infection. Twenty pigs were challenged by aerosol containing H1N2 (A/swine/Denmark/12687/03) influenza......Swine influenza is a highly infectious respiratory disease in pigs caused by influenza A virus. Activation of a frontline of pattern-recognition receptors (PRRs) expressed by epithelial cells as well as immune cells of the upper respiratory tract, leads to a potent type 1 interferon (IFN) release......, this response must be tightly regulated. Recently, microRNA (miRNA) has been proposed to play an important role in modulating and fine tuning the innate immune response in order to avoid such harmful overreactions. Little is known about the significance of miRNA regulation in the lung during acute influenza...

  18. 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...

  19. 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.

  20. Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1) virus infection during pregnancy.

    Science.gov (United States)

    Savic, Miloje; Dembinski, Jennifer L; Laake, Ida; Hungnes, Olav; Cox, Rebecca; Oftung, Fredrik; Trogstad, Lill; Mjaaland, Siri

    2017-01-01

    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(H1N1)pdm09 (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.

  1. Impact of removing mucosal barrier injury laboratory-confirmed bloodstream infections from central line-associated bloodstream infection rates in the National Healthcare Safety Network, 2014.

    Science.gov (United States)

    See, Isaac; Soe, Minn M; Epstein, Lauren; Edwards, Jonathan R; Magill, Shelley S; Thompson, Nicola D

    2017-03-01

    Central line-associated bloodstream infection (CLABSI) event data reported to the National Healthcare Safety Network from 2014, the first year of required use of the mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) definition, were analyzed to assess the impact of removing MBI-LCBI events from CLABSI rates. CLABSI rates decreased significantly in some location types after removing MBI-LCBI events, and MBI-LCBI events will be removed from publicly reported CLABSI rates. Published by Elsevier Inc.

  2. Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen.

    Science.gov (United States)

    Lambert Emo, Kris; Hyun, Young-Min; Reilly, Emma; Barilla, Christopher; Gerber, Scott; Fowell, Deborah; Kim, Minsoo; Topham, David J

    2016-09-01

    During a primary influenza infection, cytotoxic CD8+ T cells need to infiltrate the infected airways and engage virus-infected epithelial cells. The factors that regulate T cell motility in the infected airway tissue are not well known. To more precisely study T cell infiltration of the airways, we developed an experimental model system using the trachea as a site where live imaging can be performed. CD8+ T cell motility was dynamic with marked changes in motility on different days of the infection. In particular, significant changes in average cell velocity and confinement were evident on days 8-10 during which the T cells abruptly but transiently increase velocity on day 9. Experiments to distinguish whether infection itself or antigen affect motility revealed that it is antigen, not active infection per se that likely affects these changes as blockade of peptide/MHC resulted in increased velocity. These observations demonstrate that influenza tracheitis provides a robust experimental foundation to study molecular regulation of T cell motility during acute virus infection.

  3. Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen.

    Directory of Open Access Journals (Sweden)

    Kris Lambert Emo

    2016-09-01

    Full Text Available During a primary influenza infection, cytotoxic CD8+ T cells need to infiltrate the infected airways and engage virus-infected epithelial cells. The factors that regulate T cell motility in the infected airway tissue are not well known. To more precisely study T cell infiltration of the airways, we developed an experimental model system using the trachea as a site where live imaging can be performed. CD8+ T cell motility was dynamic with marked changes in motility on different days of the infection. In particular, significant changes in average cell velocity and confinement were evident on days 8-10 during which the T cells abruptly but transiently increase velocity on day 9. Experiments to distinguish whether infection itself or antigen affect motility revealed that it is antigen, not active infection per se that likely affects these changes as blockade of peptide/MHC resulted in increased velocity. These observations demonstrate that influenza tracheitis provides a robust experimental foundation to study molecular regulation of T cell motility during acute virus infection.

  4. Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice.

    Directory of Open Access Journals (Sweden)

    Susu Duan

    2015-02-01

    Full Text Available The recent emergence of a novel H7N9 influenza A virus (IAV causing severe human infections in China raises concerns about a possible pandemic. The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8(+ cytotoxic T lymphocyte (CTL memory specific for epitopes conserved between H7N9 and previously encountered IAVs. In the present study, the heterosubtypic immunity generated by prior H9N2 or H1N1 infections significantly, but variably, reduced morbidity and mortality, pulmonary virus load and time to clearance in mice challenged with the H7N9 virus. In all cases, the recall of established CTL memory was characterized by earlier, greater airway infiltration of effectors targeting the conserved or cross-reactive H7N9 IAV peptides; though, depending on the priming IAV, each case was accompanied by distinct CTL epitope immunodominance hierarchies for the prominent K(bPB(1703, D(bPA(224, and D(bNP(366 epitopes. While the presence of conserved, variable, or cross-reactive epitopes between the priming H9N2 and H1N1 and the challenge H7N9 IAVs clearly influenced any change in the immunodominance hierarchy, the changing patterns were not tied solely to epitope conservation. Furthermore, the total size of the IAV-specific memory CTL pool after priming was a better predictor of favorable outcomes than the extent of epitope conservation or secondary CTL expansion. Modifying the size of the memory CTL pool significantly altered its subsequent protective efficacy on disease severity or virus clearance, confirming the important role of heterologous priming. These findings establish that both the protective efficacy of heterosubtypic immunity and CTL immunodominance hierarchies are reflective of the immunological history of the host, a finding that has implications for understanding human CTL responses and the rational design of CTL-mediated vaccines.

  5. Poultry farms as a source of avian influenza A (H7N9) virus reassortment and human infection

    OpenAIRE

    Wu, Donglin; Zou, Shumei; Bai, Tian; Li, Jing; Zhao, Xiang; Yang, Lei; Liu, Hongmin; Li, Xiaodan; Yang, Xianda; Xin, Li; Xu, Shuang; Zou, Xiaohui; Li, Xiyan; Wang, Ao; Guo, Junfeng

    2015-01-01

    Live poultry markets are a source of human infection with avian influenza A (H7N9) virus. On February 21, 2014, a poultry farmer infected with H7N9 virus was identified in Jilin, China, and H7N9 and H9N2 viruses were isolated from the patient's farm. Reassortment between these subtype viruses generated five genotypes, one of which caused the human infection. The date of H7N9 virus introduction to the farm is estimated to be between August 21, 2013 (95% confidence interval [CI] June 6, 2013-Oc...

  6. Transmission of equine influenza virus during an outbreak is characterized by frequent mixed infections and loose transmission bottlenecks.

    Directory of Open Access Journals (Sweden)

    Joseph Hughes

    2012-12-01

    Full Text Available The ability of influenza A viruses (IAVs to cross species barriers and evade host immunity is a major public health concern. Studies on the phylodynamics of IAVs across different scales - from the individual to the population - are essential for devising effective measures to predict, prevent or contain influenza emergence. Understanding how IAVs spread and evolve during outbreaks is critical for the management of epidemics. Reconstructing the transmission network during a single outbreak by sampling viral genetic data in time and space can generate insights about these processes. Here, we obtained intra-host viral sequence data from horses infected with equine influenza virus (EIV to reconstruct the spread of EIV during a large outbreak. To this end, we analyzed within-host viral populations from sequences covering 90% of the infected yards. By combining gene sequence analyses with epidemiological data, we inferred a plausible transmission network, in turn enabling the comparison of transmission patterns during the course of the outbreak and revealing important epidemiological features that were not apparent using either approach alone. The EIV populations displayed high levels of genetic diversity, and in many cases we observed distinct viral populations containing a dominant variant and a number of related minor variants that were transmitted between infectious horses. In addition, we found evidence of frequent mixed infections and loose transmission bottlenecks in these naturally occurring populations. These frequent mixed infections likely influence the size of epidemics.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. An innovative influenza vaccination policy: targeting last season's patients.

    Science.gov (United States)

    Yamin, Dan; Gavious, Arieh; Solnik, Eyal; Davidovitch, Nadav; Balicer, Ran D; Galvani, Alison P; Pliskin, Joseph S

    2014-05-01

    Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks.

  9. An innovative influenza vaccination policy: targeting last season's patients.

    Directory of Open Access Journals (Sweden)

    Dan Yamin

    2014-05-01

    Full Text Available Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks.

  10. Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Stacey Ann Gorski

    2013-09-01

    Full Text Available Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may also be tissue protective. Interleukin (IL-5 is a prototypical type 2 cytokine that is essential for eosinophil maturation and egress out of the bone marrow. However, little is known about the cellular source and underlying cellular and molecular basis for the regulation of IL-5 production during respiratory virus infection. Using a mouse model of influenza virus infection, we found a robust transient release of IL-5 into infected airways along with a significant and progressive accumulation of eosinophils into the lungs, particularly during the recovery phase of infection, i.e. following virus clearance. The cellular source of the IL-5 was group 2 innate lymphoid cells (ILC2 infiltrating the infected lungs. Interestingly, the progressive accumulation of eosinophils following virus clearance is reflected in the rapid expansion of c-kit⁺ IL-5 producing ILC2. We further demonstrate that the enhanced capacity for IL-5 production by ILC2 during recovery is concomitant with the enhanced expression of the IL-33 receptor subunit, ST2, by ILC2. Lastly, we show that NKT cells, as well as alveolar macrophages (AM, are endogenous sources of IL-33 that enhance IL-5 production from ILC2. Collectively, these results reveal that c-kit⁺ ILC2 interaction with IL-33 producing NKT and AM leads to abundant production of IL-5 by ILC2 and accounts for the accumulation of eosinophils observed during the recovery phase of influenza infection.

  11. 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

  12. 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.

  13. High probability of avian influenza virus (H7N7) transmission from poultry to humans active in disease control on infected farms

    NARCIS (Netherlands)

    M.E.H. Bos (Marian); D.E. te Beest (Dennis); M. van Boven (Michiel); M.R.D.R.B. van Holle; A. Meijer (Adam); A. Bosman (Arnold); Y.M. Mulder (Yonne); M.P.G. Koopmans D.V.M. (Marion); A. Stegeman (Arjan)

    2010-01-01

    textabstractAn epizootic of avian influenza (H7N7) caused a large number of human infections in The Netherlands in 2003. We used data from this epizootic to estimate infection probabilities for persons involved in disease control on infected farms. Analyses were based on databases containing

  14. Morphological and molecular confirmation of Myxobolus cerebralis myxospores infecting wild‑caught and cultured trout in North Carolina (SE USA).

    Science.gov (United States)

    Ruiz, Carlos F; Rash, Jacob M; Arias, Cova R; Besler, Doug A; Orélis-Ribeiro, Raphael; Womble, Matthew R; Roberts, Jackson R; Warren, Micah B; Ray, Candis L; Lafrentz, Stacey; Bullard, Stephen A

    2017-11-21

    We used microscopy and molecular biology to provide the first documentation of infections of Myxobolus cerebralis (Myxozoa: Myxobolidae), the etiological agent of whirling disease, in trout (Salmonidae) from North Carolina (USA) river basins. A total of 1085 rainbow trout Oncorhynchus mykiss, 696 brown trout Salmo trutta, and 319 brook trout Salvelinus fontinalis from 43 localities across 9 river basins were screened. Myxospores were observed microscopically in pepsin-trypsin digested heads of rainbow and brown trout from the Watauga River Basin. Those infections were confirmed using the prescribed nested polymerase chain reaction (PCR; 18S rDNA), which also detected infections in rainbow, brown, and brook trout from the French Broad River Basin and the Yadkin Pee-Dee River Basin. Myxospores were 9.0-10.0 µm (mean ± SD = 9.6 ± 0.4; N = 119) long, 8.0-10.0 µm (8.8 ± 0.6; 104) wide, and 6.0-7.5 µm (6.9 ± 0.5; 15) thick and had polar capsules 4.0-6.0 µm (5.0 ± 0.5; 104) long, 2.5-3.5 µm (3.1 ± 0.3; 104) wide, and with 5 or 6 polar filament coils. Myxospores from these hosts and rivers were morphologically indistinguishable and molecularly identical, indicating conspecificity, and the resulting 18S rDNA and ITS-1 sequences derived from these myxospores were 99.5-100% and 99.3-99.8% similar, respectively, to published GenBank sequences ascribed to M. cerebralis. This report comprises the first taxonomic circumscription and molecular confirmation of M. cerebralis in the southeastern USA south of Virginia.

  15. Outbreak of Zika Virus Infection, Chiapas State, Mexico, 2015, and First Confirmed Transmission by Aedes aegypti Mosquitoes in the Americas.

    Science.gov (United States)

    Guerbois, Mathilde; Fernandez-Salas, Ildefonso; Azar, Sasha R; Danis-Lozano, Rogelio; Alpuche-Aranda, Celia M; Leal, Grace; Garcia-Malo, Iliana R; Diaz-Gonzalez, Esteban E; Casas-Martinez, Mauricio; Rossi, Shannan L; Del Río-Galván, Samanta L; Sanchez-Casas, Rosa M; Roundy, Christopher M; Wood, Thomas G; Widen, Steven G; Vasilakis, Nikos; Weaver, Scott C

    2016-11-01

     After decades of obscurity, Zika virus (ZIKV) has spread through the Americas since 2015 accompanied by congenital microcephaly and Guillain-Barré syndrome. Although these epidemics presumably involve transmission by Aedes aegypti, no direct evidence of vector involvement has been reported, prompting speculation that other mosquitoes such as Culex quinquefasciatus could be involved.  We detected an outbreak of ZIKV infection in southern Mexico in late 2015. Sera from suspected ZIKV-infected patients were analyzed for viral RNA and antibodies. Mosquitoes were collected in and around patient homes and tested for ZIKV.  Of 119 suspected ZIKV-infected patients, 25 (21%) were confirmed by RT-PCR of serum collected 1-8 days after the onset of signs and symptoms including rash, arthralgia, headache, pruritus, myalgia, and fever. Of 796 mosquitoes collected, A. aegypti yielded ZIKV detection by RT-PCR in 15 of 55 pools (27.3%). No ZIKV was detected in C. quinquefasciatus ZIKV sequences derived from sera and mosquitoes showed a monophyletic relationship suggestive of a point source introduction from Guatemala.  These results demonstrate the continued, rapid northward progression of ZIKV into North America with typically mild disease manifestations, and implicate A. aegypti for the first time as a principal vector in North America. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. 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

  17. Serial Metabolome Changes in a Prospective Cohort of Subjects with Influenza Viral Infection and Comparison with Dengue Fever.

    Science.gov (United States)

    Cui, Liang; Fang, Jinling; Ooi, Eng Eong; Lee, Yie Hou

    2017-07-07

    Influenza virus infection (IVI) and dengue virus infection (DVI) are major public health threats. Between IVI and DVI, clinical symptoms can be overlapping yet infection-specific, but host metabolome changes are not well-described. Untargeted metabolomics and targeted oxylipinomic analyses were performed on sera serially collected at three phases of infection from a prospective cohort study of adult subjects with either H3N2 influenza infection or dengue fever. Untargeted metabolomics identified 26 differential metabolites, and major perturbed pathways included purine metabolism, fatty acid biosynthesis and β-oxidation, tryptophan metabolism, phospholipid catabolism, and steroid hormone pathway. Alterations in eight oxylipins were associated with the early symptomatic phase of H3N2 flu infection, were mostly arachidonic acid-derived, and were enriched in the lipoxygenase pathway. There was significant overlap in metabolome profiles in both infections. However, differences specific to IVI and DVI were observed. DVI specifically attenuated metabolites including serotonin, bile acids and biliverdin. Additionally, metabolome changes were more persistent in IVI in which metabolites such as hypoxanthine, inosine, and xanthine of the purine metabolism pathway remained significantly elevated at 21-27 days after fever onset. This study revealed the dynamic metabolome changes in IVI subjects and provided biochemical insights on host physiological similarities and differences between IVI and DVI.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. Putative Human and Avian Risk Factors for Avian Influenza Virus Infections in Backyard Poultry in Egypt

    Science.gov (United States)

    Sheta, Basma M.; Fuller, Trevon L.; Larison, Brenda; Njabo, Kevin Y.; Ahmed, Ahmed Samy; Harrigan, Ryan; Chasar, Anthony; Aziz, Soad Abdel; Khidr, Abdel-Aziz A.; Elbokl, Mohamed M.; Habbak, Lotfy Z.; Smith, Thomas B.

    2014-01-01

    Highly pathogenic influenza A virus subtype H5N1 causes significant poultry mortality in the six countries where it is endemic and can also infect humans. Egypt has reported the third highest number of poultry outbreaks (n=1,084) globally. The objective of this cross-sectional study was to identify putative risk factors for H5N1 infections in backyard poultry in 16 villages in Damietta, El Gharbia, Fayoum, and Menofia governorates from 2010–2012. Cloacal and tracheal swabs and serum samples from domestic (n=1242)and wild birds (n=807) were tested for H5N1 via RT-PCR and hemagglutination inhibition, respectively. We measured poultry rearing practices with questionnaires (n=306 households) and contact rates among domestic and wild bird species with scan sampling. Domestic birds (chickens, ducks, and geese, n = 51) in three governorates tested positive for H5N1 by PCR or serology. A regression model identified a significant correlation between H5N1 in poultry and the practice of disposing of dead poultry and poultry feces in the garbage (F = 15.7, p< 0.0001). In addition, contact between domestic and wild birds was more frequent in villages where we detected H5N1 in backyard flocks (F= 29.5, p< 0.0001). PMID:24315038

  1. 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...

  2. Expression Dynamics of Innate Immunity in Influenza Virus-Infected Swine

    Directory of Open Access Journals (Sweden)

    Massimo Amadori

    2017-04-01

    Full Text Available The current circulating swine influenza virus (IV subtypes in Europe (H1N1, H1N2, and H3N2 are associated with clinical outbreaks of disease. However, we showed that pigs could be susceptible to other IV strains that are able to cross the species barrier. In this work, we extended our investigations into whether different IV strains able to cross the species barrier might give rise to different innate immune responses that could be associated with pathological lesions. For this purpose, we used the same samples collected in a previous study of ours, in which healthy pigs had been infected with a H3N2 Swine IV and four different H3N8 IV strains circulating in different animal species. Pigs had been clinically inspected and four subjects/group were sacrificed at 3, 6, and 21 days post infection. In the present study, all groups but mock exhibited antibody responses to IV nucleoprotein protein. Pulmonary lesions and high-titered viral replication were observed in pigs infected with the swine-adapted virus. Interestingly, pigs infected with avian and seal H3N8 strains also showed moderate lesions and viral replication, whereas equine and canine IVs did not cause overt pathological signs, and replication was barely detectable. Swine IV infection induced interferon (IFN-alpha and interleukin-6 responses in bronchoalveolar fluids (BALF at day 3 post infection, as opposed to the other non-swine-adapted virus strains. However, IFN-alpha responses to the swine-adapted virus were not associated with an increase of the local, constitutive expression of IFN-alpha genes. Remarkably, the Equine strain gave rise to a Serum Amyloid A response in BALF despite little if any replication. Each virus strain could be associated with expression of cytokine genes and/or proteins after infection. These responses were observed well beyond the period of virus replication, suggesting a prolonged homeostatic imbalance of the innate immune system.

  3. Aspectos epidemiológicos da infecção por Haemophilus influenzae tipo b Epidemiologic aspects of Haemophilus influenzae type b infection

    Directory of Open Access Journals (Sweden)

    Maria Angela Loguercio Bouskela

    2000-05-01

    Brazilian and international epidemiologic data obtained from several bibliographic databases (MEDLINE, 1966 to 1995; LILACS, 1982 to 1995; Thesis Databank, 1980 to 1995; and Dissertation Abstracts, 1988 to 1994. The incidence of Hib infection in Brazil was analyzed for individual states and for different ages, including within the first year of life. Meningitis cases were used as an incidence marker because of the difficulty in identifying the causative organism in such other infections as pneumonia, osteomyelitis, epiglottitis, cellulitis, and endocarditis. Our analysis showed that the nationwide Brazilian data masked the regional incidence and lethality of H. influenzae. For example, in 1991 the national incidence was 18.4 per 100 000 children under 1 year of age. In the same period, the Federal District had an incidence of 175 per 100 000 among children between 4 and 6 months of age. Similarly, the North of Brazil had a 35% case fatality rate in 1987, whereas the rate was 22% for Brazil as a whole. This study raises issues concerning the relevant epidemiologic factors associated with Hib infection and the costs and benefits of prophylaxis and vaccination in the age groups most at risk.

  4. Emergence of the virulence-associated PB2 E627K substitution in a fatal human case of highly pathogenic avian influenza virus A(H7N7) infection as determined by Illumina ultra-deep sequencing

    NARCIS (Netherlands)

    Jonges, Marcel; Welkers, Matthijs R. A.; Jeeninga, Rienk E.; Meijer, Adam; Schneeberger, Peter; Fouchier, Ron A. M.; de Jong, Menno D.; Koopmans, Marion

    2014-01-01

    Avian influenza viruses are capable of crossing the species barrier and infecting humans. Although evidence of human-to-human transmission of avian influenza viruses to date is limited, evolution of variants toward more-efficient human-to-human transmission could result in a new influenza virus

  5. Premedication with Clarithromycin Is Effective against Secondary Bacterial Pneumonia during Influenza Virus Infection in a Pulmonary Emphysema Mouse Model.

    Science.gov (United States)

    Harada, Tatsuhiko; Ishimatsu, Yuji; Hara, Atsuko; Morita, Towako; Nakashima, Shota; Kakugawa, Tomoyuki; Sakamoto, Noriho; Kosai, Kosuke; Izumikawa, Koichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

    2016-09-01

    Secondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A/PR8/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation. Premedication with CAM improved pathologic responses and bacterial load 2 days after S. pneumoniae inoculation. Survival rates were higher in emphysema mice than control mice. While CAM premedication did not affect viral titers or exert antibacterial activity against S. pneumoniae in the lungs, it enhanced host defense and reduced inflammation, as evidenced by the significant reductions in total cell and neutrophil counts and interferon (IFN)-γ levels in bronchoalveolar lavage fluid and lung homogenates. These results suggest that CAM protects against SBP during influenza in elastase-induced emphysema mice by reducing IFN-γ production, thus enhancing immunity to SBP, and by decreasing neutrophil infiltration into the lung to prevent injury. Accordingly, CAM may be an effective strategy to prevent secondary bacterial pneumonia in COPD patients in areas in which vaccines are inaccessible or limited. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  6. 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.

  7. Evaluation of a new point-of-care test for influenza A and B virus in travellers with influenza-like symptoms.

    Science.gov (United States)

    Weitzel, T; Schnabel, E; Dieckmann, S; Börner, U; Schweiger, B

    2007-07-01

    Point-of-care (POC) tests for influenza facilitate clinical case management, and might also be helpful in the care of travellers who are at special risk for influenza infection. To evaluate influenza POC testing in travellers, a new assay, the ImmunoCard STAT! Flu A and B, was used to investigate travellers presenting with influenza-like symptoms. Influenza virus infection was diagnosed in 27 (13%) of 203 patients by influenza virus-specific PCR and viral culture. The POC test had sensitivity and specificity values of 64% and 99% for influenza A, and 67% and 100% for influenza B, respectively. Combined sensitivity and specificity were 67% and 99%, respectively, yielding positive and negative predictive values of 95%, and positive and negative likelihood ratios of 117 and 0.34, respectively. The convenient application, excellent specificity and high positive likelihood ratio of the POC test allowed rapid identification of influenza cases. However, negative test results might require confirmation by other methods because of limitations in sensitivity. Overall, influenza POC testing appeared to be a useful tool for the management of travellers with influenza-like symptoms.

  8. Advances in influenza vaccination

    NARCIS (Netherlands)

    L.A. Reperant (Leslie); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2014-01-01

    textabstractInfluenza virus infections yearly cause high morbidity and mortality burdens in humans, and the development of a new influenza pandemic continues to threaten mankind as a Damoclean sword. Influenza vaccines have been produced by using egg-based virus growth and passaging techniques that

  9. Bird Flu (Avian Influenza)

    Science.gov (United States)

    Bird flu (avian influenza) Overview Bird flu is caused by a type of influenza virus that rarely infects humans. More than a ... for Disease Control and Prevention estimates that seasonal influenza is responsible for ... heat destroys avian viruses, cooked poultry isn't a health threat. ...

  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. Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.

    Science.gov (United States)

    Donovan, Chantal; Seow, Huei Jiunn; Bourke, Jane E; Vlahos, Ross

    2016-05-01

    β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, the aim of the present study was to assess the effects of the β2-adrenoceptor agonist salbutamol (SALB) on small airway reactivity using mouse precision cut lung slices (PCLS) prepared from CS-exposed mice and from CS-exposed mice treated with influenza A virus (Mem71, H3N1). CS exposure alone reduced SALB potency and efficacy associated with decreased β2-adrenoceptor mRNA expression, and increased tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression. This impaired relaxation was restored by day 12 in the absence of further CS exposure. In PCLS prepared after Mem71 infection alone, responses to SALB were transient and were not well maintained. CS exposure prior to Mem71 infection almost completely abolished relaxation, although β2-adrenoceptor and TNFα and IL-1β expression were unaltered. The present study has shown decreased sensitivity to SALB after CS or a combination of CS and Mem71 occurs by different mechanisms. In addition, the PCLS technique and our models of CS and influenza infection provide a novel setting for assessment of alternative bronchodilators. © 2016 The Author(s).

  12. Protocatechuic acid, a novel active substance against avian influenza virus H9N2 infection.

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    Changbo Ou

    Full Text Available Influenza virus H9N2 subtype has triggered co-infection with other infectious agents, resulting in huge economical losses in the poultry industry. Our current study aims to evaluate the antiviral activity of protocatechuic acid (PCA against a virulent H9N2 strain in a mouse model. 120 BALB/c mice were divided into one control group, one untreated group, one 50 mg/kg amantadine hydrochloride-treated group and three PCA groups treated 12 hours post-inoculation with 40, 20 or 10 mg/kg PCA for 7 days. All the infected animals were inoculated intranasally with 0.2 ml of a A/Chicken/Hebei/4/2008(H9N2 inoculum. A significant body weight loss was found in the 20 mg/kg and 40 mg/kg PCA-treated and amantadine groups as compared to the control group. The 14 day survivals were 94.4%, 100% and 95% in the PCA-treated groups and 94.4% in the amantadine hydrochloride group, compared to less than 60% in the untreated group. Virus loads were less in the PCA-treated groups compared to the amantadine-treated or the untreated groups. Neutrophil cells in BALF were significantly decreased while IFN-γ, IL-2, TNF-α and IL-6 decreased significantly at days 7 in the PCA-treated groups compared to the untreated group. Furthermore, a significantly decreased CD4+/CD8+ ratio and an increased proportion of CD19 cells were observed in the PCA-treated groups and amantadine-treated group compared to the untreated group. Mice administered with PCA exhibited a higher survival rate and greater viral clearance associated with an inhibition of inflammatory cytokines and activation of CD8+ T cell subsets. PCA is a promising novel agent against bird flu infection in the poultry industry.

  13. Economic Evaluation and Budget Impact Analysis of Vaccination against Haemophilus influenzae Type b Infection in Thailand

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    Surachai Kotirum

    2017-11-01

    Full Text Available Current study aimed to estimate clinical and economic outcomes of providing the Haemophilus influenzae type b (Hib vaccination as a national vaccine immunization program in Thailand. A decision tree combined with Markov model was developed to simulate relevant costs and health outcomes covering lifetime horizon in societal and health care payer perspectives. This analysis considered children aged under 5 years old whom preventive vaccine of Hib infection are indicated. Two combined Hib vaccination schedules were considered: three-dose series (3 + 0 and three-dose series plus a booster does (3 + 1 compared with no vaccination. Budget impact analysis was also performed under Thai government perspective. The outcomes were reported as Hib-infected cases averted and incremental cost-effectiveness ratios (ICERs in 2014 Thai baht (THB ($ per quality-adjusted life year (QALY gained. In base-case scenario, the model estimates that 3,960 infected cases, 59 disability cases, and 97 deaths can be prevented by national Hib vaccination program. The ICER for 3 + 0 schedule was THB 1,099 ($34 per QALY gained under societal perspective. The model was sensitive to pneumonia incidence among aged under 5 years old and direct non-medical care cost per episode of Hib pneumonia. Hib vaccination is very cost-effective in the Thai context. The budget impact analysis showed that Thai government needed to invest an additional budget of 110 ($3.4 million to implement Hib vaccination program. Policy makers should consider our findings for adopting this vaccine into national immunization program.

  14. Burden of laboratory-confirmed Campylobacter infections in Guatemala 2008–2012: Results from a facility-based surveillance system

    Science.gov (United States)

    Benoit, Stephen R.; Lopez, Beatriz; Arvelo, Wences; Henao, Olga; Parsons, Michele B.; Reyes, Lissette; Moir, Juan Carlos; Lindblade, Kim

    2015-01-01

    Introduction Campylobacteriosis is one of the leading causes of gastroenteritis worldwide. This study describes the epidemiology of laboratory-confirmed Campylobacter diarrheal infections in two facility-based surveillance sites in Guatemala. Methods Clinical, epidemiologic, and laboratory data were collected on patients presenting with acute diarrhea from select healthcare facilities in the departments of Santa Rosa and Quetzaltenango, Guatemala, from January 2008 through August 2012. Stool specimens were cultured for Campylobacter and antimicrobial susceptibility testing was performed on a subset of isolates. Multidrug resistance (MDR) was defined as resistance to ≥3 antimicrobial classes. Results Campylobacter was isolated from 306 (6.0%) of 5137 stool specimens collected. For children Guatemala; antimicrobial resistance was high, and treatment regimens in the ambulatory setting which included metronidazole and trimethoprim-sulfamethoxazole and lacked oral rehydration were sub-optimal. PMID:24534336

  15. Burden of laboratory-confirmed Campylobacter infections in Guatemala 2008-2012: results from a facility-based surveillance system.

    Science.gov (United States)

    Benoit, Stephen R; Lopez, Beatriz; Arvelo, Wences; Henao, Olga; Parsons, Michele B; Reyes, Lissette; Moir, Juan Carlos; Lindblade, Kim

    2014-03-01

    Campylobacteriosis is one of the leading causes of gastroenteritis worldwide. This study describes the epidemiology of laboratory-confirmed Campylobacter diarrheal infections in two facility-based surveillance sites in Guatemala. Clinical, epidemiologic, and laboratory data were collected on patients presenting with acute diarrhea from select healthcare facilities in the departments of Santa Rosa and Quetzaltenango, Guatemala, from January 2008 through August 2012. Stool specimens were cultured for Campylobacter and antimicrobial susceptibility testing was performed on a subset of isolates. Multidrug resistance (MDR) was defined as resistance to ≥3 antimicrobial classes. Campylobacter was isolated from 306 (6.0%) of 5137 stool specimens collected. For children Guatemala; antimicrobial resistance was high, and treatment regimens in the ambulatory setting which included metronidazole and trimethoprim-sulfamethoxazole and lacked oral rehydration were sub-optimal. Published by Elsevier Ltd.

  16. 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....

  17. 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.

  18. Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses.

    Science.gov (United States)

    Janulíková, J; Stropkovská, A; Bobišová, Z; Košík, I; Mucha, V; Kostolanský, F; Varečková, E

    2015-06-01

    In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.

  19. Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Virus Infection in a Murine Model▿

    Science.gov (United States)

    Norton, Elizabeth B.; Clements, John D.; Voss, Thomas G.; Cárdenas-Freytag, Lucia

    2010-01-01

    Prophylactic or therapeutic immunomodulation is an antigen-independent strategy that induces nonspecific immune system activation, thereby enhancing host defense to disease. In this study, we investigated the effect of prophylactic immunomodulation on the outcome of influenza virus infection using three bacterially derived immune-enhancing agents known for promoting distinct immunological profiles. BALB/c mice were treated nasally with either cholera toxin (CT), a mutant form of the CT-related Escherichia coli heat-labile enterotoxin designated LT(R192G), or CpG oligodeoxynucleotide. Mice were subsequently challenged with a lethal dose of influenza A/PR/8/34 virus 24 h after the last immunomodulation treatment and either monitored for survival or sacrificed postchallenge for viral and immunological analysis. Treatment with the three immunomodulators prevented or delayed mortality and weight loss, but only CT and LT(R192G) significantly reduced initial lung viral loads as measured by plaque assay. Analysis performed 4 days postinfection indicated that prophylactic treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers of CD4 T cells, B cells, and dendritic cells and altered costimulatory marker expression in the airways of infected mice, coinciding with reduced expression of pulmonary chemokines and the appearance of inducible bronchus-associated lymphoid tissue-like structures in the lungs. Collectively, these results suggest that, despite different immunomodulatory mechanisms, CT, LT(R192G), and CpG induce an initial inflammatory process and enhance the immune response to primary influenza virus challenge while preventing potentially damaging chemokine expression. These studies provide insight into the immunological parameters and immune modulation strategies that have the potential to enhance the nonspecific host response to influenza virus infection. PMID:20053748

  20. In Silico Prediction and Experimental Confirmation of HA Residues Conferring Enhanced Human Receptor Specificity of H5N1 Influenza A Viruses

    Science.gov (United States)

    Schmier, Sonja; Mostafa, Ahmed; Haarmann, Thomas; Bannert, Norbert; Ziebuhr, John; Veljkovic, Veljko; Dietrich, Ursula; Pleschka, Stephan

    2015-06-01

    Newly emerging influenza A viruses (IAV) pose a major threat to human health by causing seasonal epidemics and/or pandemics, the latter often facilitated by the lack of pre-existing immunity in the general population. Early recognition of candidate pandemic influenza viruses (CPIV) is of crucial importance for restricting virus transmission and developing appropriate therapeutic and prophylactic strategies including effective vaccines. Often, the pandemic potential of newly emerging IAV is only fully recognized once the virus starts to spread efficiently causing serious disease in humans. Here, we used a novel phylogenetic algorithm based on the informational spectrum method (ISM) to identify potential CPIV by predicting mutations in the viral hemagglutinin (HA) gene that are likely to (differentially) affect critical interactions between the HA protein and target cells from bird and human origin, respectively. Predictions were subsequently validated by generating pseudotyped retrovirus particles and genetically engineered IAV containing these mutations and characterizing potential effects on virus entry and replication in cells expressing human and avian IAV receptors, respectively. Our data suggest that the ISM-based algorithm is suitable to identify CPIV among IAV strains that are circulating in animal hosts and thus may be a new tool for assessing pandemic risks associated with specific strains.

  1. Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.

    Science.gov (United States)

    Qi, Wenbao; Jia, Weixin; Liu, Di; Li, Jing; Bi, Yuhai; Xie, Shumin; Li, Bo; Hu, Tao; Du, Yingying; Xing, Li; Zhang, Jiahao; Zhang, Fuchun; Wei, Xiaoman; Eden, John-Sebastian; Li, Huanan; Tian, Huaiyu; Li, Wei; Su, Guanming; Lao, Guangjie; Xu, Chenggang; Xu, Bing; Liu, Wenjun; Zhang, Guihong; Ren, Tao; Holmes, Edward C; Cui, Jie; Shi, Weifeng; Gao, George F; Liao, Ming

    2018-01-15

    Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant. IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Modelling the species jump : towards assessing the risk of human infection from novel avian influenzas

    NARCIS (Netherlands)

    Hill, A A; Dewé, T; Kosmider, R; Von Dobschuetz, S; Munoz, O; Hanna, A; Fusaro, A; De Nardi, M; Howard, W; Stevens, K; Kelly, L; Havelaar, A|info:eu-repo/dai/nl/072306122; Stärk, K

    The scientific understanding of the driving factors behind zoonotic and pandemic influenzas is hampered by complex interactions between viruses, animal hosts and humans. This complexity makes identifying influenza viruses of high zoonotic or pandemic risk, before they emerge from animal populations,

  4. Sialylglycan-Assembled Supra-Dots for Ratiometric Probing and Blocking of Human-Infecting Influenza Viruses.

    Science.gov (United States)

    Wang, Chang-Zheng; Han, Hai-Hao; Tang, Xin-Ying; Zhou, Dong-Ming; Wu, Changfeng; Chen, Guo-Rong; He, Xiao-Peng; Tian, He

    2017-08-02

    The seasonal outbreak of influenza causes significant morbidity and mortality worldwide because a number of influenza virus (IV) strains have been shown to infect and circulate in humans. Development of effective means to timely monitor as well as block IVs is still a challenging task. Whereas conventional fluorescence probes rely on a fluorimetric change upon recognizing IVs, here we developed simple "Supra-dots" that are formed through the aqueous supramolecular assembly between a blue-emitting polymer dot and red-emitting sialylglycan probes for the ratiometric detection of IVs. Tuning the Förster resonance energy transfer from polymer dots to glycan probes by selective sialylglycan-virus recognition enables the fluorescence ratiometric determination of IVs, whereas the presence of unselective, control viruses quenched the fluorescence of the Supra-dots. Meanwhile, we show that the Supra-dots can effectively inhibit the invasion of a human-infecting IV toward a human cell line, thereby making possible a unique bifunctional, supramolecular probe for influenza theranostics.

  5. Influenza A virus infection engenders a poor antibody response against the ectodomain of matrix protein 2

    Directory of Open Access Journals (Sweden)

    Wunner William

    2006-12-01

    Full Text Available Abstract Background Matrix protein 2 (M2 is an integral tetrameric membrane protein of influenza A virus (IAV. Its ectodomain (M2e shows remarkably little diversity amongst human IAV strains. As M2e-specific antibodies (Abs have been shown to reduce the severity of infection in animals, M2e is being studied for its capability of providing protection against a broad range of IAV strains. Presently, there is little information about the concentration of M2e-specific Abs in humans. Two previous studies made use of ELISA and Western blot against M2e peptides and recombinant M2 protein as immunosorbents, respectively, and reported Ab titers to be low or undetectable. An important caveat is that these assays may not have detected all Abs capable of binding to native tetrameric M2e. Therefore, we developed an assay likely to detect all M2e tetramer-specific Abs. Results We generated a HeLa cell line that expressed full length tetrameric M2 (HeLa-M2 or empty vector (HeLa-C10 under the control of the tetracycline response element. These cell lines were then used in parallel as immunosorbents in ELISA. The assay was standardized and M2e-specific Ab titers quantified by means of purified murine or chimeric (mouse variable regions, human constant regions M2e-specific Abs in the analysis of mouse and human sera, respectively. We found that the cell-based ELISA was substantially more effective than immobilized M2e peptide in detecting M2e-specific Abs in sera of mice that had recovered from repetitive IAV infections. Still, titers remained low ( Conclusion The results provide convincing evidence that M2e-specific Ab-mediated protection is currently lacking or suboptimal in humans.

  6. Influenza virus in a natural host, the mallard: experimental infection data.

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    Elsa Jourdain

    Full Text Available Wild waterfowl, particularly dabbling ducks such as mallards (Anas platyrhynchos, are considered the main reservoir of low-pathogenic avian influenza viruses (LPAIVs. They carry viruses that may evolve and become highly pathogenic for poultry or zoonotic. Understanding the ecology of LPAIVs in these natural hosts is therefore essential. We assessed the clinical response, viral shedding and antibody production of juvenile mallards after intra-esophageal inoculation of two LPAIV subtypes previously isolated from wild congeners. Six ducks, equipped with data loggers that continually monitored body temperature, heart rate and activity, were successively inoculated with an H7N7 LPAI isolate (day 0, the same H7N7 isolate again (day 21 and an H5N2 LPAI isolate (day 35. After the first H7N7 inoculation, the ducks remained alert with no modification of heart rate or activity. However, body temperature transiently increased in four individuals, suggesting that LPAIV strains may have minor clinical effects on their natural hosts. The excretion patterns observed after both re-inoculations differed strongly from those observed after the primary H7N7 inoculation, suggesting that not only homosubtypic but also heterosubtypic immunity exist. Our study suggests that LPAI infection has minor clinically measurable effects on mallards and that mallard ducks are able to mount immunological responses protective against heterologous infections. Because the transmission dynamics of LPAIVs in wild populations is greatly influenced by individual susceptibility and herd immunity, these findings are of high importance. Our study also shows the relevance of using telemetry to monitor disease in animals.

  7. Evaluating surveillance strategies for the early detection of low pathogenicity avian influenza infections.

    Science.gov (United States)

    Comin, Arianna; Stegeman, Arjan; Marangon, Stefano; Klinkenberg, Don

    2012-01-01

    In recent years, the early detection of low pathogenicity avian influenza (LPAI) viruses in poultry has become increasingly important, given their potential to mutate into highly pathogenic viruses. However, evaluations of LPAI surveillance have mainly focused on prevalence and not on the ability to act as an early warning system. We used a simulation model based on data from Italian LPAI epidemics in turkeys to evaluate different surveillance strategies in terms of their performance as early warning systems. The strategies differed in terms of sample size, sampling frequency, diagnostic tests, and whether or not active surveillance (i.e., routine laboratory testing of farms) was performed, and were also tested under different epidemiological scenarios. We compared surveillance strategies by simulating within-farm outbreaks. The output measures were the proportion of infected farms that are detected and the farm reproduction number (R(h)). The first one provides an indication of the sensitivity of the surveillance system to detect within-farm infections, whereas R(h) reflects the effectiveness of outbreak detection (i.e., if detection occurs soon enough to bring an epidemic under control). Increasing the sampling frequency was the most effective means of improving the timeliness of detection (i.e., it occurs earlier), whereas increasing the sample size increased the likelihood of detection. Surveillance was only effective in preventing an epidemic if actions were taken within two days of sampling. The strategies were not affected by the quality of the diagnostic test, although performing both serological and virological assays increased the sensitivity of active surveillance. Early detection of LPAI outbreaks in turkeys can be achieved by increasing the sampling frequency for active surveillance, though very frequent sampling may not be sustainable in the long term. We suggest that, when no LPAI virus is circulating yet and there is a low risk of virus introduction

  8. Evaluating surveillance strategies for the early detection of low pathogenicity avian influenza infections.

    Directory of Open Access Journals (Sweden)

    Arianna Comin

    Full Text Available In recent years, the early detection of low pathogenicity avian influenza (LPAI viruses in poultry has become increasingly important, given their potential to mutate into highly pathogenic viruses. However, evaluations of LPAI surveillance have mainly focused on prevalence and not on the ability to act as an early warning system. We used a simulation model based on data from Italian LPAI epidemics in turkeys to evaluate different surveillance strategies in terms of their performance as early warning systems. The strategies differed in terms of sample size, sampling frequency, diagnostic tests, and whether or not active surveillance (i.e., routine laboratory testing of farms was performed, and were also tested under different epidemiological scenarios. We compared surveillance strategies by simulating within-farm outbreaks. The output measures were the proportion of infected farms that are detected and the farm reproduction number (R(h. The first one provides an indication of the sensitivity of the surveillance system to detect within-farm infections, whereas R(h reflects the effectiveness of outbreak detection (i.e., if detection occurs soon enough to bring an epidemic under control. Increasing the sampling frequency was the most effective means of improving the timeliness of detection (i.e., it occurs earlier, whereas increasing the sample size increased the likelihood of detection. Surveillance was only effective in preventing an epidemic if actions were taken within two days of sampling. The strategies were not affected by the quality of the diagnostic test, although performing both serological and virological assays increased the sensitivity of active surveillance. Early detection of LPAI outbreaks in turkeys can be achieved by increasing the sampling frequency for active surveillance, though very frequent sampling may not be sustainable in the long term. We suggest that, when no LPAI virus is circulating yet and there is a low risk of virus

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Epidemiology of Hospital Admissions with Influenza during the 2013/2014 Northern Hemisphere Influenza Season: Results from the Global Influenza Hospital Surveillance Network

    Science.gov (United States)

    Puig-Barberà, Joan; Natividad-Sancho, Angels; Trushakova, Svetlana; Sominina, Anna; Pisareva, Maria; Ciblak, Meral A.; Badur, Selim; Yu, Hongjie; Cowling, Benjamin J.; El Guerche-Séblain, Clotilde; Mira-Iglesias, Ainara; Kisteneva, Lidiya; Stolyarov, Kirill; Yurtcu, Kubra; Feng, Luzhao; López-Labrador, Xavier; Burtseva, Elena

    2016-01-01

    Background The Global Influenza Hospital Surveillance Network was established in 2012 to obtain valid epidemiologic data on hospital admissions with influenza-like illness. Here we describe the epidemiology of admissions with influenza within the Northern Hemisphere sites during the 2013/2014 influenza season, identify risk factors for severe outcomes and complications, and assess the impact of different influenza viruses on clinically relevant outcomes in at-risk populations. Methods Eligible consecutive admissions were screened for inclusion at 19 hospitals in Russia, Turkey, China, and Spain using a prospective, active surveillance approach. Patients that fulfilled a common case definition were enrolled and epidemiological data were collected. Risk factors for hospitalization with laboratory-confirmed influenza were identified by multivariable logistic regression. Findings 5303 of 9507 consecutive admissions were included in the analysis. Of these, 1086 were influenza positive (534 A(H3N2), 362 A(H1N1), 130 B/Yamagata lineage, 3 B/Victoria lineage, 40 untyped A, and 18 untyped B). The risk of hospitalization with influenza (adjusted odds ratio [95% confidence interval]) was elevated for patients with cardiovascular disease (1.63 [1.33–2.02]), asthma (2.25 [1.67–3.03]), immunosuppression (2.25 [1.23–4.11]), renal disease (2.11 [1.48–3.01]), liver disease (1.94 [1.18–3.19], autoimmune disease (2.97 [1.58–5.59]), and pregnancy (3.84 [2.48–5.94]). Patients without comorbidities accounted for 60% of admissions with influenza. The need for intensive care or in-hospital death was not significantly different between patients with or without influenza. Influenza vaccination was associated with a lower risk of confirmed influenza (adjusted odds ratio = 0.61 [0.48–0.77]). Conclusions Influenza infection was detected among hospital admissions with and without known risk factors. Pregnancy and underlying comorbidity increased the risk of detecting influenza

  12. Cytokine release from human peripheral blood leucocytes incubated with endotoxin with and without prior infection with influenza virus

    DEFF Research Database (Denmark)

    Banner, Jytte; Smith, H; Sweet, C

    1993-01-01

    Previous work with a neonatal ferret model for human SIDS had indicated that inflammation caused by a combination of influenza virus and bacterial endotoxin may be a cause of human SIDS. To determine whether cytokines may be involved in this inflammatory response, levels of interleukin (IL)-1 beta......, IL-6 and tumour necrosis factor (TNF)-alpha were examined, using ELISA assays, in culture supernatants of human peripheral blood leucocytes infected with influenza virus and subsequently incubated with endotoxin. Levels of TNF-alpha were increased compared to cells incubated with virus or endotoxin...... alone. Levels of IL-1 beta were also increased whereas levels of IL-6 were generally not enhanced. Cytokines appeared within 1-2 h of stimulation with virus or endotoxin and increased subsequently to reach maximum titres between 16 and 20 h post treatment. While levels of cytokine were much lower when...

  13. In Vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination

    Directory of Open Access Journals (Sweden)

    Park Su-Jin

    2010-11-01

    Full Text Available Abstract Background Alpinia katsumadai (AK extracts and fractions were tested for in vitro antiviral activities against influenza virus type A, specially human A/PR/8/34 (H1N1 and avian A/Chicken/Korea/MS96/96 (H9N2, by means of time-of-addition experiments; pre-treatment, simultaneous treatment, and post treatment. Results In pre-treatment assay, the AK extracts and AK fractions did not show significant antiviral activity. During the simultaneous treatment assay, one AK extract and five AK fractions designated as AK-1 to AK-3, AK-5, AK-10, and AK-11 showed complete inhibition of virus infectivity against A/PR/8/34 (H1N1 and A/Chicken/Korea/MS96/96 (H9N2. The 50% effective inhibitory concentrations (EC50 of these one AK extracts and five AK fractions with exception of the AK-9 were from 0.8 ± 1.4 to 16.4 ± 4.5 μg/mL against A/PR/8/34 (H1N1. The two AK extracts and three AK fractions had EC50 values ranging from μg/mL against A/Chicken/Korea/MS96/96 (H9N2. By the hemagglutination inhibition (HI assay, the two AK extracts and five AK fractions completely inhibited viral adsorption onto chicken RBCs at less than 100 μg/mL against both A/PR/8/34 (H1N1 and A/Chicken/Korea/MS96/96 (H9N2. Interestingly, only AK-3 was found with inhibition for both viral attachment and viral replication after showing extended antiviral activity during the post treatment assay and quantitative real-time PCR. Conclusions These results suggest that AK extracts and fractions had strong anti-influenza virus activity that can inhibit viral attachment and/or viral replication, and may be used as viral prophylaxis.

  14. Culture confirmation of gonococcal infection by recall of subjects found to be positive by nucleic acid amplification tests in general practice

    DEFF Research Database (Denmark)

    Møller, Jens Kjølseth

    2010-01-01

    To evaluate a routine notification of general practitioners to recall nucleic acid amplification test (NAAT)-positive subjects for culture of Neisseria gonorrhoeae to confirm gonococcal infection in the community....

  15. ASSESSMENT OF EFFICACY IN APPLICATION OF TOPICAL IMMUNOLOGIC RESPONSE MODIFIER FOR PREVENTION OF INFLUENZA AND ACUTE RESPIRATORY INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    I.N. Lytkina

    2009-01-01

    Full Text Available The purpose of this work was to assess the efficacy of bacterial lysate for prevention of acute respiratory infections. The article provides results of monitoring children in the orphanage who were administered the medication of this group as a prophylactic drug against acute respiratory infections. Children also from orphanages who were not administered the medication were selected as a control group. It was found that out of 80 children who underwent preventive treatment, only 26 children fell ill, while out of 80 children in the control group so did 78 orphans. The results achieved allowed the topical immunologic response modifier to be recommended as a general preventive medication for wide use in children in the period of seasonal respiratory infection incidence rate pickup.Key words: influenza, acute respiratory infections, preventive treatment, children.

  16. Fucosyltransferase Induction during Influenza Virus Infection Is Required for the Generation of Functional Memory CD4+ T Cells

    Science.gov (United States)

    Carrette, Florent; Henriquez, Monique L.; Fujita, Yu

    2018-01-01

    T cells mediating influenza vira