WorldWideScience

Sample records for high growth influenza

  1. High growth reassortant influenza vaccine viruses: new approaches to their control.

    Science.gov (United States)

    Robertson, J S; Nicolson, C; Newman, R; Major, D; Dunleavy, U; Wood, J M

    1992-09-01

    When a new strain of an influenza virus is required to be incorporated into influenza vaccine, attempts are made to recombine such strains with laboratory adapted viruses, which will grow to high titre in order to improve the yield of the vaccine strain. It is important that such high growth reassortant vaccine strains are not contaminated with genes coding for the antigenic determinants of the high growth laboratory strain. We describe the characterization of two recent high growth reassortants and the application of the polymerase chain reaction to ensure their genetic identity and purity.

  2. Molecular signature of high yield (growth influenza a virus reassortants prepared as candidate vaccine seeds.

    Directory of Open Access Journals (Sweden)

    Manojkumar Ramanunninair

    Full Text Available Human influenza virus isolates generally grow poorly in embryonated chicken eggs. Hence, gene reassortment of influenza A wild type (wt viruses is performed with a highly egg adapted donor virus, A/Puerto Rico/8/1934 (PR8, to provide the high yield reassortant (HYR viral 'seeds' for vaccine production. HYR must contain the hemagglutinin (HA and neuraminidase (NA genes of wt virus and one to six 'internal' genes from PR8. Most studies of influenza wt and HYRs have focused on the HA gene. The main objective of this study is the identification of the molecular signature in all eight gene segments of influenza A HYR candidate vaccine seeds associated with high growth in ovo.The genomes of 14 wt parental viruses, 23 HYRs (5 H1N1; 2, 1976 H1N1-SOIV; 2, 2009 H1N1pdm; 2 H2N2 and 12 H3N2 and PR8 were sequenced using the high-throughput sequencing pipeline with big dye terminator chemistry.Silent and coding mutations were found in all internal genes derived from PR8 with the exception of the M gene. The M gene derived from PR8 was invariant in all 23 HYRs underlining the critical role of PR8 M in high yield phenotype. None of the wt virus derived internal genes had any silent change(s except the PB1 gene in X-157. The highest number of recurrent silent and coding mutations was found in NS. With respect to the surface antigens, the majority of HYRs had coding mutations in HA; only 2 HYRs had coding mutations in NA.In the era of application of reverse genetics to alter influenza A virus genomes, the mutations identified in the HYR gene segments associated with high growth in ovo may be of great practical benefit to modify PR8 and/or wt virus gene sequences for improved growth of vaccine 'seed' viruses.

  3. Adaptation of high-growth influenza H5N1 vaccine virus in Vero cells: implications for pandemic preparedness.

    Directory of Open Access Journals (Sweden)

    Yu-Fen Tseng

    Full Text Available Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14, a reassortant virus between A/Vietnam/1194/2004 (H5N1 virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15 was generated and can grow over 10(8 TCID(50/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes.

  4. Transforming growth factor-β: activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis.

    Directory of Open Access Journals (Sweden)

    Christina M Carlson

    2010-10-01

    Full Text Available Transforming growth factor-beta (TGF-β, a multifunctional cytokine regulating several immunologic processes, is expressed by virtually all cells as a biologically inactive molecule termed latent TGF-β (LTGF-β. We have previously shown that TGF-β activity increases during influenza virus infection in mice and suggested that the neuraminidase (NA protein mediates this activation. In the current study, we determined the mechanism of activation of LTGF-β by NA from the influenza virus A/Gray Teal/Australia/2/1979 by mobility shift and enzyme inhibition assays. We also investigated whether exogenous TGF-β administered via a replication-deficient adenovirus vector provides protection from H5N1 influenza pathogenesis and whether depletion of TGF-β during virus infection increases morbidity in mice. We found that both the influenza and bacterial NA activate LTGF-β by removing sialic acid motifs from LTGF-β, each NA being specific for the sialic acid linkages cleaved. Further, NA likely activates LTGF-β primarily via its enzymatic activity, but proteases might also play a role in this process. Several influenza A virus subtypes (H1N1, H1N2, H3N2, H5N9, H6N1, and H7N3 except the highly pathogenic H5N1 strains activated LTGF-β in vitro and in vivo. Addition of exogenous TGF-β to H5N1 influenza virus-infected mice delayed mortality and reduced viral titers whereas neutralization of TGF-β during H5N1 and pandemic 2009 H1N1 infection increased morbidity. Together, these data show that microbe-associated NAs can directly activate LTGF-β and that TGF-β plays a pivotal role protecting the host from influenza pathogenesis.

  5. Highly pathogenic avian influenza.

    Science.gov (United States)

    Swayne, D E; Suarez, D L

    2000-08-01

    Highly pathogenic (HP) avian influenza (AI) (HPAI) is an extremely contagious, multi-organ systemic disease of poultry leading to high mortality, and caused by some H5 and H7 subtypes of type A influenza virus, family Orthomyxoviridae. However, most AI virus strains are mildly pathogenic (MP) and produce either subclinical infections or respiratory and/or reproductive diseases in a variety of domestic and wild bird species. Highly pathogenic avian influenza is a List A disease of the Office International des Epizooties, while MPAI is neither a List A nor List B disease. Eighteen outbreaks of HPAI have been documented since the identification of AI virus as the cause of fowl plague in 1955. Mildly pathogenic avian influenza viruses are maintained in wild aquatic bird reservoirs, occasionally crossing over to domestic poultry and causing outbreaks of mild disease. Highly pathogenic avian influenza viruses do not have a recognised wild bird reservoir, but can occasionally be isolated from wild birds during outbreaks in domestic poultry. Highly pathogenic avian influenza viruses have been documented to arise from MPAI viruses through mutations in the haemagglutinin surface protein. Prevention of exposure to the virus and eradication are the accepted methods for dealing with HPAI. Control programmes, which imply allowing a low incidence of infection, are not an acceptable method for managing HPAI, but have been used during some outbreaks of MPAI. The components of a strategy to deal with MPAI or HPAI include surveillance and diagnosis, biosecurity, education, quarantine and depopulation. Vaccination has been used in some control and eradication programmes for AI.

  6. 76 FR 24793 - Highly Pathogenic Avian Influenza

    Science.gov (United States)

    2011-05-03

    .... APHIS-2006-0074] RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant Health... any subtype of highly pathogenic avian influenza is considered to exist. The interim rule also imposed... avian influenza, or that have moved through regions where any subtype of highly pathogenic avian...

  7. 77 FR 34783 - Highly Pathogenic Avian Influenza

    Science.gov (United States)

    2012-06-12

    ... [Docket No. APHIS-2006-0074] RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal and Plant... regions where any subtype of highly pathogenic avian influenza (HPAI) is considered to exist. The interim... avian influenza (HPAI). On January 24, 2011, we published in the Federal Register (76 FR 4046-4056...

  8. Current situation on highly pathogenic avian influenza

    Science.gov (United States)

    Avian influenza is one of the most important diseases affecting the poultry industry worldwide. Avian influenza viruses can cause a range of clinical disease in poultry. Viruses that cause severe disease and mortality are referred to as highly pathogenic avian influenza (HPAI) viruses. The Asian ...

  9. Novel H7N9 influenza virus shows low infectious dose, high growth rate, and efficient contact transmission in the guinea pig model.

    Science.gov (United States)

    Gabbard, Jon D; Dlugolenski, Daniel; Van Riel, Debby; Marshall, Nicolle; Galloway, Summer E; Howerth, Elizabeth W; Campbell, Patricia J; Jones, Cheryl; Johnson, Scott; Byrd-Leotis, Lauren; Steinhauer, David A; Kuiken, Thijs; Tompkins, S Mark; Tripp, Ralph; Lowen, Anice C; Steel, John

    2014-02-01

    The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation.

  10. Novel H7N9 Influenza Virus Shows Low Infectious Dose, High Growth Rate, and Efficient Contact Transmission in the Guinea Pig Model

    Science.gov (United States)

    Gabbard, Jon D.; Dlugolenski, Daniel; Van Riel, Debby; Marshall, Nicolle; Galloway, Summer E.; Howerth, Elizabeth W.; Campbell, Patricia J.; Jones, Cheryl; Johnson, Scott; Byrd-Leotis, Lauren; Steinhauer, David A.; Kuiken, Thijs; Tompkins, S. Mark; Tripp, Ralph; Lowen, Anice C.

    2014-01-01

    The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation. PMID:24227867

  11. USGS highly pathogenic avian influenza research strategy

    Science.gov (United States)

    Harris, M. Camille; Miles, A. Keith; Pearce, John M.; Prosser, Diann J.; Sleeman, Jonathan M.; Whalen, Mary E.

    2015-09-09

    Avian influenza viruses are naturally occurring in wild birds such as ducks, geese, swans, and gulls. These viruses generally do not cause illness in wild birds, however, when spread to poultry they can be highly pathogenic and cause illness and death in backyard and commercial farms. Outbreaks may cause devastating agricultural economic losses and some viral strains have the potential to infect people directly. Furthermore, the combination of avian influenza viruses with mammalian viruses can result in strains with the ability to transmit from person to person, possibly leading to viruses with pandemic potential. All known pandemic influenza viruses have had some genetic material of avian origin. Since 1996, a strain of highly pathogenic avian influenza (HPAI) virus, H5N1, has caused infection in wild birds, losses to poultry farms in Eurasia and North Africa, and led to the deaths of several hundred people. Spread of the H5N1 virus and other influenza strains from China was likely facilitated by migratory birds. In December 2014, HPAI was detected in poultry in Canada and migratory birds in the United States. Since then, HPAI viruses have spread to large parts of the United States and will likely continue to spread through migratory bird flyways and other mechanisms throughout North America. In the United States, HPAI viruses have severely affected the poultry industry with millions of domestic birds dead or culled. These strains of HPAI are not known to cause disease in humans; however, the Centers for Disease Control and Prevention (CDC) advise caution when in close contact with infected birds. Experts agree that HPAI strains currently circulating in wild birds of North America will likely persist for the next few years. This unprecedented situation presents risks to the poultry industry, natural resource management, and potentially human health. Scientific knowledge and decision support tools are urgently needed to understand factors affecting the persistence

  12. 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

  13. Novel H7N9 influenza virus shows low infectious dose, high growth rate, and efficient contact transmission in the Guinea pig model

    NARCIS (Netherlands)

    J.D. Gabbard (Jon); D. Dlugolenski (Daniel); D.A.J. van Riel (Debby); N. Marshall (Nicolle); S.E. Galloway (Summer); E.W. Howerth (Elizabeth); P.J. Campbell (Patricia); C. Jones (Catherine); S. Johnson (Scott); L. Byrd-Leotis (Lauren); L. Steinhauer (Laura); T. Kuiken (Thijs); S.M. Tompkins (S. Mark); R.A. Tripp (Ralph); A.C. Lowen (Anice); J. Steel (John)

    2014-01-01

    textabstractThe zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or

  14. Pathogenicity of highly pathogenic avian influenza virus in mammals

    NARCIS (Netherlands)

    de Wit, Emmie; Kawaoka, Yoshihiro; de Jong, Menno D.; Fouchier, Ron A. M.

    2008-01-01

    In recent years, there has been an increase in outbreaks of highly pathogenic avian influenza (HPAI) in poultry. Occasionally, these outbreaks have resulted in transmission of influenza viruses to humans and other mammals, with symptoms ranging from conjunctivitis to pneumonia and death. Here, the

  15. 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...

  16. (Highly pathogenic) avian influenza as a zoonotic agent.

    Science.gov (United States)

    Kalthoff, Donata; Globig, Anja; Beer, Martin

    2010-01-27

    Zoonotic agents challenging the world every year afresh are influenza A viruses. In the past, human pandemics caused by influenza A viruses had been occurring periodically. Wild aquatic birds are carriers of the full variety of influenza virus A subtypes, and thus, most probably constitute the natural reservoir of all influenza A viruses. Whereas avian influenza viruses in their natural avian reservoir are generally of low pathogenicity (LPAIV), some have gained virulence by mutation after transmission and adaptation to susceptible gallinaceous poultry. Those so-called highly pathogenic avian influenza viruses (HPAIV) then cause mass die-offs in susceptible birds and lead to tremendous economical losses when poultry is affected. Besides a number of avian influenza virus subtypes that have sporadically infected mammals, the HPAIV H5N1 Asia shows strong zoonotic characteristics and it was transmitted from birds to different mammalian species including humans. Theoretically, pandemic viruses might derive directly from avian influenza viruses or arise after genetic reassortment between viruses of avian and mammalian origin. So far, HPAIV H5N1 already meets two conditions for a pandemic virus: as a new subtype it has been hitherto unseen in the human population and it has infected at least 438 people, and caused severe illness and high lethality in 262 humans to date (August 2009). The acquisition of efficient human-to-human transmission would complete the emergence of a new pandemic virus. Therefore, fighting H5N1 at its source is the prerequisite to reduce pandemic risks posed by this virus. Other influenza viruses regarded as pandemic candidates derive from subtypes H2, H7, and H9 all of which have infected humans in the past. Here, we will give a comprehensive overview on avian influenza viruses in concern to their zoonotic potential. Copyright 2009 Elsevier B.V. All rights reserved.

  17. An Outbreak Of Highly Pathogenic Avian Influenza (Hpai) In A Mixed ...

    African Journals Online (AJOL)

    An Outbreak Of Highly Pathogenic Avian Influenza (Hpai) In A Mixed Farm By The Introduction Of A Water Fowl. ... C A Meseko, A T Oladokun, B Shehu. Abstract. Avian influenza (AI) is caused by a range of Influenza type A viruses of high and low pathogenicity (Fauci, 2005). H5N1 Highly Pathogenic Avian Influenza (HPAI) ...

  18. The epizootiology of the highly pathogenic avian influenza prior to ...

    African Journals Online (AJOL)

    The epizootiology of the highly pathogenic avian influenza prior to the anticipated pandemic of the early twenty first century. ... Transmission of highly pathogenic H5N1 from domestic fowls back to migratory waterfowl in western China has increased the geographic spread. This has grave consequences for the poultry ...

  19. [Highly pathogenic avian influenza--monitoring of migratory waterfowl].

    Science.gov (United States)

    Otsuki, Koichi; Ito, Toshihiro

    2006-10-01

    Since 1979, the group belonging to Departments of Veterinary Microbiology, Veterinary Public Health and the Avian Zoonoses Research Centre, Faculty of Agriculture, Tottori University is continuing isolation of avian influenza virus from such migratory waterfowls as whistling swan, pintail and tufted dugs flying from Siberia and/or northern China. They have already isolated many interesting influenza viruses. Serotype of the isolates is various; some H5 and H7 and human types of viruses were also isolated; and its pathogenicity for chickens is not high. It was interested that low pathogenic H5N3 virus isolated from whistling swan acquired severe pathogenicity during passage in chicks.

  20. 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...

  1. Influenza

    Directory of Open Access Journals (Sweden)

    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.

  2. Free-grazing ducks and highly pathogenic avian influenza, Thailand

    NARCIS (Netherlands)

    Gilbert, Marius; Chaitaweesup, P.; Parakamawongsa, T.; Premashthira, S.; Tiensin, T.; Kalpravidh, W.; Wagner, H.; Slingenbergh, J.

    Thailand has recently had 3 epidemic waves of highly pathogenic avian influenza (HPAI); virus was again detected in July 2005. Risk factors need to be identified to better understand disease ecology and assist HPAI surveillance and detection. This study analyzed the spatial distribution of HPAI

  3. Review of highly pathogenic avian influenza outbreaks in poultry in ...

    African Journals Online (AJOL)

    All the confirmed highly pathogenic avian influenza cases that were diagnosed in Zaria at the Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria, were reviewed in this study. The outbreaks occurred between the months of December, 2006 and March, 2007. The clinical signs and postmortem lesions ...

  4. Rapidly expanding range of highly pathogenic avian influenza viruses

    Science.gov (United States)

    Hall, Jeffrey S.; Dusek, Robert J.; Spackman, Erica

    2015-01-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus’ propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

  5. Transmission of highly pathogenic avian influenza H7 virus

    NARCIS (Netherlands)

    Bos, M.E.H.

    2009-01-01

    Knowledge of the transmission of highly pathogenic avian influenza (HPAI) virus still has gaps, complicating epidemic control. A model was developed to back-calculate the day HPAI virus was introduced into a flock, based on within-flock mortality data of the Dutch HPAI H7N7 epidemic (2003). The

  6. Do recommended high-risk adults benefit from a first influenza vaccination?

    NARCIS (Netherlands)

    Hak, E; Buskens, E; Nichol, K L; Verheij, T J M

    2006-01-01

    It is unknown whether a first influenza vaccination protects high-risk adults from severe morbidity and mortality during influenza epidemics. As part of the PRISMA nested case-control study, we aimed to evaluate the effectiveness of first-time and repeat influenza vaccinations in adult persons

  7. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    Energy Technology Data Exchange (ETDEWEB)

    Hashem, Anwar M. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada); Van Domselaar, Gary [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Li, Changgui; Wang, Junzhi [National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China); She, Yi-Min; Cyr, Terry D. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Sui, Jianhua [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); He, Runtao [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Marasco, Wayne A. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada)

    2010-12-10

    Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  8. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    International Nuclear Information System (INIS)

    Hashem, Anwar M.; Van Domselaar, Gary; Li, Changgui; Wang, Junzhi; She, Yi-Min; Cyr, Terry D.; Sui, Jianhua; He, Runtao; Marasco, Wayne A.; Li, Xuguang

    2010-01-01

    Research highlights: → The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. → Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. → The universal antibodies cross-neutralize different influenza A subtypes. → The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  9. (Highly pathogenic) Avian Influenza as a zoonotic agent

    OpenAIRE

    Kalthoff , Donata; Globig , Anja; Beer , Martin

    2010-01-01

    Summary Zoonotic agents challenging the world every year afresh are influenza A viruses. In the past, human pandemics caused by influenza A viruses had been occurring periodically. Wild aquatic birds are carriers of the full variety of influenza virus A subtypes, and thus, most probably constitute the natural reservoir of all influenza A viruses. Whereas avian influenza viruses in their natural avian reservoir are generally of low pathogenicity (LPAIV), some have gained virulence b...

  10. Mutations to PB2 and NP proteins of an avian influenza virus combine to confer efficient growth in primary human respiratory cells.

    Science.gov (United States)

    Danzy, Shamika; Studdard, Lydia R; Manicassamy, Balaji; Solorzano, Alicia; Marshall, Nicolle; García-Sastre, Adolfo; Steel, John; Lowen, Anice C

    2014-11-01

    Influenza pandemics occur when influenza A viruses (IAV) adapted to other host species enter humans and spread through the population. Pandemics are relatively rare due to host restriction of IAV: strains adapted to nonhuman species do not readily infect, replicate in, or transmit among humans. IAV can overcome host restriction through reassortment or adaptive evolution, and these are mechanisms by which pandemic strains arise in nature. To identify mutations that facilitate growth of avian IAV in humans, we have adapted influenza A/duck/Alberta/35/1976 (H1N1) (dk/AB/76) virus to a high-growth phenotype in differentiated human tracheo-bronchial epithelial (HTBE) cells. Following 10 serial passages of three independent lineages, the bulk populations showed similar growth in HTBE cells to that of a human seasonal virus. The coding changes present in six clonal isolates were determined. The majority of changes were located in the polymerase complex and nucleoprotein (NP), and all isolates carried mutations in the PB2 627 domain and regions of NP thought to interact with PB2. Using reverse genetics, the impact on growth and polymerase activity of individual and paired mutations in PB2 and NP was evaluated. The results indicate that coupling of the mammalian-adaptive mutation PB2 E627K or Q591K to selected mutations in NP further augments the growth of the corresponding viruses. In addition, minimal combinations of three (PB2 Q236H, E627K, and NP N309K) or two (PB2 Q591K and NP S50G) mutations were sufficient to recapitulate the efficient growth in HTBE cells of dk/AB/76 viruses isolated after 10 passages in this substrate. Influenza A viruses adapted to birds do not typically grow well in humans. However, as has been seen recently with H5N1 and H7N9 subtype viruses, productive and virulent infection of humans with avian influenza viruses can occur. The ability of avian influenza viruses to adapt to new host species is a consequence of their high mutation rate that

  11. USGS role and response to highly pathogenic avian influenza

    Science.gov (United States)

    Harris, M. Camille; Miles, A. Keith; Pearce, John M.; Prosser, Diann J.; Sleeman, Jonathan M.; Whalen, Mary E.

    2015-09-09

    Avian influenza viruses are naturally occurring in wild birds such as ducks, geese, swans, and gulls. These viruses generally do not cause illness in wild birds, however, when spread to poultry they can be highly pathogenic and cause illness and death in backyard and commercial farms. Outbreaks may cause devastating agricultural economic losses and some viral strains have the potential to infect people directly. Furthermore, the combination of avian influenza viruses with mammalian viruses can result in strains with the ability to transmit from person to person, possibly leading to viruses with pandemic potential. All known pandemic influenza viruses have had some genetic material of avian origin. Since 1996, a strain of highly pathogenic avian influenza (HPAI) virus, H5N1, has caused infection in wild birds, losses to poultry farms in Eurasia and North Africa, and led to the deaths of several hundred people. Spread of the H5N1 virus and other influenza strains from China was likely facilitated by migratory birds. In December 2014, HPAI was detected in poultry in Canada and migratory birds in the United States. Since then, HPAI viruses have spread to large parts of the United States and will likely continue to spread through migratory bird flyways and other mechanisms throughout North America. In the United States, HPAI viruses have severely affected the poultry industry with millions of domestic birds dead or culled. These strains of HPAI are not known to cause disease in humans; however, the Centers for Disease Control and Prevention (CDC) advise caution when in close contact with infected birds. Experts agree that HPAI strains currently circulating in wild birds of North America will likely persist for the next few years. This unprecedented situation presents risks to the poultry industry, natural resource management, and potentially human health. Scientific knowledge and decision support tools are urgently needed to understand factors affecting the persistence

  12. Influenza or not influenza: Analysis of a case of high fever that happened 2000 years ago in Biblical time

    Directory of Open Access Journals (Sweden)

    Leung Ting F

    2010-07-01

    Full Text Available Abstract The Bible describes the case of a woman with high fever cured by our Lord Jesus Christ. Based on the information provided by the gospels of Mark, Matthew and Luke, the diagnosis and the possible etiology of the febrile illness is discussed. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. If the postulation is indeed correct, the woman with fever in the Bible is among one of the very early description of human influenza disease. Infectious diseases continue to be a threat to humanity, and influenza has been with us since the dawn of human history. We analysed a case of high fever that happened 2000 years ago in Biblical time and discussed possible etiologies.

  13. Emerging influenza

    NARCIS (Netherlands)

    E. de Wit (Emmie); R.A.M. Fouchier (Ron)

    2008-01-01

    textabstractIn 1918 the Spanish influenza pandemic, caused by an avian H1N1 virus, resulted in over 50 million deaths worldwide. Several outbreaks of H7 influenza A viruses have resulted in human cases, including one fatal case. Since 1997, the outbreaks of highly pathogenic avian influenza (HPAI)

  14. Genetic Data Provide Evidence for Wind-Mediated Transmission of Highly Pathogenic Avian Influenza

    NARCIS (Netherlands)

    Ypma, R.J.F.; Jonges, M.; Bataille, A.M.A.; Stegeman, J.A.; Koch, G.; van Boven, R.M.; Koopmans, M.; van Ballegooijen, W.M.; Wallinga, J.

    2013-01-01

    Outbreaks of highly pathogenic avian influenza in poultry can cause severe economic damage and represent a public health threat. Development of efficient containment measures requires an understanding of how these influenza viruses are transmitted between farms. However, the actual mechanisms of

  15. Serosurvey of antibody to highly pathogenic avian influenza (H5N1 ...

    African Journals Online (AJOL)

    Avian influenza is a disease of economic and public health importance that has been described in most domestic animals and humans. Highly pathogenic avian influenza H5N1 epidemic in Nigeria was observed in agro-ecological zones where pigs and chickens are raised in shared environment with chances of ...

  16. Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh

    DEFF Research Database (Denmark)

    Haider, Najmul; Sturm-Ramirez, K.; Khan, S. U.

    2017-01-01

    a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize...... and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5......Mortality in ducks and geese caused by highly pathogenic avian influenza A(H5N1) infection had not been previously identified in Bangladesh. In June-July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify...

  17. 75 FR 69046 - Notice of Determination of the High Pathogenic Avian Influenza Subtype H5N1 Status of Czech...

    Science.gov (United States)

    2010-11-10

    ... Avian Influenza Subtype H5N1 Status of Czech Republic and Sweden AGENCY: Animal and Plant Health... the highly pathogenic avian influenza (HPAI) subtype H5N1 status of the Czech Republic and Sweden... status of the Czech Republic and Sweden relative to highly pathogenic avian influenza (HPAI) subtype H5N1...

  18. Strategy for distribution of influenza vaccine to high-risk groups and children.

    Science.gov (United States)

    Longini, Ira M; Halloran, M Elizabeth

    2005-02-15

    Despite evidence that vaccinating schoolchildren against influenza is effective in limiting community-level transmission, the United States has had a long-standing government strategy of recommending that vaccine be concentrated primarily in high-risk groups and distributed to those people who keep the health system and social infrastructure operating. Because of this year's influenza vaccine shortage, a plan was enacted to distribute the limited vaccine stock to these groups first. This vaccination strategy, based on direct protection of those most at risk, has not been very effective in reducing influenza morbidity and mortality. Although it is too late to make changes this year, the current influenza vaccine crisis affords the opportunity to examine an alternative for future years. The alternative plan, supported by mathematical models and influenza field studies, would be to concentrate vaccine in schoolchildren, the population group most responsible for transmission, while also covering the reachable high-risk groups, who would also receive considerable indirect protection. In conjunction with a plan to ensure an adequate vaccine supply, this alternative influenza vaccination strategy would help control interpandemic influenza and be instrumental in preparing for pandemic influenza. The effectiveness of the alternative plan could be assessed through nationwide community studies.

  19. Highly Pathogenic Avian Influenza Virus among Wild Birds in Mongolia

    Science.gov (United States)

    Gilbert, Martin; Jambal, Losolmaa; Karesh, William B.; Fine, Amanda; Shiilegdamba, Enkhtuvshin; Dulam, Purevtseren; Sodnomdarjaa, Ruuragchaa; Ganzorig, Khuukhenbaatar; Batchuluun, Damdinjav; Tseveenmyadag, Natsagdorj; Bolortuya, Purevsuren; Cardona, Carol J.; Leung, Connie Y. H.; Peiris, J. S. Malik; Spackman, Erica; Swayne, David E.; Joly, Damien O.

    2012-01-01

    Mongolia combines a near absence of domestic poultry, with an abundance of migratory waterbirds, to create an ideal location to study the epidemiology of highly pathogenic avian influenza virus (HPAIV) in a purely wild bird system. Here we present the findings of active and passive surveillance for HPAIV subtype H5N1 in Mongolia from 2005–2011, together with the results of five outbreak investigations. In total eight HPAIV outbreaks were confirmed in Mongolia during this period. Of these, one was detected during active surveillance employed by this project, three by active surveillance performed by Mongolian government agencies, and four through passive surveillance. A further three outbreaks were recorded in the neighbouring Tyva Republic of Russia on a lake that bisects the international border. No HPAIV was isolated (cultured) from 7,855 environmental fecal samples (primarily from ducks), or from 2,765 live, clinically healthy birds captured during active surveillance (primarily shelducks, geese and swans), while four HPAIVs were isolated from 141 clinically ill or dead birds located through active surveillance. Two low pathogenic avian influenza viruses (LPAIV) were cultured from ill or dead birds during active surveillance, while environmental feces and live healthy birds yielded 56 and 1 LPAIV respectively. All Mongolian outbreaks occurred in 2005 and 2006 (clade 2.2), or 2009 and 2010 (clade 2.3.2.1); all years in which spring HPAIV outbreaks were reported in Tibet and/or Qinghai provinces in China. The occurrence of outbreaks in areas deficient in domestic poultry is strong evidence that wild birds can carry HPAIV over at least moderate distances. However, failure to detect further outbreaks of clade 2.2 after June 2006, and clade 2.3.2.1 after June 2010 suggests that wild birds migrating to and from Mongolia may not be competent as indefinite reservoirs of HPAIV, or that HPAIV did not reach susceptible populations during our study. PMID:22984464

  20. 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.

  1. Expected cost effectiveness of high-dose trivalent influenza vaccine in US seniors.

    Science.gov (United States)

    Chit, Ayman; Roiz, Julie; Briquet, Benjamin; Greenberg, David P

    2015-01-29

    Seniors are particularly vulnerable to complications resulting from influenza infection. Numerous influenza vaccines are available to immunize US seniors, and practitioners must decide which product to use. Options include trivalent and quadrivalent standard-dose inactivated influenza vaccines (IIV3 and IIV4 respectively), as well as a high-dose IIV3 (HD). Our research examines the public health impact, budget impact, and cost-utility of HD versus IIV3 and IIV4 for immunization of US seniors 65 years of age and older. Our model was based on US influenza-related health outcome data. Health care costs and vaccine prices were obtained from the Centers for Medicare and Medicaid Services. Efficacies of IIV3 and IIV4 were estimated from various meta-analyses of IIV3 efficacy. The results of a head-to-head randomized controlled trial of HD vs. IIV3 were used to estimate relative efficacy of HD. Conservatively, herd protection was not considered. Compared to IIV3, HD would avert 195,958 cases of influenza, 22,567 influenza-related hospitalizations, and 5423 influenza-related deaths among US seniors. HD generates 29,023 more Quality Adjusted Life Years (QALYs) and a net societal budget impact of $154 million. The Incremental Cost Effectiveness Ratio (ICER) for this comparison is $5299/QALY. 71% of the probabilistic sensitivity analysis (PSA) simulations were seniors. Our conclusions were robust in the face of sensitivity analyses. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus

    OpenAIRE

    Ma, Jingjiao; Lee, Jinhwa; Liu, Haixia; Mena, Ignacio; Davis, A. Sally; Sunwoo, Sun Young; Lang, Yuekun; Duff, Michael; Morozov, Igor; Li, Yuhao; Yang, Jianmei; García-Sastre, Adolfo; Richt, Juergen A.; Ma, Wenjun

    2017-01-01

    Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5Nx viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines ha...

  3. Highly pathogenic avian influenza viruses and generation of novel reassortants,United States, 2014–2015

    Science.gov (United States)

    Dong-Hun Lee,; Justin Bahl,; Mia Kim Torchetti,; Mary Lea Killian,; Ip, Hon S.; David E Swayne,

    2016-01-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses.

  4. Outbreak of highly pathogenic avian influenza in Minnesota in 2015.

    Science.gov (United States)

    Fitzpatrick, Ann; Mor, Sunil K; Thurn, Mary; Wiedenman, Elizabeth; Otterson, Tracy; Porter, Robert E; Patnayak, Devi P; Lauer, Dale C; Voss, Shauna; Rossow, Stephanie; Collins, James E; Goyal, Sagar M

    2017-03-01

    The incursion of highly pathogenic avian influenza (HPAI) into the United States during 2014 resulted in an unprecedented foreign animal disease (FAD) event; 232 outbreaks were reported from 21 states. The disease affected 49.6 million birds and resulted in economic losses of $950 million. Minnesota is the largest turkey-producing state, accounting for 18% of U.S. turkey production. Areas with concentrated numbers of turkeys in Minnesota were the epicenter of the outbreak. The first case was presumptively diagnosed in the last week of February 2015 at the Minnesota Veterinary Diagnostic Laboratory (MVDL) and confirmed as HPAI H5N2 at the National Veterinary Services Laboratories on March 4, 2015. A total of 110 farms were affected in Minnesota, and the MVDL tested >17,000 samples from March to July 2015. Normal service was maintained to other clients of the laboratory during this major FAD event, but challenges were encountered with communications, staff burnout and fatigue, training requirements of volunteer technical staff, test kit validation, and management of specific pathogen-free egg requirements.

  5. "Boom" and "Bust" cycles in virus growth suggest multiple selective forces in influenza a evolution

    Directory of Open Access Journals (Sweden)

    Marquart Mary E

    2011-04-01

    Full Text Available Abstract Background Influenza A virus evolution in humans is driven at least in part by mutations allowing the virus to escape antibody neutralization. Little is known about the evolution of influenza in birds, a major reservoir of influenza A. Methods Neutralizing polyclonal antiserum was raised in chicken against reassortant influenza virus, CalX, bearing the hemagglutinin (HA and neuraminidase (NA of A/California/7/2004 [H3N2]. CalX was serially passaged in the presence of anti-CalX polyclonal IgY to derive viruses capable of growth in the presence of antibody. Results Polyclonal chicken antibody neutralized both HA activity and infection by CalX, but had no effect on a strain bearing an earlier human H3 and an irrelevant neuraminidase (A/Memphis/71-Bellamy/42 [H3N1]. Surprisingly, most of the antibody-resistant viruses were still at least partially sensitive to neutralization of HA activity and viral infection. Although mutant HA genes bearing changes that might affect antibody neutralization were identified, the vast majority of HA sequences obtained were identical to wild type, and no individual mutant sequence was found in more than one passage, suggesting that those mutations that were observed did not confer sufficient selective advantage to come to dominate the population. Different passages yielded infectious foci of varying size and plaques of varying size and morphology. Yields of infectious virus and relative frequency of different morphologies changed markedly from passage to passage. Sequences of bulk, uncloned PCR products from antibody-resistant passages indicated changes in the PB2 and PA proteins with respect to the wild type virus. Conclusions Each antibody-selected passage consisted of a variety of different cocirculating populations, rather than pure populations of virus able to escape antibody by changes in antibody epitopes. The ability to escape antibody is apparently due to changes in genes encoding the viral

  6. Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.

    Science.gov (United States)

    Hussain, Althaf I; Cordeiro, Melissa; Sevilla, Elizabeth; Liu, Jonathan

    2010-05-14

    Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced

  7. Motivating factors for high rates of influenza vaccination among healthcare workers.

    Science.gov (United States)

    Hakim, Hana; Gaur, Aditya H; McCullers, Jonathan A

    2011-08-11

    Recent guidance from related regulatory agencies and medical societies supports mandatory vaccination of healthcare workers (HCW) against influenza. At St. Jude Children's Research Hospital, a pediatric oncology referral center, more than 90% of HCWs receive vaccine each year without a policy mandating immunization. Factors associated with HCW uptake of influenza vaccines have not previously been evaluated in a high compliance rate setting. A structured, anonymous, electronic questionnaire was distributed in August 2010 to employees (HCW and non-HCW). Demographics, prior receipt of influenza vaccines, reasons for acceptance or refusal of seasonal and 2009 H1N1 pandemic vaccine, and attitudes on mandatory vaccination were assessed. 95.0% of 925 HCWs and 63.1% of all 3227 qualifying employees responded to the survey. 93.8% and 75.2% of HCW reported receiving seasonal and 2009 H1N1 influenza vaccines, respectively, in the 2009-2010 season. Benefits to self and/or patients were cited as the most frequent reasons for accepting seasonal (83.5% and 78.3%, respectively) and 2009 H1N1 (85.9% and 81.1%, respectively) vaccination. 36.6% of HCWs opposed mandating influenza vaccination; 88.2% and 59.9% of whom reported receiving the seasonal and 2009 H1N1 influenza vaccines, respectively. Violation of freedom of choice and personal autonomy were the most frequently reported reasons for opposition. In this cohort of HCWs with a high influenza vaccination rate, realistic assessments of the potential benefits of vaccination appear to have driven the choice to accept immunization. Despite this, mandating vaccination was viewed unfavorably by a significant minority of vaccinated individuals. Employee concerns over autonomy should be addressed as institutions transition to mandatory vaccination policies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. 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)

  9. Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1

    Directory of Open Access Journals (Sweden)

    Sosna William A

    2010-09-01

    Full Text Available Abstract Background There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1 virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1 through intranasal verses inhalation routes was analyzed. Results Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1. The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret. Conclusions Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1 is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.

  10. Immune response to inactivated influenza virus vaccine: antibody reactivity with epidemic influenza B viruses of two highly distinct evolutionary lineages.

    Science.gov (United States)

    Pyhälä, R; Kleemola, M; Kumpulainen, V; Vartiainen, E; Lappi, S; Pönkä, A; Cantell, K

    1992-01-01

    Vaccination of adults (healthy female employees potentially capable of transmitting influenza to high-risk persons; n = 104) in autumn 1990 with a trivalent influenza virus vaccine containing B/Yamagata/16/88 induced a low antibody response to B/Finland/150/90, a recent variant of B/Victoria/2/87-like viruses, as compared with the antibody response to B/Finland/172/91, a current variant in the lineage of B/Yamagata/16/88-like viruses. Up to the end of the epidemic season, the antibody status declined but was still significantly better than before the vaccination. The results suggest that the vaccine strain was appropriate for the outbreak of 1990 to 1991 in Finland, but may provide unsatisfactory protection against B/Victoria/2/87-like viruses. Evidence is given that use of Madin-Darby canine kidney (MDCK)-grown virus as an antigen in the haemagglutination inhibition test (HI) may provide more reliable information about the protective antibodies than use of untreated or ether-treated egg-grown viruses. Significantly higher postvaccination and postepidemic antibody titres were recorded among subjects who exhibited the antibody before vaccination than among seronegative subjects. A significantly higher response rate among initially seronegative people than among seropositive people was recorded for antibody to B/Finland/150/90, but no clear evidence was obtained that the pre-existing antibody could have had a negative effect on the antibody production.

  11. 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

  12. Genetic data provide evidence for wind-mediated transmission of highly pathogenic avian influenza.

    Science.gov (United States)

    Ypma, Rolf J F; Jonges, Marcel; Bataille, Arnaud; Stegeman, Arjan; Koch, Guus; van Boven, Michiel; Koopmans, Marion; van Ballegooijen, W Marijn; Wallinga, Jacco

    2013-03-01

    Outbreaks of highly pathogenic avian influenza in poultry can cause severe economic damage and represent a public health threat. Development of efficient containment measures requires an understanding of how these influenza viruses are transmitted between farms. However, the actual mechanisms of interfarm transmission are largely unknown. Dispersal of infectious material by wind has been suggested, but never demonstrated, as a possible cause of transmission between farms. Here we provide statistical evidence that the direction of spread of avian influenza A(H7N7) is correlated with the direction of wind at date of infection. Using detailed genetic and epidemiological data, we found the direction of spread by reconstructing the transmission tree for a large outbreak in the Netherlands in 2003. We conservatively estimate the contribution of a possible wind-mediated mechanism to the total amount of spread during this outbreak to be around 18%.

  13. Deaths among wild birds during highly pathogenic avian influenza A(H5N8) virus outbreak, the Netherlands

    NARCIS (Netherlands)

    Kleyheeg, Erik; Slaterus, Roy; Bodewes, Rogier; Rijks, Jolianne M.; Spierenburg, Marcel A.H.; Beerens, Nancy; Kelder, Leon; Poen, Marjolein J.; Stegeman, Jan A.; Fouchier, Ron A.M.; Kuiken, Thijs; Jeugd, van der Henk P.

    2017-01-01

    During autumn–winter 2016–2017, highly pathogenic avian influenza A(H5N8) viruses caused mass die-offs among wild birds in the Netherlands. Among the ≈13,600 birds reported dead, most were tufted ducks (Aythya fuligula) and Eurasian wigeons (Anas penelope). Recurrence of avian influenza outbreaks

  14. An emerging avian influenza A virus H5N7 is a genetic reassortant of highly pathogenic genes

    DEFF Research Database (Denmark)

    Bragstad, K.; Jørgensen, Poul Henrik; Handberg, Kurt

    2006-01-01

    We full genome characterised the newly discovered avian influenza virus H5N7 subtype combination isolated from a stock of Danish game ducks to investigate the composition of the genome and possible features of high pathogenicity. It was found that the haemagglutinin and the acidic polymerase gene...... low pathogenic avian influenza A viruses. (c) 2006 Elsevier Ltd. All rights reserved....

  15. Deaths among Wild Birds during Highly Pathogenic Avian Influenza A(H5N8) Virus Outbreak, the Netherlands

    NARCIS (Netherlands)

    Kleyheeg, Erik; Slaterus, Roy; Bodewes, Rogier; Rijks, Jolianne M.; Spierenburg, Marcel A.H.; Beerens, Nancy; Kelder, Leon; Poen, Marjolein J.; Stegeman, Jan A.; Fouchier, Ron A. M.; Kuiken, Thijs; Jeugd, Henk P. van der

    2017-01-01

    During autumn–winter 2016–2017, highly pathogenic avian influenza A(H5N8) viruses caused mass die-offs among wild birds in the Netherlands. Among the ≈13,600 birds reported dead, most were tufted ducks (Aythya fuligula) and Eurasian wigeons (Anas penelope). Recurrence of avian influenza outbreaks

  16. Isolation of a highly pathogenic influenza virus from turkeys.

    Science.gov (United States)

    McNulty, M S; Allan, G M; McCracken, R M; McParland, P J

    1985-01-01

    An influenza virus was isolated from turkeys with an acute disease causing 30% mortality. The virus was subtyped as H5 N8. The nomenclature A/turkey/Ireland/83 (H5 N8) is proposed for this isolate. The virus had an ICPI of 1.80 to 1.85 for 1-day-old chicks and an IVPI of 2.74 for 6-week-old chickens. Following oronasal inoculation of juvenile and adult turkeys, chickens and ducks with the isolate, 100% mortality occurred in turkeys and chickens. No clinical signs were observed in inoculated ducks, but all developed serum antibody titres against the virus.

  17. Influenza vaccination coverage and reasons to refrain among high-risk persons in four European countries.

    NARCIS (Netherlands)

    Kroneman, M.; Essen, G.A. van; Paget, J.

    2006-01-01

    This paper examines influenza vaccine coverage using a population base of an average of 2300 persons in each of four European countries (Germany, Spain, Poland and Sweden). The reasons for non-vaccination of those in the high-risk groups were explored by questionnaire. The vaccine coverage rate

  18. Novel Eurasian Highly Pathogenic Influenza A H5 Viruses in Wild Birds, Washington, USA, 2014

    Centers for Disease Control (CDC) Podcasts

    2015-03-24

    Sarah Gregory reads an abridged version of the article, Novel Eurasian Highly Pathogenic Influenza A H5 Viruses in Wild Birds, Washington, USA, 2014.  Created: 3/24/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/13/2015.

  19. Use of Epidemiologic Models in the Control of Highly Pathogenic Avian Influenza

    NARCIS (Netherlands)

    Stegeman, J.A.; Bouma, A.; Jong, de M.C.M.

    2010-01-01

    In the past decades, mathematical models have become more and more accepted as a tool to develop surveillance programs and to evaluate the efficacy of intervention measures for the control of infectious diseases such as highly pathogenic avian influenza. Predictive models are used to simulate the

  20. Epidemiological models to assist the management of highly pathogenic avian influenza

    NARCIS (Netherlands)

    Stegeman, J.A.; Bouma, A.; Jong, de M.C.M.

    2011-01-01

    In recent decades, epidemiological models have been used more and more frequently as a tool for the design of programmes for the management of infectious diseases such as highly pathogenic avian influenza. Predictive models are used to simulate the effects of various control measures on the spread

  1. Highly pathogenic avian influenza H5N1 in Mainland China

    NARCIS (Netherlands)

    X.-L. Li (Xin-Lou); K. Liu (Kun); H.-W. Yao (Hong-Wu); Y. Sun (Ye); W.-J. Chen (Wan-Jun); R.-X. Sun (Ruo-Xi); S.J. de Vlas (Sake); L.Q. Fang (Lily); W.-C. Cao (Wu-Chun)

    2015-01-01

    textabstractHighly pathogenic avian influenza (HPAI) H5N1 has posed a significant threat to both humans and birds, and it has spanned large geographic areas and various ecological systems throughout Asia, Europe and Africa, but especially in mainland China. Great efforts in control and prevention of

  2. Novel Eurasian highly pathogenic influenza A H5 viruses in wild birds, Washington, USA

    Science.gov (United States)

    Ip, Hon S.; Kim Torchetti, Mia; Crespo, Rocio; Kohrs, Paul; DeBruyn, Paul; Mansfield, Kristin G.; Baszler, Timothy; Badcoe, Lyndon; Bodenstein, Barbara L.; Shearn-Bochsler, Valerie I.; Killian, Mary Lea; Pederson, Janice C.; Hines, Nichole; Gidlewski, Thomas; DeLiberto, Thomas; Sleeman, Jonathan M.

    2015-01-01

    Novel Eurasian lineage avian influenza A(H5N8) virus has spread rapidly and globally since January 2014. In December 2014, H5N8 and reassortant H5N2 viruses were detected in wild birds in Washington, USA, and subsequently in backyard birds. When they infect commercial poultry, these highly pathogenic viruses pose substantial trade issues.

  3. Highly pathogenic avian influenza virus (H5N1) isolated from whooper swans, Japan.

    Science.gov (United States)

    Uchida, Yuko; Mase, Masaji; Yoneda, Kumiko; Kimura, Atsumu; Obara, Tsuyoshi; Kumagai, Seikou; Saito, Takehiko; Yamamoto, Yu; Nakamura, Kikuyasu; Tsukamoto, Kenji; Yamaguchi, Shigeo

    2008-09-01

    On April 21, 2008, four whooper swans were found dead at Lake Towada, Akita prefecture, Japan. Highly pathogenic avian influenza virus of the H5N1 subtype was isolated from specimens of the affected birds. The hemagglutinin (HA) gene of the isolate belongs to clade 2.3.2 in the HA phylogenetic tree.

  4. Novel Eurasian highly pathogenic avian influenza A H5 viruses in wild birds, Washington, USA, 2014.

    Science.gov (United States)

    Ip, Hon S; Torchetti, Mia Kim; Crespo, Rocio; Kohrs, Paul; DeBruyn, Paul; Mansfield, Kristin G; Baszler, Timothy; Badcoe, Lyndon; Bodenstein, Barbara; Shearn-Bochsler, Valerie; Killian, Mary Lea; Pedersen, Janice C; Hines, Nichole; Gidlewski, Thomas; DeLiberto, Thomas; Sleeman, Jonathan M

    2015-05-01

    Novel Eurasian lineage avian influenza A(H5N8) virus has spread rapidly and globally since January 2014. In December 2014, H5N8 and reassortant H5N2 viruses were detected in wild birds in Washington, USA, and subsequently in backyard birds. When they infect commercial poultry, these highly pathogenic viruses pose substantial trade issues.

  5. Silent spread of highly pathogenic Avian Influenza H5N1 virus amongst vaccinated commercial layers

    NARCIS (Netherlands)

    Poetri, O.N.; Boven, M.; Claassen, I.J.T.M.; Koch, G.; Wibawan, I.W.; Stegeman, A.; Broek, van den J.; Bouma, A.

    2014-01-01

    The aim of this study was to determine whether a single vaccination of commercial layer type chickens with an inactivated vaccine containing highly pathogenic avian influenza virus strain H5N1 A/chicken/Legok/2003, carried out on the farm, was sufficient to protect against infection with the

  6. Controlling highly pathogenic avian influenza outbreaks : An epidemiological and economic model analysis

    NARCIS (Netherlands)

    Backer, J. A.; van Roermund, H. J W; Fischer, Egil; van Asseldonk, M. A P M; Bergevoet, R. H M

    2015-01-01

    Outbreaks of highly pathogenic avian influenza (HPAI) can cause large losses for the poultry sector and for animal disease controlling authorities, as well as risks for animal and human welfare. In the current simulation approach epidemiological and economic models are combined to compare different

  7. Towards an improved vaccination programme against highly pathogenic avian influenza in Indonesia

    NARCIS (Netherlands)

    Poetri, O.N.

    2014-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 are considered to be a major threat for both the poultry industry and public health, and Indonesia is one of the HPAI H5N1 endemic country with the highest incidence of human cases worldwide. The control measures of HPAI, like stamping-out were

  8. Simultaneous and complete genome sequencing of influenza A and B with high coverage by Illumina MiSeq Platform.

    Science.gov (United States)

    Rutvisuttinunt, Wiriya; Chinnawirotpisan, Piyawan; Simasathien, Sriluck; Shrestha, Sanjaya K; Yoon, In-Kyu; Klungthong, Chonticha; Fernandez, Stefan

    2013-11-01

    Active global surveillance and characterization of influenza viruses are essential for better preparation against possible pandemic events. Obtaining comprehensive information about the influenza genome can improve our understanding of the evolution of influenza viruses and emergence of new strains, and improve the accuracy when designing preventive vaccines. This study investigated the use of deep sequencing by the next-generation sequencing (NGS) Illumina MiSeq Platform to obtain complete genome sequence information from influenza virus isolates. The influenza virus isolates were cultured from 6 respiratory acute clinical specimens collected in Thailand and Nepal. DNA libraries obtained from each viral isolate were mixed and all were sequenced simultaneously. Total information of 2.6 Gbases was obtained from a 455±14 K/mm2 density with 95.76% (8,571,655/8,950,724 clusters) of the clusters passing quality control (QC) filters. Approximately 93.7% of all sequences from Read1 and 83.5% from Read2 contained high quality sequences that were ≥Q30, a base calling QC score standard. Alignments analysis identified three seasonal influenza A H3N2 strains, one 2009 pandemic influenza A H1N1 strain and two influenza B strains. The nearly entire genomes of all six virus isolates yielded equal or greater than 600-fold sequence coverage depth. MiSeq Platform identified seasonal influenza A H3N2, 2009 pandemic influenza A H1N1and influenza B in the DNA library mixtures efficiently. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh

    Science.gov (United States)

    Haider, N.; Sturm-Ramirez, K.; Khan, S. U.; Rahman, M. Z.; Sarkar, S.; Poh, M. K.; Shivaprasad, H. L.; Kalam, M. A.; Paul, S. K.; Karmakar, P. C.; Balish, A.; Chakraborty, A.; Mamun, A. A.; Mikolon, A. B.; Davis, C. T.; Rahman, M.; Donis, R. O.; Heffelfinger, J. D.; Luby, S. P.; Zeidner, N.

    2015-01-01

    Summary Mortality in ducks and geese caused by highly pathogenic avian influenza A (H5N1) infection had not been previously identified in Bangladesh. In June–July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize influenza virus infection. In the six villages, among the 240 surveyed households and 11 small-scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide

  10. Unusually High Mortality in Waterfowl Caused by Highly Pathogenic Avian Influenza A(H5N1) in Bangladesh.

    Science.gov (United States)

    Haider, N; Sturm-Ramirez, K; Khan, S U; Rahman, M Z; Sarkar, S; Poh, M K; Shivaprasad, H L; Kalam, M A; Paul, S K; Karmakar, P C; Balish, A; Chakraborty, A; Mamun, A A; Mikolon, A B; Davis, C T; Rahman, M; Donis, R O; Heffelfinger, J D; Luby, S P; Zeidner, N

    2017-02-01

    Mortality in ducks and geese caused by highly pathogenic avian influenza A(H5N1) infection had not been previously identified in Bangladesh. In June-July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize influenza virus infection. In the six villages, among the 240 surveyed households and 11 small-scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide appropriate

  11. Rapid and highly informative diagnostic assay for H5N1 influenza viruses.

    Directory of Open Access Journals (Sweden)

    Nader Pourmand

    Full Text Available A highly discriminative and information-rich diagnostic assay for H5N1 avian influenza would meet immediate patient care needs and provide valuable information for public health interventions, e.g., tracking of new and more dangerous variants by geographic area as well as avian-to-human or human-to-human transmission. In the present study, we have designed a rapid assay based on multilocus nucleic acid sequencing that focuses on the biologically significant regions of the H5N1 hemagglutinin gene. This allows the prediction of viral strain, clade, receptor binding properties, low- or high-pathogenicity cleavage site and glycosylation status. H5 HA genes were selected from nine known high-pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in biologically significant regions of hemagglutinin and/or their ability to cause infection in humans. We devised a consensus pre-programmed pyrosequencing strategy, which may be used as a faster, more accurate alternative to de novo sequencing. The available data suggest that the assay described here is a reliable, rapid, information-rich and cost-effective approach for definitive diagnosis of H5N1 avian influenza. Knowledge of the predicted functional sequences of the HA will enhance H5N1 avian influenza surveillance efforts.

  12. 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.

  13. Equine H7N7 influenza A viruses are highly pathogenic in mice without adaptation: potential use as an animal model.

    OpenAIRE

    Kawaoka, Y

    1991-01-01

    Equine H7N7 influenza A viruses, representing a broad range of isolates, were lethal in mice without adaptation. After repeated passages, A/Equine/London/1416/73 acquired neurotropism upon intranasal infection. Thus, mice infected with equine influenza A viruses provide a model system for the study of highly virulent mammalian influenza viruses.

  14. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    International Nuclear Information System (INIS)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude; Wang, Yue; Liao, Guoyang

    2012-01-01

    Highlights: ► Vero cell-based HPAI H5N1 vaccine with stable high yield. ► Stable high yield derived from the YNVa H3N2 backbone. ► H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  15. High-yield production of a stable Vero cell-based vaccine candidate against the highly pathogenic avian influenza virus H5N1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Fangye; Zhou, Jian; Ma, Lei; Song, Shaohui; Zhang, Xinwen; Li, Weidong; Jiang, Shude [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China); Wang, Yue [National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Yingxin Lane 100, Xicheng District, Beijing 100052, People' s Republic of China (China); Liao, Guoyang [No. 5, Department of Bioproducts, Institute of Medical Biology, Chinese Academy of Medical Science and Pecking Union Medical College, Jiaoling Avenue 935, Kunming, Yunnan Province 650102, People' s Republic of China (China)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Vero cell-based HPAI H5N1 vaccine with stable high yield. Black-Right-Pointing-Pointer Stable high yield derived from the YNVa H3N2 backbone. Black-Right-Pointing-Pointer H5N1/YNVa has a similar safety and immunogenicity to H5N1delta. -- Abstract: Highly pathogenic avian influenza (HPAI) viruses pose a global pandemic threat, for which rapid large-scale vaccine production technology is critical for prevention and control. Because chickens are highly susceptible to HPAI viruses, the supply of chicken embryos for vaccine production might be depleted during a virus outbreak. Therefore, developing HPAI virus vaccines using other technologies is critical. Meeting vaccine demand using the Vero cell-based fermentation process has been hindered by low stability and yield. In this study, a Vero cell-based HPAI H5N1 vaccine candidate (H5N1/YNVa) with stable high yield was achieved by reassortment of the Vero-adapted (Va) high growth A/Yunnan/1/2005(H3N2) (YNVa) virus with the A/Anhui/1/2005(H5N1) attenuated influenza vaccine strain (H5N1delta) using the 6/2 method. The reassorted H5N1/YNVa vaccine maintained a high hemagglutination (HA) titer of 1024. Furthermore, H5N1/YNVa displayed low pathogenicity and uniform immunogenicity compared to that of the parent virus.

  16. High antiviral effects of hibiscus tea extract on the H5 subtypes of low and highly pathogenic avian influenza viruses.

    Science.gov (United States)

    Baatartsogt, Tugsbaatar; Bui, Vuong N; Trinh, Dai Q; Yamaguchi, Emi; Gronsang, Dulyatad; Thampaisarn, Rapeewan; Ogawa, Haruko; Imai, Kunitoshi

    2016-10-01

    Viral neuraminidase inhibitors are widely used as synthetic anti-influenza drugs for the prevention and treatment of influenza. However, drug-resistant influenza A virus variants, including H5N1 highly pathogenic avian influenza viruses (HPAIVs), have been reported. Therefore, the discovery of novel and effective antiviral agents is warranted. We screened the antiviral effects of 11 herbal tea extracts (hibiscus, black tea, tencha, rosehip tea, burdock tea, green tea, jasmine tea, ginger tea, lavender tea, rose tea and oak tea) against the H5N1 HPAIV in vitro. Among the tested extracts, only the hibiscus extract and its fractionated extract (frHibis) highly and rapidly reduced the titers of all H5 HPAIVs and low pathogenic AIVs (LPAIVs) used in the pre-treatment tests of Madin-Darby canine kidney (MDCK) cells that were inoculated with a mixture of the virus and the extract. Immunogold electron microscopy showed that anti-H5 monoclonal antibodies could not bind to the deformed H5 virus particles pretreated with frHibis. In post-treatment tests of MDCK cells cultured in the presence of frHibis after infection with H5N1 HPAIV, the frHibis inhibited viral replication and the expression of viral antigens and genes. Among the plants tested, hibiscus showed the most prominent antiviral effects against both H5 HPAIV and LPAIV.

  17. The Role of Extracellular Histones in Influenza Virus Pathogenesis.

    Science.gov (United States)

    Ashar, Harshini K; Mueller, Nathan C; Rudd, Jennifer M; Snider, Timothy A; Achanta, Mallika; Prasanthi, Maram; Pulavendran, Sivasami; Thomas, Paul G; Ramachandran, Akhilesh; Malayer, Jerry R; Ritchey, Jerry W; Rajasekhar, Rachakatla; Chow, Vincent T K; Esmon, Charles T; Teluguakula, Narasaraju

    2018-01-01

    Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza. Mice infected with influenza virus displayed high accumulation of extracellular histones, with widespread pulmonary microvascular thrombosis. Occluded pulmonary blood vessels with vascular thrombi often exhibited endothelial necrosis surrounded by hemorrhagic effusions and pulmonary edema. Histones released during influenza induced cytotoxicity and showed strong binding to platelets within thrombi in infected mouse lungs. Nasal wash samples from influenza-infected patients also showed increased accumulation of extracellular histones, suggesting a possible clinical relevance of elevated histones in pulmonary injury. Although histones inhibited influenza growth in vitro, in vivo treatment with histones did not yield antiviral effects and instead exacerbated lung pathology. Blocking with antihistone antibodies caused a marked decrease in lung pathology in lethal influenza-challenged mice and improved protection when administered in combination with the antiviral agent oseltamivir. These findings support the pathogenic effects of extracellular histones in that pulmonary injury during influenza was exacerbated. Targeting histones provides a novel therapeutic approach to influenza pneumonia. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Risk maps for the spread of highly pathogenic avian influenza in poultry.

    Directory of Open Access Journals (Sweden)

    Gert Jan Boender

    2007-04-01

    Full Text Available Devastating epidemics of highly contagious animal diseases such as avian influenza, classical swine fever, and foot-and-mouth disease underline the need for improved understanding of the factors promoting the spread of these pathogens. Here the authors present a spatial analysis of the between-farm transmission of a highly pathogenic H7N7 avian influenza virus that caused a large epidemic in The Netherlands in 2003. The authors developed a method to estimate key parameters determining the spread of highly transmissible animal diseases between farms based on outbreak data. The method allows for the identification of high-risk areas for propagating spread in an epidemiologically underpinned manner. A central concept is the transmission kernel, which determines the probability of pathogen transmission from infected to uninfected farms as a function of interfarm distance. The authors show how an estimate of the transmission kernel naturally provides estimates of the critical farm density and local reproduction numbers, which allows one to evaluate the effectiveness of control strategies. For avian influenza, the analyses show that there are two poultry-dense areas in The Netherlands where epidemic spread is possible, and in which local control measures are unlikely to be able to halt an unfolding epidemic. In these regions an epidemic can only be brought to an end by the depletion of susceptible farms by infection or massive culling. The analyses provide an estimate of the spatial range over which highly pathogenic avian influenza viruses spread between farms, and emphasize that control measures aimed at controlling such outbreaks need to take into account the local density of farms.

  19. Wild bird surveillance for highly pathogenic avian influenza H5 in North America

    Science.gov (United States)

    Flint, Paul L.; Pearce, John M.; Franson, J. Christian; Derksen, Dirk V.

    2015-01-01

    It is unknown how the current Asian origin highly pathogenic avian influenza H5 viruses arrived, but these viruses are now poised to become endemic in North America. Wild birds harbor these viruses and have dispersed them at regional scales. What is unclear is how the viruses may be moving from the wild bird reservoir into poultry holdings. Active surveillance of live wild birds is likely the best way to determine the true distribution of these viruses. We also suggest that sampling be focused on regions with the greatest risk for poultry losses and attempt to define the mechanisms of transfer to enhance biosecurity. Responding to the recent outbreaks of highly pathogenic avian influenza in North America requires an efficient plan with clear objectives and potential management outcomes.

  20. Identification of high risk areas for avian influenza outbreaks in California using disease distribution models.

    Directory of Open Access Journals (Sweden)

    Jaber Belkhiria

    Full Text Available The coexistence of different types of poultry operations such as free range and backyard flocks, large commercial indoor farms and live bird markets, as well as the presence of many areas where wild and domestic birds co-exist, make California susceptible to avian influenza outbreaks. The 2014-2015 highly pathogenic Avian Influenza (HPAI outbreaks affecting California and other states in the United States have underscored the need for solutions to protect the US poultry industry against this devastating disease. We applied disease distribution models to predict where Avian influenza is likely to occur and the risk for HPAI outbreaks is highest. We used observations on the presence of Low Pathogenic Avian influenza virus (LPAI in waterfowl or water samples at 355 locations throughout the state and environmental variables relevant to the disease epidemiology. We used two algorithms, Random Forest and MaxEnt, and two data-sets Presence-Background and Presence-Absence data. The models performed well (AUCc > 0.7 for testing data, particularly those using Presence-Background data (AUCc > 0.85. Spatial predictions were similar between algorithms, but there were large differences between the predictions with Presence-Absence and Presence-Background data. Overall, predictors that contributed most to the models included land cover, distance to coast, and broiler farm density. Models successfully identified several counties as high-to-intermediate risk out of the 8 counties with observed outbreaks during the 2014-2015 HPAI epizootics. This study provides further insights into the spatial epidemiology of AI in California, and the high spatial resolution maps may be useful to guide risk-based surveillance and outreach efforts.

  1. 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.

  2. A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.

    Directory of Open Access Journals (Sweden)

    Nicola Clementi

    Full Text Available The interest in broad-range anti-influenza A monoclonal antibodies (mAbs has recently been strengthened by the identification of anti-hemagglutinin (HA mAbs endowed with heterosubtypic neutralizing activity to be used in the design of "universal" prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.

  3. An isolate of Haemophilus haemolyticus produces a bacteriocin-like substance that inhibits the growth of nontypeable Haemophilus influenzae.

    Science.gov (United States)

    Latham, Roger D; Gell, David A; Fairbairn, Rory L; Lyons, A Bruce; Shukla, Shakti D; Cho, Kum Yin; Jones, David A; Harkness, Nick M; Tristram, Stephen G

    2017-04-01

    Nontypeable Haemophilus influenzae (NTHi) frequently colonises the upper respiratory tract and is an important cause of respiratory infections. Resistance to antibiotics is an emerging trend in NTHi and alternative prevention or treatment strategies are required. Haemophilus haemolyticus is a common commensal occupying the same niche as NTHi and, if able to produce substances that inhibit NTHi growth, may have a role as a probiotic. In this study, ammonium sulphate extracts from broth culture of 100 H. haemolyticus isolates were tested for the presence of substances inhibitory to NTHi using a well diffusion assay. One isolate produced a substance that consistently inhibited the growth of NTHi. The substance was inactivated by protease enzymes and had a molecular size of ca. 30 kDa as determined by size exclusion chromatography. When the substance was tested against bacteria from eight Gram-negative and three Gram-positive genera, only Haemophilus spp. were inhibited. Quantitative PCR testing showed the substance to be different to 'haemocin', the previously described bacteriocin of H. influenzae type b. These molecular characteristics, together with narrow-spectrum activity, suggest the substance may be a novel bacteriocin, and there is potential for this H. haemolyticus isolate to function as a probiotic for reduction of colonisation and subsequent infection with NTHi. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  4. Using extreme value theory approaches to forecast the probability of outbreak of highly pathogenic influenza in Zhejiang, China.

    Directory of Open Access Journals (Sweden)

    Jiangpeng Chen

    Full Text Available Influenza is a contagious disease with high transmissibility to spread around the world with considerable morbidity and mortality and presents an enormous burden on worldwide public health. Few mathematical models can be used because influenza incidence data are generally not normally distributed. We developed a mathematical model using Extreme Value Theory (EVT to forecast the probability of outbreak of highly pathogenic influenza.The incidence data of highly pathogenic influenza in Zhejiang province from April 2009 to November 2013 were retrieved from the website of Health and Family Planning Commission of Zhejiang Province. MATLAB "VIEM" toolbox was used to analyze data and modelling. In the present work, we used the Peak Over Threshold (POT model, assuming the frequency as a Poisson process and the intensity to be Pareto distributed, to characterize the temporal variability of the long-term extreme incidence of highly pathogenic influenza in Zhejiang, China.The skewness and kurtosis of the incidence of highly pathogenic influenza in Zhejiang between April 2009 and November 2013 were 4.49 and 21.12, which indicated a "fat tail" distribution. A QQ plot and a mean excess plot were used to further validate the features of the distribution. After determining the threshold, we modeled the extremes and estimated the shape parameter and scale parameter by the maximum likelihood method. The results showed that months in which the incidence of highly pathogenic influenza is about 4462/2286/1311/487 are predicted to occur once every five/three/two/one year, respectively.Despite the simplicity, the present study successfully offers the sound modeling strategy and a methodological avenue to implement forecasting of an epidemic in the midst of its course.

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

    Science.gov (United States)

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

    2013-01-01

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

  6. Low-pathogenic influenza A viruses in North American diving ducks contribute to the emergence of a novel highly pathogenic influenza A(H7N8) virus

    Science.gov (United States)

    Xu, Yifei; Ramey, Andrew M.; Bowman, Andrew S; DeLiberto, Thomas J.; Killian, Mary Lea; Krauss, Scott; Nolting, Jacqueline M.; Torchetti, Mia Kim; Reeves, Andrew B.; Webby, Richard J.; Stallknecht, David E.; Wan, Xiu-Feng

    2017-01-01

    Introductions of low-pathogenic avian influenza (LPAI) viruses of subtypes H5 and H7 into poultry from wild birds have the potential to mutate to highly pathogenic avian influenza (HPAI) viruses, but such viruses' origins are often unclear. In January 2016, a novel H7N8 HPAI virus caused an outbreak in turkeys in Indiana, USA. To determine the virus's origin, we sequenced the genomes of 441 wild-bird origin influenza A viruses (IAVs) from North America and subjected them to evolutionary analyses. The results showed that the H7N8 LPAI virus most likely circulated among diving ducks in the Mississippi flyway during autumn 2015 and was subsequently introduced to Indiana turkeys, in which it evolved high pathogenicity. Preceding the outbreak, an isolate with six gene segments (PB2, PB1, PA, HA, NA, and NS) sharing >99% sequence identity with those of H7N8 turkey isolates was recovered from a diving duck sampled in Kentucky, USA. H4N8 IAVs from other diving ducks possessed five H7N8-like gene segments (PB2, PB1, NA, MP, and NS; >98% sequence identity). Our findings suggest that viral gene constellations circulating among diving ducks can contribute to the emergence of IAVs that affect poultry. Therefore, diving ducks may serve an important and understudied role in the maintenance, diversification, and transmission of IAVs in the wild-bird reservoir.

  7. Applying Central Composite Design and Response Surface Methodology to Optimize Growth and Biomass Production of Haemophilus influenzae Type b.

    Science.gov (United States)

    Momen, Seyed Bahman; Siadat, Seyed Davar; Akbari, Neda; Ranjbar, Bijan; Khajeh, Khosro

    2016-06-01

    Haemophilus influenzae type b (Hib) is the leading cause of bacterial meningitis, otitis media, pneumonia, cellulitis, bacteremia, and septic arthritis in infants and young children. The Hib capsule contains the major virulence factor, and is composed of polyribosyl ribitol phosphate (PRP) that can induce immune system response. Vaccines consisting of Hib capsular polysaccharide (PRP) conjugated to a carrier protein are effective in the prevention of the infections. However, due to costly processes in PRP production, these vaccines are too expensive. To enhance biomass, in this research we focused on optimizing Hib growth with respect to physical factors such as pH, temperature, and agitation by using a response surface methodology (RSM). We employed a central composite design (CCD) and a response surface methodology to determine the optimum cultivation conditions for growth and biomass production of H. influenzae type b. The treatment factors investigated were initial pH, agitation, and temperature, using shaking flasks. After Hib cultivation and determination of dry biomass, analysis of experimental data was performed by the RSM-CCD. The model showed that temperature and pH had an interactive effect on Hib biomass production. The dry biomass produced in shaking flasks was about 5470 mg/L, which was under an initial pH of 8.5, at 250 rpm and 35° C. We found CCD and RSM very effective in optimizing Hib culture conditions, and Hib biomass production was greatly influenced by pH and incubation temperature. Therefore, optimization of the growth factors to maximize Hib production can lead to 1) an increase in bacterial biomass and PRP productions, 2) lower vaccine prices, 3) vaccination of more susceptible populations, and 4) lower risk of Hib infections.

  8. 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.

  9. A High Diversity of Eurasian Lineage Low Pathogenicity Avian Influenza A Viruses Circulate among Wild Birds Sampled in Egypt

    Science.gov (United States)

    Gerloff, Nancy A.; Jones, Joyce; Simpson, Natosha; Balish, Amanda; ElBadry, Maha Adel; Baghat, Verina; Rusev, Ivan; de Mattos, Cecilia C.; de Mattos, Carlos A.; Zonkle, Luay Elsayed Ahmed; Kis, Zoltan; Davis, C. Todd; Yingst, Sam; Cornelius, Claire; Soliman, Atef; Mohareb, Emad; Klimov, Alexander; Donis, Ruben O.

    2013-01-01

    Surveillance for influenza A viruses in wild birds has increased substantially as part of efforts to control the global movement of highly pathogenic avian influenza A (H5N1) virus. Studies conducted in Egypt from 2003 to 2007 to monitor birds for H5N1 identified multiple subtypes of low pathogenicity avian influenza A viruses isolated primarily from migratory waterfowl collected in the Nile Delta. Phylogenetic analysis of 28 viral genomes was performed to estimate their nearest ancestors and identify possible reassortants. Migratory flyway patterns were included in the analysis to assess gene flow between overlapping flyways. Overall, the viruses were most closely related to Eurasian, African and/or Central Asian lineage low pathogenicity viruses and belonged to 15 different subtypes. A subset of the internal genes seemed to originate from specific flyways (Black Sea-Mediterranean, East African-West Asian). The remaining genes were derived from a mixture of viruses broadly distributed across as many as 4 different flyways suggesting the importance of the Nile Delta for virus dispersal. Molecular clock date estimates suggested that the time to the nearest common ancestor of all viruses analyzed ranged from 5 to 10 years, indicating frequent genetic exchange with viruses sampled elsewhere. The intersection of multiple migratory bird flyways and the resulting diversity of influenza virus gene lineages in the Nile Delta create conditions favoring reassortment, as evident from the gene constellations identified by this study. In conclusion, we present for the first time a comprehensive phylogenetic analysis of full genome sequences from low pathogenic avian influenza viruses circulating in Egypt, underscoring the significance of the region for viral reassortment and the potential emergence of novel avian influenza A viruses, as well as representing a highly diverse influenza A virus gene pool that merits continued monitoring. PMID:23874653

  10. Highly Pathogenic H5N1 Avian Influenza Viruses Exhibit Few Barriers to Gene Flow in Vietnam

    Science.gov (United States)

    Carrel, Margaret; Wan, Xiu-Feng; Nguyen, Tung; Emch, Michael

    2013-01-01

    Locating areas where genetic change is inhibited can illuminate underlying processes that drive evolution of pathogens. The persistence of highly pathogenic H5N1 avian influenza in Vietnam since 2003, and the continuous molecular evolution of Vietnamese avian influenza viruses, indicates that local environmental factors are supportive not only of incidence but also of viral adaptation. This article explores whether gene flow is constant across Vietnam, or whether there exist boundary areas where gene flow exhibits discontinuity. Using a dataset of 125 highly pathogenic H5N1 avian influenza viruses, principal components analysis and wombling analysis are used to indicate the location, magnitude, and statistical significance of genetic boundaries. Results show that a small number of geographically minor boundaries to gene flow in highly pathogenic H5N1 avian influenza viruses exist in Vietnam, but that overall there is little division in genetic exchange. This suggests that differences in genetic characteristics of viruses from one region to another are not the result of barriers to H5N1 viral exchange in Vietnam, and that H5N1 avian influenza is able to spread relatively unimpeded across the country. PMID:22350419

  11. Seasonal influenza vaccine coverage among high-risk populations in Thailand, 2010-2012.

    Science.gov (United States)

    Owusu, Jocelynn T; Prapasiri, Prabda; Ditsungnoen, Darunee; Leetongin, Grit; Yoocharoen, Pornsak; Rattanayot, Jarowee; Olsen, Sonja J; Muangchana, Charung

    2015-01-29

    The Advisory Committee on Immunization Practice of Thailand prioritizes seasonal influenza vaccinations for populations who are at highest risk for serious complications (pregnant women, children 6 months-2 years, persons ≥65 years, persons with chronic diseases, obese persons), and healthcare personnel and poultry cullers. The Thailand government purchases seasonal influenza vaccine for these groups. We assessed vaccination coverage among high-risk groups in Thailand from 2010 to 2012. National records on persons who received publicly purchased vaccines from 2010 to 2012 were analyzed by high-risk category. Denominator data from multiple sources were compared to calculate coverage. Vaccine coverage was defined as the proportion of individuals in each category who received the vaccine. Vaccine wastage was defined as the proportion of publicly purchased vaccines that were not used. From 2010 to 2012, 8.18 million influenza vaccines were publicly purchased (range, 2.37-3.29 million doses/year), and vaccine purchases increased 39% over these years. Vaccine wastage was 9.5%. Approximately 5.7 million (77%) vaccine doses were administered to persons ≥65 years and persons with chronic diseases, 1.4 million (19%) to healthcare personnel/poultry cullers, 82,570 (1.1%) to children 6 months-2 years, 78,885 (1.1%) to obese persons, 26,481 (0.4%) to mentally disabled persons, and 17,787 (0.2%) to pregnant women. Between 2010 and 2012, coverage increased among persons with chronic diseases (8.6% versus 14%; pThailand. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

    Science.gov (United States)

    Quach, Caroline

    2014-12-01

    Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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.

  14. [A case of human highly pathogenic avian influenza in Shenzhen, China: application of field epidemiological study].

    Science.gov (United States)

    Zhang, Shun-Xiang; Cheng, Jin-Quan; Ma, Han-Wu; He, Jian-Fan; Cheng, Xiao-Wen; Jiang, Li-Juan; Mou, Jin; Wu, Chun-Li; Lv, Xing; Zhang, Shao-Hua; Zhang, Ya-De; Wu, Yong-Sheng; Wang, Xin

    2008-03-01

    Based on analyzing the characteristics of a case with human avian influenza and the effects of field epidemiological study. An emergency-response-system was started up to follow the probable human Highly Pathogenic Avian Influenza case initially detected by the "Undefined Pneumonia Surveillance System of Shenzhen". Public health professionals administered several epidemiologic investigations and giving all the contacts of the patient with a 7-day-long medical observation for temporally related influenza-like illness. Reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for H5 and N1 was applied to test respiratory tract samples and/or throat swabs of the patient and all his contacts specific for the hemagglutinin gene of influenza A H5N1. Activities and strategies such as media response,notification in the public, communications with multiple related sectors, social participation and information exchange with Hong Kong were involved in field control and management. The patient was a male, 31 years old,with an occupation as a truck driver in a factory,and had been residing in Shenzhen for 7 years. Started with an influenza-like syndrome, the patient received treatment on the 4th day of the onset, from a clinic and on the 6th day from a regular hospital. On the 8th day of the disease course, he was confirmed by Shenzhen Center for Disease Control and Prevention as human avian flu case and was then transferred to Intensive Care Unit (ICU). On the 83rd day of commence, the patients was healed and released from the hospital. The patient had no significant exposure to sick poultry or poultry that died from the illness before the onset of the disease. The patient and five family members lived together, but no family member was affected and no contact showed positive results for H5N1. A small food market with live poultry, which was under formal supervision and before illness the patient once visited, located near his apartment. Totally, 35 swabs from live

  15. Highly pathogenic avian influenza A (H5N1) virus in wildlife: diagnostics, epidemiology and molecular characteristics

    NARCIS (Netherlands)

    Keawcharoen, J.

    2010-01-01

    Since 2003, highly pathogenic avian influenza virus subtype H5N1 outbreaks have been reported in Southeast Asia causing high mortality in poultry and have also been found to cross the species barrier infecting human and other mammalian species. Thailand is one of the countries severely affected by

  16. Incorporating risk communication into highly pathogenic avian influenza preparedness and response efforts.

    Science.gov (United States)

    Voss, Shauna J; Malladi, Sasidhar; Sampedro, Fernando; Snider, Tim; Goldsmith, Timothy; Hueston, William D; Lauer, Dale C; Halvorson, David A

    2012-12-01

    A highly pathogenic avian influenza (HPAI) outbreak in the United States will initiate a federal emergency response effort that will consist of disease control and eradication efforts, including quarantine and movement control measures. These movement control measures will not only apply to live animals but also to animal products. However, with current egg industry "just-in-time" production practices, limited storage is available to hold eggs. As a result, stop movement orders can have significant unintended negative consequences, including severe disruptions to the food supply chain. Because stakeholders' perceptions of risk vary, waiting to initiate communication efforts until an HPAI event occurs can hinder disease control efforts, including the willingness of producers to comply with the response, and also can affect consumers' demand for the product. A public-private-academic partnership was formed to assess actual risks involved in the movement of egg industry products during an HPAI event through product specific, proactive risk assessments. The risk analysis process engaged a broad representation of stakeholders and promoted effective risk management and communication strategies before an HPAI outbreak event. This multidisciplinary team used the risk assessments in the development of the United States Department of Agriculture, Highly Pathogenic Avian Influenza Secure Egg Supply Plan, a comprehensive response plan that strives to maintain continuity of business. The collaborative approach that was used demonstrates how a proactive risk communication strategy that involves many different stakeholders can be valuable in the development of a foreign animal disease response plan and build working relationships, trust, and understanding.

  17. Isolation and characterization of highly pathogenic avian influenza virus subtype H5N1 from donkeys

    Science.gov (United States)

    2010-01-01

    Background The highly pathogenic H5N1 is a major avian pathogen that crosses species barriers and seriously affects humans as well as some mammals. It mutates in an intensified manner and is considered a potential candidate for the possible next pandemic with all the catastrophic consequences. Methods Nasal swabs were collected from donkeys suffered from respiratory distress. The virus was isolated from the pooled nasal swabs in specific pathogen free embryonated chicken eggs (SPF-ECE). Reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing of both haemagglutingin and neuraminidase were performed. H5 seroconversion was screened using haemagglutination inhibition (HI) assay on 105 donkey serum samples. Results We demonstrated that H5N1 jumped from poultry to another mammalian host; donkeys. Phylogenetic analysis showed that the virus clustered within the lineage of H5N1 from Egypt, closely related to 2009 isolates. It harboured few genetic changes compared to the closely related viruses from avian and humans. The neuraminidase lacks oseltamivir resistant mutations. Interestingly, HI screening for antibodies to H5 haemagglutinins in donkeys revealed high exposure rate. Conclusions These findings extend the host range of the H5N1 influenza virus, possess implications for influenza virus epidemiology and highlight the need for the systematic surveillance of H5N1 in animals in the vicinity of backyard poultry units especially in endemic areas. PMID:20398268

  18. Isolation and characterization of highly pathogenic avian influenza virus subtype H5N1 from donkeys

    Directory of Open Access Journals (Sweden)

    Abdel-Ghany Ahmad E

    2010-04-01

    Full Text Available Abstract Background The highly pathogenic H5N1 is a major avian pathogen that crosses species barriers and seriously affects humans as well as some mammals. It mutates in an intensified manner and is considered a potential candidate for the possible next pandemic with all the catastrophic consequences. Methods Nasal swabs were collected from donkeys suffered from respiratory distress. The virus was isolated from the pooled nasal swabs in specific pathogen free embryonated chicken eggs (SPF-ECE. Reverse transcriptase polymerase chain reaction (RT-PCR and sequencing of both haemagglutingin and neuraminidase were performed. H5 seroconversion was screened using haemagglutination inhibition (HI assay on 105 donkey serum samples. Results We demonstrated that H5N1 jumped from poultry to another mammalian host; donkeys. Phylogenetic analysis showed that the virus clustered within the lineage of H5N1 from Egypt, closely related to 2009 isolates. It harboured few genetic changes compared to the closely related viruses from avian and humans. The neuraminidase lacks oseltamivir resistant mutations. Interestingly, HI screening for antibodies to H5 haemagglutinins in donkeys revealed high exposure rate. Conclusions These findings extend the host range of the H5N1 influenza virus, possess implications for influenza virus epidemiology and highlight the need for the systematic surveillance of H5N1 in animals in the vicinity of backyard poultry units especially in endemic areas.

  19. 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.

  20. Genetic Characterization of Continually Evolving Highly Pathogenic H5N6 Influenza Viruses in China, 2012–2016

    Science.gov (United States)

    Li, Meng; Zhao, Na; Luo, Jing; Li, Yuan; Chen, Lin; Ma, Jiajun; Zhao, Lin; Yuan, Guohui; Wang, Chengmin; Wang, Yutian; Liu, Yanhua; He, Hongxuan

    2017-01-01

    H5N6 is a highly pathogenic avian influenza (HPAI) and a zoonotic disease that causes recurring endemics in East Asia. At least 155 H5N6 outbreaks, including 15 human infections, have been reported in China. These repeated outbreaks have increased concern that the H5N6 virus may cross over to humans and cause a pandemic. In February, 2016, peafowls in a breeding farm exhibited a highly contagious disease. Post-mortem examinations, including RT-PCR, and virus isolation, confirmed that the highly pathogenic H5N6 influenza virus was the causative agent, and the strain was named A/Pavo Cristatus/Jiangxi/JA1/2016. In animal experiments, it exhibited high pathogenicity in chickens and an estimated median lethal dose in mice of ~104.3 TCID50. A phylogenetic analysis showed that JA1/2016 was clustered in H5 clade 2.3.4.4. FG594-like H5N6 virus from Guangdong Province was the probable predecessor of JA1/2016, and the estimated divergence time was June 2014. Furthermore, we found that H5N6 influenza viruses can be classified into the two following groups: Group 1 and Group 2. Group 2 influenza viruses have not been detected since the end of 2014, whereas Group 1 influenza viruses have continually evolved and reassorted with the “gene pool” circulating in south China, resulting in the rise of novel subtypes of this influenza virus. An increase in the number of its identified hosts, the expanding range of its distribution, and the continual evolution of H5N6 AIVs enhance the risk that an H5N6 virus may spread to other continents and cause a pandemic. PMID:28293218

  1. Genetic Characterization of Continually Evolving Highly Pathogenic H5N6 Influenza Viruses in China, 2012-2016.

    Science.gov (United States)

    Li, Meng; Zhao, Na; Luo, Jing; Li, Yuan; Chen, Lin; Ma, Jiajun; Zhao, Lin; Yuan, Guohui; Wang, Chengmin; Wang, Yutian; Liu, Yanhua; He, Hongxuan

    2017-01-01

    H5N6 is a highly pathogenic avian influenza (HPAI) and a zoonotic disease that causes recurring endemics in East Asia. At least 155 H5N6 outbreaks, including 15 human infections, have been reported in China. These repeated outbreaks have increased concern that the H5N6 virus may cross over to humans and cause a pandemic. In February, 2016, peafowls in a breeding farm exhibited a highly contagious disease. Post-mortem examinations, including RT-PCR, and virus isolation, confirmed that the highly pathogenic H5N6 influenza virus was the causative agent, and the strain was named A/ Pavo Cristatus /Jiangxi/JA1/2016. In animal experiments, it exhibited high pathogenicity in chickens and an estimated median lethal dose in mice of ~10 4.3 TCID 50 . A phylogenetic analysis showed that JA1/2016 was clustered in H5 clade 2.3.4.4. FG594-like H5N6 virus from Guangdong Province was the probable predecessor of JA1/2016, and the estimated divergence time was June 2014. Furthermore, we found that H5N6 influenza viruses can be classified into the two following groups: Group 1 and Group 2. Group 2 influenza viruses have not been detected since the end of 2014, whereas Group 1 influenza viruses have continually evolved and reassorted with the "gene pool" circulating in south China, resulting in the rise of novel subtypes of this influenza virus. An increase in the number of its identified hosts, the expanding range of its distribution, and the continual evolution of H5N6 AIVs enhance the risk that an H5N6 virus may spread to other continents and cause a pandemic.

  2. Influenza Photos

    Science.gov (United States)

    ... Polio Whooping cough Influenza (flu) Rabies Yellow fever Influenza Photos Photographs accompanied by text that reads "Courtesy ... of these photos are quite graphic. Shows how influenza germs spread through the air when someone coughs ...

  3. Highly pathogenic avian influenza virus subtype H5N1 in mute swans (Cygnus olor) in Central Bosnia.

    Science.gov (United States)

    Goletić, Teufik; Gagić, Abdulah; Residbegović, Emina; Kustura, Aida; Kavazović, Aida; Savić, Vladimir; Harder, Timm; Starick, Elke; Prasović, Senad

    2010-03-01

    In order to determine the actual prevalence of avian influenza viruses (AIVs) in wild birds in Bosnia and Herzegovina, extensive surveillance was carried out between October 2005 and April 2006. A total of 394 samples representing 41 bird species were examined for the presence of influenza A virus using virus isolation in embryonated chicken eggs, PCR, and nucleotide sequencing. AIV subtype H5N1 was detected in two mute swans (Cygnus olor). The isolates were determined to be highly pathogenic avian influenza (HPAI) virus and the hemagglutinin sequence was closely similar to A/Cygnus olor/Astrakhan/ Ast05-2-10/2005 (H5N1). This is the first report of HPAI subtype H5N1 in Bosnia and Herzegovina.

  4. Experimental infection of macaques with a wild water bird-derived highly pathogenic avian influenza virus (H5N1.

    Directory of Open Access Journals (Sweden)

    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.

  5. Isolation of recombinant phage antibodies targeting the hemagglutinin cleavage site of highly pathogenic avian influenza virus.

    Directory of Open Access Journals (Sweden)

    Jinhua Dong

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses, which have emerged in poultry and other wildlife worldwide, contain a characteristic multi-basic cleavage site (CS in the hemagglutinin protein (HA. Because this arginine-rich CS is unique among influenza virus subtypes, antibodies against this site have the potential to specifically diagnose pathogenic H5N1. By immunizing mice with the CS peptide and screening a phage display library, we isolated four antibody Fab fragment clones that specifically bind the antigen peptide and several HPAI H5N1 HA proteins in different clades. The soluble Fab fragments expressed in Escherichia coli bound the CS peptide and the H5N1 HA protein with nanomolar affinity. In an immunofluorescence assay, these Fab fragments stained cells infected with HPAI H5N1 but not those infected with a less virulent strain. Lastly, all the Fab clones could detect the CS peptide and H5N1 HA protein by open sandwich ELISA. Thus, these recombinant Fab fragments will be useful novel reagents for the rapid and specific detection of HPAI H5N1 virus.

  6. Modelling the wind-borne spread of highly pathogenic avian influenza virus between farms.

    Directory of Open Access Journals (Sweden)

    Amos Ssematimba

    Full Text Available A quantitative understanding of the spread of contaminated farm dust between locations is a prerequisite for obtaining much-needed insight into one of the possible mechanisms of disease spread between farms. Here, we develop a model to calculate the quantity of contaminated farm-dust particles deposited at various locations downwind of a source farm and apply the model to assess the possible contribution of the wind-borne route to the transmission of Highly Pathogenic Avian Influenza virus (HPAI during the 2003 epidemic in the Netherlands. The model is obtained from a Gaussian Plume Model by incorporating the dust deposition process, pathogen decay, and a model for the infection process on exposed farms. Using poultry- and avian influenza-specific parameter values we calculate the distance-dependent probability of between-farm transmission by this route. A comparison between the transmission risk pattern predicted by the model and the pattern observed during the 2003 epidemic reveals that the wind-borne route alone is insufficient to explain the observations although it could contribute substantially to the spread over short distance ranges, for example, explaining 24% of the transmission over distances up to 25 km.

  7. The transmissibility of highly pathogenic avian influenza in commercial poultry in industrialised countries.

    Directory of Open Access Journals (Sweden)

    Tini Garske

    2007-04-01

    Full Text Available With the increased occurrence of outbreaks of H5N1 worldwide there is concern that the virus could enter commercial poultry farms with severe economic consequences.We analyse data from four recent outbreaks of highly pathogenic avian influenza (HPAI in commercial poultry to estimate the farm-to-farm reproductive number for HPAI. The reproductive number is a key measure of the transmissibility of HPAI at the farm level because it can be used to evaluate the effectiveness of the control measures. In these outbreaks the mean farm-to-farm reproductive number prior to controls ranged from 1.1 to 2.4, with the maximum farm-based reproductive number in the range 2.2 to 3.2. Enhanced bio-security, movement restrictions and prompt isolation of the infected farms in all four outbreaks substantially reduced the reproductive number, but it remained close to the threshold value 1 necessary to ensure the disease will be eradicated.Our results show that depending on the particular situation in which an outbreak of avian influenza occurs, current controls might not be enough to eradicate the disease, and therefore a close monitoring of the outbreak is required. The method we used for estimating the reproductive number is straightforward to implement and can be used in real-time. It therefore can be a useful tool to inform policy decisions.

  8. A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

    Science.gov (United States)

    This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

  9. Macrophage-derived insulin-like growth factor-1 affects influenza vaccine efficacy through the regulation of immune cell homeostasis.

    Science.gov (United States)

    Yoon, Il-Sub; Park, Hyelim; Kwak, Hye-Won; Woo Jung, Yong; Nam, Jae-Hwan

    2017-08-24

    The level of antibody production induced by a vaccine involves a variety of host factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important role in lymphocyte maturation and antibody expression. Here, we investigated the role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were about two- to fourfold lower in MIKO mice than in WT mice. Moreover, MIKO mice showed a relatively weak booster effect of repeated immunization. In contrast, antigen-nonspecific total IgG was about threefold higher in MIKO mice than in WT mice. After viral challenge, the viral titer and the pathological damage in lungs of MIKO mice were higher than those in WT mice despite vaccination. Interestingly, the proportions of proinflammatory immune cells including M1 macrophages, Th1 and Th17 cells was higher in unvaccinated MIKO mice than in unvaccinated WT mice. This suggests that nonspecific activation of immune cells may paradoxically impair the response to the vaccine. In addition, although the proportions of T follicular helper (Tfh) cells and GL-7 + germinal center (GC) B cells were higher in MIKO mice than in WT mice, the population of CD138 + B220 + antibody-secreting plasmablasts was lower in MIKO mice, which may be a cause of the low influenza-specific antibody titer in MIKO mice. Taken together, these results suggest that macrophage-derived IGF-1 might play an important role in the vaccine-triggered immune response by regulating immune cell homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults.

    Science.gov (United States)

    Raviotta, Jonathan M; Smith, Kenneth J; DePasse, Jay; Brown, Shawn T; Shim, Eunha; Nowalk, Mary Patricia; Wateska, Angela; France, Glenson S; Zimmerman, Richard K

    2017-10-09

    High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50-64year-olds. Markov model CE analysis compared 5 strategies in 50-64year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided. The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values. Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Different environmental drivers of highly pathogenic avian influenza H5N1 outbreaks in poultry and wild birds

    NARCIS (Netherlands)

    Si, Y.; Boer, de W.F.; Gong, P.

    2013-01-01

    A large number of highly pathogenic avian influenza (HPAI) H5N1 outbreaks in poultry and wild birds have been reported in Europe since 2005. Distinct spatial patterns in poultry and wild birds suggest that different environmental drivers and potentially different spread mechanisms are operating.

  12. Widespread detection of highly pathogenic H5 influenza viruses in wild birds from the Pacific Flyway of the United States.

    Science.gov (United States)

    Bevins, S N; Dusek, R J; White, C L; Gidlewski, T; Bodenstein, B; Mansfield, K G; DeBruyn, P; Kraege, D; Rowan, E; Gillin, C; Thomas, B; Chandler, S; Baroch, J; Schmit, B; Grady, M J; Miller, R S; Drew, M L; Stopak, S; Zscheile, B; Bennett, J; Sengl, J; Brady, Caroline; Ip, H S; Spackman, E; Killian, M L; Torchetti, M K; Sleeman, J M; Deliberto, T J

    2016-07-06

    A novel highly pathogenic avian influenza virus belonging to the H5 clade 2.3.4.4 variant viruses was detected in North America in late 2014. Motivated by the identification of these viruses in domestic poultry in Canada, an intensive study was initiated to conduct highly pathogenic avian influenza surveillance in wild birds in the Pacific Flyway of the United States. A total of 4,729 hunter-harvested wild birds were sampled and highly pathogenic avian influenza virus was detected in 1.3% (n = 63). Three H5 clade 2.3.4.4 subtypes were isolated from wild birds, H5N2, H5N8, and H5N1, representing the wholly Eurasian lineage H5N8 and two novel reassortant viruses. Testing of 150 additional wild birds during avian morbidity and mortality investigations in Washington yielded 10 (6.7%) additional highly pathogenic avian influenza isolates (H5N8 = 3 and H5N2 = 7). The geographically widespread detection of these viruses in apparently healthy wild waterfowl suggest that the H5 clade 2.3.4.4 variant viruses may behave similarly in this taxonomic group whereby many waterfowl species are susceptible to infection but do not demonstrate obvious clinical disease. Despite these findings in wild waterfowl, mortality has been documented for some wild bird species and losses in US domestic poultry during the first half of 2015 were unprecedented.

  13. Immunity to current H5 highly pathogenic avian influenza viruses: From vaccines to adaptive immunity in wild birds

    Science.gov (United States)

    Following the 2014-2015 outbreaks of H5N2 and H5N8 highly pathogenic avian influenza (HPAI) in the U.S., studies were performed to assess the immunity required for protection against future outbreaks should they occur. We assessed the ability of vaccines to induce protection of chickens and turkeys...

  14. 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

  15. Novel Highly Pathogenic Avian Influenza A(H5N6) Virus in the Netherlands, December 2017.

    Science.gov (United States)

    Beerens, Nancy; Koch, Guus; Heutink, Rene; Harders, Frank; Vries, D P Edwin; Ho, Cynthia; Bossers, Alex; Elbers, Armin

    2018-04-17

    A novel highly pathogenic avian influenza A(H5N6) virus affecting wild birds and commercial poultry was detected in the Netherlands in December 2017. Phylogenetic analysis demonstrated that the virus is a reassortant of H5N8 clade 2.3.4.4 viruses and not related to the Asian H5N6 viruses that caused human infections.

  16. Surveillance for highly pathogenic avian influenza virus in wild birds during outbreaks in domestic poultry, Minnesota, 2015

    Science.gov (United States)

    Jennelle, Christopher S.; Carstensen, Michelle; Hildebrand, Erik C.; Cornicelli, Louis; Wolf, Paul C.; Grear, Daniel A.; Ip, Hon S.; VanDalen, Kaci K.; Minicucci, Larissa A.

    2016-01-01

    In 2015, a major outbreak of highly pathogenic avian influenza virus (HPAIV) infection devastated poultry facilities in Minnesota, USA. To clarify the role of wild birds, we tested 3,139 waterfowl fecal samples and 104 sick and dead birds during March 9–June 4, 2015. HPAIV was isolated from a Cooper’s hawk but not from waterfowl.

  17. Variable epidemiology of the three outbreaks of unrelated highly pathogenic avian influenza viruses in the United States, 2014-2017

    Science.gov (United States)

    Three unrelated highly pathogenic avian influenza (HPAI) outbreaks have occurred in the United States (US) during 2014-2017. Late in 2014, Canada reported the first outbreak of an H5N2 reassortment virus between the A/goose/Guangdong/1/1996 (Gs/GD)-lineage H5Nx clade 2.3.4.4A HPAI and North American...

  18. Outdoor ranging of poultry: a major risk factor for the introduction and development of high pathogenicity Avian Influenza

    NARCIS (Netherlands)

    Koch, G.; Elbers, A.R.W.

    2006-01-01

    High-Pathogenicity Avian Influenza (HPAI) is an extremely infectious viral disease of poultry. Public health concerns were raised when six persons died in Hong Kong in 1997 after exposure to HPAI-infected poultry. Its danger became imminent in the recent HPAI epidemic in South-East Asia when the

  19. 2.1 Natural History of Highly Pathogenic Avian Influenza H5N1

    Science.gov (United States)

    Sonnberg, Stephanie; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    The ecology of highly pathogenic avian influenza (HPAI) H5N1 has significantly changed from sporadic outbreaks in terrestrial poultry to persistent circulation in terrestrial and aquatic poultry and potentially in wild waterfowl. A novel genotype of HPAI H5N1 arose in 1996 in southern China and through ongoing mutation, reassortment, and natural selection, has diverged into distinct lineages and expanded into multiple reservoir hosts. The evolution of Goose/Guangdong-lineage highly pathogenic H5N1 viruses is ongoing: while stable interactions exist with some reservoir hosts, these viruses are continuing to evolve and adapt to others, and pose an un-calculable risk to sporadic hosts, including humans. PMID:23735535

  20. Characterizing wild bird contact and seropositivity to highly pathogenic avian influenza A (H5N1) virus in Alaskan residents.

    Science.gov (United States)

    Reed, Carrie; Bruden, Dana; Byrd, Kathy K; Veguilla, Vic; Bruce, Michael; Hurlburt, Debby; Wang, David; Holiday, Crystal; Hancock, Kathy; Ortiz, Justin R; Klejka, Joe; Katz, Jacqueline M; Uyeki, Timothy M

    2014-09-01

    Highly pathogenic avian influenza A (HPAI) H5N1 viruses have infected poultry and wild birds on three continents with more than 600 reported human cases (59% mortality) since 2003. Wild aquatic birds are the natural reservoir for avian influenza A viruses, and migratory birds have been documented with HPAI H5N1 virus infection. Since 2005, clade 2.2 HPAI H5N1 viruses have spread from Asia to many countries. We conducted a cross-sectional seroepidemiological survey in Anchorage and western Alaska to identify possible behaviors associated with migratory bird exposure and measure seropositivity to HPAI H5N1. We enrolled rural subsistence bird hunters and their families, urban sport hunters, wildlife biologists, and a comparison group without bird contact. We interviewed participants regarding their exposures to wild birds and collected blood to perform serologic testing for antibodies against a clade 2.2 HPAI H5N1 virus strain. Hunters and wildlife biologists reported exposures to wild migratory birds that may confer risk of infection with avian influenza A viruses, although none of the 916 participants had evidence of seropositivity to HPAI H5N1. We characterized wild bird contact among Alaskans and behaviors that may influence risk of infection with avian influenza A viruses. Such knowledge can inform surveillance and risk communication surrounding HPAI H5N1 and other influenza viruses in a population with exposure to wild birds at a crossroads of intercontinental migratory flyways. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Nathalie Schnepf

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

  2. Subtyping of swine influenza viruses using a high-throughput real time PCR platform

    DEFF Research Database (Denmark)

    Goecke, Nicole Bakkegård; Krog, Jesper Schak; Hjulsager, Charlotte Kristiane

    ). The results revealed that the performance of the dynamic chip was similar to conventional real time analysis. Discussion and conclusion. Application of the chip for subtyping of swine influenza has resulted in a significant reduction in time, cost and working hours. Thereby, it is possible to offer diagnostic...... test and subsequent subtyping is performed by real time RT-PCR (RT-qPCR) but several assays are needed to cover the wide range of circulating subtypes which is expensive,resource and time demanding. To mitigate these restrictions the high-throughput qPCR platform BioMark (Fluidigm) has been explored...... services with reduced price and turnover time which will facilitate choice of vaccines and by that lead to reduction of antibiotic used....

  3. 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.

  4. Highly pathogenic influenza A(H5N1 virus survival in complex artificial aquatic biotopes.

    Directory of Open Access Journals (Sweden)

    Viseth Srey Horm

    Full Text Available BACKGROUND: Very little is known regarding the persistence of Highly Pathogenic Avian Influenza (HPAI H5N1 viruses in aquatic environments in tropical countries, although environmental materials have been suggested to play a role as reservoirs and sources of transmission for H5N1 viruses. METHODOLOGY/PRINCIPAL FINDINGS: The survival of HPAI H5N1 viruses in experimental aquatic biotopes (water, mud, aquatic flora and fauna relevant to field conditions in Cambodia was investigated. Artificial aquatic biotopes, including simple ones containing only mud and water, and complex biotopes involving the presence of aquatic flora and fauna, were set up. They were experimentally contaminated with H5N1 virus. The persistence of HPAI H5N1 virus (local avian and human isolates was determined by virus isolation in embryonated chicken eggs and by real-time reverse-polymerase chain reaction. Persistence of infectious virus did not exceed 4 days, and was only identified in rain water. No infectious virus particles were detected in pond and lake water or mud even when high inoculum doses were used. However, viral RNA persisted up to 20 days in rain water and 7 days in pond or lake water. Viral RNA was also detected in mud samples, up to 14 days post-contamination in several cases. Infectious virus and viral RNA was detected in few cases in the aquatic fauna and flora, especially in bivalves and labyrinth fish, although these organisms seemed to be mostly passive carriers of the virus rather than host allowing virus replication. CONCLUSIONS/SIGNIFICANCE: Although several factors for the survival and persistence of HPAI viruses in the environment are still to be elucidated, and are particularly hard to control in laboratory conditions, our results, along with previous data, support the idea that environmental surveillance is of major relevance for avian influenza control programs.

  5. Highly sensitive detection of influenza virus in saliva by real-time PCR method using sugar chain-immobilized gold nanoparticles; application to clinical studies

    Directory of Open Access Journals (Sweden)

    Yasuo Suda

    2015-09-01

    Full Text Available A highly sensitive and convenient method for detecting influenza virus was developed using modified end-point melt curve analysis of a RT-qPCR SYBR Green method and influenza virus-binding sugar chain-immobilized gold-nanoparticles (SGNP. Because SGNPs capture influenza viruses, the virus-SGNP complex was separated easily by centrifugation. Viral RNA was detected at very low concentrations, suggesting that SGNP increased sensitivity compared with standard methods. This method was applied to clinical studies. Influenza viruses were detected in saliva of patients or inpatients who had been considered influenza-free by a rapid diagnostic assay of nasal swabs. Furthermore, the method was applied to a human trial of prophylactic anti-influenza properties of yogurt containing Lactobacillus acidophilus L-92. The incidence of influenza viruses in saliva of the L-92 group was found to be significantly lower compared to the control group. Thus, this method was useful for monitoring the course of anti-influenza treatment or preventive measures against nosocomial infection.

  6. Avian influenza

    DEFF Research Database (Denmark)

    EFSA Panel on Animal Health and Welfare; More, Simon; Bicout, Dominique

    2017-01-01

    Previous introductions of highly pathogenic avian influenza virus (HPAIV) to the EU were most likely via migratory wild birds. A mathematical model has been developed which indicated that virus amplification and spread may take place when wild bird populations of sufficient size within EU become ...... of implementing specific biosecurity measures on reducing the probability of AIV entering into a poultry holding. Human diligence is pivotal to select, implement and maintain specific, effective biosecurity measures....

  7. Seasonal Influenza: An Overview

    Science.gov (United States)

    Li, Christina; Freedman, Marian

    2009-01-01

    Seasonal influenza is a major cause of morbidity and mortality in the United States. It also has major social and economic consequences in the form of high rates of absenteeism from school and work as well as significant treatment and hospitalization costs. In fact, annual influenza epidemics and the resulting deaths and lost days of productivity…

  8. Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus.

    Science.gov (United States)

    Ma, Jingjiao; Lee, Jinhwa; Liu, Haixia; Mena, Ignacio; Davis, A Sally; Sunwoo, Sun Young; Lang, Yuekun; Duff, Michael; Morozov, Igor; Li, Yuhao; Yang, Jianmei; García-Sastre, Adolfo; Richt, Juergen A; Ma, Wenjun

    2017-01-01

    Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5N x viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines have been demonstrated to be efficacious and safe in poultry. Herein, we developed an NDV-based H5 vaccine (NDV-H5) that expresses a codon-optimized ectodomain of the hemagglutinin from the A/chicken/Iowa/04-20/2015 (H5N2) virus and evaluated its efficacy in chickens. Results showed that both live and inactivated NDV-H5 vaccines induced hemagglutinin inhibition antibody titers against the H5N2 virus in immunized chickens after prime and booster, and both NDV-H5 vaccines completely protected chickens from lethal challenge with the highly pathogenic H5N2 A/turkey/Minnesota/9845-4/2015 virus. No clinical signs and only minimal virus shedding was observed in both vaccinated groups. In contrast, all mock-vaccinated, H5N2-infected chickens shed virus and died within 5 days post challenge. Furthermore, one dose of the live NDV-H5 vaccine also provided protection of 90% chickens immunized by coarse spraying; after exposure to H5N2 challenge, sera from vaccinated surviving chickens neutralized both highly pathogenic H5N1 and H5N8 viruses. Taken together, our results suggest that the NDV-based H5 vaccine is able to protect chickens against intercontinental highly pathogenic H5N x viruses and can be used by mass application to protect the poultry industry.

  9. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  10. 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.

  11. 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.

  12. Genetic characterization of highly pathogenic avian influenza A H5N8 viruses isolated from wild birds in Egypt.

    Science.gov (United States)

    Kandeil, Ahmed; Kayed, Ahmed; Moatasim, Yassmin; Webby, Richard J; McKenzie, Pamela P; Kayali, Ghazi; Ali, Mohamed A

    2017-07-01

    A newly emerged H5N8 influenza virus was isolated from green-winged teal in Egypt during December 2016. In this study, we provide a detailed characterization of full genomes of Egyptian H5N8 viruses and some virological features. Genetic analysis demonstrated that the Egyptian H5N8 viruses are highly pathogenic avian influenza viruses. Phylogenetic analysis revealed that the genome of the Egyptian H5N8 viruses was related to recently characterized reassortant H5N8 viruses of clade 2.3.4.4 isolated from different Eurasian countries. Multiple peculiar mutations were characterized in the Egyptian H5N8 viruses, which probably permits transmission and virulence of these viruses in mammals. The Egyptian H5N8 viruses preferentially bound to avian-like receptors rather than human-like receptors. Also, the Egyptian H5N8 viruses were fully sensitive to amantadine and neuraminidase inhibitors. Chicken sera raised against commercial inactivated avian influenza-H5 vaccines showed no or very low reactivity with the currently characterized H5N8 viruses in agreement with the genetic dissimilarity. Surveillance of avian influenza in waterfowl provides early warning of specific threats to poultry and human health and hence should be continued.

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

    Directory of Open Access Journals (Sweden)

    Yonghui Zhang

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

  14. Highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide.

    Science.gov (United States)

    Matsubara, Teruhiko; Ujie, Michiko; Yamamoto, Takashi; Akahori, Miku; Einaga, Yasuaki; Sato, Toshinori

    2016-08-09

    The progression of influenza varies according to age and the presence of an underlying disease; appropriate treatment is therefore required to prevent severe disease. Anti-influenza therapy, such as with neuraminidase inhibitors, is effective, but diagnosis at an early phase of infection before viral propagation is critical. Here, we show that several dozen plaque-forming units (pfu) of influenza virus (IFV) can be detected using a boron-doped diamond (BDD) electrode terminated with a sialic acid-mimic peptide. The peptide was used instead of the sialyloligosaccharide receptor, which is the common receptor of influenza A and B viruses required during the early phase of infection, to capture IFV particles. The peptide, which was previously identified by phage-display technology, was immobilized by click chemistry on the BDD electrode, which has excellent electrochemical characteristics such as low background current and weak adsorption of biomolecules. Electrochemical impedance spectroscopy revealed that H1N1 and H3N2 IFVs were detectable in the range of 20-500 pfu by using the peptide-terminated BDD electrode. Our results demonstrate that the BDD device integrated with the receptor-mimic peptide has high sensitivity for detection of a low number of virus particles in the early phase of infection.

  15. A commercial ELISA detects high levels of human H5 antibody but cross-reacts with influenza A antibodies.

    Science.gov (United States)

    Stelzer-Braid, Sacha; Wong, Bruce; Robertson, Peter; Lynch, Garry W; Laurie, Karen; Shaw, Robert; Barr, Ian; Selleck, Paul W; Baleriola, Cristina; Escott, Ros; Katsoulotos, Gregory; Rawlinson, William D

    2008-10-01

    Commercial serological assays to determine influenza A H5N1 infection are available, although the accuracy and reproducibility of these are not reported in detail. This study aimed to assess the validity of a commercial ELISA H5 hemagglutinin (HA) antibody kit. A commercial ELISA for detection of antibodies towards influenza A H5 HA was evaluated using human sera from vaccinated individuals. The ELISA was used to screen 304 sera with elevated influenza A complement fixation titres collected between the period 1995-2007. The ELISA was found to be accurate for sera with high levels of anti-H5 antibodies, and would be useful in clinical settings where a rapid result is required. Thirteen of the stored sera were positive using the ELISA, but were confirmed as negative for H5N1 exposure using further serological tests. Absorption studies suggested that antibodies towards seasonal H3N2 and H1N1 influenza may cross-react with H5 antigen, giving false positive results with the ELISA.

  16. Vapor bubble growth in highly superheated liquid

    International Nuclear Information System (INIS)

    Pavlov, P.A.

    1981-01-01

    Dynamics of the bubble growth in the volume of the uniformally superheated liquid is considered. It is supposed that its growth is hampered by heat transfer. An asymptotic expression for the bubble growth rate at high superheatings when heat hold by liquid is comparable with heat of steam formation, is found by the automodel solution of the heat transfer equation. Writing the radius square in the form of a functional applicable for the calculation of steam formation at the pressure change in superheated liquid is suggested for eveluation calculations [ru

  17. High conservation level of CD8(+) T cell immunogenic regions within an unusual H1N2 human influenza variant.

    Science.gov (United States)

    Komadina, Naomi; Quiñones-Parra, Sergio M; Kedzierska, Katherine; McCaw, James M; Kelso, Anne; Leder, Karin; McVernon, Jodie

    2016-10-01

    Current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza A subtypes. Next generation vaccines capable of eliciting CD8(+) T cell (CTL) mediated cross-protective immunity may offer a long-term alternative strategy. However, measuring pre- and existing levels of CTL cross-protection in humans is confounded by differences in infection histories across individuals. During 2000-2003, H1N2 viruses circulated persistently in the human population for the first time and we hypothesized that the viral nucleoprotein (NP) contained novel CTL epitopes that may have contributed to the survival of the viruses. This study describes the immunogenic NP peptides of H1N1, H2N2, and H3N2 influenza viruses isolated from humans over the past century, 1918-2003, by comparing this historical dataset to reference NP peptides from H1N2 that circulated in humans during 2000-2003. Observed peptides sequences ranged from highly conserved (15%) to highly variable (12%), with variation unrelated to reported immunodominance. No unique NP peptides which were exclusive to the H1N2 viruses were noted. However, the virus had inherited the NP from a recently emerged H3N2 variant containing novel peptides, which may have assisted its persistence. Any advantage due to this novelty was subsequently lost with emergence of a newer H3N2 variant in 2003. Our approach has potential to provide insight into the population context in which influenza viruses emerge, and may help to inform immunogenic peptide selection for CTL-inducing influenza vaccines. J. Med. Virol. 88:1725-1732, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses

    OpenAIRE

    Dybing, Jody K.; Schultz-Cherry, Stacey; Swayne, David E.; Suarez, David L.; Perdue, Michael L.

    2000-01-01

    In 1997, an outbreak of virulent H5N1 avian influenza virus occurred in poultry in Hong Kong (HK) and was linked to a direct transmission to humans. The factors associated with transmission of avian influenza virus to mammals are not fully understood, and the potential risk of other highly virulent avian influenza A viruses infecting and causing disease in mammals is not known. In this study, two avian and one human HK-origin H5N1 virus along with four additional highly pathogenic H5 avian in...

  19. Meningitis - H. influenzae

    Science.gov (United States)

    H. influenzae meningitis; H. flu meningitis; Haemophilus influenzae type b meningitis ... H. influenzae meningitis is caused by Haemophilus influenzae type b bacteria. This illness is not the same ...

  20. Comparative pathology of chickens experimentally inoculated with avian influenza viruses of low and high pathogenicity.

    Science.gov (United States)

    Mo, I P; Brugh, M; Fletcher, O J; Rowland, G N; Swayne, D E

    1997-01-01

    Pathologic changes and distribution of viral antigen as determined by immunohistochemistry were compared among 4-wk-old specific-pathogen-free chickens inoculated intratracheally with avian influenza virus (AIV) isolates of either low or high pathogenicity. Viruses of low pathogenicity, previously characterized as mildly pathogenic (MP), included A/chicken/Pennsylvania/21525/83 (H5N2) (MP-Penn) and A/chicken/Alabama/7395/75 (H4N8) (MP-Alab). Viruses of high pathogenicity included A/chicken/Pennsylvania/1370/83 (H5N2), A/chicken/Victoria/A185/85 (H7N7), and A/turkey/Ontario/7732/66 (H5N9). Extremely variable clinical signs ranging from mild respiratory distress to high mortality were present among chickens inoculated with these viruses. Chickens inoculated with highly pathogenic (HP) virus had histologic lesions of necrosis and inflammation in cloacal bursa, thymus, spleen, heart, pancreas, kidney, brain, trachea, lung, and skeletal muscle, whereas chickens inoculated with MP virus had histologic lesions most frequently in lung and trachea or lacked histologic lesions. Immunospecific staining for avian influenza viral proteins was most common in cells within heart, lung, kidney, brain, and pancreas of chicken inoculated with HP viruses, but immunospecific staining was present only and infrequently in trachea and lung of chickens inoculated with MP-Penn AIV. MP-Alab did not produce lesions nor have viral antigen in inoculated chickens but did produce serologic evidence of infection. The pattern of organ involvement and viral antigen distribution in chickens intratracheally inoculated with HP AIV isolates indicates a common capability to spread beyond the respiratory tract and confirms the pantrophic replicative, pathobiologic, and lethal nature of the viruses. However, variability in severity and lesion distribution exists between different HP AIVs. By contrast, MP viruses had the ability to replicate in respiratory or enteric tracts or both and produce lesions

  1. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  2. Demonstrating the use of high-volume electronic medical claims data to monitor local and regional influenza activity in the US.

    Directory of Open Access Journals (Sweden)

    Cécile Viboud

    Full Text Available Fine-grained influenza surveillance data are lacking in the US, hampering our ability to monitor disease spread at a local scale. Here we evaluate the performances of high-volume electronic medical claims data to assess local and regional influenza activity.We used electronic medical claims data compiled by IMS Health in 480 US locations to create weekly regional influenza-like-illness (ILI time series during 2003-2010. IMS Health captured 62% of US outpatient visits in 2009. We studied the performances of IMS-ILI indicators against reference influenza surveillance datasets, including CDC-ILI outpatient and laboratory-confirmed influenza data. We estimated correlation in weekly incidences, peak timing and seasonal intensity across datasets, stratified by 10 regions and four age groups (<5, 5-29, 30-59, and 60+ years. To test IMS-Health performances at the city level, we compared IMS-ILI indicators to syndromic surveillance data for New York City. We also used control data on laboratory-confirmed Respiratory Syncytial Virus (RSV activity to test the specificity of IMS-ILI for influenza surveillance.Regional IMS-ILI indicators were highly synchronous with CDC's reference influenza surveillance data (Pearson correlation coefficients rho≥0.89; range across regions, 0.80-0.97, P<0.001. Seasonal intensity estimates were weakly correlated across datasets in all age data (rho≤0.52, moderately correlated among adults (rho≥0.64 and uncorrelated among school-age children. IMS-ILI indicators were more correlated with reference influenza data than control RSV indicators (rho = 0.93 with influenza v. rho = 0.33 with RSV, P<0.05. City-level IMS-ILI indicators were highly consistent with reference syndromic data (rho≥0.86.Medical claims-based ILI indicators accurately capture weekly fluctuations in influenza activity in all US regions during inter-pandemic and pandemic seasons, and can be broken down by age groups and fine geographical areas

  3. Pathogenicity and Transmission of H5 and H7 Highly Pathogenic Avian Influenza Viruses in Mallards

    Science.gov (United States)

    Costa-Hurtado, Mar; Shepherd, Eric; DeJesus, Eric; Smith, Diane; Spackman, Erica; Kapczynski, Darrell R.; Suarez, David L.; Stallknecht, David E.; Swayne, David E.

    2016-01-01

    ABSTRACT Wild aquatic birds have been associated with the intercontinental spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the A/goose/Guangdong/1/96 (Gs/GD) lineage during 2005, 2010, and 2014, but dispersion by wild waterfowl has not been implicated with spread of other HPAI viruses. To better understand why Gs/GD H5 HPAI viruses infect and transmit more efficiently in waterfowl than other HPAI viruses, groups of mallard ducks were challenged with one of 14 different H5 and H7 HPAI viruses, including a Gs/GD lineage H5N1 (clade 2.2) virus from Mongolia, part of the 2005 dispersion, and the H5N8 and H5N2 index HPAI viruses (clade 2.3.4.4) from the United States, part of the 2014 dispersion. All virus-inoculated ducks and contact exposed ducks became infected and shed moderate to high titers of the viruses, with the exception that mallards were resistant to Ck/Pennsylvania/83 and Ck/Queretaro/95 H5N2 HPAI virus infection. Clinical signs were only observed in ducks challenged with the H5N1 2005 virus, which all died, and with the H5N8 and H5N2 2014 viruses, which had decreased weight gain and fever. These three viruses were also shed in higher titers by the ducks, which could facilitate virus transmission and spread. This study highlights the possible role of wild waterfowl in the spread of HPAI viruses. IMPORTANCE The spread of H5 subtype highly pathogenic avian influenza (HPAI) viruses of the Gs/GD lineage by migratory waterfowl is a serious concern for animal and public health. H5 and H7 HPAI viruses are considered to be adapted to gallinaceous species (chickens, turkeys, quail, etc.) and less likely to infect and transmit in wild ducks. In order to understand why this is different with certain Gs/GD lineage H5 HPAI viruses, we compared the pathogenicity and transmission of several H5 and H7 HPAI viruses from previous poultry outbreaks to Gs/GD lineage H5 viruses, including H5N1 (clade 2.2), H5N8 and H5N2 (clade 2.3.4.4) viruses, in

  4. High seroprevalence of antibodies to avian influenza viruses among wild waterfowl in Alaska: implications for surveillance

    Science.gov (United States)

    Wilson, Heather M.; Hall, Jeffery S.; Flint, Paul L.; Franson, J. Christian; Ely, Craig R.; Schmutz, Joel A.; Samuel, Michael D.

    2013-01-01

    We examined seroprevalence (presence of detectable antibodies in serum) for avian influenza viruses (AIV) among 4,485 birds, from 11 species of wild waterfowl in Alaska (1998–2010), sampled during breeding/molting periods. Seroprevalence varied among species (highest in eiders (Somateria and Polysticta species), and emperor geese (Chen canagica)), ages (adults higher than juveniles), across geographic locations (highest in the Arctic and Alaska Peninsula) and among years in tundra swans (Cygnus columbianus). All seroprevalence rates in excess of 60% were found in marine-dependent species. Seroprevalence was much higher than AIV infection based on rRT-PCR or virus isolation alone. Because pre-existing AIV antibodies can infer some protection against highly pathogenic AIV (HPAI H5N1), our results imply that some wild waterfowl in Alaska could be protected from lethal HPAIV infections. Seroprevalence should be considered in deciphering patterns of exposure, differential infection, and rates of AIV transmission. Our results suggest surveillance programs include species and populations with high AIV seroprevalences, in addition to those with high infection rates. Serologic testing, including examination of serotype-specific antibodies throughout the annual cycle, would help to better assess spatial and temporal patterns of AIV transmission and overall disease dynamics.

  5. Isolation and characterization of virus of highly pathogenic avian influenza H5 subtype of chicken from outbreaks in Indonesia

    Directory of Open Access Journals (Sweden)

    Agus Wiyono

    2004-03-01

    Full Text Available A study on the isolation and characterization of Highly Pathogenic Avian Influenza of chicken from outbreaks in Indonesia was conducted at Indonesian Research Institute for Veterinary Science. Outbreaks of avian disease had been reported in Indonesia since August 2003 affecting commercial layer, broiler, quail, and ostrich and also native chicken with showing clinical signs such as cyanosis of wattle and comb, nasal discharges and hypersalivation, subcutaneous ptechiae on foot and leg, diarre and sudden high mortality. The aim of this study is to isolate and characterize the causal agent of the disease. Samples of serum, feather follicle, tracheal swab, as well as organs of proventriculus, intestine, caecal tonsil, trachea and lungs were collected from infected animals. Serum samples were tested haemaglutination/haemaglutination inhibition to Newcastle Disease and Egg Drop Syndrome viruses. Isolation of virus of the causal agent of the outbreak was conducted from samples of feather follicle, tracheal swab, and organs using 11 days old specific pathogen free (SPF embryonated eggs. The isolated viruses were then characterised by agar gel precipitation test using swine influenza reference antisera, by haemaglutination inhibition using H1 to H15 reference antisera, and by electron microscope examination. The pathogenicity of the viruses was confirmed by intravenous pathogenicity index test and its culture in Chicken Embryo Fibroblast primary cell culture without addition of trypsin. The study revealed that the causative agent of the outbreaks of avian disease in Indonesia was avian influenza H5 subtype virus based upon serological tests, virus isolation and characterization using swine influenza reference antisera, and electron microscope examination. While subtyping of the viruses using H1 to H15 reference antisera suggested that the virus is very likely to be an avian influenza H5N1 subtype virus. The pathogenicity test confirmed that the viruses

  6. Rapid Diagnostic Assay for Intact Influenza Virus Using a High Affinity Hemagglutinin Binding Protein.

    Science.gov (United States)

    Anderson, Caitlin E; Holstein, Carly A; Strauch, Eva-Maria; Bennett, Steven; Chevalier, Aaron; Nelson, Jorgen; Fu, Elain; Baker, David; Yager, Paul

    2017-06-20

    Influenza is a ubiquitous and recurring infection that results in approximately 500 000 deaths globally each year. Commercially available rapid diagnostic tests are based upon detection of the influenza nucleoprotein, which are limited in that they are unable to differentiate by species and require an additional viral lysis step. Sample preprocessing can be minimized or eliminated by targeting the intact influenza virus, thereby reducing assay complexity and leveraging the large number of hemagglutinin proteins on the surface of each virus. Here, we report the development of a paper-based influenza assay that targets the hemagglutinin protein; the assay employs a combination of antibodies and novel computationally designed, recombinant affinity proteins as the capture and detection agents. This system leverages the customizability of recombinant protein design to target the conserved receptor-binding pocket of the hemagglutinin protein and to match the trimeric nature of hemagglutinin for improved avidity. Using this assay, we demonstrate the first instance of intact influenza virus detection using a combination of antibody and affinity proteins within a porous network. The recombinant head region binder based assays yield superior analytical sensitivity as compared to the antibody based assay, with lower limits of detection of 3.54 × 10 7 and 1.34 × 10 7 CEID 50 /mL for the mixed and all binder stacks, respectively. Not only does this work describe the development of a novel influenza assay, it also demonstrates the power of recombinant affinity proteins for use in rapid diagnostic assays.

  7. 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.

  8. Identifying High Growth Firms in India

    DEFF Research Database (Denmark)

    Aggarwal, Aradhna; Sato, Takahiro

    Over the past two decades, considerable interest has grown in high growth firms (HGFs). However, the concept of HGFs still remains controversial. One of the most controversial issues is size and age of these firms. The present study argues that the current literature on HGFs may offer little help...

  9. A high compression crystal growth system

    International Nuclear Information System (INIS)

    Nieman, H.F.; Walton, A.A.; Powell, B.M.; Dolling, G.

    1980-01-01

    This report describes the construction and operating procedure for a high compression crystal growth system, capable of growing single crystals from the fluid phase over the temperature range of 4.2 K to 300 K, at pressures up to 900 MPa. Some experimental results obtained with the system are given for solid β-nitrogen. (auth)

  10. 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...

  11. An expost economic assessment of the intervention against highly pathogenic avian influenza in Nigeria

    Directory of Open Access Journals (Sweden)

    Mohamadou L. Fadiga

    2014-05-01

    Full Text Available This study assesses the intervention against avian influenza in Nigeria. It applied a simple compartmental model to define endemic and burn-out scenarios for the risk of spread of HPAI in Nigeria. It followed with the derivation of low and high mortality risks associated to each scenario. The estimated risk parameters were subsequently used to stochastically simulate the trajectory of the disease, had no intervention been carried out. Overall, the intervention costs US$ 41 million, which was yearly dis- bursed in various amounts over the 2006-2010 period. The key output variables (incremental net benefit, disease cost, and benefit cost ratio were estimated for each randomly drawn risk parameter. With a 12% annual discount rate, the results show that the intervention was economically justified under the endemic scenario with high mortality risk. On average, incremental benefit under this scenario amounted to US$ 63.7 million, incremental net benefit to US$27.2 million, and benefit cost ratio estimated to 1.75.

  12. Control of highly pathogenic avian influenza in Quang Tri province, Vietnam: voices from the human-animal interface.

    Science.gov (United States)

    Farrell, Penny C; Hunter, Cynthia; Truong, Bui; Bunning, Michel

    2015-01-01

    Highly pathogenic avian influenza (HPAI) is caused by the haemagglutinin 5, neuraminidase 1 (H5N1) influenza A virus. Around 80% of households in rural Vietnam raise poultry, which provides food security and nutrition to their households and beyond. Of these, around 15-20% are semi-commercial producers, producing at least 28% of the country's chicken. Through learning the experiences of these semi-commercial farmers, this study aimed to explore the local understandings and sociocultural aspects of HPAI's impact, particularly the aetiology, diagnosis, and the prevention and control methods in one Vietnamese rural province. This study was conducted in Quang Tri province, Vietnam. Quang Tri province has eight districts. Five of these districts were at high risk of HPAI during the study period, of which three were selected for the present study. Within these three districts, six communes were randomly selected for the study from the list of intervention communes in Quang Tri province. Six out of the 26 intervention communes in Quang Tri were therefore selected. Participants were randomly selected and recruited from lists of semi-commercial farmers, village animal health workers, village human health workers and local authorities so that the study population (representative population) included an amount of variability similar to that of the wider population. A key benefit of this village-level control program was the residential proximity of animal and human health professionals. Participants were well aware of the typical clinical signs for avian influenza and of the reporting process for suspect cases. However there was extensive room for improvement in Quang Tri province regarding access to the HPAI vaccine, essential medical equipment for animal use, and available financial support. This qualitative research study provided an important insight for in-country policy makers and international stakeholders. It is vital that there are continued efforts to prevent and

  13. Stability of different influenza subtypes: How can high hydrostatic pressure be a useful tool for vaccine development?

    Science.gov (United States)

    Dumard, Carlos Henrique; Barroso, Shana P C; Santos, Ana Clara V; Alves, Nathalia S; Couceiro, José Nelson S S; Gomes, Andre M O; Santos, Patricia S; Silva, Jerson L; Oliveira, Andréa C

    2017-12-01

    Avian influenza A viruses can cross naturally into mammals and cause severe diseases, as observed for H5N1. The high lethality of human infections causes major concerns about the real risk of a possible pandemic of severe diseases to which human susceptibility may be high and universal. High hydrostatic pressure (HHP) is a valuable tool for studies regarding the folding of proteins and the assembly of macromolecular structures such as viruses; furthermore, HHP has already been demonstrated to promote viral inactivation. Here, we investigated the structural stability of avian and human influenza viruses using spectroscopic and light-scattering techniques. We found that both particles have similar structural stabilities and that HHP promotes structural changes. HHP induced slight structural changes to both human and avian influenza viruses, and these changes were largely reversible when the pressure returned to its initial level. The spectroscopic data showed that H3N2 was more pressure-sensitive than H3N8. Structural changes did not predict changes in protein function, as H3N2 fusion activity was not affected, while H3N8 fusion activity drastically decreased. The fusion activity of H1N1 was also strongly affected by HHP. In all cases, HHP caused inactivation of the different influenza viruses. HHP may be a useful tool for vaccine development, as it induces minor and reversible structural changes that may be associated with partial preservation of viral biological activities and may potentiate their immunogenic response while abolishing their infectivity. We also confirmed that, although pressure does not promote drastic changes in viral particle structure, it can distinctly affect viral fusion activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Community preparedness for highly pathogenic Avian influenza on Bali and Lombok, Indonesia.

    Science.gov (United States)

    Hunter, C; Birden, H H; Toribio, J-A; Booy, R; Abdurrahman, M; Ambarawati, A I G A A; Adiputra, N

    2014-01-01

    The Asia-Pacific region is the likeliest location for the next significant outbreak of highly pathogenic avian influenza (HPAI). Indonesia has experienced HPAI H5N1 outbreaks in poultry and humans each year since 2003 and has had the highest case fatality rate for human cases. The purposes of this study were to capture the knowledge of avian influenza and of poultry-raising practices in two regions of Indonesia and to evaluate the impact and extent of activities undertaken to 2010 through the National Strategic Plan for Avian Influenza Control at the village level. A combination of quantitative and qualitative methods was used to investigate the multiple influences on behaviours, decisions and actions taken by poultry-raising households, and by villages and communities, regarding the threat of HPAI. Between June 2010 and May 2011 a structured survey of 400 households was conducted on Lombok and of 402 on Bali, inviting Sector 3 (small-scale independent commercial poultry farms) and Sector 4 (village household) poultry raisers to participate. Focus groups and in-depth interviews were convened with key stakeholders, including livestock and animal health and public health officials, community leaders and villagers. From the focus group and in-depth interviews, it appears that the flow of information through the national HPAI control program has been efficient at the top levels (from national to provincial, then to districts and subdistricts). However, these findings show that effective transmission of information from subdistrict to rural village level and from village leaders to community members has been limited. The degree of community preparedness for HPAI on Bali and Lombok appears minimal. Knowledge of government activities was more extensive at Bali sites, while only limited government programs and activities occurred at the village level on Lombok. Activities conducted by government agencies from provincial to village level were limited in scope and need to be

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

    Science.gov (United States)

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

    2010-05-01

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

  16. Avian influenza

    Science.gov (United States)

    Bird flu; H5N1; H5N2; H5N8; H7N9; Avian influenza A (HPAI) H5 ... The first avian influenza in humans was reported in Hong Kong in 1997. It was called avian influenza (H5N1). The outbreak was linked ...

  17. Risk factors and clusters of Highly Pathogenic Avian Influenza H5N1 outbreaks in Bangladesh

    Science.gov (United States)

    Loth, Leo; Gilbert, Marius; Osmani, Mozaffar G.; Kalam, Abul M.; Xiao, Xiangming

    2016-01-01

    Between March 2007 and July 2009, 325 Highly Pathogenic Avian Influenza (HPAI, subtype H5N1) outbreaks in poultry were reported in 154 out of a total of 486 sub-districts in Bangladesh. This study analyzed the temporal and spatial patterns of HPAI H5N1 outbreaks and quantified the relationship between several spatial risk factors and HPAI outbreaks in sub-districts in Bangladesh. We assessed spatial autocorrelation and spatial dependence, and identified clustering sub-districts with disease statistically similar to or dissimilar from their neighbors. Three significant risk factors associated to HPAI H5N1 virus outbreaks were identified; the quadratic log-transformation of human population density [humans per square kilometer, P = 0.01, OR 1.15 (95% CI: 1.03–1.28)], the log-transformation of the total commercial poultry population [number of commercial poultry per sub-district, P Bangladesh to target surveillance and to concentrate response efforts in areas where disease is likely to occur. Concentrating response efforts may help to combat HPAI more effectively, reducing the environmental viral load and so reducing the number of disease incidents. PMID:20554337

  18. Identifying risk factors of highly pathogenic avian influenza (H5N1 subtype) in Indonesia.

    Science.gov (United States)

    Loth, Leo; Gilbert, Marius; Wu, Jianmei; Czarnecki, Christina; Hidayat, Muhammad; Xiao, Xiangming

    2011-10-01

    Highly pathogenic avian influenza (HPAI), subtype H5N1, was first officially reported in Indonesia in 2004. Since then the disease has spread and is now endemic in large parts of the country. This study investigated the statistical relationship between a set of risk factors and the presence or absence of HPAI in Indonesia during 2006 and 2007. HPAI was evaluated through participatory disease surveillance (PDS) in backyard village chickens (the study population), and risk factors included descriptors of people and poultry distribution (separating chickens, ducks and production sectors), poultry movement patterns and agro-ecological conditions. The study showed that the risk factors "elevation", "human population density" and "rice cropping" were significant in accounting for the spatial variation of the PDS-defined HPAI cases. These findings were consistent with earlier studies in Thailand and Vietnam. In addition "commercial poultry population", and two indicators of market locations and transport; "human settlements" and "road length", were identified as significant risk factors in the models. In contrast to several previous studies carried out in Southeast Asia, domestic backyard ducks were not found to be a significant risk factor in Indonesia. The study used surrogate estimates of market locations and marketing chains and further work should focus on the actual location of the live bird markets, and on the flow of live poultry and poultry products between them, so that patterns of possible transmission, and regions of particular risk could be better inferred. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Multivalent HA DNA vaccination protects against highly pathogenic H5N1 avian influenza infection in chickens and mice.

    Directory of Open Access Journals (Sweden)

    Srinivas Rao

    Full Text Available Sustained outbreaks of highly pathogenic avian influenza (HPAI H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses.The ability of DNA vaccines encoding hemagglutinin (HA proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 microg DNA given twice either by intramuscular needle injection or with a needle-free device.DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates.

  20. The ecology and age structure of a highly pathogenic avian influenza virus outbreak in wild mute swans.

    Science.gov (United States)

    Pybus, O G; Perrins, C M; Choudhury, B; Manvell, R J; Nunez, A; Schulenburg, B; Sheldon, B C; Brown, I H

    2012-12-01

    The first UK epizootic of highly pathogenic (HP) H5N1 influenza in wild birds occurred in 2008, in a population of mute swans that had been the subject of ornithological study for decades. Here we use an innovative combination of ornithological, phylogenetic and immunological approaches to investigate the ecology and age structure of HP H5N1 in nature. We screened samples from swans and waterbirds using PCR and sequenced HP H5N1-positive samples. The outbreak's origin was investigated by linking bird count data with a molecular clock analysis of sampled virus sequences. We used ringing records to reconstruct the age-structure of outbreak mortality, and we estimated the age distribution of prior exposure to avian influenza. Outbreak mortality was low and all HP H5N1-positive mute swans in the affected population were <3 years old. Only the youngest age classes contained an appreciable number of individuals with no detectable antibody responses to viral nucleoprotein. Phylogenetic analysis indicated that the outbreak strain circulated locally for ~1 month before detection and arrived when the immigration rate of migrant waterbirds was highest. Our data are consistent with the hypothesis that HP H5N1 epizootics in wild swans exhibit limited mortality due to immune protection arising from previous exposure. Our study population may represent a valuable resource for investigating the natural ecology and epidemiology of avian influenza.

  1. New treatments for influenza

    Directory of Open Access Journals (Sweden)

    Barik Sailen

    2012-09-01

    Full Text Available Abstract Influenza has a long history of causing morbidity and mortality in the human population through routine seasonal spread and global pandemics. The high mutation rate of the RNA genome of the influenza virus, combined with assortment of its multiple genomic segments, promote antigenic diversity and new subtypes, allowing the virus to evade vaccines and become resistant to antiviral drugs. There is thus a continuing need for new anti-influenza therapy using novel targets and creative strategies. In this review, we summarize prospective future therapeutic regimens based on recent molecular and genomic discoveries.

  2. New treatments for influenza.

    Science.gov (United States)

    Barik, Sailen

    2012-09-13

    Influenza has a long history of causing morbidity and mortality in the human population through routine seasonal spread and global pandemics. The high mutation rate of the RNA genome of the influenza virus, combined with assortment of its multiple genomic segments, promote antigenic diversity and new subtypes, allowing the virus to evade vaccines and become resistant to antiviral drugs. There is thus a continuing need for new anti-influenza therapy using novel targets and creative strategies. In this review, we summarize prospective future therapeutic regimens based on recent molecular and genomic discoveries.

  3. Metabolic versatility in Haemophilus influenzae: a metabolomic and genomic analysis

    Directory of Open Access Journals (Sweden)

    Dk Seti Maimonah Pg eOthman

    2014-03-01

    Full Text Available Haemophilus influenzae is a host adapted human pathogen known to contribute to a variety of acute and chronic diseases of the upper and lower respiratory tract as well as the middle ear. At the sites of infection as well as during growth as a commensal the environmental conditions encountered by H. influenzae will vary significantly, especially in terms of oxygen availability, however, the mechanisms by which the bacteria can adapt their metabolism to cope with such changes have not been studied in detail. Using targeted metabolomics the spectrum of metabolites produced during growth of H. influenzae on glucose in RPMI-based medium was found to change from acetate as the main product during aerobic growth to formate as the major product during anaerobic growth. This is likely caused by a switch in the major pyruvate degrading route. Neither lactate nor succinate or fumarate were major products of H. influenzae growth under any condition studied Gene expression studies and enzyme activity data revealed that despite an identical genetic makeup and very similar metabolite production profiles, H. influenzae strain Rd appeared to favour glucose degradation via the PPP, while strain 2019, a clinical isolate, showed higher expression of enzymes involved in glycolysis. Components of the respiratory chain were most highly expressed during microaerophilic and anaerobic growth in both strains, but again clear differences existed in the expression of genes associated e.g. with NADH oxidation, nitrate and nitrite reduction in the two strains studied.Together our results indicate that H. influenzae uses a specialized type of metabolism that could be termed ‘respiration assisted fermentation’ where the respiratory chain likely serves to alleviate redox imbalances caused by incomplete glucose oxidation, and at the same time provides a means of converting a variety of compounds including nitrite and nitrate that arise as part of the host defence mechanisms.

  4. The PB2, PA, HA, NP, and NS genes of a highly pathogenic avian influenza virus A/whooper swan/Mongolia/3/2005 (H5N1 are responsible for pathogenicity in ducks

    Directory of Open Access Journals (Sweden)

    Kajihara Masahiro

    2013-02-01

    Full Text Available Abstract Background Wild ducks are the natural hosts of influenza A viruses. Duck influenza, therefore, has been believed inapparent infection with influenza A viruses, including highly pathogenic avian influenza viruses (HPAIVs in chickens. In fact, ducks experimentally infected with an HPAIV strain, A/Hong Kong/483/1997 (H5N1 (HK483, did not show any clinical signs. Another HPAIV strain, A/whooper swan/Mongolia/3/2005 (H5N1 (MON3 isolated from a dead swan, however, caused neurological dysfunction and death in ducks. Method To understand the mechanism whereby MON3 shows high pathogenicity in ducks, HK483, MON3, and twenty-four reassortants generated between these two H5N1 viruses were compared for their pathogenicity in domestic ducks. Results None of the ducks infected with MON3-based single-gene reassortants bearing the PB2, NP, or NS gene segment of HK483 died, and HK483-based single-gene reassortants bearing PB2, NP, or NS genes of MON3 were not pathogenic in ducks, suggesting that multiple gene segments contribute to the pathogenicity of MON3 in ducks. All the ducks infected with the reassortant bearing PB2, PA, HA, NP, and NS gene segments of MON3 died within five days post-inoculation, as did those infected with MON3. Each of the viruses was assessed for replication in ducks three days post-inoculation. MON3 and multi-gene reassortants pathogenic in ducks were recovered from all of the tissues examined and replicated with high titers in the brains and lungs. Conclusion The present results indicate that multigenic factors are responsible for efficient replication of MON3 in ducks. In particular, virus growth in the brain might correlate with neurological dysfunction and the disease severity.

  5. High-throughput sequencing of natively paired antibody chains provides evidence for original antigenic sin shaping the antibody response to influenza vaccination.

    Science.gov (United States)

    Tan, Yann-Chong; Blum, Lisa K; Kongpachith, Sarah; Ju, Chia-Hsin; Cai, Xiaoyong; Lindstrom, Tamsin M; Sokolove, Jeremy; Robinson, William H

    2014-03-01

    We developed a DNA barcoding method to enable high-throughput sequencing of the cognate heavy- and light-chain pairs of the antibodies expressed by individual B cells. We used this approach to elucidate the plasmablast antibody response to influenza vaccination. We show that >75% of the rationally selected plasmablast antibodies bind and neutralize influenza, and that antibodies from clonal families, defined by sharing both heavy-chain VJ and light-chain VJ sequence usage, do so most effectively. Vaccine-induced heavy-chain VJ regions contained on average >20 nucleotide mutations as compared to their predicted germline gene sequences, and some vaccine-induced antibodies exhibited higher binding affinities for hemagglutinins derived from prior years' seasonal influenza as compared to their affinities for the immunization strains. Our results show that influenza vaccination induces the recall of memory B cells that express antibodies that previously underwent affinity maturation against prior years' seasonal influenza, suggesting that 'original antigenic sin' shapes the antibody response to influenza vaccination. Published by Elsevier Inc.

  6. 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.

  7. Non-Attenuation Of Highly Pathogenic Avian Influenza H5N1 By ...

    African Journals Online (AJOL)

    Avian influenza H5N1 represents one of the most researched viruses in laboratories world-wide in recent times with regards to its epidemiology, ecology, biology and geography. The virus has caused 409 human cases and 256 human fatalities to date. Some laboratory activities and other lab related works predispose ...

  8. Public health concerns of highly pathogenic avian influenza H5N1 endemicity in Africa

    Directory of Open Access Journals (Sweden)

    Olubunmi Gabriel Fasanmi

    2017-10-01

    Full Text Available Highly pathogenic avian influenza virus (HPAIV H5N1 was first officially reported in Africa in 2006; thereafter this virus has spread rapidly from Nigeria to 11 other African countries. This study was aimed at utilizing data from confirmed laboratory reports to carry out a qualitative evaluation of the factors responsible for HPAI H5N1 persistence in Africa and the public health implications; and to suggest appropriate control measures. Relevant publications were sought from data banks and repositories of FAO, OIE, WHO, and Google scholars. Substantiated data on HPAI H5N1 outbreaks in poultry in Africa and in humans across the world were mined. HPAI H5N1 affects poultry and human populations, with Egypt having highest human cases (346 globally. Nigeria had a reinfection from 2014 to 2015, with outbreaks in Cote d'Ivoire, Ghana, Niger, Nigeria, and Burkina Faso throughout 2016 unabated. The persistence of this virus in Africa is attributed to the survivability of HPAIV, ability to evolve other subtypes through genetic reassortment, poor biosecurity compliance at the live bird markets and poultry farms, husbandry methods and multispecies livestock farming, poultry vaccinations, and continuous shedding of HPAIV, transboundary transmission of HPAIV through poultry trades; and transcontinental migratory birds. There is, therefore, the need for African nations to realistically reassess their status, through regular surveillance and be transparent with HPAI H5N1 outbreak data. Also, it is important to have an understanding of HPAIV migration dynamics which will be helpful in epidemiological modeling, disease prevention, control and eradication measures.

  9. Model-based evaluation of highly and low pathogenic avian influenza dynamics in wild birds.

    Directory of Open Access Journals (Sweden)

    Viviane Hénaux

    Full Text Available There is growing interest in avian influenza (AI epidemiology to predict disease risk in wild and domestic birds, and prevent transmission to humans. However, understanding the epidemic dynamics of highly pathogenic (HPAI viruses remains challenging because they have rarely been detected in wild birds. We used modeling to integrate available scientific information from laboratory and field studies, evaluate AI dynamics in individual hosts and waterfowl populations, and identify key areas for future research. We developed a Susceptible-Exposed-Infectious-Recovered (SEIR model and used published laboratory challenge studies to estimate epidemiological parameters (rate of infection, latency period, recovery and mortality rates, considering the importance of age classes, and virus pathogenicity. Infectious contact leads to infection and virus shedding within 1-2 days, followed by relatively slower period for recovery or mortality. We found a shorter infectious period for HPAI than low pathogenic (LP AI, which may explain that HPAI has been much harder to detect than LPAI during surveillance programs. Our model predicted a rapid LPAI epidemic curve, with a median duration of infection of 50-60 days and no fatalities. In contrast, HPAI dynamics had lower prevalence and higher mortality, especially in young birds. Based on field data from LPAI studies, our model suggests to increase surveillance for HPAI in post-breeding areas, because the presence of immunologically naïve young birds is predicted to cause higher HPAI prevalence and bird losses during this season. Our results indicate a better understanding of the transmission, infection, and immunity-related processes is required to refine predictions of AI risk and spread, improve surveillance for HPAI in wild birds, and develop disease control strategies to reduce potential transmission to domestic birds and/or humans.

  10. Model-based evaluation of highly and low pathogenic avian influenza dynamics in wild birds

    Science.gov (United States)

    Hénaux, Viviane; Samuel, Michael D.; Bunck, Christine M.

    2010-01-01

    There is growing interest in avian influenza (AI) epidemiology to predict disease risk in wild and domestic birds, and prevent transmission to humans. However, understanding the epidemic dynamics of highly pathogenic (HPAI) viruses remains challenging because they have rarely been detected in wild birds. We used modeling to integrate available scientific information from laboratory and field studies, evaluate AI dynamics in individual hosts and waterfowl populations, and identify key areas for future research. We developed a Susceptible-Exposed-Infectious-Recovered (SEIR) model and used published laboratory challenge studies to estimate epidemiological parameters (rate of infection, latency period, recovery and mortality rates), considering the importance of age classes, and virus pathogenicity. Infectious contact leads to infection and virus shedding within 1–2 days, followed by relatively slower period for recovery or mortality. We found a shorter infectious period for HPAI than low pathogenic (LP) AI, which may explain that HPAI has been much harder to detect than LPAI during surveillance programs. Our model predicted a rapid LPAI epidemic curve, with a median duration of infection of 50–60 days and no fatalities. In contrast, HPAI dynamics had lower prevalence and higher mortality, especially in young birds. Based on field data from LPAI studies, our model suggests to increase surveillance for HPAI in post-breeding areas, because the presence of immunologically naïve young birds is predicted to cause higher HPAI prevalence and bird losses during this season. Our results indicate a better understanding of the transmission, infection, and immunity-related processes is required to refine predictions of AI risk and spread, improve surveillance for HPAI in wild birds, and develop disease control strategies to reduce potential transmission to domestic birds and/or humans.

  11. Overexpression and Purification of C-terminal Fragment of the Passenger Domain of Hap Protein from Nontypeable Haemophilus influenzae in a Highly Optimized Escherichia coli Expression System

    Science.gov (United States)

    Tabatabaee, Akram; Siadat, Seyed Davar; Moosavi, Seyed Fazllolah; Aghasadeghi, Mohammad Reza; Memarnejadian, Arash; Pouriayevali, Mohammad Hassan; Yavari, Neda

    2013-01-01

    Background Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract disease and initiates infection by colonization in nasopharynx. The Haemophilus influenzae (H. influenzae) Hap adhesin is an auto transporter protein that promotes initial interaction with human epithelial cells. Hap protein contains a 110 kDa internal passenger domain called “HapS” and a 45 kDa C-terminal translocator domain called “Hapβ”. Hap adhesive activity has been recently reported to be connected to its Cell Binding Domain (CBD) which resides within the 311 C-terminal residues of the internal passenger domain of the protein. Furthermore, immunization with this CBD protein has been shown to prevent bacterial nasopharynx colonization in animal models. Methods To provide enough amounts of pure HapS protein for vaccine studies, we sought to develop a highly optimized system to overexpress and purify the protein in large quantities. To this end, pET24a-cbd plasmid harboring cbd sequence from NTHi ATCC49766 was constructed and its expression was optimized by testing various expression parameters such as growth media, induction temperature, IPTG inducer concentration, induction stage and duration. SDS-PAGE and Western-blotting were used for protein analysis and confirmation and eventually the expressed protein was easily purified via immobilized metal affinity chromatography (IMAC) using Ni-NTA columns. Results The highest expression level of target protein was achieved when CBD expressing E. coli BL21 (DE3) cells were grown at 37°C in 2xTY medium with 1.0 mM IPTG at mid-log phase (OD600 nm equal to 0.6) for 5 hrs. Amino acid sequence alignment of expressed CBD protein with 3 previously published CBD amino acid sequences were more than %97 identical and antigenicity plot analysis further revealed 9 antigenic domains which appeared to be well conserved among different analyzed CBD sequences. Conclusion Due to the presence of high similarity among CBD from NTHi ATCC

  12. Spatiotemporal Structure of Molecular Evolution of H5N1 Highly Pathogenic Avian Influenza Viruses in Vietnam

    OpenAIRE

    Carrel, Margaret A.; Emch, Michael; Jobe, R. Todd; Moody, Aaron; Wan, Xiu-Feng

    2010-01-01

    Background Vietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and...

  13. Identifying antigenicity associated sites in highly pathogenic H5N1 influenza virus hemagglutinin by using sparse learning

    OpenAIRE

    Cai, Zhipeng; Ducatez, Mariette F.; Yang, Jialiang; Zhang, Tong; Long, Li-Ping; Boon, Adrianus C.; Webby, Richard J.; Wan, Xiu-Feng

    2012-01-01

    Since the isolation of A/goose/Guangdong/1/1996 (H5N1) in farmed geese in southern China, highly pathogenic H5N1 avian influenza viruses have posed a continuous threat to both public and animal health. The non-synonymous mutation of the H5 hemagglutinin gene has resulted in antigenic drift, leading to difficulties in both clinical diagnosis and vaccine strain selection. Characterizing H5N1’s antigenic profiles would help resolve these problems. In this study, a novel sparse learning method wa...

  14. Identifying antigenicity-associated sites in highly pathogenic H5N1 influenza virus hemagglutinin by using sparse learning.

    OpenAIRE

    Cai, Zhipeng; Yang, Jialiang; Zhang, Tong; Long, Li-Ping; Boon, Adrianus C; Webby, Richard J; Wan, Xiu-Feng

    2012-01-01

    Since the isolation of A/goose/Guangdong/1/1996 (H5N1) in farmed geese in southern China, highly pathogenic H5N1 avian influenza viruses have posed a continuous threat to both public and animal health. The non-synonymous mutation of the H5 hemagglutinin (HA) gene has resulted in antigenic drift, leading to difficulties in both clinical diagnosis and vaccine strain selection. Characterizing H5N1's antigenic profiles would help resolve these problems. In this study, a novel sparse learning meth...

  15. Influenza surveillance

    Directory of Open Access Journals (Sweden)

    Karolina Bednarska

    2016-04-01

    Full Text Available Influenza surveillance was established in 1947. From this moment WHO (World Health Organization has been coordinating international cooperation, with a goal of monitoring influenza virus activity, effective diagnostic of the circulating viruses and informing society about epidemics or pandemics, as well as about emergence of new subtypes of influenza virus type A. Influenza surveillance is an important task, because it enables people to prepare themselves for battle with the virus that is constantly mutating, what leads to circulation of new and often more virulent strains of influenza in human population. As vaccination is the most effective method of fighting the virus, one of the major tasks of GISRS is developing an optimal antigenic composition of the vaccine for the current epidemic season. European Influenza Surveillance Network (EISN has also developed over the years. EISN is running integrated epidemiological and virological influenza surveillance, to provide appropriate data to public health experts in member countries, to enable them undertaking relevant activities based on the current information about influenza activity. In close cooperation with GISRS and EISN are National Influenza Centres - national institutions designated by the Ministry of Health in each country.

  16. A comprehensive analysis of Italian web pages mentioning squalene-based influenza vaccine adjuvants reveals a high prevalence of misinformation.

    Science.gov (United States)

    Panatto, Donatella; Amicizia, Daniela; Arata, Lucia; Lai, Piero Luigi; Gasparini, Roberto

    2018-04-03

    Squalene-based adjuvants have been included in influenza vaccines since 1997. Despite several advantages of adjuvanted seasonal and pandemic influenza vaccines, laypeople's perception of such formulations may be hesitant or even negative under certain circumstances. Moreover, in Italian, the term "squalene" has the same root as such common words as "shark" (squalo), "squalid" and "squalidness" that tend to have negative connotations. This study aimed to quantitatively and qualitatively analyze a representative sample of Italian web pages mentioning squalene-based adjuvants used in influenza vaccines. Every effort was made to limit the subjectivity of judgments. Eighty-four unique web pages were assessed. A high prevalence (47.6%) of pages with negative or ambiguous attitudes toward squalene-based adjuvants was established. Compared with web pages reporting balanced information on squalene-based adjuvants, those categorized as negative/ambiguous had significantly lower odds of belonging to a professional institution [adjusted odds ratio (aOR) = 0.12, p = .004], and significantly higher odds of containing pictures (aOR = 1.91, p = .034) and being more readable (aOR = 1.34, p = .006). Some differences in wording between positive/neutral and negative/ambiguous web pages were also observed. The most common scientifically unsound claims concerned safety issues and, in particular, claims linking squalene-based adjuvants to the Gulf War Syndrome and autoimmune disorders. Italian users searching the web for information on vaccine adjuvants have a high likelihood of finding unbalanced and misleading material. Information provided by institutional websites should be not only evidence-based but also carefully targeted towards laypeople. Conversely, authors writing for non-institutional websites should avoid sensationalism and provide their readers with more balanced information.

  17. Spatiotemporal structure of molecular evolution of H5N1 highly pathogenic avian influenza viruses in Vietnam.

    Science.gov (United States)

    Carrel, Margaret A; Emch, Michael; Jobe, R Todd; Moody, Aaron; Wan, Xiu-Feng

    2010-01-08

    Vietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and there were nine newly emerged reassortants from 2001 to 2007 in Vietnam. H5N1 viruses in Vietnam cluster distinctly around Hanoi and Ho Chi Minh City. However, the nature of the relationship between genetic divergence and geographic patterns is still unclear. In this study, we hypothesized that genetic distances between H5N1 viruses in Vietnam are correlated with geographic distances, as the result of distinct population and environment patterns along Vietnam's long north to south longitudinal extent. Based on this hypothesis, we combined spatial statistical methods with genetic analytic techniques and explicitly used geographic space to explore genetic evolution of H5N1 highly pathogenic avian influenza viruses at the sub-national scale in Vietnam. Our dataset consisted of 125 influenza viruses (with whole genome sets) isolated in Vietnam from 2003 to 2007. Our results document the significant effect of space and time on genetic evolution and the rise of two regional centers of genetic mixing by 2007. These findings give insight into processes underlying viral evolution and suggest that genetic differentiation is associated with the distance between concentrations of human and poultry populations around Hanoi and Ho Chi Minh City. The results show that genetic evolution of H5N1 viruses in Vietnamese domestic poultry is highly correlated with the location and spread of those viruses in geographic space. This correlation varies by scale, time, and gene, though a classic isolation by

  18. Spatiotemporal structure of molecular evolution of H5N1 highly pathogenic avian influenza viruses in Vietnam.

    Directory of Open Access Journals (Sweden)

    Margaret A Carrel

    2010-01-01

    Full Text Available Vietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10: e3462 demonstrated that there have been at least six independent H5N1 introductions into Vietnam and there were nine newly emerged reassortants from 2001 to 2007 in Vietnam. H5N1 viruses in Vietnam cluster distinctly around Hanoi and Ho Chi Minh City. However, the nature of the relationship between genetic divergence and geographic patterns is still unclear.In this study, we hypothesized that genetic distances between H5N1 viruses in Vietnam are correlated with geographic distances, as the result of distinct population and environment patterns along Vietnam's long north to south longitudinal extent. Based on this hypothesis, we combined spatial statistical methods with genetic analytic techniques and explicitly used geographic space to explore genetic evolution of H5N1 highly pathogenic avian influenza viruses at the sub-national scale in Vietnam. Our dataset consisted of 125 influenza viruses (with whole genome sets isolated in Vietnam from 2003 to 2007. Our results document the significant effect of space and time on genetic evolution and the rise of two regional centers of genetic mixing by 2007. These findings give insight into processes underlying viral evolution and suggest that genetic differentiation is associated with the distance between concentrations of human and poultry populations around Hanoi and Ho Chi Minh City.The results show that genetic evolution of H5N1 viruses in Vietnamese domestic poultry is highly correlated with the location and spread of those viruses in geographic space. This correlation varies by scale, time, and gene, though a classic

  19. Evolution of highly pathogenic avian H5N1 influenza viruses

    Energy Technology Data Exchange (ETDEWEB)

    Macken, Catherine A [Los Alamos National Laboratory; Green, Margaret A [Los Alamos National Laboratory

    2009-01-01

    Highly pathogenic avian H5N1 viruses have circulated in Southeast Asia for more than a decade, are now endemic in parts of this region, and have also spread to more than 60 countries on three continents. The evolution of these viruses is characterized by frequent reassortment events that have created a significant number of different genotypes, both transient and longer lasting. However, fundamental questions remain about the generation and perpetuation of this substantial genetic diversity. These gaps in understanding may, in part, be due to the difficulties of genotyping closely related viruses, and limitations in the size of the data sets used in analysis. Using our recently published novel genotyping procedure ('two-time test'), which is amenable to high throughput analysis and provides an increased level of resolution relative to previous analyses, we propose a detailed model for the evolution and diversification of avian H5N1 viruses. Our analysis suggests that (i) all current H5N1 genotypes are derived from a single, clearly defined sequence of initial reassortment events; (ii) reassortment of the polymerase and NP genes may have played an important role in avian H5N1 virus evolution; (iii) the current genotype Z viruses have diverged into three distinguishable sub-genotypes in the absence of reassortment; (iv) some potentially significant molecular changes appear to be correlated with particular genotypes (for example, reassortment of the internal genes is often paralleled by a change in the HA clade); and (v) as noted in earlier studies of avian influenza A virus evolution, novel segments are typically derived from different donors (i.e., there is no obvious pattern of gene linkage in reassortment). The model of avian H5N1 viral evolution by reassortment and mutation that emerges from our study provides a context within which significant amino acid changes may be revealed; it also may help in predicting the 'success' of newly emerging

  20. Methods for molecular surveillance of influenza

    OpenAIRE

    Wang, Ruixue; Taubenberger, Jeffery K

    2010-01-01

    Molecular-based techniques for detecting influenza viruses have become an integral component of human and animal surveillance programs in the last two decades. The recent pandemic of the swine-origin influenza A virus (H1N1) and the continuing circulation of highly pathogenic avian influenza A virus (H5N1) further stress the need for rapid and accurate identification and subtyping of influenza viruses for surveillance, outbreak management, diagnosis and treatment. There has been remarkable pr...

  1. Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015.

    Science.gov (United States)

    Bi, Yuhai; Zhang, Zhenjie; Liu, Wenjun; Yin, Yanbo; Hong, Jianmin; Li, Xiangdong; Wang, Haiming; Wong, Gary; Chen, Jianjun; Li, Yunfeng; Ru, Wendong; Gao, Ruyi; Liu, Di; Liu, Yingxia; Zhou, Boping; Gao, George F; Shi, Weifeng; Lei, Fumin

    2015-08-11

    Approximately 100 migratory birds, including whooper swans and pochards, were found dead in the Sanmenxia Reservoir Area of China during January 2015. The causative agent behind this outbreak was identified as H5N1 highly pathogenic avian influenza virus (HPAIV). Genetic and phylogenetic analyses revealed that this Sanmenxia H5N1 virus was a novel reassortant, possessing a Clade 2.3.2.1c HA gene and a H9N2-derived PB2 gene. Sanmenxia Clade 2.3.2.1c-like H5N1 viruses possess the closest genetic identity to A/Alberta/01/2014 (H5N1), which recently caused a fatal respiratory infection in Canada with signs of meningoencephalitis, a highly unusual symptom with influenza infections in humans. Furthermore, this virus was shown to be highly pathogenic to both birds and mammals, and demonstrate tropism for the nervous system. Due to the geographical location of Sanmenxia, these novel H5N1 viruses also have the potential to be imported to other regions through the migration of wild birds, similar to the H5N1 outbreak amongst migratory birds in Qinghai Lake during 2005. Therefore, further investigation and monitoring is required to prevent this novel reassortant virus from becoming a new threat to public health.

  2. A review of highly pathogenic avian influenza in birds, with an emphasis on Asian H5N1 and recommendations for prevention and control.

    Science.gov (United States)

    Kelly, Terra R; Hawkins, Michelle G; Sandrock, Christian E; Boyce, Walter M

    2008-03-01

    Avian influenza is a disease of both veterinary and public health importance. Influenza A viruses infect a range of hosts, including humans, and can cause significant morbidity and mortality. These viruses have high genetic variability, and new strains develop through both mutation and reassortment. Modes of transmission as well as the location of viral shedding may differ both by host species and by viral strain. Clinical signs of influenza A virus infection in birds vary considerably depending on the viral subtype, environmental factors, and age, health status, and species of the bird and range from decreased egg production and gastrointestinal manifestations to nervous system disorders and respiratory signs. Most commonly, peracute death with minimal clinical disease is observed in poultry infected with a highly pathogenic avian influenza virus. There are various prevention and control strategies for avian influenza, including education, biosecurity, surveillance, culling of infected animals, and vaccination. These strategies will differ by institution and current federal regulations. Each institution should have an established biosecurity protocol that can be properly instituted. Lastly, human health precautions, such as proper hand hygiene, personal protective equipment, and employee health monitoring, are imperative for at-risk individuals.

  3. Animal and human influenzas.

    Science.gov (United States)

    Peiris, M; Yen, H-L

    2014-08-01

    Influenza type A viruses affect humans and other animals and cause significant morbidity, mortality and economic impact. Influenza A viruses are well adapted to cross species barriers and evade host immunity. Viruses that cause no clinical signs in wild aquatic birds may adapt in domestic poultry to become highly pathogenic avian influenza viruses which decimate poultry flocks. Viruses that cause asymptomatic infection in poultry (e.g. the recently emerged A/H7N9 virus) may cause severe zoonotic disease and pose a major pandemic threat. Pandemic influenza arises at unpredictable intervals from animal viruses and, in its global spread, outpaces current technologies for making vaccines against such novel viruses. Confronting the threat of influenza in humans and other animals is an excellent example of a task that requires a One Health approach. Changes in travel, trade in livestock and pets, changes in animal husbandry practices, wet markets and complex marketing chains all contribute to an increased risk of the emergence of novel influenza viruses with the ability to cross species barriers, leading to epizootics or pandemics. Coordinated surveillance at the animal- human interface for pandemic preparedness, risk assessment, risk reduction and prevention at source requires coordinated action among practitioners in human and animal health and the environmental sciences. Implementation of One Health in the field can be challenging because of divergent short-term objectives. Successful implementation requires effort, mutual trust, respect and understanding to ensure that long-term goals are achieved without adverse impacts on agricultural production and food security.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  5. Vaccination with recombinant RNA replicon particles protects chickens from H5N1 highly pathogenic avian influenza virus.

    Directory of Open Access Journals (Sweden)

    Stefan J Halbherr

    Full Text Available Highly pathogenic avian influenza viruses (HPAIV of subtype H5N1 not only cause a devastating disease in domestic chickens and turkeys but also pose a continuous threat to public health. In some countries, H5N1 viruses continue to circulate and evolve into new clades and subclades. The rapid evolution of these viruses represents a problem for virus diagnosis and control. In this work, recombinant vesicular stomatitis virus (VSV vectors expressing HA of subtype H5 were generated. To comply with biosafety issues the G gene was deleted from the VSV genome. The resulting vaccine vector VSV*ΔG(HA was propagated on helper cells providing the VSV G protein in trans. Vaccination of chickens with a single intramuscular dose of 2×10⁸ infectious replicon particles without adjuvant conferred complete protection from lethal H5N1 infection. Subsequent application of the same vaccine strongly boosted the humoral immune response and completely prevented shedding of challenge virus and transmission to sentinel birds. The vaccine allowed serological differentiation of infected from vaccinated animals (DIVA by employing a commercially available ELISA. Immunized chickens produced antibodies with neutralizing activity against multiple H5 viruses representing clades 1, 2.2, 2.5, and low-pathogenic avian influenza viruses (classical clade. Studies using chimeric H1/H5 hemagglutinins showed that the neutralizing activity was predominantly directed against the globular head domain. In summary, these results suggest that VSV replicon particles are safe and potent DIVA vaccines that may help to control avian influenza viruses in domestic poultry.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-15

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

  7. Ecological Determinants of Highly Pathogenic Avian Influenza (H5N1) Outbreaks in Bangladesh

    Science.gov (United States)

    Ahmed, Syed S. U.; Ersbøll, Annette K.; Biswas, Paritosh K.; Christensen, Jens P.; Hannan, Abu S. M. A.; Toft, Nils

    2012-01-01

    Background The agro-ecology and poultry husbandry of the south Asian and south-east Asian countries share common features, however, with noticeable differences. Hence, the ecological determinants associated with risk of highly pathogenic avian influenza (HPAI-H5N1) outbreaks are expected to differ between Bangladesh and e.g., Thailand and Vietnam. The primary aim of the current study was to establish ecological determinants associated with the risk of HPAI-H5N1 outbreaks at subdistrict level in Bangladesh. The secondary aim was to explore the performance of two different statistical modeling approaches for unmeasured spatially correlated variation. Methodology/Principal Findings An ecological study at subdistrict level in Bangladesh was performed with 138 subdistricts with HPAI-H5N1 outbreaks during 2007–2008, and 326 subdistricts with no outbreaks. The association between ecological determinants and HPAI-H5N1 outbreaks was examined using a generalized linear mixed model. Spatial clustering of the ecological data was modeled using 1) an intrinsic conditional autoregressive (ICAR) model at subdistrict level considering their first order neighbors, and 2) a multilevel (ML) model with subdistricts nested within districts. Ecological determinants significantly associated with risk of HPAI-H5N1 outbreaks at subdistrict level were migratory birds' staging areas, river network, household density, literacy rate, poultry density, live bird markets, and highway network. Predictive risk maps were derived based on the resulting models. The resulting models indicate that the ML model absorbed some of the covariate effect of the ICAR model because of the neighbor structure implied in the two different models. Conclusions/Significance The study identified a new set of ecological determinants related to river networks, migratory birds' staging areas and literacy rate in addition to already known risk factors, and clarified that the generalized concept of free grazing duck and

  8. 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.

  9. Experimental challenge and pathology of highly pathogenic avian influenza virus H5N1 in dunlin (Calidris alpina), an intercontinental migrant shorebird species

    Science.gov (United States)

    Hall, Jeffrey S.; Franson, J. Christian; Gill, Robert E.; Meteyer, Carol U.; TeSlaa, Joshua L.; Nashold, Sean W.; Dusek, Robert J.; Ip, Hon S.

    2011-01-01

    Background Shorebirds (Charadriiformes) are considered one of the primary reservoirs of avian influenza. Because these species are highly migratory, there is concern that infected shorebirds may be a mechanism by which highly pathogenic avian influenza virus (HPAIV) H5N1 could be introduced into North America from Asia. Large numbers of dunlin (Calidris alpina) migrate from wintering areas in central and eastern Asia, where HPAIV H5N1 is endemic, across the Bering Sea to breeding areas in Alaska. Low pathogenic avian influenza virus has been previously detected in dunlin, and thus, dunlin represent a potential risk to transport HPAIV to North America. To date no experimental challenge studies have been performed in shorebirds.

  10. High-resolution computed tomography findings of influenza virus pneumonia. A comparative study between seasonal and novel (H1N1) influenza virus pneumonia

    International Nuclear Information System (INIS)

    Tanaka, Nobuyuki; Kunihiro, Yoshie; Matsunaga, Naofumi; Hasegawa, Shunji; Ichiyama, Takashi; Emoto, Takuya; Suda, Hiroki

    2012-01-01

    The purpose of this study was to evaluate the high-resolution computed tomography (HRCT) findings of novel influenza virus (n-IFV) pneumonia and compare them with the findings for seasonal (s-IFV) pneumonia. We evaluated 29 cases of pure IFV pneumonia that occurred between 1990 and 2010. We evaluated the existence, extent, and patterns of HRCT findings and compared these features between s-IFV and n-IFV. Consolidation was less frequent in s-IFV than in n-IFV (40.0 vs. 84.2%, respectively; p=0.014). Consolidation with a loss of volume was frequent in n-IFV (62.5%). There was no significant difference in the occurrence of ground-glass opacity (GGO) between s-IFV and n-IFV (100 vs. 84.2%, respectively). GGO with reticular opacities was more frequent in s-IFV than in n-IFV (70.0 vs. 25.0%, respectively; p=0.024). The frequency of nodules was not significantly different between the two groups. The mosaic pattern was more frequent in s-IFV than in n-IFV patients (80.0 vs. 15.8%, respectively; p=0.0007). Mucoid impaction was more frequent in patients with n-IFV than with s-IFV (52.6 vs. 10.0%, respectively; p=0.025). Consolidation and mucoid impaction were more frequent in n-IFV, whereas GGO with reticular opacities and a mosaic pattern occurred more frequently in s-IFV; otherwise, there were no significant differences between the two groups. (author)

  11. Principles for vaccine protection in chickens and domestic waterfowl against avian influenza: emphasis on Asian H5N1 high pathogenicity avian influenza.

    Science.gov (United States)

    Swayne, David E

    2006-10-01

    The H5N1 highly pathogenic (HP) avian influenza (AI) epizootic began with reports of mortality from China in 1996 and, by June 2005, caused outbreaks of disease in nine additional Asian countries, affecting or resulting in culling of over 200 million birds. Vaccines can be used in programs to prevent, manage, or eradicate AI. However, vaccines should only be used as part of a comprehensive control strategy that also includes biosecurity, quarantine, surveillance and diagnostics, education, and elimination of infected poultry. Potent AI vaccines, when properly used, can prevent disease and death, increase resistance to infection, reduce field virus replication and shedding, and reduce virus transmission, but do not provide "sterilizing immunity" in the field; i.e., vaccination does not completely prevent AI virus replication. Inactivated AI vaccines and a recombinant fowlpox-H5-AI vaccine are licensed and used in various countries. Vaccines have been shown to protect chickens, geese, and ducks from H5 HPAI. The inactivated vaccines prevented disease and mortality in chickens and geese, and reduced the ability of the field virus to replicate in gastrointestinal and respiratory tracts. Although the Asian H5N1 HPAI virus did not cause disease or mortality in ducks, the use of inactivated vaccine did reduce field virus replication in the respiratory and intestinal tracts. The inactivated vaccine protected geese from morbidity and mortality, and reduced challenge virus replication. The recombinant fowlpox-H5-AI vaccine has provided similar protection, but the vaccine is used only in chickens and with the advantage of application at 1 day of age in the hatchery.

  12. Protective Efficacy of Newcastle Disease Virus Expressing Soluble Trimeric Hemagglutinin against Highly Pathogenic H5N1 Influenza in Chickens and Mice

    NARCIS (Netherlands)

    Cornelissen, A.H.M.; Leeuw, de O.S.; Tacken, M.G.J.; Klos, H.C.; Vries, de R.P.; Boer-Luijtze, de E.A.; Zoelen-Bos, van D.J.; Rigter, A.; Rottier, P.J.M.; Moormann, R.J.M.; Haan, de C.A.M.

    2012-01-01

    Background: Highly pathogenic avian influenza virus (HPAIV) causes a highly contagious often fatal disease in poultry, resulting in significant economic losses in the poultry industry. HPAIV H5N1 also poses a major public health threat as it can be transmitted directly from infected poultry to

  13. Practices associated with Highly Pathogenic Avian Influenza spread in traditional poultry marketing chains: Social and economic perspectives.

    Science.gov (United States)

    Paul, Mathilde; Baritaux, Virginie; Wongnarkpet, Sirichai; Poolkhet, Chaithep; Thanapongtharm, Weerapong; Roger, François; Bonnet, Pascal; Ducrot, Christian

    2013-04-01

    In developing countries, smallholder poultry production contributes to food security and poverty alleviation in rural areas. However, traditional poultry marketing chains have been threatened by the epidemics caused by the Highly Pathogenic Avian Influenza (H5N1) virus. The article presents a value chain analysis conducted on the traditional poultry marketing chain in the rural province of Phitsanulok, Thailand. The analysis is based on quantitative data collected on 470 backyard chicken farms, and on qualitative data collected on 28 poultry collectors, slaughterhouses and market retailers, using semi-structured interviews. The article examines the organization of poultry marketing chains in time and space, and shows how this may contribute to the spread of Highly Pathogenic Avian Influenza H5N1 in the small-scale poultry sector. The article also discusses the practices and strategies developed by value chain actors facing poultry mortality, with their economic and social determinants. More broadly, this study also illustrates how value chain analysis can contribute to a better understanding of the complex mechanisms associated with the spread of epidemics in rural communities. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Low pathogenic avian influenza viruses in wild migratory waterfowl in a region of high poultry production, Delmarva, Maryland

    Science.gov (United States)

    Prosser, Diann J.; Densmore, Christine L.; Hindman, Larry J.; Iwanowicz, Deborah; Ottinger, Christopher A.; Iwanowicz, Luke R.; Driscoll, Cindy P.; Nagel, Jessica L.

    2017-01-01

    Migratory waterfowl are natural reservoirs for low pathogenic avian influenza viruses (AIVs) and may contribute to the long-distance dispersal of these pathogens as well as spillover into domestic bird populations. Surveillance for AIVs is critical to assessing risks for potential spread of these viruses among wild and domestic bird populations. The Delmarva Peninsula on the east coast of the United States is both a key convergence point for migratory Atlantic waterfowl populations and a region with high poultry production (>4,700 poultry meat facilities). Sampling of key migratory waterfowl species occurred at 20 locations throughout the Delmarva Peninsula in fall and winter of 2013–14. Samples were collected from 400 hunter-harvested or live-caught birds via cloacal and oropharyngeal swabs. Fourteen of the 400 (3.5%) birds sampled tested positive for the AIV matrix gene using real-time reverse transcriptase PCR, all from five dabbling duck species. Further characterization of the 14 viral isolates identified two hemagglutinin (H3 and H4) and four neuraminidase (N2, N6, N8, and N9) subtypes, which were consistent with isolates reported in the Influenza Research Database for this region. Three of 14 isolates contained multiple HA or NA subtypes. This study adds to the limited baseline information available for AIVs in migratory waterfowl populations on the Delmarva Peninsula, particularly prior to the highly pathogenic AIV A(H5N8) and A(H5N2) introductions to the United States in late 2014.

  15. Low Pathogenic Avian Influenza Viruses in Wild Migratory Waterfowl in a Region of High Poultry Production, Delmarva, Maryland.

    Science.gov (United States)

    Prosser, Diann J; Densmore, Christine L; Hindman, Larry J; Iwanowicz, Deborah D; Ottinger, Chris A; Iwanowicz, Luke R; Driscoll, Cindy P; Nagel, Jessica L

    2017-03-01

    Migratory waterfowl are natural reservoirs for low pathogenic avian influenza viruses (AIVs) and may contribute to the long-distance dispersal of these pathogens as well as spillover into domestic bird populations. Surveillance for AIVs is critical to assessing risks for potential spread of these viruses among wild and domestic bird populations. The Delmarva Peninsula on the east coast of the United States is both a key convergence point for migratory Atlantic waterfowl populations and a region with high poultry production (>4,700 poultry meat facilities). Sampling of key migratory waterfowl species occurred at 20 locations throughout the Delmarva Peninsula in fall and winter of 2013-14. Samples were collected from 400 hunter-harvested or live-caught birds via cloacal and oropharyngeal swabs. Fourteen of the 400 (3.5%) birds sampled tested positive for the AIV matrix gene using real-time reverse transcriptase PCR, all from five dabbling duck species. Further characterization of the 14 viral isolates identified two hemagglutinin (H3 and H4) and four neuraminidase (N2, N6, N8, and N9) subtypes, which were consistent with isolates reported in the Influenza Research Database for this region. Three of 14 isolates contained multiple HA or NA subtypes. This study adds to the limited baseline information available for AIVs in migratory waterfowl populations on the Delmarva Peninsula, particularly prior to the highly pathogenic AIV A(H5N8) and A(H5N2) introductions to the United States in late 2014.

  16. Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems

    Directory of Open Access Journals (Sweden)

    McDermott Jason E

    2011-11-01

    Full Text Available Abstract Background Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades. Results In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well-studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms. Conclusions This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models.

  17. Avian influenza surveillance and diagnosis

    Science.gov (United States)

    Rapid detection and accurate identification of low (LPAI) and high pathogenicity avian influenza (HPAI) is critical to controlling infections and disease in poultry. Test selection and algorithms for the detection and diagnosis of avian influenza virus (AIV) in poultry may vary somewhat among differ...

  18. Characterization of H5N6 highly pathogenic avian influenza viruses isolated from wild and captive birds in the winter season of 2016-2017 in Northern Japan.

    Science.gov (United States)

    Hiono, Takahiro; Okamatsu, Masatoshi; Matsuno, Keita; Haga, Atsushi; Iwata, Ritsuko; Nguyen, Lam Thanh; Suzuki, Mizuho; Kikutani, Yuto; Kida, Hiroshi; Onuma, Manabu; Sakoda, Yoshihiro

    2017-09-01

    On 15 November 2016, a black swan that had died in a zoo in Akita prefecture, northern Japan, was strongly suspected to have highly pathogenic avian influenza (HPAI); an HPAI virus (HPAIV) belonging to the H5N6 subtype was isolated from specimens taken from the bird. After the initial report, 230 cases of HPAI caused by H5N6 viruses from wild birds, captive birds, and domestic poultry farms were reported throughout the country during the winter season. In the present study, 66 H5N6 HPAIVs isolated from northern Japan were further characterized. Phylogenetic analysis of the hemagglutinin gene showed that the H5N6 viruses isolated in northern Japan clustered into Group C of Clade 2.3.4.4 together with other isolates collected in Japan, Korea and Taiwan during the winter season of 2016-2017. The antigenicity of the Japanese H5N6 isolate differed slightly from that of HPAIVs isolated previously in Japan and China. The virus exhibited high pathogenicity and a high replication capacity in chickens, whereas virus growth was slightly lower in ducks compared with that of an H5N8 HPAIV isolate collected in Japan in 2014. Comprehensive analyses of Japanese isolates, including those from central, western, and southern Japan, as well as rapid publication of this information are essential for facilitating greater control of HPAIVs. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  19. Influenza (Flu) Viruses

    Science.gov (United States)

    ... Types Seasonal Avian Swine Variant Pandemic Other Influenza (Flu) Viruses Language: English (US) Español Recommend on Facebook ... influenza circulate and cause illness. More Information about Flu Viruses Types of Influenza Viruses Influenza A and ...

  20. Pathogenesis, Transmissibility, and Tropism of a Highly Pathogenic Avian Influenza A(H7N7) Virus Associated With Human Conjunctivitis in Italy, 2013.

    Science.gov (United States)

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

    2017-09-15

    H7 subtype influenza viruses represent a persistent public health threat because of their continued detection in poultry and ability to cause human infection. An outbreak of highly pathogenic avian influenza H7N7 virus in Italy during 2013 resulted in 3 cases of human conjunctivitis. We determined the pathogenicity and transmissibility of influenza A/Italy/3/2013 virus in mouse and ferret models and examined the replication kinetics of this virus in several human epithelial cell types. The moderate virulence observed in mammalian models and the capacity for transmission in a direct contact model underscore the need for continued study of H7 subtype viruses. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. 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.

  2. Airborne Detection of H5N8 Highly Pathogenic Avian Influenza Virus Genome in Poultry Farms, France.

    Science.gov (United States)

    Scoizec, Axelle; Niqueux, Eric; Thomas, Rodolphe; Daniel, Patrick; Schmitz, Audrey; Le Bouquin, Sophie

    2018-01-01

    In southwestern France, during the winter of 2016-2017, the rapid spread of highly pathogenic avian influenza H5N8 outbreaks despite the implementation of routine control measures, raised the question about the potential role of airborne transmission in viral spread. As a first step to investigate the plausibility of that transmission, air samples were collected inside, outside and downwind from infected duck and chicken facilities. H5 avian influenza virus RNA was detected in all samples collected inside poultry houses, at external exhaust fans and at 5 m distance from poultry houses. For three of the five flocks studied, in the sample collected at 50-110 m distance, viral genomic RNA was detected. The measured viral air concentrations ranged between 4.3 and 6.4 log 10 RNA copies per m 3 , and their geometric mean decreased from external exhaust fans to the downwind measurement point. These findings are in accordance with the possibility of airborne transmission and question the procedures for outbreak depopulation.

  3. Airborne Detection of H5N8 Highly Pathogenic Avian Influenza Virus Genome in Poultry Farms, France

    Directory of Open Access Journals (Sweden)

    Axelle Scoizec

    2018-02-01

    Full Text Available In southwestern France, during the winter of 2016–2017, the rapid spread of highly pathogenic avian influenza H5N8 outbreaks despite the implementation of routine control measures, raised the question about the potential role of airborne transmission in viral spread. As a first step to investigate the plausibility of that transmission, air samples were collected inside, outside and downwind from infected duck and chicken facilities. H5 avian influenza virus RNA was detected in all samples collected inside poultry houses, at external exhaust fans and at 5 m distance from poultry houses. For three of the five flocks studied, in the sample collected at 50–110 m distance, viral genomic RNA was detected. The measured viral air concentrations ranged between 4.3 and 6.4 log10 RNA copies per m3, and their geometric mean decreased from external exhaust fans to the downwind measurement point. These findings are in accordance with the possibility of airborne transmission and question the procedures for outbreak depopulation.

  4. 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.

  5. 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.

  6. Isolation and identification of highly pathogenic avian influenza virus subtype H5N1 in peafowl (Pavo cristatus).

    Science.gov (United States)

    Ismail, Mahmoud Moussa; Khan, Owais Ahmed; Cattoli, Giovanni; Lu, Huaguang

    2010-03-01

    An outbreak of highly pathogenic avian influenza (HPAI) virus subtype H5N1 was first diagnosed in a "backyard" flock of peafowl (Pavo cristatus) raised on palace premises in the Kingdom of Saudi Arabia in December 3, 2007. The flock consisted of 40 peafowl, and their ages ranged from 3 to 5 years old. Affected birds suffered from depression, anorexia, and white diarrhea. Four dead birds were submitted for HPAI diagnosis at the Central Veterinary Diagnostic Laboratory in Riyadh. Brain and liver tissues and tracheal and cloacal swabs were taken from the dead birds and processed for a real-time reverse transcriptase (RT)-PCR test and virus isolation in specific-pathogen-free embryonating chicken eggs. The H5N1 subtype of avian influenza virus was isolated from the four dead birds and identified by a real-time RT-PCR before and after egg inoculation. The virus isolates were characterized as HPAI H5N1 virus by sequencing analysis. Phylogenetic comparisons revealed that the H5N1 viruses isolated from peafowl belong to the genetic clade 2.2 according to the World Health Organization nomenclature. The peafowl H5N1 virus falls into 2.2.2 sublineage II and clusters with the H5N1 viruses isolated from poultry in Saudi Arabia in 2007-08.

  7. Human infection with a highly pathogenic avian influenza A (H5N6) virus in Yunnan province, China.

    Science.gov (United States)

    Xu, Wen; Li, Hong; Jiang, Li

    2016-01-01

    Highly pathogenic avian influenza A H5N6 virus has caused four human infections in China. This study reports the preliminary findings of the first known human case of H5N6 in Yunnan province. The patient initially developed symptoms of sore throat and coughing on 27 January 2015. The disease rapidly progressed to severe pneumonia, multiple organ dysfunctions and acute respiratory distress syndrome and the patient died on 6 February. Virological analysis determined that the virus belonged to H5 clade 2.3.4.4 and it has obtained partial ability for mammalian adaptation and amantadine resistance. Environmental investigation found H5 in 63% of the samples including poultry faeces, tissues, cage surface swabs and sewage from local live poultry markets by real-time RT-PCR. These findings suggest that the expanding and enhancing of surveillance in both avian and humans are necessary to monitor the evolution of H5 influenza virus and to facilitate early detection of suspected cases.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-15

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

  9. Modeling and roles of meteorological factors in outbreaks of highly pathogenic avian influenza H5N1.

    Directory of Open Access Journals (Sweden)

    Paritosh K Biswas

    Full Text Available The highly pathogenic avian influenza A virus subtype H5N1 (HPAI H5N1 is a deadly zoonotic pathogen. Its persistence in poultry in several countries is a potential threat: a mutant or genetically reassorted progenitor might cause a human pandemic. Its world-wide eradication from poultry is important to protect public health. The global trend of outbreaks of influenza attributable to HPAI H5N1 shows a clear seasonality. Meteorological factors might be associated with such trend but have not been studied. For the first time, we analyze the role of meteorological factors in the occurrences of HPAI outbreaks in Bangladesh. We employed autoregressive integrated moving average (ARIMA and multiplicative seasonal autoregressive integrated moving average (SARIMA to assess the roles of different meteorological factors in outbreaks of HPAI. Outbreaks were modeled best when multiplicative seasonality was incorporated. Incorporation of any meteorological variable(s as inputs did not improve the performance of any multivariable models, but relative humidity (RH was a significant covariate in several ARIMA and SARIMA models with different autoregressive and moving average orders. The variable cloud cover was also a significant covariate in two SARIMA models, but air temperature along with RH might be a predictor when moving average (MA order at lag 1 month is considered.

  10. H5N2 Highly Pathogenic Avian Influenza Viruses from the US 2014-2015 outbreak have an unusually long pre-clinical period in turkeys

    OpenAIRE

    Spackman, Erica; Pantin-Jackwood, Mary J.; Kapczynski, Darrell R.; Swayne, David E.; Suarez, David L.

    2016-01-01

    Background From December 2014 through June 2015, the US experienced the most costly highly pathogenic avian influenza (HPAI) outbreak to date. Most cases in commercial poultry were caused by an H5N2 strain which was a reassortant with 5 Eurasian lineage genes, including a clade 2.3.4.4 goose/Guangdong/1996 lineage hemagglutinin, and 3 genes from North American wild waterfowl low pathogenicity avian influenza viruses. The outbreak primarily affected turkeys and table-egg layer type chickens. T...

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

    OpenAIRE

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

    2011-01-01

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

  12. Influenza C virus high seroprevalence rates observed in 3 different population groups.

    Science.gov (United States)

    Salez, Nicolas; Mélade, Julien; Pascalis, Hervé; Aherfi, Sarah; Dellagi, Koussay; Charrel, Rémi N; Carrat, Fabrice; de Lamballerie, Xavier

    2014-08-01

    The epidemiology of Influenza C virus (FLUCV) infections remains poorly characterised. Here, we have examined the age- and location-specific seroprevalence of antibodies against FLUCV in 1441 sera from metropolitan continental France (Marseille), South-West Indian Ocean French territories (Reunion Island) and United-Kingdom (Edinburgh) using a combination of haemagglutination inhibition, virus neutralisation and ELISA assays. Our results show that immunity to FLUCV is common in all locations studied (global seroprevalence values >50%) and that the first immunising contacts generally occur early in life (i.e., in the 0-4 year-old age group). The latter item is further supported by the detection of FLUCV RNA by RT-PCR in naso-pharyngeal samples collected in patient attending the Emergency Room of the Public hospitals of Marseille, France with a large majority of children under 10 years-old: 17 (60.7%) in children ≤3 yo, 10 (35.7%) in the 4-10 yo age group and 1 (3.6%) in an adult (49yo). The temporal distribution of cases was atypical with regard to influenza (a large proportion of cases occurred in spring and summer) and the clinical presentation was diverse, including but being not limited to classical Influenza-like-Ilnesses. Altogether, our results indicate an intense circulation of FLUCV in the different study areas and an early occurrence of infection in human life. Flu C appears to be a widely under-diagnosed and under-studied human paediatric disease that obviously deserves further clinical and epidemiological characterisation. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  13. PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection

    Directory of Open Access Journals (Sweden)

    Wang Qiang

    2012-06-01

    Full Text Available Abstract Background Although gene exchange is not likely to occur freely, reassortment between the H5N1 highly pathogenic avian influenza virus (HPAIV and currently circulating human viruses is a serious concern. The PA polymerase subunit of H5N1 HPAIV was recently reported to activate the influenza replicon activity. Methods The replicon activities of PR8 and WSN strains (H1N1 of influenza containing PA from HPAIV A/Cambodia/P0322095/2005 (H5N1 and the activity of the chimeric RNA polymerase were analyzed. A reassortant WSN virus containing the H5N1 Cambodia PA (C-PA was then reconstituted and its growth in cells and pathogenicity in mice examined. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities of C-PA-infected cells were compared with those of WSN-infected cells. Results The activity of the chimeric RNA polymerase was slightly higher than that of WSN, and C-PA replicated better than WSN in cells. However, the multi-step growth of C-PA and its pathogenicity in mice were lower than those of WSN. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities were strongly induced in early infection in C-PA-infected cells but not in WSN-infected cells. Conclusions Apoptosis and interferon were strongly induced early in C-PA infection, which protected the uninfected cells from expansion of viral infection. In this case, these classical host-virus interactions contributed to the attenuation of this strongly replicating virus.

  14. Vaccine protection of chickens against antigenically diverse H5 highly pathogenic avian influenza isolates with a live HVT vector vaccine expressing the influenza hemagglutinin gene derived from a clade 2.2 avian influenza virus.

    Science.gov (United States)

    Kapczynski, Darrell R; Esaki, Motoyuki; Dorsey, Kristi M; Jiang, Haijun; Jackwood, Mark; Moraes, Mauro; Gardin, Yannick

    2015-02-25

    Vaccination is an important tool in the protection of poultry against avian influenza (AI). For field use, the overwhelming majority of AI vaccines produced are inactivated whole virus formulated into an oil emulsion. However, recombinant vectored vaccines are gaining use for their ability to induce protection against heterologous isolates and ability to overcome maternal antibody interference. In these studies, we compared protection of chickens provided by a turkey herpesvirus (HVT) vector vaccine expressing the hemagglutinin (HA) gene from a clade 2.2 H5N1 strain (A/swan/Hungary/4999/2006) against homologous H5N1 as well as heterologous H5N1 and H5N2 highly pathogenic (HP) AI challenge. The results demonstrated all vaccinated birds were protected from clinical signs of disease and mortality following homologous challenge. In addition, oral and cloacal swabs taken from challenged birds demonstrated that vaccinated birds had lower incidence and titers of viral shedding compared to sham-vaccinated birds. Following heterologous H5N1 or H5N2 HPAI challenge, 80-95% of birds receiving the HVT vector AI vaccine at day of age survived challenge with fewer birds shedding virus after challenge than sham vaccinated birds. In vitro cytotoxicity analysis demonstrated that splenic T lymphocytes from HVT-vector-AI vaccinated chickens recognized MHC-matched target cells infected with H5, as well as H6, H7, or H9 AI virus. Taken together, these studies provide support for the use of HVT vector vaccines expressing HA to protect poultry against multiple lineages of HPAI, and that both humoral and cellular immunity induced by live vaccines likely contributes to protection. Published by Elsevier Ltd.

  15. Swine Influenza/Variant Influenza Viruses

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Pandemic Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español Recommend ...

  16. Transmission of highly pathogenic avian influenza H5N1 virus in Pekin ducks is significantly reduced by a genetically distant H5N2 vaccine

    NARCIS (Netherlands)

    Goot, van der J.A.; Boven, van M.; Stegeman, A.; Water, van de S.G.P.; Jong, de M.C.M.; Koch, G.

    2008-01-01

    Domestic ducks play an important role in the epidemiology of H5N1 avian influenza. Although it is known that vaccines that have a high homology with the challenge virus are able to prevent infection in ducks, little is yet known about the ability of genetically more distant vaccines in preventing

  17. Estimating the between-farm transmission rates for highly pathogenic avian influenza subtype H5N1 epidemics in Bangladesh between 2007 and 2013

    NARCIS (Netherlands)

    Ssematimba, A.; Okike, I.; Ahmed, G.M.; Yamage, M.; Boender, G.J.; Hagenaars, T.J.; Bett, B.

    2018-01-01

    Highly Pathogenic Avian Influenza (HPAI) is classified by the World Organization for Animal Health as one of the notifiable diseases. Its occurrence is associated with severe socio-economic impacts and is also zoonotic. Bangladesh HPAI epidemic data for the period between 2007 and 2013 were obtained

  18. Pulmonary immunization of chickens using non-adjuvanted spray-freeze dried whole inactivated virus vaccine completely protects against highly pathogenic H5N1 avian influenza virus

    NARCIS (Netherlands)

    Peeters, Ben; Tonnis, Wouter F.; Murugappan, Senthil; Rottier, Peter; Koch, Guus; Frijlink, Henderik W.; Huckriede, Anke; Hinrichs, Wouter L. J.

    2014-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus is a major threat to public health as well as to the global poultry industry. Most fatal human infections are caused by contact with infected poultry. Therefore, preventing the virus from entering the poultry population is a priority. This is,

  19. Adaption of wild-bird origin H5Nx highly pathogenic avian influenza virus Clade 2.3.4.4 in vaccinated poultry

    Science.gov (United States)

    The 2014-2015 incursion of H5Nx clade 2.3.4.4 high pathogenicity avian influenza (HPAI) virus caused the largest animal health emergency in U.S. history and renewed interest in developing vaccines against these newly emergent viruses. Our previous research demonstrated several H5 vaccines with varyi...

  20. Reoccurrence of H5Nx clade 2.3.4.4 highly pathogenic avian influenza viruses in wild birds during 2016

    Science.gov (United States)

    The Asian-origin H5N1 A/goose/Guangdong/1/1996 (Gs/GD) lineage of high pathogenicity avian influenza viruses (HPAIV) has become widespread across four continents, affecting poultry, wild birds and humans. H5N1 HPAIV has evolved into multiple hemagglutinin (HA) genetic clades and reassorting with dif...

  1. The highly pathogenic avian influenza A (H7N7) virus epidemic in the Netherlands in 2003 - lessons learned from the first five outbreaks

    NARCIS (Netherlands)

    Elbers, A.R.W.; Fabri, T.; Vries, T.S.; Wit, de J.J.; Pijpers, A.; Koch, G.

    2004-01-01

    Clinical signs and gross lesions observed in poultry submitted for postmortem examination (PME) from the first five infected poultry flocks preceding the detection of the primary outbreak of highly pathogenic avian influenza (HPAI) of subtype H7N7 during the 2003 epidemic in the Netherlands are

  2. Risk reduction modeling of high pathogenicity avian influenza virus titers in non-pasteurized liquid egg obtained from infected but undetected chicken flocks

    Science.gov (United States)

    Control of highly pathogenic avian influenza (HPAI) has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a containment area under permit. Non-pasteurized liquid egg (NPLE) is one such commodity for which movements ma...

  3. Host-specific exposure and fatal neurologic disease in wild raptors from highly pathogenic avian influenza virus H5N1 during the 2006 outbreak in Germany

    NARCIS (Netherlands)

    J.M.A. van den Brand (Judith); O. Krone (Oliver); P.U. Wolf (Peter U.); M.W.G. van de Bildt (Marco); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2015-01-01

    textabstractRaptors may contract highly pathogenic avian influenza virus H5N1 by hunting or scavenging infected prey. However, natural H5N1 infection in raptors is rarely reported. Therefore, we tested raptors found dead during an H5N1 outbreak in wild waterbirds in Mecklenburg-Western Pomerania,

  4. Airborne transmission of a highly pathogenic avian influenza strain H5N1 between groups of chickens quantified in an experimental setting.

    NARCIS (Netherlands)

    Spekreijse, D.; Bouma, A.; Koch, G.; Stegeman, J.A.

    2011-01-01

    Highly pathogenic avian influenza (HPAI) is a devastating viral disease of poultry and quick control of outbreaks is vital. Airborne transmission has often been suggested as a route of transmission between flocks, but knowledge of the rate of transmission via this route is sparse. In the current

  5. Local amplification of highly pathogenic avian influenza H5N8 viruses in wild birds in the Netherlands, 2016 to 2017

    NARCIS (Netherlands)

    Poen, Marjolein J.; Bestebroer, Theo M.; Vuong, Oanh; Scheuer, Rachel D.; Jeugd, van der Henk P.; Kleyheeg, Erik; Eggink, Dirk; Lexmond, Pascal; Brand, van den Judith M.A.; Begeman, Lineke; Vliet, van der Stefan; Müskens, Gerhard J.D.M.; Majoor, Frank A.; Koopmans, Marion P.G.; Kuiken, Thijs; Fouchier, Ron A.M.

    2018-01-01

    Introduction: Highly pathogenic avian influenza (HPAI) viruses of subtype H5N8 were re-introduced into the Netherlands by late 2016, after detections in southeast Asia and Russia. This second H5N8 wave resulted in a large number of outbreaks in poultry farms and the deaths of large numbers of wild

  6. Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

    NARCIS (Netherlands)

    Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

    2016-01-01

    The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration

  7. Local amplification of highly pathogenic avian influenza H5N8 viruses in wild birds in the Netherlands, 2016 to 2017

    NARCIS (Netherlands)

    Poen, Marjolein J; Bestebroer, Theo M; Vuong, Oanh; Scheuer, Rachel D; van der Jeugd, Henk P; Kleyheeg, Erik; Eggink, Dirk; Lexmond, Pascal; van den Brand, Judith M A; Begeman, Lineke; van der Vliet, Stefan; Müskens, Gerhard J D M; Majoor, Frank A; Koopmans, Marion P G; Kuiken, Thijs; Fouchier, Ron A M

    IntroductionHighly pathogenic avian influenza (HPAI) viruses of subtype H5N8 were re-introduced into the Netherlands by late 2016, after detections in south-east Asia and Russia. This second H5N8 wave resulted in a large number of outbreaks in poultry farms and the deaths of large numbers of wild

  8. Protection of mice against lethal infection with highly pathogenic H7N7 influenza A virus by using a recombinant low-pathogenicity vaccine strain.

    NARCIS (Netherlands)

    V.J. Munster (Vincent); M.I. Spronken (Monique); T.M. Bestebroer (Theo); C. Baas (Chantal); W.E.Ph. Beyer (Walter); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); E. de Wit (Emmie)

    2005-01-01

    textabstractIn 2003, an outbreak of highly pathogenic avian influenza occurred in The Netherlands. The avian H7N7 virus causing the outbreak was also detected in 88 humans suffering from conjunctivitis or mild respiratory symptoms and one person who died of pneumonia and acute respiratory distress

  9. Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005

    NARCIS (Netherlands)

    Adlhoch, C.; Gossner, C.; Koch, G.; Brown, I.; Bouwstra, R.J.; Verdonck, F.; Penttinen, P.; Harder, T.

    2014-01-01

    Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are

  10. Multiple reassorted viruses as cause of highly pathogenic avian influenza A(H5N8) virus epidemic, the Netherlands, 2016

    NARCIS (Netherlands)

    Beerens, Nancy; Heutink, Rene; Bergervoet, Saskia A.; Harders, Frank; Bossers, Alex; Koch, Guus

    2017-01-01

    In 2016, an epidemic of highly pathogenic avian influenza A virus subtype H5N8 in the Netherlands caused mass deaths among wild birds, and several commercial poultry farms and captive bird holdings were affected. We performed complete genome sequencing to study the relationship between the wild bird

  11. Avian And Other Zoonotic Influenza

    Science.gov (United States)

    ... of Avian Influenza A(H5N1) Avian influenza: guidelines. recommendations, descriptions Global Influenza and Surveillance Response System (GISRS) Food safety authorities network OIE Avian Influenza ...

  12. 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.

  13. Tropism and Infectivity of Influenza Virus, Including Highly Pathogenic Avian H5N1 Virus, in Ferret Tracheal Differentiated Primary Epithelial Cell Cultures

    Science.gov (United States)

    Zeng, Hui; Goldsmith, Cynthia S.; Maines, Taronna R.; Belser, Jessica A.; Gustin, Kortney M.; Pekosz, Andrew; Zaki, Sherif R.; Katz, Jacqueline M.

    2013-01-01

    Tropism and adaptation of influenza viruses to new hosts is partly dependent on the distribution of the sialic acid (SA) receptors to which the viral hemagglutinin (HA) binds. Ferrets have been established as a valuable in vivo model of influenza virus pathogenesis and transmission because of similarities to humans in the distribution of HA receptors and in clinical signs of infection. In this study, we developed a ferret tracheal differentiated primary epithelial cell culture model that consisted of a layered epithelium structure with ciliated and nonciliated cells on its apical surface. We found that human-like (α2,6-linked) receptors predominated on ciliated cells, whereas avian-like (α2,3-linked) receptors, which were less abundant, were presented on nonciliated cells. When we compared the tropism and infectivity of three human (H1 and H3) and two avian (H1 and H5) influenza viruses, we observed that the human influenza viruses primarily infected ciliated cells and replicated efficiently, whereas a highly pathogenic avian H5N1 virus (A/Vietnam/1203/2004) replicated efficiently within nonciliated cells despite a low initial infection rate. Furthermore, compared to other influenza viruses tested, VN/1203 virus replicated more efficiently in cells isolated from the lower trachea and at a higher temperature (37°C) compared to a lower temperature (33°C). VN/1203 virus infection also induced higher levels of immune mediator genes and cell death, and virus was recovered from the basolateral side of the cell monolayer. This ferret tracheal differentiated primary epithelial cell culture system provides a valuable in vitro model for studying cellular tropism, infectivity, and the pathogenesis of influenza viruses. PMID:23255802

  14. Assessing exposure risks for aquatic organisms posed by Tamiflu use under seasonal influenza and pandemic conditions

    International Nuclear Information System (INIS)

    Chen, Wei-Yu; Lin, Chia-Jung; Liao, Chung-Min

    2014-01-01

    Environmental pollution by anti-influenza drugs is increasingly recognized as a threat to aquatic environments. However, little is known about empirical data on risk effects posed by environmentally relevant concentrations of anti-influenza drug based on recently published ecotoxicological researches in Taiwan. Here we linked ecotoxicology models with an epidemiological scheme to assess exposure risks of aquatic organisms and environmental hazards posed by antiviral oseltamivir (Tamiflu) use in Taiwan. Built on published bioassays, we used probabilistic risk assessment model to estimate potential threats of environmentally relevant hazards on algae, daphnid, and zerbrafish. We found that Tamiflu use was unlikely to pose a significant chronic environmental risk to daphnia and zebrafish during seasonal influenza. However, the chronic environmental risk posed by Tamiflu use during pandemic was alarming. We conclude that no significant risk to algal growth was found during seasonal influenza and high pandemic Tamiflu use. -- Highlights: • Environmentally relevant concentrations of anti-influenza drug have ecotoxicologically important effects. • Tamiflu is unlikely to pose a significant chronic environmental risk during seasonal influenza. • Chronic environmental risk posed by Tamiflu during pandemic is alarming. • Tertiary process in sewage treatment plants is crucial in mitigating Tamiflu exposure risk. -- A probabilistic framework can be used for assessing exposure risks posed by environmentally relevant concentrations of anti-influenza drug in aquatic ecosystems

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

    Directory of Open Access Journals (Sweden)

    Chiara Rafanelli

    2010-12-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  17. High Inter-Individual Diversity of Point Mutations, Insertions, and Deletions in Human Influenza Virus Nucleoprotein-Specific Memory B Cells.

    Directory of Open Access Journals (Sweden)

    Sven Reiche

    Full Text Available The diversity of virus-specific antibodies and of B cells among different individuals is unknown. Using single-cell cloning of antibody genes, we generated recombinant human monoclonal antibodies from influenza nucleoprotein-specific memory B cells in four adult humans with and without preceding influenza vaccination. We examined the diversity of the antibody repertoires and found that NP-specific B cells used numerous immunoglobulin genes. The heavy chains (HCs originated from 26 and the kappa light chains (LCs from 19 different germ line genes. Matching HC and LC chains gave rise to 43 genetically distinct antibodies that bound influenza NP. The median lengths of the CDR3 of the HC, kappa and lambda LC were 14, 9 and 11 amino acids, respectively. We identified changes at 13.6% of the amino acid positions in the V gene of the antibody heavy chain, at 8.4% in the kappa and at 10.6 % in the lambda V gene. We identified somatic insertions or deletions in 8.1% of the variable genes. We also found several small groups of clonal relatives that were highly diversified. Our findings demonstrate broadly diverse memory B cell repertoires for the influenza nucleoprotein. We found extensive variation within individuals with a high number of point mutations, insertions, and deletions, and extensive clonal diversification. Thus, structurally conserved proteins can elicit broadly diverse and highly mutated B-cell responses.

  18. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Directory of Open Access Journals (Sweden)

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

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

    Science.gov (United States)

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

    2018-06-13

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  2. Insight into Alternative Approaches for Control of Avian Influenza in Poultry, with Emphasis on Highly Pathogenic H5N1

    Directory of Open Access Journals (Sweden)

    Hafez M. Hafez

    2012-11-01

    Full Text Available Highly pathogenic avian influenza virus (HPAIV of subtype H5N1 causes a devastating disease in poultry but when it accidentally infects humans it can cause death. Therefore, decrease the incidence of H5N1 in humans needs to focus on prevention and control of poultry infections. Conventional control strategies in poultry based on surveillance, stamping out, movement restriction and enforcement of biosecurity measures did not prevent the virus spreading, particularly in developing countries. Several challenges limit efficiency of the vaccines to prevent outbreaks of HPAIV H5N1 in endemic countries. Alternative and complementary approaches to reduce the current burden of H5N1 epidemics in poultry should be encouraged. The use of antiviral chemotherapy and natural compounds, avian-cytokines, RNA interference, genetic breeding and/or development of transgenic poultry warrant further evaluation as integrated intervention strategies for control of HPAIV H5N1 in poultry.

  3. Molecular epidemiology of circulating highly pathogenic avian influenza (H5N1) virus in chickens, in Bangladesh, 2007-2010

    DEFF Research Database (Denmark)

    Ahmed, Syed Sayeem Uddin; Themudo, Goncalo Espregueira Cruz; Christensen, Jens Peter

    2012-01-01

    Bangladesh has been severely hit by highly pathogenic avian influenza H5N1 (HPAI-H5N1). However, little is known about the genetic diversity and the evolution of the circulating viruses in Bangladesh. In the present study, we analyzed the hemagglutinin gene of 30 Bangladeshi chicken isolates from...... several amino acid substitutions, but they are not indicative of adaptation toward human infection. The Mantel correlation test confirmed significant correlation between genetic distances and temporal distances between the viruses. The Bayesian tree shows that isolates from waves 3 and 4 derived from...... virus in Bangladesh. Furthermore, the formation of a subclade capable of transmission to humans cannot be ruled out. The findings of this study might provide valuable information for future surveillance, prevention and control programme....

  4. Factors that determine the evolution of high-growth businesses

    Directory of Open Access Journals (Sweden)

    Oriol Amat

    2013-09-01

    Full Text Available Objective: The study herein discusses research aimed at elucidating the factors that contribute to a business’ ability to maintain high growth. Design/Methodology/Perspective: The database from the Iberian Balance Sheet Analysis System (SABI, from its initials in Spanish was used to identify 250 industrial Catalonian businesses with high growth during 2004-2007. These companies participated in a survey on strategies and management practices; in 2013, they were re-analyzed to investigate the factors that contributed to continued growth for certain companies. Contributions: Through diverse statistical techniques, business policies related to quality, innovation, internationalization and finance were shown to influence business growth and sustainability over time. Limitations of the Research: This study focuses on industrial businesses at least ten years old in Catalonia; thus, the conclusions may differ in other geographic locations and economic sectors, as well as for smaller businesses. Practical Implications: Because growth is a measure of business success, identifying variables that contribute to high growth and its sustainability is helpful for businesses that seek to adopt effective policies. Social Implications: Generating employment is one of the primary contributions by high-growth businesses. For years with high unemployment, authorities may be interested in corporate policies that strengthen high-growth businesses. Originality/Added Value: High-growth businesses have been studied throughout the world, but this is the first study to investigate the evolution of businesses after a high-growth phase.

  5. TEST KIT FOR THE DETECTION AND GENOTYPING OF HIGHLY PATHOGENIC INFLUENZA VIRUS A H5N1 BY REAL-TIME POLYMERASE CHAIN REACTION

    Directory of Open Access Journals (Sweden)

    S. V. Stepaniuk

    2014-06-01

    Full Text Available Results of the annual monitoring of epizooties indicate that highly pathogenic HPAI/H5N1 avian influenza widely circulated in Eurasian region. Over a period of 2010–2013 years more than 165 cases of outbreaks in 14 countries were found out. Ukraine became one of the first countries in Europe where in Autonomous Republic of Crimea in October 2005 outbreak of avian epizootic with HPAI/H5N1 was documented and until February 2008 more than 236,000 poultry were killed. Since then the question of monitoring of infected both migrating birds and poultry in places of cross contact in Ukraine remains of high priority. The test system is developed for identification and genotyping A H5N1 on three genes (M, H5 and N1 HPAI/H5N1 in real-time mode for polymerase chain reaction. Test kit capacity to detect HPAI/h5n1avian influenza virus and differentiate it from the other viral infection agents of birds and animals were studied by testing of HPAI/H5N1 virus isolated during mass infection outbreak in Crimea in 2005 and cultural specimens of other viral pathogens. It was established that the «DIA Real Avian Influenza» test kit was capable to detect RNA influenza A virus of high pathogenic H5N1 strains having high sensitivity (100% while RNA of the Crimean HPAI/H5N1 isolate studying and specificity (100% while RNA viruses of Newcastle birds disease, fowl powershift, syndrome of drop in egg production and horse influenza studying.

  6. Surveillance plan for the early detection of H5N1 highly pathogenic avian influenza virus in migratory birds in the United States: surveillance year 2009

    Science.gov (United States)

    Brand, Christopher J.

    2009-01-01

    Executive Summary: This Surveillance Plan (Plan) describes plans for conducting surveillance of wild birds in the United States and its Territories and Freely-Associated States to provide for early detection of the introduction of the H5N1 Highly Pathogenic Avian Influenza (HPAI) subtype of the influenza A virus by migratory birds during the 2009 surveillance year, spanning the period of April 1, 2009 - March 31, 2010. The Plan represents a continuation of surveillance efforts begun in 2006 under the Interagency Strategic Plan for the Early Detection of H5N1 Highly Pathogenic Avian Influenza in Wild Migratory Birds (U.S. Department of Agriculture and U.S. Department of the Interior, 2006). The Plan sets forth sampling plans by: region, target species or species groups to be sampled, locations of sampling, sample sizes, and sampling approaches and methods. This Plan will be reviewed annually and modified as appropriate for subsequent surveillance years based on evaluation of information from previous years of surveillance, changing patterns and threats of H5N1 HPAI, and changes in funding availability for avian influenza surveillance. Specific sampling strategies will be developed accordingly within each of six regions, defined here as Alaska, Hawaiian/Pacific Islands, Lower Pacific Flyway (Washington, Oregon, California, Idaho, Nevada, Arizona), Central Flyway, Mississippi Flyway, and Atlantic Flyway.

  7. Rapid diagnosis of equine influenza by highly sensitive silver amplification immunochromatography system.

    Science.gov (United States)

    Yamanaka, Takashi; Nemoto, Manabu; Bannai, Hiroshi; Tsujimura, Koji; Kondo, Takashi; Matsumura, Tomio; Fu, Tao Qi Huang; Fernandez, Charlene Judith; Gildea, Sarah; Cullinane, Ann

    2017-06-16

    Equine influenza (EI) is a respiratory disease caused by equine influenza A virus (EIV, H3N8) infection. Rapid diagnosis is essential to limit the disease spread. We previously reported that some rapid antigen detection (RAD) tests are fit for diagnosing EI although their sensitivity is not optimal. Here, we evaluated the performance of the newly developed RAD test using silver amplification immunochromatography (Quick Chaser Auto Flu A, B: QCA) to diagnose EI. The detection limits of QCA for EIVs were five-fold lower than the conventional RAD tests. The duration of virus antigen detection in the infected horses was longer than the conventional RAD tests. We conclude that QCA could be a valuable diagnostic method for EI.

  8. Use of M2e ELISAs for longitudinal surveillance of commercial poultry in Indonesia vaccinated against highly pathogenic avian influenza.

    Science.gov (United States)

    Wibowo, Michael Haryadi; Tarigan, Simson; Sumarningsih; Artanto, Sidna; Indriani, Risa; Anggoro, Dito; Putra, Cahyaditya Pratama; Idris, Syafrison; Untari, Tri; Asmara, Widya; Tabbu, Charles Rangga; Ignjatovic, Jagoda

    2017-11-01

    In countries where highly pathogenic avian influenza virus (HPAIV) H5N1 is endemic and controlled by vaccination, post-vaccination serological monitoring is essential to differentiate vaccinated poultry from those that are infected. The objectives of this study were to validate two experimental ELISAs that detect antibodies raised against the M2e protein of avian influenza virus that can be used for DIVA purposes. Results from the sM2e and tM2e ELISAs were compared with other conventional tests for the detection of H5N1influenza virus (virus isolation and RT-PCR) using samples collected from 16 commercial flocks in Indonesia. These comprised vaccinated layers aged between 18 and 68 weeks old that were sampled at ten-weekly intervals. A small number of sera were positive in sM2e and tM2e ELISA, 14 (0.6%) and 17 (0.7%) respectively, with low OD 420 (0.1-0.3), but only 4 sera were positive in both tests. At the flock level, the incidence of M2e positive sera was low (4%), well below previously established minimum of 40% for an HPAIV H5N1-infected flock. Conventional M and H5 gene RT-PCRs indicated that none of 16 flocks were infected at any time during the study. No virus was isolated from any of the 480 pooled swab samples, except from one, for which the combined data analysis suggest to be the result of a laboratory cross-contamination. Clinical disease, mortalities or reduction in production performance, indicative of field H5N1 challenge, were not observed either in any of the flocks. Birds from two surveyed flocks, challenged in the laboratory with an Indonesian HPAIV H5N1 developed M2e antibodies in 50% and 55% of surviving birds with OD 420 in the range of 0.35-1.47 in tM2e ELISA, confirming the validity of the criteria established for use of M2e ELISA for DIVA purposes. Overall these results showed that the tM2e ELISA could be a useful monitoring tool to ascertain freedom from H5N1 infections in vaccinated commercial poultry. Copyright © 2017 Elsevier B

  9. 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.

  10. 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

  11. U.S. Geological Survey science strategy for highly pathogenic avian influenza in wildlife and the environment (2016–2020)

    Science.gov (United States)

    Harris, M. Camille; Pearce, John M.; Prosser, Diann J.; White, C. LeAnn; Miles, A. Keith; Sleeman, Jonathan M.; Brand, Christopher J.; Cronin, James P.; De La Cruz, Susan; Densmore, Christine L.; Doyle, Thomas W.; Dusek, Robert J.; Fleskes, Joseph P.; Flint, Paul L.; Guala, Gerald F.; Hall, Jeffrey S.; Hubbard, Laura E.; Hunt, Randall J.; Ip, Hon S.; Katz, Rachel A.; Laurent, Kevin W.; Miller, Mark P.; Munn, Mark D.; Ramey, Andy M.; Richards, Kevin D.; Russell, Robin E.; Stokdyk, Joel P.; Takekawa, John Y.; Walsh, Daniel P.

    2016-08-18

    IntroductionThrough the Science Strategy for Highly Pathogenic Avian Influenza (HPAI) in Wildlife and the Environment, the USGS will assess avian influenza (AI) dynamics in an ecological context to inform decisions made by resource managers and policymakers from the local to national level. Through collection of unbiased scientific information on the ecology of AI viruses and wildlife hosts in a changing world, the U.S. Geological Survey (USGS) will enhance the development of AI forecasting tools and ensure this information is integrated with a quality decision process for managing HPAI.The overall goal of this USGS Science Strategy for HPAI in Wildlife and the Environment goes beyond document­ing the occurrence and distribution of AI viruses in wild birds. The USGS aims to understand the epidemiological processes and environmental factors that influence HPAI distribution and describe the mechanisms of transmission between wild birds and poultry. USGS scientists developed a conceptual model describing the process linking HPAI dispersal in wild waterfowl to the outbreaks in poul­try. This strategy focuses on five long-term science goals, which include:Science Goal 1—Augment the National HPAI Surveillance Plan;Science Goal 2—Determine mechanisms of HPAI disease spread in wildlife and the environment;Science Goal 3—Characterize HPAI viruses circulating in wildlife;Science Goal 4—Understand implications of avian ecol­ogy on HPAI spread; andScience Goal 5—Develop HPAI forecasting and decision-making tools.These goals will help define and describe the processes outlined in the conceptual model with the ultimate goal of facilitating biosecurity and minimizing transfer of diseases across the wildlife-poultry interface. The first four science goals are focused on scientific discovery and the fifth goal is application-based. Decision analyses in the fifth goal will guide prioritization of proposed actions in the first four goals.

  12. Evolution of highly pathogenic H5N1 avian influenza viruses in Vietnam between 2001 and 2007.

    Directory of Open Access Journals (Sweden)

    Xiu-Feng Wan

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses have caused dramatic economic losses to the poultry industry of Vietnam and continue to pose a serious threat to public health. As of June 2008, Vietnam had reported nearly one third of worldwide laboratory confirmed human H5N1 infections. To better understand the emergence, spread and evolution of H5N1 in Vietnam we studied over 300 H5N1 avian influenza viruses isolated from Vietnam since their first detection in 2001. Our phylogenetic analyses indicated that six genetically distinct H5N1 viruses were introduced into Vietnam during the past seven years. The H5N1 lineage that evolved following the introduction in 2003 of the A/duck/Hong Kong/821/2002-like viruses, with clade 1 hemagglutinin (HA, continued to predominate in southern Vietnam as of May 2007. A virus with a clade 2.3.4 HA newly introduced into northern Vietnam in 2007, reassorted with pre-existing clade 1 viruses, resulting in the emergence of novel genotypes with neuraminidase (NA and/or internal gene segments from clade 1 viruses. A total of nine distinct genotypes have been present in Vietnam since 2001, including five that were circulating in 2007. At least four of these genotypes appear to have originated in Vietnam and represent novel H5N1 viruses not reported elsewhere. Geographic and temporal analyses of H5N1 infection dynamics in poultry suggest that the majority of viruses containing new genes were first detected in northern Vietnam and subsequently spread to southern Vietnam after reassorting with pre-existing local viruses in northern Vietnam. Although the routes of entry and spread of H5N1 in Vietnam remain speculative, enhanced poultry import controls and virologic surveillance efforts may help curb the entry and spread of new HPAI viral genes.

  13. Military and Military Medical Support in Highly Pathogenic Avian Influenza (HPAI/H5N1) Pandemic Scenario

    International Nuclear Information System (INIS)

    Taleski, V.

    2007-01-01

    Avian influenza (Bird flu) is a highly contagious viral disease affecting mainly chickens, turkeys, ducks, other birds and mammals. Reservoirs for HPAI /H5N1 virus are shore birds and waterfowl (asymptomatic, excrete virus in feces for a long periods of time), live bird markets and commercial swine facilities. Virus tends to cycle between pigs and birds. HPAI (H5N1) virus is on every 'top ten' list available for potential agricultural bio-weapon agents. The threat of a HPAI/H5N1 pandemic is a definitively global phenomenon and the response must be global. A number of National plans led to various measures of preventing and dealing with epidemics/pandemics. Lessons learned form the pandemic history indicated essential role of military and military medical support to civil authorities in a crisis situation. Based on International Military Medical Avian Influenza Pandemic workshop (Vienna 2006), an expected scenario would involve 30-50% outpatients, 20-30% hospital admission, 2-3% deaths, 10-20% complicated cases. Activities of civil hospital may be reduced by 50%. Benefits of military support could be in: Transportation of patients (primarily by air); Mass vaccination and provision of all other preventive measures (masks, Tamiflu); Restriction of movements; Infection control of health care facilities; Field hospitals for triage and quarantine, military barracks to treat milder cases and military hospitals for severe cases; Deal with corpses; Stockpiling (vaccines, antiviral, antibiotics, protective equipment, supplies); Training; Laboratories; Ensure public safety, etc. With the aim of minimizing the risk of a pandemic spread by means of rapid and uncomplicated cooperation, an early warning system has to be established to improve surveillance, improve international contacts (WHO, ECDC, CDC), establish Platform for sharing information, close contacts of national and international military and civilian surveillance networks and databases, cooperation between military

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

    Science.gov (United States)

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

    2010-05-19

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

  15. Growth limitation of Lemna minor due to high plant density

    NARCIS (Netherlands)

    Driever, S.M.; Nes, van E.H.; Roijackers, R.M.M.

    2005-01-01

    The effect of high population densities on the growth rate of Lemna minor (L.) was studied under laboratory conditions at 23°C in a medium with sufficient nutrients. At high population densities, we found a non-linear decreasing growth rate with increasing L. minor density. Above a L. minor biomass

  16. Determination of preventive behaviors for pandemic influenza A/H1N1 based on protection motivation theory among female high school students in Isfahan, Iran.

    Science.gov (United States)

    Sharifirad, Gholamreza; Yarmohammadi, Parastoo; Sharifabad, Mohammad Ali Morowati; Rahaei, Zohreh

    2014-01-01

    Influenza A/H1N1 pandemic has recently threatened the health of world's population more than ever. Non-pharmaceutical measures are important to prevent the spread of influenza A/H1N1 and to prevent a pandemic. Effective influenza pandemic management requires understanding of the factors influencing preventive behavioral. This study reports on predictors of students' preventive behaviors for pandemic influenza A/H1N1 using variables based on the protection motivation theory (PMT). In a cross-sectional study, multiple-stage randomized sampling was used to select 300 female students in Isfahan who completed a questionnaire in December 2009. Data were collected using a self-report questionnaire based on PMT. The statistical analysis of the data included bivariate correlations, Mann-Whitney, Kruskal-Wallis, and linear regression. The mean age of participants was 15.62 (SE = 1.1) years old. Majority of participants were aware regarding pandemic influenza A/H1N1 (87.3%, 262 out of 300). Results showed that, protection motivation was highly significant relationship with preventive behavior and predicted 34% of its variance. We found all of the variables with the exception of perceived susceptibility, perceived severity, and response cost were related with protection motivation and explained 22% of its variance. Promotion of students' self-efficacy, and intention to protect themselves from a health threat should be priorities of any programs aimed at promoting preventive behaviors among students. It is also concluded that the protection motivation theory may be used in developing countries, like Iran, as a framework for prevention interventions in an attempt to improve the preventive behaviors of students.

  17. Could Changes in the Agricultural Landscape of Northeastern China Have Influenced the Long-Distance Transmission of Highly Pathogenic Avian Influenza H5Nx Viruses?

    Directory of Open Access Journals (Sweden)

    Marius Gilbert

    2017-12-01

    Full Text Available In the last few years, several reassortant subtypes of highly pathogenic avian influenza viruses (HPAI H5Nx have emerged in East Asia. These new viruses, mostly of subtype H5N1, H5N2, H5N6, and H5N8 belonging to clade 2.3.4.4, have been found in several Asian countries and have caused outbreaks in poultry in China, South Korea, and Vietnam. HPAI H5Nx also have spread over considerable distances with the introduction of viruses belonging to the same 2.3.4.4 clade in the U.S. (2014–2015 and in Europe (2014–2015 and 2016–2017. In this paper, we examine the emergence and spread of these new viruses in Asia in relation to published datasets on HPAI H5Nx distribution, movement of migratory waterfowl, avian influenza risk models, and land-use change analyses. More specifically, we show that between 2000 and 2015, vast areas of northeast China have been newly planted with rice paddy fields (3.21 million ha in Heilongjiang, Jilin, and Liaoning in areas connected to other parts of Asia through migratory pathways of wild waterfowl. We hypothesize that recent land use changes in northeast China have affected the spatial distribution of wild waterfowl, their stopover areas, and the wild-domestic interface, thereby altering transmission dynamics of avian influenza viruses across flyways. Detailed studies of the habitat use by wild migratory birds, of the extent of the wild–domestic interface, and of the circulation of avian influenza viruses in those new planted areas may help to shed more light on this hypothesis, and on the possible impact of those changes on the long-distance patterns of avian influenza transmission.

  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. Longitudinal changes of pneumonia complicating novel influenza A (H1N1 by high-resolution computed tomography

    Directory of Open Access Journals (Sweden)

    Feng Feng

    2015-06-01

    Conclusion: HRCT may play a role in detecting and characterizing pulmonary lesions for the cases of pneumonia complicating influenza A. In addition, it may contribute to monitoring longitudinal changes of pneumonia and assessing therapeutic response.

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

    Directory of Open Access Journals (Sweden)

    Nicholas J Negovetich

    2011-04-01

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

  1. Novel H5N8 clade 2.3.4.4 highly pathogenic avian influenza virus in wild awuatic birds, Russia, 2016

    Science.gov (United States)

    H5N1 high pathogenicity avian influenza virus (HPAIV) emerged in 1996 in Guangdong China (Gs/GD) and has evolved into multiple genetic clades. Since 2008, HPAIV H5 clade 2.3.4 with N2, N5 and N8 neuraminidase subtypes have been identified in mainland China and outbreak of HPAIV H5N8 clade 2.3.4.4 ou...

  2. Evidence for common ancestry among viruses isolated from wild birds in Beringia and highly pathogenic intercontinental reassortant H5N1 and H5N2 influenza A viruses

    Science.gov (United States)

    Ramey, Andy M.; Reeves, Andrew; Teslaa, Joshua L.; Nashold, Sean W.; Donnelly, Tyrone F.; Bahl, Justin; Hall, Jeffrey S.

    2016-01-01

    Highly pathogenic clade 2.3.4.4 H5N8, H5N2, and H5N1 influenza A viruses were first detected in wild, captive, and domestic birds in North America in November–December 2014. In this study, we used wild waterbird samples collected in Alaska prior to the initial detection of clade 2.3.4.4 H5 influenza A viruses in North America to assess the evidence for: (1) dispersal of highly pathogenic influenza A viruses from East Asia to North America by migratory birds via Alaska and (2) ancestral origins of clade 2.3.4.4 H5 reassortant viruses in Beringia. Although we did not detect highly pathogenic influenza A viruses in our sample collection from western Alaska, we did identify viruses that contained gene segments sharing recent common ancestry with intercontinental reassortant H5N2 and H5N1 viruses. Results of phylogenetic analyses and estimates for times of most recent common ancestry support migratory birds sampled in Beringia as maintaining viral diversity closely related to novel highly pathogenic influenza A virus genotypes detected in North America. Although our results do not elucidate the route by which highly pathogenic influenza A viruses were introduced into North America, genetic evidence is consistent with the hypothesized trans-Beringian route of introduction via migratory birds.

  3. High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

    International Nuclear Information System (INIS)

    Yin Jiangmei; Dai Anlan; Laddy, Dominick J.; Yan Jian; Arango, Tatiana; Khan, Amir S.; Lewis, Mark G.; Andersen, Hanne; Kutzler, Michele A.; Draghia-Akli, Ruxandra; Weiner, David B.; Boyer, Jean D.

    2009-01-01

    Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhanced the production of IFN-γ (0.5 mg) and the proliferation of CD4 + and CD8 + T cells, as well as T CM levels in proliferating CD8 + T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-γ and the proliferation of CD4 + and CD8 + T cells and T CM levels in the proliferating CD4 + and CD8 + T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.

  4. Assessing the risk of highly pathogenic avian influenza H5N1 transmission through poultry movements in Bali, Indonesia.

    Science.gov (United States)

    Roche, Sharon E; Cogger, Naomi; Garner, M Graeme; Putra, Anak Agung Gde; Toribio, Jenny-Ann L M L

    2014-03-01

    Indonesia continues to report the highest number of human and poultry cases of highly pathogenic avian influenza H5N1. The disease is considered to be endemic on the island of Bali. Live bird markets are integral in the poultry supply chain on Bali and are important, nutritionally and culturally, for the rural and urban human populations. Due to the lack of biosecurity practiced along the supply chain from producer to live bird markets, there is a need to understand the risks associated with the spread of H5N1 through live bird movements for effective control. Resources to control H5N1 in Indonesia are very limited and cost effective strategies are needed. We assessed the probability a live bird market is infected through live poultry movements and assessed the effects of implementing two simple and low cost control measures on this risk. Results suggest there is a high risk a live bird market is infected (0.78), and risk mitigation strategies such as detecting and removing infected poultry from markets reduce this risk somewhat (range 0.67-0.76). The study demonstrates the key role live poultry movements play in transmitting H5N1 and the need to implement a variety of control measures to reduce disease spread. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Victims and vectors: highly pathogenic avian influenza H5N1 and the ecology of wild birds

    Science.gov (United States)

    Takekawa, John Y.; Prosser, Diann J.; Newman, Scott H.; Muzaffar, Sabir Bin; Hill, Nichola J.; Yan, Baoping; Xiao, Xiangming; Lei, Fumin; Li, Tianxian; Schwarzbach, Steven E.; Howell, Judd A.

    2010-01-01

    The emergence of highly pathogenic avian influenza (HPAI) viruses has raised concerns about the role of wild birds in the spread and persistence of the disease. In 2005, an outbreak of the highly pathogenic subtype H5N1 killed more than 6,000 wild waterbirds at Qinghai Lake, China. Outbreaks have continued to periodically occur in wild birds at Qinghai Lake and elsewhere in Central China and Mongolia. This region has few poultry but is a major migration and breeding area for waterbirds in the Central Asian Flyway, although relatively little is known about migratory movements of different species and connectivity of their wetland habitats. The scientific debate has focused on the role of waterbirds in the epidemiology, maintenance and spread of HPAI H5N1: to what extent are they victims affected by the disease, or vectors that have a role in disease transmission? In this review, we summarise the current knowledge of wild bird involvement in the ecology of HPAI H5N1. Specifically, we present details on: (1) origin of HPAI H5N1; (2) waterbirds as LPAI reservoirs and evolution into HPAI; (3) the role of waterbirds in virus spread and persistence; (4) key biogeographic regions of outbreak; and (5) applying an ecological research perspective to studying AIVs in wild waterbirds and their ecosystems.

  6. Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

    Science.gov (United States)

    Luczo, Jasmina M.; Stambas, John; Durr, Peter A.; Michalski, Wojtek P.

    2015-01-01

    Summary The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:26467906

  7. High dimensional neurocomputing growth, appraisal and applications

    CERN Document Server

    Tripathi, Bipin Kumar

    2015-01-01

    The book presents a coherent understanding of computational intelligence from the perspective of what is known as "intelligent computing" with high-dimensional parameters. It critically discusses the central issue of high-dimensional neurocomputing, such as quantitative representation of signals, extending the dimensionality of neuron, supervised and unsupervised learning and design of higher order neurons. The strong point of the book is its clarity and ability of the underlying theory to unify our understanding of high-dimensional computing where conventional methods fail. The plenty of application oriented problems are presented for evaluating, monitoring and maintaining the stability of adaptive learning machine. Author has taken care to cover the breadth and depth of the subject, both in the qualitative as well as quantitative way. The book is intended to enlighten the scientific community, ranging from advanced undergraduates to engineers, scientists and seasoned researchers in computational intelligenc...

  8. Synergy of two low-affinity NLSs determines the high avidity of influenza A virus nucleoprotein NP for human importin α isoforms.

    Science.gov (United States)

    Wu, Wei; Sankhala, Rajeshwer S; Florio, Tyler J; Zhou, Lixin; Nguyen, Nhan L T; Lokareddy, Ravi K; Cingolani, Gino; Panté, Nelly

    2017-09-12

    The influenza A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral genome and functions as an adapter between the virus and the host cell machinery. NPs from all strains of influenza A viruses contain two nuclear localization signals (NLSs): a well-studied monopartite NLS1 and a less-characterized NLS2, thought to be bipartite. Through site-directed mutagenesis and functional analysis, we found that NLS2 is also monopartite and is indispensable for viral infection. Atomic structures of importin α bound to two variants of NLS2 revealed NLS2 primarily binds the major-NLS binding site of importin α, unlike NLS1 that associates with the minor NLS-pocket. Though peptides corresponding to NLS1 and NLS2 bind weakly to importin α, the two NLSs synergize in the context of the full length NP to confer high avidity for importin α7, explaining why the virus efficiently replicates in the respiratory tract that exhibits high levels of this isoform. This study, the first to functionally characterize NLS2, demonstrates NLS2 plays an important and unexpected role in influenza A virus infection. We propose NLS1 and NLS2 form a bipartite NLS in trans, which ensures high avidity for importin α7 while preventing non-specific binding to viral RNA.

  9. Pathology of natural infections by H5N1 highly pathogenic avian influenza virus in mute (Cygnus olor) and whooper (Cygnus cygnus) swans.

    Science.gov (United States)

    Teifke, J P; Klopfleisch, R; Globig, A; Starick, E; Hoffmann, B; Wolf, P U; Beer, M; Mettenleiter, T C; Harder, T C

    2007-03-01

    Mortality in wild aquatic birds due to infection with highly pathogenic avian influenza viruses (HPAIV) is a rare event. During the recent outbreak of highly pathogenic avian influenza in Germany, mortality due to H5N1 HPAIV was observed among mute and whooper swans as part of a rapid spread of this virus. In contrast to earlier reports, swans appeared to be highly susceptible and represented the mainly affected species. We report gross and histopathology and distribution of influenza virus antigen in mute and whooper swans that died after natural infection with H5N1 HPAIV. At necropsy, the most reliable lesions were multifocal hemorrhagic necrosis in the pancreas, pulmonary congestion and edema, and subepicardial hemorrhages. Major histologic lesions were acute pancreatic necrosis, multifocal necrotizing hepatitis, and lymphoplasmacytic encephalitis with neuronal necrosis. Adrenals displayed consistently scattered cortical and medullary necrosis. In spleen and Peyer's patches, mild lymphocyte necrosis was present. Immunohistochemical demonstration of HPAIV nucleoprotein in pancreas, adrenals, liver, and brain was strongly consistent with histologic lesions. In the brain, a large number of neurons and glial cells, especially Purkinje cells, showed immunostaining. Occasionally, ependymal cells of the spinal cord were also positive. In the lungs, influenza virus antigen was identified in a few endothelial cells but not within pneumocytes. The infection of the central nervous system supports the view that the neurotropism of H5N1 HPAIV leads to nervous disturbances with loss of orientation. More investigations are necessary to clarify the mechanisms of the final circulatory failure, lung edema, and rapid death of the swans.

  10. Isolation of an H5N8 Highly Pathogenic Avian Influenza Virus Strain from Wild Birds in Seoul, a Highly Urbanized Area in South Korea.

    Science.gov (United States)

    Kwon, Jung-Hoon; Lee, Dong-Hun; Jeong, Jei-Hyun; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Noh, Jin-Yong; Hong, Woo-Tack; Jeong, Sol; Gwon, Gyeong-Bin; Lee, Sang-Won; Choi, In-Soo; Song, Chang-Seon

    2017-07-01

    Asian-lineage H5 highly pathogenic avian influenza viruses (HPAIV) have caused recurrent outbreaks in poultry and wild birds. In January 2014, H5N8 HPAIV caused outbreaks in South Korea and subsequently spread to East Asia, Europe, and North America. We report the isolation of an H5N8 HPAIV strain from wild birds in Seoul, the most-developed city in South Korea. We analyzed the complete genome sequence of this isolate and estimated its origin using a phylogenetic analysis. The Seoul H5N8 isolate clustered phylogenetically with strains isolated from migratory wild birds but was distinct from Korean poultry isolates. This H5N8 virus was likely introduced into the urbanized city by migratory wild birds. Therefore, wild bird habitats in urbanized areas should be carefully monitored for HPAIV.

  11. Deep sequencing of H7N8 avian influenza viruses from surveillance zone supports H7N8 high pathogenicity avian influenza was limited to a single outbreak farm in Indiana during 2016.

    Science.gov (United States)

    Lee, Dong-Hun; Torchetti, Mia Kim; Killian, Mary Lea; Swayne, David E

    2017-07-01

    In mid-January 2016, an outbreak of H7N8 high-pathogenicity avian influenza virus (HPAIV) in commercial turkeys occurred in Indiana. Surveillance within the 10km control zone identified H7N8 low-pathogenicity avian influenza virus (LPAIV) in nine surrounding turkey flocks but no other HPAIV-affected premises. We sequenced four of the H7N8 HPAIV isolated from the single farm and nine LPAIV identified during control zone surveillance. Evaluation included phylogenetic network analysis indicating close relatedness across the HPAIV and LPAIV, and that the progenitor H7N8 LPAIV spread among the affected turkey farms in Indiana, followed by spontaneous mutation to HPAIV on a single premise through acquisition of three basic amino acids at the hemagglutinin cleavage site. Deep sequencing of the available viruses failed to identify subpopulations in either the HPAIV or LPAIV suggesting mutation to HPAIV likely occurred on a single farm and the HPAIV did not spread to epidemiologically linked LPAIV-affected farms. Published by Elsevier Inc.

  12. Highly Pathogenic H5N1 Influenza A Virus Strains Provoke Heterogeneous IFN-α/β Responses That Distinctively Affect Viral Propagation in Human Cells

    Science.gov (United States)

    Matthaei, Markus; Budt, Matthias; Wolff, Thorsten

    2013-01-01

    The fatal transmissions of highly pathogenic avian influenza A viruses (IAV) of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I interferons (IFN-α/β) are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human H5N1 IAV infections is limited and contradictory. We hypothesized an important role for the IFN system in limiting productive infection of avian H5N1 strains in human cells. Hence, we examined IFN-α/β gene activation by different avian and human H5N1 isolates, if the IFN-α/β response restricts H5N1 growth and whether the different strains were equally capable to regulate the IFN-α/β system via their IFN-antagonistic NS1 proteins. Two human H5N1 isolates and a seasonal H3N2 strain propagated efficiently in human respiratory cells and induced little IFN-β, whereas three purely avian H5N1 strains were attenuated for replication and provoked higher IFN secretion. Replication of avian viruses was significantly enhanced on interferon-deficient cells, and exogenous IFN potently limited the growth of all strains in human cells. Moreover, IFN-α/β activation by all strains depended on retinoic acid-inducible gene I excluding principal differences in receptor activation between the different viruses. Interestingly, all H5N1 NS1 proteins suppressed IFN-α/β induction comparably well to the NS1 of seasonal IAV. Thus, our study shows that H5N1 strains are heterogeneous in their capacity to activate human cells in an NS1-independent manner. Our findings also suggest that H5N1 viruses need to acquire adaptive changes to circumvent strong IFN-α/β activation in human host cells. Since no single amino acid polymorphism could be associated with a respective high- or low induction phenotype we propose that the necessary adaptations to overcome the human IFN

  13. Highly pathogenic H5N1 influenza A virus strains provoke heterogeneous IFN-α/β responses that distinctively affect viral propagation in human cells.

    Directory of Open Access Journals (Sweden)

    Markus Matthaei

    Full Text Available The fatal transmissions of highly pathogenic avian influenza A viruses (IAV of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I interferons (IFN-α/β are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human H5N1 IAV infections is limited and contradictory. We hypothesized an important role for the IFN system in limiting productive infection of avian H5N1 strains in human cells. Hence, we examined IFN-α/β gene activation by different avian and human H5N1 isolates, if the IFN-α/β response restricts H5N1 growth and whether the different strains were equally capable to regulate the IFN-α/β system via their IFN-antagonistic NS1 proteins. Two human H5N1 isolates and a seasonal H3N2 strain propagated efficiently in human respiratory cells and induced little IFN-β, whereas three purely avian H5N1 strains were attenuated for replication and provoked higher IFN secretion. Replication of avian viruses was significantly enhanced on interferon-deficient cells, and exogenous IFN potently limited the growth of all strains in human cells. Moreover, IFN-α/β activation by all strains depended on retinoic acid-inducible gene I excluding principal differences in receptor activation between the different viruses. Interestingly, all H5N1 NS1 proteins suppressed IFN-α/β induction comparably well to the NS1 of seasonal IAV. Thus, our study shows that H5N1 strains are heterogeneous in their capacity to activate human cells in an NS1-independent manner. Our findings also suggest that H5N1 viruses need to acquire adaptive changes to circumvent strong IFN-α/β activation in human host cells. Since no single amino acid polymorphism could be associated with a respective high- or low induction phenotype we propose that the necessary adaptations to

  14. Clinical and Pathologic Characterization of an Outbreak of Highly Pathogenic Avian Influenza H7N8 in Commercial Turkeys in Southern Indiana.

    Science.gov (United States)

    Burcham, Grant N; Ramos-Vara, José A; Murphy, Duane A

    2017-09-01

    Highly pathogenic avian influenza (HPAI) is a systemic lethal disease of poultry caused by several subtypes of influenza A virus and classified on the basis of serologic reactions to hemagglutinin and neuraminidase surface glycoproteins. In January 2016, a novel subtype of HPAI-H7N8-was diagnosed in a commercial turkey (Meleagris gallopavo) flock in southern Indiana. Clinical signs and history included increased mortality, dyspnea, head tremors, recumbency, and somnolent or unaware birds. Postmortem examination of six recently dead birds showed red-tinged mucous in the choana and trachea and marked pulmonary edema. Histologic lesions in the brain included severe, multifocal lymphohistiocytic meningoencephalitis with foci of malacia, neuronal necrosis, and neuronophagia. All anatomic locations of the brain were affected, although histologic changes in the cerebellum were considered mild. Other histologic lesions included pulmonary congestion and edema, splenic congestion and lymphoid depletion, fibrinoid necrosis of vessels within the spleen, and multifocal pancreatic acinar necrosis. Immunohistochemistry (IHC) was weakly positive for influenza A in the brain; IHC was negative in other tissues tested. The clinical and pathologic characteristics of this case matched previously published material concerning HPAI and add to instances of known or suspected mutation of a low pathogenic virus to a highly pathogenic virus.

  15. Cross talk between animal and human influenza viruses.

    Science.gov (United States)

    Ozawa, Makoto; Kawaoka, Yoshihiro

    2013-01-01

    Although outbreaks of highly pathogenic avian influenza in wild and domestic birds have been posing the threat of a new influenza pandemic for the past decade, the first pandemic of the twenty-first century came from swine viruses. This fact emphasizes the complexity of influenza viral ecology and the difficulty of predicting influenza viral dynamics. Complete control of influenza viruses seems impossible. However, we must minimize the impact of animal and human influenza outbreaks by learning lessons from past experiences and recognizing the current status. Here, we review the most recent influenza virology data in the veterinary field, including aspects of zoonotic agents and recent studies that assess the pandemic potential of H5N1 highly pathogenic avian influenza viruses.

  16. The potential spread of highly pathogenic avian influenza virus via dynamic contacts between poultry premises in Great Britain

    Directory of Open Access Journals (Sweden)

    Kao Rowland R

    2011-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI viruses have had devastating effects on poultry industries worldwide, and there is concern about the potential for HPAI outbreaks in the poultry industry in Great Britain (GB. Critical to the potential for HPAI to spread between poultry premises are the connections made between farms by movements related to human activity. Movement records of catching teams and slaughterhouse vehicles were obtained from a large catching company, and these data were used in a simulation model of HPAI spread between farms serviced by the catching company, and surrounding (geographic areas. The spread of HPAI through real-time movements was modelled, with the addition of spread via company personnel and local transmission. Results The model predicted that although large outbreaks are rare, they may occur, with long distances between infected premises. Final outbreak size was most sensitive to the probability of spread via slaughterhouse-linked movements whereas the probability of onward spread beyond an index premises was most sensitive to the frequency of company personnel movements. Conclusions Results obtained from this study show that, whilst there is the possibility that HPAI virus will jump from one cluster of farms to another, movements made by catching teams connected fewer poultry premises in an outbreak situation than slaughterhouses and company personnel. The potential connection of a large number of infected farms, however, highlights the importance of retaining up-to-date data on poultry premises so that control measures can be effectively prioritised in an outbreak situation.

  17. Seroprevalence of antibodies against highly pathogenic avian influenza A (H5N1 virus among poultry workers in Bangladesh, 2009.

    Directory of Open Access Journals (Sweden)

    Sharifa Nasreen

    Full Text Available We conducted a cross-sectional study in 2009 to determine the seroprevalence and risk factors for highly pathogenic avian influenza A (H5N1 [HPAI H5N1] virus antibodies among poultry workers at farms and live bird markets with confirmed/suspected poultry outbreaks during 2009 in Bangladesh. We tested sera by microneutralization assay using A/Bangladesh/207095/2008 (H5N1; clade 2.2.2 virus with confirmation by horse red blood cell hemagglutination inhibition and H5-specific Western blot assays. We enrolled 212 workers from 87 farms and 210 workers from three live bird markets. One hundred and two farm workers (48% culled poultry. One hundred and ninety-three farm workers (91% and 178 market workers (85% reported direct contact with poultry that died during a laboratory confirmed HPAI H5N1 poultry farm outbreak or market poultry die-offs from suspected HPAI H5N1. Despite exposure to sick poultry, no farm or market poultry workers were seropositive for HPAI H5N1 virus antibodies (95% confidence interval 0-1%.

  18. A Stakeholder Survey on Live Bird Market Closures Policy for Controlling Highly Pathogenic Avian Influenza in Vietnam

    Directory of Open Access Journals (Sweden)

    Thi Thanh Thuy Nguyen

    2017-08-01

    Full Text Available Extensive research in Vietnam and elsewhere has shown that live bird markets (LBMs play a significant role in the ecology and zoonotic transmission of avian influenzas (AIs including H5N1 and H7N9. Vietnam has a large number of LBMs reflecting the consumer preferences for live poultry. Under pressure to mitigate risks for H7N9 and other zoonotic AIs, Vietnam is considering, among other mitigation measures, temporary closures of LBMs as a policy to reduce risk of AI outbreaks. However, the efficacy of market closure is debated, particularly because little is known about how poultry traders may react, and whether trading may emerge outside formal marketplaces. Combining efforts of anthropologists, economists, sociologists, and veterinarians can be useful to elucidate the drivers behind poultry traders’ reactions and better understanding the barriers to implementing risk mitigation measures. In this paper, we present results from a stakeholder survey of LBM stakeholders in Vietnam. Our qualitative data show that trading outside formal markets is very likely to occur in the event of a temporary LBM market closure. Our data show that the poultry value chain in Vietnam remains highly flexible, with traders willing and able to trade poultry in many possible locations. Our results indicate that simplification of the poultry value chain along with strict enforcement, engagement of stakeholders, and adequate communication would be a necessary prerequisite before market closure could be an effective policy.

  19. Determining the phylogenetic and phylogeographic origin of highly pathogenic avian influenza (H7N3) in Mexico.

    Science.gov (United States)

    Lu, Lu; Lycett, Samantha J; Leigh Brown, Andrew J

    2014-01-01

    Highly pathogenic (HP) avian influenza virus (AIV) H7N3 outbreaks occurred 3 times in the Americas in the past 10 years and caused severe economic loss in the affected regions. In June/July 2012, new HP H7N3 outbreaks occurred at commercial farms in Jalisco, Mexico. Outbreaks continued to be identified in neighbouring states in Mexico till August 2013. To explore the origin of this outbreak, time resolved phylogenetic trees were generated from the eight segments of full-length AIV sequences in North America using BEAST. Location, subtype, avian host species and pathogenicity were modelled as discrete traits upon the trees using continuous time Markov chains. A further joint analysis among segments was performed using a hierarchical phylogenetic model (HPM) which allowed trait rates (location, subtype, host species) to be jointly inferred across different segments. The complete spatial diffusion process was visualised through virtual globe software. Our result indicated the Mexico HP H7N3 originated from the large North America low pathogenicity AIV pool through complicated reassortment events. Different segments were contributed by wild waterfowl from different N. American flyways. Five of the eight segments (HA, NA, NP, M, NS) were introduced from wild birds migrating along the central North American flyway, and PB2, PB1 and PA were introduced via the western North American flyway. These results highlight a potential role for Mexico as a hotspot of virus reassortment as it is where wild birds from different migration routes mix during the winter.

  20. Pathogenicity of the Korean H5N8 highly pathogenic avian influenza virus in commercial domestic poultry species.

    Science.gov (United States)

    Lee, Dong-Hun; Kwon, Jung-Hoon; Noh, Jin-Yong; Park, Jae-Keun; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Lee, Joong-Bok; Park, Seung-Yong; Choi, In-Soo; Lee, Sang-Won; Song, Chang-Seon

    2016-01-01

    In 2014, the highly pathogenic avian influenza (HPAI) virus H5N8 triggered outbreaks in wild birds and poultry farms in South Korea. In the present study, we investigated the pathogenicity of the H5N8 HPAI virus, belonging to the clade 2.3.4.4, in different species of poultry. For this, we examined clinical signs and viral shedding levels following intranasal inoculation of the virus in 3-week-old commercial layer chickens and quails, 10-week-old Korean native chickens, and 8-week-old Muscovy ducks. Intranasal inoculation with 10(6.0) viruses at 50% egg-infective dose resulted in 100% mortality in the layer chickens (8/8) and quails (4/4), but 60% and 0% deaths in the Korean native chickens (3/5) and Muscovy ducks (0/4), respectively. In addition, transmission of the inoculated virus to contact-exposed birds was evident in all the species used in this study. Based on our results, we conclude that the H5N8 HPAI virus has lower pathogenicity and transmissibility in poultry species compared with previously reported H5N1 HPAI viruses.

  1. Lessons learned from research and surveillance directed at highly pathogenic influenza A viruses in wild birds inhabiting North America

    Science.gov (United States)

    Ramey, Andy M.; DeLiberto, Thomas J.; Berhane, Yohannes; Swayne, David E.; Stallknecht, David E.

    2018-01-01

    Following detections of highly pathogenic (HP) influenza A viruses (IAVs) in wild birds inhabiting East Asia after the turn of the millennium, the intensity of sampling of wild birds for IAVs increased throughout much of North America. The objectives for many research and surveillance efforts were directed towards detecting Eurasian origin HP IAVs and understanding the potential of such viruses to be maintained and dispersed by wild birds. In this review, we highlight five important lessons learned from research and surveillance directed at HP IAVs in wild birds inhabiting North America: (1) Wild birds may disperse IAVs between North America and adjacent regions via migration, (2) HP IAVs can be introduced to wild birds in North America, (3) HP IAVs may cross the wild bird-poultry interface in North America, (4) The probability of encountering and detecting a specific virus may be low, and (5) Population immunity of wild birds may influence HP IAV outbreaks in North America. We review empirical support derived from research and surveillance efforts for each lesson learned and, furthermore, identify implications for future surveillance efforts, biosecurity, and population health. We conclude our review by identifying five additional areas in which we think future mechanistic research relative to IAVs in wild birds in North America are likely to lead to other important lessons learned in the years ahead.

  2. Lessons learned from research and surveillance directed at highly pathogenic influenza A viruses in wild birds inhabiting North America.

    Science.gov (United States)

    Ramey, Andrew M; DeLiberto, Thomas J; Berhane, Yohannes; Swayne, David E; Stallknecht, David E

    2018-05-01

    Following detections of highly pathogenic (HP) influenza A viruses (IAVs) in wild birds inhabiting East Asia after the turn of the millennium, the intensity of sampling of wild birds for IAVs increased throughout much of North America. The objectives for many research and surveillance efforts were directed towards detecting Eurasian origin HP IAVs and understanding the potential of such viruses to be maintained and dispersed by wild birds. In this review, we highlight five important lessons learned from research and surveillance directed at HP IAVs in wild birds inhabiting North America: (1) Wild birds may disperse IAVs between North America and adjacent regions via migration, (2) HP IAVs can be introduced to wild birds in North America, (3) HP IAVs may cross the wild bird-poultry interface in North America, (4) The probability of encountering and detecting a specific virus may be low, and (5) Population immunity of wild birds may influence HP IAV outbreaks in North America. We review empirical support derived from research and surveillance efforts for each lesson learned and, furthermore, identify implications for future surveillance efforts, biosecurity, and population health. We conclude our review by identifying five additional areas in which we think future mechanistic research relative to IAVs in wild birds in North America are likely to lead to other important lessons learned in the years ahead. Published by Elsevier Inc.

  3. A Stakeholder Survey on Live Bird Market Closures Policy for Controlling Highly Pathogenic Avian Influenza in Vietnam.

    Science.gov (United States)

    Nguyen, Thi Thanh Thuy; Fearnley, Lyle; Dinh, Xuan Tung; Tran, Thi Tram Anh; Tran, Trong Tung; Nguyen, Van Trong; Tago, Damian; Padungtod, Pawin; Newman, Scott H; Tripodi, Astrid

    2017-01-01

    Extensive research in Vietnam and elsewhere has shown that live bird markets (LBMs) play a significant role in the ecology and zoonotic transmission of avian influenzas (AIs) including H5N1 and H7N9. Vietnam has a large number of LBMs reflecting the consumer preferences for live poultry. Under pressure to mitigate risks for H7N9 and other zoonotic AIs, Vietnam is considering, among other mitigation measures, temporary closures of LBMs as a policy to reduce risk of AI outbreaks. However, the efficacy of market closure is debated, particularly because little is known about how poultry traders may react, and whether trading may emerge outside formal marketplaces. Combining efforts of anthropologists, economists, sociologists, and veterinarians can be useful to elucidate the drivers behind poultry traders' reactions and better understanding the barriers to implementing risk mitigation measures. In this paper, we present results from a stakeholder survey of LBM stakeholders in Vietnam. Our qualitative data show that trading outside formal markets is very likely to occur in the event of a temporary LBM market closure. Our data show that the poultry value chain in Vietnam remains highly flexible, with traders willing and able to trade poultry in many possible locations. Our results indicate that simplification of the poultry value chain along with strict enforcement, engagement of stakeholders, and adequate communication would be a necessary prerequisite before market closure could be an effective policy.

  4. Pathobiology and transmission of highly and low pathogenic avian influenza viruses in European quail (Coturnix c. coturnix).

    Science.gov (United States)

    Bertran, Kateri; Dolz, Roser; Busquets, Núria; Gamino, Virginia; Vergara-Alert, Júlia; Chaves, Aida J; Ramis, Antonio; Abad, F Xavier; Höfle, Ursula; Majó, Natàlia

    2013-03-28

    European quail (Coturnix c. coturnix) may share with Japanese quail (Coturnix c. japonica) its potential as an intermediate host and reservoir of avian influenza viruses (AIV). To elucidate this question, European quail were experimentally challenged with two highly pathogenic AIV (HPAIV) (H7N1/HP and H5N1/HP) and one low pathogenic AIV (LPAIV) (H7N2/LP). Contact animals were also used to assess the viral transmission among birds. Severe neurological signs and mortality rates of 67% (H7N1/HP) and 92% (H5N1/HP) were observed. Although histopathological findings were present in both HPAIV-infected groups, H5N1/HP-quail displayed a broader viral antigen distribution and extent of microscopic lesions. Neither clinical nor pathological involvement was observed in LPAIV-infected quail. Consistent long-term viral shedding and effective transmission to naive quail was demonstrated for the three studied AIV. Drinking water arose as a possible transmission route and feathers as a potential origin of HPAIV dissemination. The present study demonstrates that European quail may play a major role in AI epidemiology, highlighting the need to further understand its putative role as an intermediate host for avian/mammalian reassortant viruses.

  5. Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Saranya Sridhar

    2015-04-01

    Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.

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

    Science.gov (United States)

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

    2014-08-19

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

  7. Bestrijding van aviaire influenza onder pluimvee: vaccinatie als aanvullende mogelijkheid

    NARCIS (Netherlands)

    Aarle, P van; Breytenbach, J; Schueller, S

    2006-01-01

    Since mid-December 2003, highly pathogenic avian influenza (HPAI) has caused an epidemic in the Asian poultry sector and avian influenza cases have been reported in Europe, the Middle East and Africa. Human fatalities catapulted avian influenza into the public arena with fears of a possible global

  8. Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Carlos J Montoya

    2007-06-01

    Full Text Available Given that highly active antiretroviral therapy (HAART has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40 against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

  9. Influenza in solid organ transplant recipients.

    Science.gov (United States)

    Martin, Spencer T; Torabi, Mina J; Gabardi, Steven

    2012-02-01

    To review available data describing the epidemiology, outcomes, prevention, and treatment of influenza virus in the solid organ transplant population and to evaluate the strengths and limitations of the current literature, with a focus on literature reviewing annual influenza strains and the recent pandemic novel influenza A/H1N1 strain. A systematic literature search (July 1980-June 2011) was performed via PubMed using the following key words: influenza, human; influenza; novel influenza A H1/N1; transplantation; solid organ transplantation; kidney transplant; renal transplant; lung transplant; heart transplant; and liver transplant. Papers were excluded if they were not written in English or were animal studies or in vitro studies. Data from fully published studies and recent reports from international conferences were included. The influenza virus presents a constant challenge to immunocompromised patients and their health care providers. The annual influenza strain introduces a highly infectious and pathogenic risk to solid organ transplant recipients. In 2009, the World Health Organization declared a pandemic as a result of a novel influenza A/H1N1 strain. The pandemic introduced an additional viral threat to solid organ transplant patients at increased risk for infectious complications. The mainstay for prevention of influenza infection in all at-risk populations is appropriate vaccination. Antiviral therapies against influenza for chemoprophylaxis and treatment of infection are available; however, dosing strategies in the solid organ transplant population are not well defined. The solid organ transplant population is at an increased risk of severe complications from influenza infection. Identifying risks, preventing illness, and appropriately treating active infection is essential in this patient population.

  10. Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata

    DEFF Research Database (Denmark)

    Dao, Trong Tuan; Nguyen, Phi Hung; Lee, Hong Sik

    2011-01-01

    The emergence of highly pathogenic influenza A virus strains, such as the new H1N1 swine influenza (novel influenza), represents a serious threat to global human health. During our course of an anti-influenza screening program on natural products, one new licochalcone G (1) and seven known (2-8) ...

  11. Pandemisk influenza

    DEFF Research Database (Denmark)

    Andersen, Nina Blom; Almlund, Pernille

    danske myndigheder kommunikerede åbent og løbende om influenza-krisen og dens trusler. Indsatsen blev anerkendt fra alle sider og førte på intet tidspunkt til alvorlig og længerevarende kritik af myndighederne. Der var tale om en tilfredsstillende krisehåndtering, hvad angår den del, der fokuserede på...... kommunikation om denne tog en drejning i forhold til selve influenza-krisen. Myndighedernes kommunikation blev mere uklar, forvirringen voksede i befolkningen, og der blev rejst kritik i offentligheden. Forløbet rejser spørgsmålene om, den samlede håndtering af kommunikationsindsatsen kunne have været mere...

  12. Nonlinear dynamics of avian influenza epidemic models.

    Science.gov (United States)

    Liu, Sanhong; Ruan, Shigui; Zhang, Xinan

    2017-01-01

    Avian influenza is a zoonotic disease caused by the transmission of the avian influenza A virus, such as H5N1 and H7N9, from birds to humans. The avian influenza A H5N1 virus has caused more than 500 human infections worldwide with nearly a 60% death rate since it was first reported in Hong Kong in 1997. The four outbreaks of the avian influenza A H7N9 in China from March 2013 to June 2016 have resulted in 580 human cases including 202 deaths with a death rate of nearly 35%. In this paper, we construct two avian influenza bird-to-human transmission models with different growth laws of the avian population, one with logistic growth and the other with Allee effect, and analyze their dynamical behavior. We obtain a threshold value for the prevalence of avian influenza and investigate the local or global asymptotical stability of each equilibrium of these systems by using linear analysis technique or combining Liapunov function method and LaSalle's invariance principle, respectively. Moreover, we give necessary and sufficient conditions for the occurrence of periodic solutions in the avian influenza system with Allee effect of the avian population. Numerical simulations are also presented to illustrate the theoretical results. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Migration of whooper swans and outbreaks of highly pathogenic avian influenza H5N1 virus in eastern Asia.

    Directory of Open Access Journals (Sweden)

    Scott H Newman

    Full Text Available Evaluating the potential involvement of wild avifauna in the emergence of highly pathogenic avian influenza H5N1 (hereafter H5N1 requires detailed analyses of temporal and spatial relationships between wild bird movements and disease emergence. The death of wild swans (Cygnus spp. has been the first indicator of the presence of H5N1 in various Asian and European countries; however their role in the geographic spread of the disease remains poorly understood. We marked 10 whooper swans (Cygnus cygnus with GPS transmitters in northeastern Mongolia during autumn 2006 and tracked their migratory movements in relation to H5N1 outbreaks. The prevalence of H5N1 outbreaks among poultry in eastern Asia during 2003-2007 peaked during winter, concurrent with whooper swan movements into regions of high poultry density. However outbreaks involving poultry were detected year round, indicating disease perpetuation independent of migratory waterbird presence. In contrast, H5N1 outbreaks involving whooper swans, as well as other migratory waterbirds that succumbed to the disease in eastern Asia, tended to occur during seasons (late spring and summer and in habitats (areas of natural vegetation where their potential for contact with poultry is very low to nonexistent. Given what is known about the susceptibility of swans to H5N1, and on the basis of the chronology and rates of whooper swan migration movements, we conclude that although there is broad spatial overlap between whooper swan distributions and H5N1 outbreak locations in eastern Asia, the likelihood of direct transmission between these groups is extremely low. Thus, our data support the hypothesis that swans are best viewed as sentinel species, and moreover, that in eastern Asia, it is most likely that their infections occurred through contact with asymptomatic migratory hosts (e.g., wild ducks at or near their breeding grounds.

  14. Migration of whooper swans and outbreaks of highly pathogenic avian influenza H5N1 virus in eastern Asia.

    Science.gov (United States)

    Newman, Scott H; Iverson, Samuel A; Takekawa, John Y; Gilbert, Martin; Prosser, Diann J; Batbayar, Nyambyar; Natsagdorj, Tseveenmyadag; Douglas, David C

    2009-05-28

    Evaluating the potential involvement of wild avifauna in the emergence of highly pathogenic avian influenza H5N1 (hereafter H5N1) requires detailed analyses of temporal and spatial relationships between wild bird movements and disease emergence. The death of wild swans (Cygnus spp.) has been the first indicator of the presence of H5N1 in various Asian and European countries; however their role in the geographic spread of the disease remains poorly understood. We marked 10 whooper swans (Cygnus cygnus) with GPS transmitters in northeastern Mongolia during autumn 2006 and tracked their migratory movements in relation to H5N1 outbreaks. The prevalence of H5N1 outbreaks among poultry in eastern Asia during 2003-2007 peaked during winter, concurrent with whooper swan movements into regions of high poultry density. However outbreaks involving poultry were detected year round, indicating disease perpetuation independent of migratory waterbird presence. In contrast, H5N1 outbreaks involving whooper swans, as well as other migratory waterbirds that succumbed to the disease in eastern Asia, tended to occur during seasons (late spring and summer) and in habitats (areas of natural vegetation) where their potential for contact with poultry is very low to nonexistent. Given what is known about the susceptibility of swans to H5N1, and on the basis of the chronology and rates of whooper swan migration movements, we conclude that although there is broad spatial overlap between whooper swan distributions and H5N1 outbreak locations in eastern Asia, the likelihood of direct transmission between these groups is extremely low. Thus, our data support the hypothesis that swans are best viewed as sentinel species, and moreover, that in eastern Asia, it is most likely that their infections occurred through contact with asymptomatic migratory hosts (e.g., wild ducks) at or near their breeding grounds.

  15. 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).

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

    Science.gov (United States)

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

    2011-09-28

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

  17. Protective immunity against influenza in pigs

    NARCIS (Netherlands)

    Heinen, Peter Paul

    2002-01-01

    Swine influenza is a highly contagious acute viral disease of the respiratory tract in pigs, which is prevalent world-wide. The disease causes considerable economic damage primarily due to reduced weight gain in finishing pigs and reduced reproductive performance of sows. In addition, influenza is a

  18. Societal and economic consequences of influenza.

    Science.gov (United States)

    Piedra, Pedro A

    2008-10-01

    High rates of vaccination coverage for preschool and school-aged children can reduce morbidity and mortality related to influenza outbreak. More focused and effective influenza prevention strategies are necessary to improve quality of life and to limit the burden of flu complications.

  19. Global spread and control of avian influenza

    Science.gov (United States)

    H5 and H7 high pathogenicity avian influenza (HPAI) viruses emerge from the mutation of H5 and H7 low pathogenicity avian influenza viruses (LPAI) after circulation in terrestrial poultry for a few weeks to years. There have been 42 distinct HPAI epizootics since 1959. The largest being the H5N1 A/G...

  20. Growth of high purity semiconductor epitaxial layers by liquid phase ...

    Indian Academy of Sciences (India)

    Unknown

    semiconductor materials in high purity form by liquid phase epitaxy (LPE) technique. Various possible sources of impurities in such ... reference to the growth of GaAs layers. The technique of growing very high purity layers ... the inner walls of the gas lines and (e) the containers for storing, handling and cleaning of the mate-.

  1. Travellers and influenza: risks and prevention.

    Science.gov (United States)

    Goeijenbier, M; van Genderen, P; Ward, B J; Wilder-Smith, A; Steffen, R; Osterhaus, A D M E

    2017-01-01

    Influenza viruses are among the major causes of serious human respiratory tract infection worldwide. In line with the high disease burden attributable to influenza, these viruses play an important, but often neglected, role in travel medicine. Guidelines and recommendations regarding prevention and management of influenza in travellers are scarce. Of special interest for travel medicine are risk populations and also circumstances that facilitate influenza virus transmission and spread, like travel by airplane or cruise ship and mass gatherings. We conducted a PUBMED/MEDLINE search for a combination of the MeSH terms Influenza virus, travel, mass gathering, large scale events and cruise ship. In addition we gathered guidelines and recommendations from selected countries and regarding influenza prevention and management in travellers. By reviewing these search results in the light of published knowledge in the fields of influenza prevention and management, we present best practice advice for the prevention and management of influenza in travel medicine. Seasonal influenza is among the most prevalent infectious diseases in travellers. Known host-associated risk factors include extremes of age and being immune-compromised, while the most relevant environmental factors are associated with holiday cruises and mass gatherings. Pre-travel advice should address influenza and its prevention for travellers, whenever appropriate on the basis of the epidemiological situation concerned. Preventative measures should be strongly recommended for travellers at high-risk for developing complications. In addition, seasonal influenza vaccination should be considered for any traveller wishing to reduce the risk of incapacitation, particularly cruise ship crew and passengers, as well as those participating in mass gatherings. Besides advice concerning preventive measures and vaccination, advice on the use of antivirals may be considered for some travellers. © International Society of

  2. Epidemiologic and Economic Analyses on Highly Pathogenic Avian Influenza H5N1 in Nigeria and Egypt

    NARCIS (Netherlands)

    Fasina, F.O.

    2015-01-01

    Influenza A viruses have caused several devastating outbreaks in poultry with some zoonotic infections and deaths in humans. To control the viruses and their continuous circulation in poultry population, an understanding of the epidemiology of the viruses is needed. An evaluation of the situation of

  3. Trade patterns facilitating highly pathogenic avian influenza virus dissemination in the free-grazing layer duck system in Vietnam.

    Science.gov (United States)

    Meyer, A; Dinh, T X; Han, T A; Do, D V; Nhu, T V; Pham, L T; Nguyen, T T T; Newman, S; Häsler, B; Pfeiffer, D U; Vergne, T

    2018-04-01

    Highly pathogenic avian influenza (HPAI) viruses continue to threaten smallholder poultry producers in several South-east Asian countries, including Vietnam. In particular, the free-grazing duck system has been repeatedly highlighted as a major risk factor for HPAI outbreaks. Free-grazing ducks, which scavenge on rice paddies after the harvest, account for a large proportion of the duck population in Vietnam and the wider South-east Asian region. However, the structure and dynamics of the free-grazing duck production from farm to consumption has not been described for Vietnam. In this study, we used a value chain approach to provide a complete picture of the actors involved in the production and marketing of free-grazing duck eggs and spent layer ducks, as well as to investigate the governance structure of this food system. Group interviews and key informant interviews were conducted in two provinces located in the Mekong River Delta (MRD) and the Red River Delta (RRD). The results presented here highlight similarities and differences in farming and trade practices between the two provinces. The trade of spent layer ducks involved large volumes of live ducks being sent to China and Cambodia for consumption, generating a substantial risk of transboundary spread of pathogens, including HPAI viruses. We describe the major role of "duck yards", which act as hubs in the northbound trade of spent layer ducks. These yards should be considered as essential links in the value chain of spent layer ducks when considering HPAI surveillance and control. The veterinary authorities are only marginally involved in the value chain activities, and their influence could be strengthened by increasing surveillance activities for instance in duck yards. Last, we discuss the dynamics of the duck value chain and further implications for future HPAI management policies. © 2017 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

  4. The effectiveness of preventative mass vaccination regimes against the incidence of highly pathogenic avian influenza on Java Island, Indonesia.

    Science.gov (United States)

    Bett, B; McLaws, M; Jost, C; Schoonman, L; Unger, F; Poole, J; Lapar, M L; Siregar, E S; Azhar, M; Hidayat, M M; Dunkle, S E; Mariner, J

    2015-04-01

    We conducted an operational research study involving backyard and semicommercial farms on Java Island, Indonesia, between April 2008 and September 2009 to evaluate the effectiveness of two preventive mass vaccination strategies against highly pathogenic avian influenza (HPAI). One regimen used Legok 2003 H5N1 vaccine, while the other used both Legok 2003 H5N1 and HB1 Newcastle disease (ND) vaccine. A total of 16 districts were involved in the study. The sample size was estimated using a formal power calculation technique that assumed a detectable effect of treatment as a 50% reduction in the baseline number of HPAI-compatible outbreaks. Within each district, candidate treatment blocks with village poultry populations ranging from 80 000 to 120 000 were created along subdistrict boundary lines. Subsequently, four of these blocks were randomly selected and assigned one treatment from a list that comprised control, vaccination against HPAI, vaccination against HPAI + ND. Four rounds of vaccination were administered at quarterly intervals beginning in July 2008. A vaccination campaign involved vaccinating 100 000 birds in a treatment block, followed by another 100 000 vaccinations 3 weeks later as a booster dose. Data on disease incidence and vaccination coverage were also collected at quarterly intervals using participatory epidemiological techniques. Compared with the unvaccinated (control) group, the incidence of HPAI-compatible events declined by 32% (P = 0.24) in the HPAI-vaccinated group and by 73% (P = 0.00) in the HPAI- and ND-vaccinated group. The effect of treatment did not vary with time or district. Similarly, an analysis of secondary data from the participatory disease and response (PDSR) database revealed that the incidence of HPAI declined by 12% in the HPAI-vaccinated group and by 24% in the HPAI + ND-vaccinated group. The results suggest that the HPAI + ND vaccination significantly reduced the incidence of HPAI-compatible events in mixed populations of

  5. The Perceived Value of Passive Animal Health Surveillance: The Case of Highly Pathogenic Avian Influenza in Vietnam.

    Science.gov (United States)

    Delabouglise, A; Antoine-Moussiaux, N; Phan, T D; Dao, D C; Nguyen, T T; Truong, B D; Nguyen, X N T; Vu, T D; Nguyen, K V; Le, H T; Salem, G; Peyre, M

    2016-03-01

    Economic evaluations are critical for the assessment of the efficiency and sustainability of animal health surveillance systems and the improvement of their efficiency. Methods identifying and quantifying costs and benefits incurred by public and private actors of passive surveillance systems (i.e. actors of veterinary authorities and private actors who may report clinical signs) are needed. This study presents the evaluation of perceived costs and benefits of highly pathogenic avian influenza (HPAI) passive surveillance in Vietnam. Surveys based on participatory epidemiology methods were conducted in three provinces in Vietnam to collect data on costs and benefits resulting from the reporting of HPAI suspicions to veterinary authorities. A quantitative tool based on stated preference methods and participatory techniques was developed and applied to assess the non-monetary costs and benefits. The study showed that poultry farmers are facing several options regarding the management of HPAI suspicions, besides reporting the following: treatment, sale or destruction of animals. The option of reporting was associated with uncertain outcome and transaction costs. Besides, actors anticipated the release of health information to cause a drop of markets prices. This cost was relevant at all levels, including farmers, veterinary authorities and private actors of the upstream sector (feed, chicks and medicine supply). One benefit associated with passive surveillance was the intervention of public services to clean farms and the environment to limit the disease spread. Private actors of the poultry sector valued information on HPAI suspicions (perceived as a non-monetary benefit) which was mainly obtained from other private actors and media. © 2015 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

  6. Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1 in Viet Nam.

    Directory of Open Access Journals (Sweden)

    Sumeet Saksena

    Full Text Available Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID, the 'convergence model' was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model's predictability. Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk. These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs.

  7. Persistence of highly pathogenic avian influenza H5N1 virus defined by agro-ecological niche

    Science.gov (United States)

    Hogerwerf, Lenny; Wallace, Rob G.; Ottaviani, Daniela; Slingenbergh, Jan; Prosser, Diann; Bergmann, Luc; Gilbert, Marius

    2010-01-01

    The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with different agro-ecological conditions, and no study has investigated the impact of such conditions on HPAI H5N1 epidemiology at the global scale. This study explores the patterns of HPAI H5N1 persistence worldwide, and for China, Indonesia, and India includes individual provinces that have reported HPAI H5N1 presence during the 2004–2008 period. Multivariate analysis of a set of 14 agricultural, environmental, climatic, and socio-economic factors demonstrates in quantitative terms that a combination of six variables discriminates the areas with human cases and persistence: agricultural population density, duck density, duck by chicken density, chicken density, the product of agricultural population density and chicken output/input ratio, and purchasing power per capita. The analysis identifies five agro-ecological clusters, or niches, representing varying degrees of disease persistence. The agro-ecological distances of all study areas to the medoid of the niche with the greatest number of human cases are used to map HPAI H5N1 risk globally. The results indicate that few countries remain where HPAI H5N1 would likely persist should it be introduced.

  8. Pathogenesis of highly pathogenic avian influenza A virus (H7N1) infection in chickens inoculated with three different doses.

    Science.gov (United States)

    Chaves, Aida J; Busquets, Nuria; Campos, Naiana; Ramis, Antonio; Dolz, Roser; Rivas, Raquel; Valle, Rosa; Abad, F Xavier; Darji, Ayub; Majo, Natalia

    2011-04-01

    To study the pathogenesis of a H7N1 highly pathogenic avian influenza virus strain, specific pathogen free chickens were inoculated with decreasing concentrations of virus: 10(5.5) median embryo lethal dose (ELD(50)) (G1), 10(3.5) ELD(50) (G2) and 10(1.5) ELD(50) (G3). Disease progression was monitored over a period of 16 days and sequential necropsies and tissue samples were collected for histological and immunohistochemical examination. Viral RNA loads were also quantified in different tissues, blood, oropharyngeal swabs, and cloacal swabs using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Clinical signs of depression, apathy, listlessness, huddling and ruffled feathers were recorded in G1 and a few G2 birds, whilst neurological signs were only observed in chickens inoculated with the highest dose. Gross lesions of haemorrhages were observed in the unfeathered skin of the comb and legs, and skeletal muscle, lung, pancreas and kidneys of birds inoculated with 10(5.5) ELD(50) and 10(3.5) ELD(50) doses. Microscopic lesions and viral antigen were demonstrated in cells of the nasal cavity, lung, heart, skeletal muscle, brain, spinal cord, gastrointestinal tract, pancreas, liver, bone marrow, thymus, bursa of Fabricius, spleen, kidney, adrenal gland and skin. Viral RNA was detected by RT-qPCR in kidney, lung, intestine, and brain samples of G1 and G2 birds. However, in birds infected with the lowest dose, viral RNA was detected only in brain and lung samples in low amounts at 5 and 7 days post infection. Interestingly, viral shedding was observed in oropharyngeal and cloacal swabs with proportionate decrease with the inoculation dose. We conclude that although an adequate infectious dose is critical in reproducing the clinical infection, chickens exposed to lower doses can be infected and shed virus representing a risk for the dissemination of the viral agent.

  9. Characteristics and management of patients with influenza in a German hospital during the 2014/2015 influenza season.

    Science.gov (United States)

    Hagel, Stefan; Ludewig, Katrin; Moeser, Anne; Baier, Michael; Löffler, Bettina; Schleenvoigt, Benjamin; Forstner, Christina; Pletz, Mathias W

    2016-10-01

    The objective of this study was to review the management of patients with influenza during the influenza season 2014/2015 (n = 197). Our study revealed a high rate of healthcare-associated influenza infection (35.5 %) and a correlation between the total number of patients with HA influenza and the number of nurses on sick leave. The results of the study underline the importance of strict hygiene management. Furthermore, widespread influenza vaccination for both high-risk patients and health care workers is recommended.

  10. Determination of preventive behaviors for pandemic influenza A/H1N1 based on protection motivation theory among female high school students in Isfahan, Iran

    OpenAIRE

    Sharifirad, Gholamreza; Yarmohammadi, Parastoo; Sharifabad, Mohammad Ali Morowati; Rahaei, Zohreh

    2014-01-01

    Introduction: Influenza A/H1N1 pandemic has recently threatened the health of world's population more than ever. Non-pharmaceutical measures are important to prevent the spread of influenza A/H1N1 and to prevent a pandemic. Effective influenza pandemic management requires understanding of the factors influencing preventive behavioral. This study reports on predictors of students’ preventive behaviors for pandemic influenza A/H1N1 using variables based on the protection motivation theory (PMT)...

  11. Immunization of rabbits with synthetic peptides derived from a highly conserved β-sheet epitope region underneath the receptor binding site of influenza A virus

    Directory of Open Access Journals (Sweden)

    Ideno S

    2013-11-01

    Full Text Available Shoji Ideno,1,3 Kaoru Sakai,1 Mikihiro Yunoki,2–4 Ritsuko Kubota-Koketsu,3,5 Yuji Inoue,3 Shota Nakamura,6 Teruo Yasunaga,6 Yoshinobu Okuno,5 Kazuyoshi Ikuta3 1Infectious Pathogen Research Section, Central Research Laboratory, Research and Development Division, Japan Blood Products Organization, Kobe, Japan; 2Research and Development Promotion Section, Research and Development Division, Japan Blood Products Organization, Tokyo, Japan; 3Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; 4Department of Veterinary Microbiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan; 5Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan; 6Department of Genome Informatics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan Background: There is increasing concern about the speed with which health care providers can administer prophylaxis and treatment in an influenza pandemic. Generally, it takes several months to manufacture an influenza vaccine by propagation of the virus in chicken eggs or cultured cells. Newer, faster protocols for the production of vaccines that induce broad-spectrum immunity are therefore highly desirable. We previously developed human monoclonal antibody B-1 that shows broadly neutralizing activity against influenza A virus H3N2. B-1 recognizes an epitope region that includes an antiparallel β-sheet structure underneath the receptor binding site of influenza hemagglutinin (HA. In this study, the efficacy of a synthetic peptide vaccine derived from this epitope region against influenza A was evaluated. Materials and methods: Two peptides were synthesized, the upper and lower peptides. These peptides comprise amino acid residues 167–187 and 225–241, respectively, of the B-1 epitope region of HA, which is involved in

  12. Experimental challenge and pathology of highly pathogenic avian influenza virus H5N1 in dunlin (Calidris alpina), an intercontinental migrant shorebird species.

    Science.gov (United States)

    Hall, Jeffrey S; Franson, J Christian; Gill, Robert E; Meteyer, Carol U; TeSlaa, Joshua L; Nashold, Sean; Dusek, Robert J; Ip, Hon S

    2011-09-01

    Shorebirds (Charadriiformes) are considered one of the primary reservoirs of avian influenza. Because these species are highly migratory, there is concern that infected shorebirds may be a mechanism by which highly pathogenic avian influenza virus (HPAIV) H5N1 could be introduced into North America from Asia. Large numbers of dunlin (Calidris alpina) migrate from wintering areas in central and eastern Asia, where HPAIV H5N1 is endemic, across the Bering Sea to breeding areas in Alaska. Low pathogenic avian influenza virus has been previously detected in dunlin, and thus, dunlin represent a potential risk to transport HPAIV to North America. To date no experimental challenge studies have been performed in shorebirds. Wild dunlin were inoculated intranasally and intrachoanally various doses of HPAIV H5N1. The birds were monitored daily for virus excretion, disease signs, morbidity, and mortality. The infectious dose of HPAIV H5N1 in dunlin was determined to be 10(1.7) EID(50)/100 μl and that the lethal dose was 10(1.83) EID(50)/100 μl. Clinical signs were consistent with neurotropic disease, and histochemical analyses revealed that infection was systemic with viral antigen and RNA most consistently found in brain tissues. Infected birds excreted relatively large amounts of virus orally (10(4) EID(50)) and smaller amounts cloacally. Dunlin are highly susceptible to infection with HPAIV H5N1. They become infected after exposure to relatively small doses of the virus and if they become infected, they are most likely to suffer mortality within 3-5 days. These results have important implications regarding the risks of transport and transmission of HPAIV H5N1 to North America by this species and raises questions for further investigation. Published 2011. This article is a US Government work and is in the public domain in the USA.

  13. Crack growth by micropore coalescence at high temperatures

    International Nuclear Information System (INIS)

    Beere, W.

    1981-01-01

    At high temperatures in the creep regime the stress distribution around a crack is different from the low temperature elastically generated distribution. The stress distribution ahead of the crack is calculated for a crack preceded by an array of growing cavities. The cavities maintain a displacement wedge ahead of the crack. When the displacement wedge is less than one-tenth the crack length the driving force for crack growth is similar to an all elastically loaded crack. When the deforming wedge exceeds the crack length the net section stress controls crack growth. An expression is derived for a crack growing by the growth and coalescence of cavities situated in the crack plane. It is predicted that at high temperatures above a critical stress intensity, the crack propagates in a brittle fashion. (author)

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

    OpenAIRE

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

    2009-01-01

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

  15. Poultry movement networks in Cambodia: implications for surveillance and control of highly pathogenic avian influenza (HPAI/H5N1).

    Science.gov (United States)

    Van Kerkhove, Maria D; Vong, Sirenda; Guitian, Javier; Holl, Davun; Mangtani, Punam; San, Sorn; Ghani, Azra C

    2009-10-23

    Movement of poultry through markets is potentially important in the circulation and spread of highly pathogenic avian influenza. However little is understood about poultry market chains in Cambodia. We conducted a cross-sectional survey of 715 rural villagers, 123 rural, peri-urban and urban market sellers and 139 middlemen from six provinces and Phnom Penh, to evaluate live poultry movement and trading practices. Direct trade links with Thailand and Vietnam were identified via middlemen and market sellers. Most poultry movement occurs via middlemen into Phnom Penh making live bird wet markets in Phnom Penh a potential hub for the spread of H5N1 and ideal for surveillance and control.

  16. Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005.

    Science.gov (United States)

    Adlhoch, C; Gossner, C; Koch, G; Brown, I; Bouwstra, R; Verdonck, F; Penttinen, P; Harder, T

    2014-12-18

    Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.

  17. Study on Efficacy of Gamma Radiation on the Inactivation of Highly Pathogenic Avian Influenza Virus H5N1 (Thai isolate) in Chicken Meat and Chicken Feces

    International Nuclear Information System (INIS)

    Pinyochon, Wasana; Piadang, Nattayana; Mulika, Ladda; Parchariyanon, Sujira; Vitittheeranon, Arag; Damrongwatapokin, Sudarat

    2006-09-01

    A study on the efficacy of gamma radiation on the inactivation of a highly pathogenic avian influenza virus H5N1 subtype, Thai isolate was carried out. The virus was in the form frozen infected allantoic fluid frozen chicken meat and frozen chicken feces. The result indicated that 9 kilo grey of gamma radiation could completely inactivated 106.0 EID50/ml of AIV infected allantoic fluid and 22 kiel grey and 15 kilo grey of gamma radiation completely inactivate 106.0 EID50/10/ grams of chicken meat and 106.0 EID50/5 grams of chicken feces respectively.

  18. Influenza vaccine strategies for solid organ transplant recipients.

    Science.gov (United States)

    Hirzel, Cédric; Kumar, Deepali

    2018-05-15

    The aim of this study was to highlight recent evidence on important aspects of influenza vaccination in solid organ transplant recipients. Influenza vaccine is the most evaluated vaccine in transplant recipients. The immunogenicity of the vaccine is suboptimal after transplantation. Newer formulations such as inactivated unadjuvanted high-dose influenza vaccine and the administration of a booster dose within the same season have shown to increase response rates. Intradermal vaccination and adjuvanted vaccines did not show clear benefit over standard influenza vaccines. Recent studies in transplant recipients do not suggest a higher risk for allograft rejection, neither after vaccination with a standard influenza vaccine nor after the administration of nonstandard formulation (high-dose, adjuvanted vaccines), routes (intradermally) or a booster dose. Nevertheless, influenza vaccine coverage in transplant recipients is still unsatisfactory low, potentially due to misinterpretation of risks and benefits. Annual influenza vaccination is well tolerated and is an important part of long-term care of solid organ transplant recipients.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Growth and high pressure studies of zirconium sulphoselenide ...

    Indian Academy of Sciences (India)

    Growth and high pressure studies of zirconium sulphoselenide single ... tance was monitored in a Bridgman opposed anvil set-up up to 8 GPa pressure to identify .... The optical band gaps of the as-grown crystals were obtained by optical ab-.

  1. State investments in high-technology job growth.

    Science.gov (United States)

    Leicht, Kevin T; Jenkins, J Craig

    2017-07-01

    Since the early 1970's state and local governments have launched an array of economic development programs designed to promote high-technology development. The question our analysis addresses is whether these programs promote long-term high-technology employment growth net of state location and agglomeration advantages. Proponents talk about an infrastructure strategy that promotes investment in public research and specialized infrastructure to attract and grow new high technology industries in specific locations, and a more decentralized entrepreneurial strategy that reinforces local agglomeration capacities by investing in new enterprises and products, promoting the development of local networks and partnerships. Our results support the entrepreneurial strategy, suggesting that state governments can accelerate high technology development by adopting market-supportive programs that complement private sector initiatives. In addition to positive direct benefits of technology deployment/transfer programs and SBIR programs, entrepreneurial programs affect change in high-technology employment in concert with existing locational and agglomeration advantages. Rural (i.e. low population density) states tend to benefit by technology development programs. Infrastructure strategy programs also facilitate high technology job growth in places where local advantages already exist. Our results suggest that critics of industrial policy are correct that high technology growth is organic and endogenous, yet state governments are able to "pick winners and losers" in ways that grow their local economy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Role of domestic ducks in the emergence of a new genotype of highly pathogenic H5N1 avian influenza A viruses in Bangladesh.

    Science.gov (United States)

    Barman, Subrata; Marinova-Petkova, Atanaska; Hasan, M Kamrul; Akhtar, Sharmin; El-Shesheny, Rabeh; Turner, Jasmine Cm; Franks, John; Walker, David; Seiler, Jon; Friedman, Kimberly; Kercher, Lisa; Jeevan, Trushar; Darnell, Daniel; Kayali, Ghazi; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G; Feeroz, Mohammed M

    2017-08-09

    Highly pathogenic avian influenza H5N1 viruses were first isolated in Bangladesh in February 2007. Subsequently, clades 2.2.2, 2.3.4.2 and 2.3.2.1a were identified in Bangladesh, and our previous surveillance data revealed that by the end of 2014, the circulating viruses exclusively comprised clade 2.3.2.1a. We recently determined the status of circulating avian influenza viruses in Bangladesh by conducting surveillance of live poultry markets and waterfowl in wetland areas from February 2015 through February 2016. Until April 2015, clade 2.3.2.1a persisted without any change in genotype. However, in June 2015, we identified a new genotype of H5N1 viruses, clade 2.3.2.1a, which quickly became predominant. These newly emerged H5N1 viruses contained the hemagglutinin, neuraminidase and matrix genes of circulating 2.3.2.1a Bangladeshi H5N1 viruses and five other genes of low pathogenic Eurasian-lineage avian influenza A viruses. Some of these internal genes were closely related to those of low pathogenic viruses isolated from ducks in free-range farms and wild birds in a wetland region of northeastern Bangladesh, where commercially raised domestic ducks have frequent contact with migratory birds. These findings indicate that migratory birds of the Central Asian flyway and domestic ducks in the free-range farms in Tanguar haor-like wetlands played an important role in the emergence of this novel genotype of highly pathogenic H5N1 viruses.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice.

    Science.gov (United States)

    Chandler, Joshua D; Hu, Xin; Ko, Eun-Ju; Park, Soojin; Lee, Young-Tae; Orr, Michael; Fernandes, Jolyn; Uppal, Karan; Kang, Sang-Moo; Jones, Dean P; Go, Young-Mi

    2016-11-01

    Influenza is a significant health concern worldwide. Viral infection induces local and systemic activation of the immune system causing attendant changes in metabolism. High-resolution metabolomics (HRM) uses advanced mass spectrometry and computational methods to measure thousands of metabolites inclusive of most metabolic pathways. We used HRM to identify metabolic pathways and clusters of association related to inflammatory cytokines in lungs of mice with H1N1 influenza virus infection. Infected mice showed progressive weight loss, decreased lung function, and severe lung inflammation with elevated cytokines [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ] and increased oxidative stress via cysteine oxidation. HRM showed prominent effects of influenza virus infection on tryptophan and other amino acids, and widespread effects on pathways including purines, pyrimidines, fatty acids, and glycerophospholipids. A metabolome-wide association study (MWAS) of the aforementioned inflammatory cytokines was used to determine the relationship of metabolic responses to inflammation during infection. This cytokine-MWAS (cMWAS) showed that metabolic associations consisted of distinct and shared clusters of 396 metabolites highly correlated with inflammatory cytokines. Strong negative associations of selected glycosphingolipid, linoleate, and tryptophan metabolites with IFN-γ contrasted strong positive associations of glycosphingolipid and bile acid metabolites with IL-1β, TNF-α, and IL-10. Anti-inflammatory cytokine IL-10 had strong positive associations with vitamin D, purine, and vitamin E metabolism. The detailed metabolic interactions with cytokines indicate that targeted metabolic interventions may be useful during life-threatening crises related to severe acute infection and inflammation. Copyright © 2016 the American Physiological Society.

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

    Directory of Open Access Journals (Sweden)

    Maria D Van Kerkhove

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

  6. 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

  7. Spatial distribution and risk factors of highly pathogenic avian influenza (HPAI) H5N1 in China

    Science.gov (United States)

    Martin, Vincent; Pfeiffer, Dirk U.; Zhou, Xiaoyan; Xiao, Xiangming; Prosser, Diann J.; Guo, Fusheng; Gilbert, Marius

    2011-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 was first encountered in 1996 in Guangdong province (China) and started spreading throughout Asia and the western Palearctic in 2004–2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV) H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript) were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT) with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967). The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds) and found that provinces with either outbreaks or HPAIV H5N1 surveillance

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

    Directory of Open Access Journals (Sweden)

    Ibrahim Thabet Hagag

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

  9. Spatial distribution and risk factors of highly pathogenic avian influenza (HPAI H5N1 in China.

    Directory of Open Access Journals (Sweden)

    Vincent Martin

    2011-03-01

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 was first encountered in 1996 in Guangdong province (China and started spreading throughout Asia and the western Palearctic in 2004-2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967. The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds and found that provinces with either outbreaks or HPAIV H5N1

  10. [An overview on swine influenza viruses].

    Science.gov (United States)

    Yang, Shuai; Zhu, Wen-Fei; Shu, Yue-Long

    2013-05-01

    Swine influenza viruses (SIVs) are respiratory pathogens of pigs. They cause both economic bur den in livestock-dependent industries and serious global public health concerns in humans. Because of their dual susceptibility to human and avian influenza viruses, pigs are recognized as intermediate hosts for genetic reassortment and interspecies transmission. Subtypes H1N1, H1N2, and H3N2 circulate in swine populations around the world, with varied origin and genetic characteristics among different continents and regions. In this review, the role of pigs in evolution of influenza A viruses, the genetic evolution of SIVs and interspecies transmission of SIVs are described. Considering the possibility that pigs might produce novel influenza viruses causing more outbreaks and pandemics, routine epidemiological surveillance of influenza viruses in pig populations is highly recommended.

  11. Concepts and applications for influenza antigenic cartography

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. A robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. However, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incompleteness, high noises, and low reactors. To overcome these challenges, we developed a computational method, temporal Matrix Completion-Multidimensional Scaling (MC-MDS), by adapting the low rank MC concept from the movie recommendation system in Netflix and the MDS method from geographic cartography construction. The application on H3N2 and 2009 pandemic H1N1 influenza A viruses demonstrates that temporal MC-MDS is effective and efficient in constructing influenza antigenic cartography. The web sever is available at http://sysbio.cvm.msstate.edu/AntigenMap. PMID:21761589

  12. High-tech Entrepreneurship and Growth: Myths and Facts

    DEFF Research Database (Denmark)

    Neergaard, Helle; Madsen, Henning; Ulhøi, John Parm

    2004-01-01

    Economic growth depends on the presence of an innovative and dynamic business sector, including the business players' ability to discover and exploit new business opportunities. Consequently, entrepreneurship has received increased attention within industrial policy. Entrepreneurs and their motives...... are, however, just as diverse as the rest of the population, thus making it impossible to apply a 'one-size-fits-all' principle when promoting entrepreneurship. This paper deals with a special kind of entrepreneurs - the high-tech entrepreneurs - in order to puncture the myths concerning their growth...

  13. High power blue LED development using different growth modes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong S.; Florescu, Doru I.; Ramer, Jeff C.; Merai, Vinod; Parekh, Aniruddh; Begarney, Michael J.; Armour, Eric A. [Veeco TurboDisc Operations, 394 Elizabeth Avenue, Somerset, NJ 08873 (United States); Lu Dong [Veeco TurboDisc Operations, 394 Elizabeth Avenue, Somerset, NJ 08873 (United States); School of Engineering, Rutgers University, Piscataway, NJ 08854 (United States)

    2004-09-01

    Blue high brightness light emitting diodes (HB-LEDs) have been developed using different growth modes in the active layers. Piezoelectric field engineering improves the optical output power in multiple quantum well (MQW) LEDs by inserting an optimized transitional superlattice (TSL) before the active MQW layers. Within single quantum well (SQW) LEDs, quasi-Quantum Dot (QD) growth for Indium localization has been realized. The SQW LED output power exceeds the strain engineered MQW LEDs. The experimental data indicates that Indium localization enhances overall quantum efficiency and results in increased output power for HB-LEDs. (copyright 2004 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  14. A low pathogenic H5N2 influenza virus isolated in Taiwan acquired high pathogenicity by consecutive passages in chickens.

    OpenAIRE

    Soda, Kosuke; Cheng, Ming-Chu; Yoshida, Hiromi; Endo, Mayumi; Lee, Shu-Hwae; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Wang, Ching-Ho; Kida, Hiroshi

    2011-01-01

    H5N2 viruses were isolated from cloacal swab samples of apparently healthy chickens in Taiwan in 2003 and 2008 during surveillance of avian influenza. Each of the viruses was eradicated by stamping out. The official diagnosis report indicated that the Intravenous Pathogenicity Indexes (IVPIs) of the isolates were 0.00 and 0.89, respectively, indicating that these were low pathogenic strains, although the hemagglutinin of the strain isolated in 2008 (Taiwan08) had multibasic amino acid residue...

  15. Effective influenza vaccines for children

    Science.gov (United States)

    Banzhoff, Angelika; Stoddard, Jeffrey J.

    2012-01-01

    Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59®, an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence.   Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad®, a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population. PMID:22327501

  16. Using high-throughput sequencing to leverage surveillance of genetic diversity and oseltamivir resistance: a pilot study during the 2009 influenza A(H1N1 pandemic.

    Directory of Open Access Journals (Sweden)

    Juan Téllez-Sosa

    Full Text Available BACKGROUND: Influenza viruses display a high mutation rate and complex evolutionary patterns. Next-generation sequencing (NGS has been widely used for qualitative and semi-quantitative assessment of genetic diversity in complex biological samples. The "deep sequencing" approach, enabled by the enormous throughput of current NGS platforms, allows the identification of rare genetic viral variants in targeted genetic regions, but is usually limited to a small number of samples. METHODOLOGY AND PRINCIPAL FINDINGS: We designed a proof-of-principle study to test whether redistributing sequencing throughput from a high depth-small sample number towards a low depth-large sample number approach is feasible and contributes to influenza epidemiological surveillance. Using 454-Roche sequencing, we sequenced at a rather low depth, a 307 bp amplicon of the neuraminidase gene of the Influenza A(H1N1 pandemic (A(H1N1pdm virus from cDNA amplicons pooled in 48 barcoded libraries obtained from nasal swab samples of infected patients (n  =  299 taken from May to November, 2009 pandemic period in Mexico. This approach revealed that during the transition from the first (May-July to second wave (September-November of the pandemic, the initial genetic variants were replaced by the N248D mutation in the NA gene, and enabled the establishment of temporal and geographic associations with genetic diversity and the identification of mutations associated with oseltamivir resistance. CONCLUSIONS: NGS sequencing of a short amplicon from the NA gene at low sequencing depth allowed genetic screening of a large number of samples, providing insights to viral genetic diversity dynamics and the identification of genetic variants associated with oseltamivir resistance. Further research is needed to explain the observed replacement of the genetic variants seen during the second wave. As sequencing throughput rises and library multiplexing and automation improves, we foresee that

  17. Spatial modeling of wild bird risk factors to investigate highly pathogenic A(H5N1) avian influenza virus transmission

    Science.gov (United States)

    Prosser, Diann J.; Hungerford, Laura L.; Erwin, R. Michael; Ottinger, Mary Ann; Takekawa, John Y.; Newman, Scott H.; Xiao, Xianming; Ellis, Erie C.

    2016-01-01

    One of the longest-persisting avian influenza viruses in history, highly pathogenic avian influenza virus (HPAIV) A(H5N1), continues to evolve after 18 years, advancing the threat of a global pandemic. Wild waterfowl (family Anatidae), are reported as secondary transmitters of HPAIV, and primary reservoirs for low-pathogenic avian influenza viruses, yet spatial inputs for disease risk modeling for this group have been lacking. Using GIS and Monte Carlo simulations, we developed geospatial indices of waterfowl abundance at 1 and 30 km resolutions and for the breeding and wintering seasons for China, the epicenter of H5N1. Two spatial layers were developed: cumulative waterfowl abundance (WAB), a measure of predicted abundance across species, and cumulative abundance weighted by H5N1 prevalence (WPR), whereby abundance for each species was adjusted based on prevalence values then totaled across species. Spatial patterns of the model output differed between seasons, with higher WAB and WPR in the northern and western regions of China for the breeding season and in the southeast for the wintering season. Uncertainty measures indicated highest error in southeastern China for both WAB and WPR. We also explored the effect of resampling waterfowl layers from 1 km to 30 km resolution for multi-scale risk modeling. Results indicated low average difference (less than 0.16 and 0.01 standard deviations for WAB and WPR, respectively), with greatest differences in the north for the breeding season and southeast for the wintering season. This work provides the first geospatial models of waterfowl abundance available for China. The indices provide important inputs for modeling disease transmission risk at the interface of poultry and wild birds. These models are easily adaptable, have broad utility to both disease and conservation needs, and will be available to the scientific community for advanced modeling applications.

  18. Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa.

    Science.gov (United States)

    Strayer, David R; Carter, William A; Stouch, Bruce C; Stittelaar, Koert J; Thoolen, Robert J M M; Osterhaus, Albert D M E; Mitchell, William M

    2014-10-01

    Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. Copyright © 2014. Published by Elsevier B.V.

  19. High Level Antibody Response to Pandemic Influenza H1N1/09 Virus Is Associated With Interferon-Induced Transmembrane Protein-3 rs12252-CC in Young Adults

    Directory of Open Access Journals (Sweden)

    Ling Qin

    2018-05-01

    Full Text Available Background: The C allele of the interferon-induced transmembrane protein-3 (IFITM3 SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%, severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections.Cohort and Method: A total 99 young healthy volunteers (18–20 years were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2, A/California/7/2009 (pdm09H1N1 and B/Jeep/3073/2013-like virus (Flu-B]. Plasma and gDNA was isolated from each volunteer before, and 14, 28, 180, 360, and 540 days after vaccination. Additionally, 68 elderlies (>65 years were also recruited as a control group to compare the levels of antibodies at baseline between the young adults and the elderly. For each sample IFITM3 rs12252 genotype was determined and antibody levels in response to pdmH1N1, H3N2 and Influenza B infection were measured for each time point.Results: We found a significantly higher level of pre-existing antibodies to pandemic influenza H1N1/09 virus (pdm09H1N1 but not to H3N2 or FluB in CC donors in comparison with CT/TT donors prior to vaccination. No impact of IFITM3 genotype in boosting influenza specific antibodies in young adults within 1 year after receiving seasonal influenza vaccination was observed. In addition, there was no difference in pdm09H1N1 specific antibody levels observed in the elderly cohort between volunteers carrying different IFITM3 genotypes. Higher levels of antibodies to pdmH1N1 were observed in elderly CC carriers when compared to the young CC carriers, but this trend was not replicated in TT carriers.Conclusion:IFITM3-rs12252 CC carriers exhibit a high level of pre-existing immunity to pdm09H1N1 compared to TT carriers in the

  20. Characterisation of a highly pathogenic H5N1 clade 2.3.2 influenza virus isolated from swans in Shanghai, China.

    Science.gov (United States)

    Zhao, Guo; Zhong, Lei; Lu, Xinlun; Hu, Jiao; Gu, Xiaobing; Kai, Yan; Song, Qingqing; Sun, Qing; Liu, Jinbao; Peng, Daxin; Wang, Xiaoquan; Liu, Xiaowen; Liu, Xiufan

    2012-02-01

    In spring 2009, one strain of H5N1 clade 2.3.2 virus was isolated from wild swans in Shanghai, indicating the importance of the wild swan in the ecology of this highly pathogenic avian influenza virus (HPAIV) in Eastern China. Pathogenicity experiments conducted in this study indicated that the virus was highly pathogenic for chickens but lowly pathogenic for mammalian hosts, as evidenced by reduced infection of mice. The analysis of complete genome sequences and genetic evolution showed that A/Swan/Shanghai/10/09 (SW/SH/09) may be derived from the strain A/silky chicken/Shantou/475/2004 (CK/ST/04), which is homologous to the influenza viruses isolated from chicken, duck, pika, little egret, swan, mandarin duck and bar-headed goose in China Hunan, China Qinghai, Mongolia, Russia, Japan, Korea, Laos and Hong Kong during 2007-2011, indicating that the virus has retro-infected diverse wild birds from chicken, and significant spread of the virus is still ongoing through overlapping migratory flyways. On the basis of the molecular analysis, we also found that there was a deletion of the glycosylation site (NSS) in amino acid 156 of the hemagglutinin (HA) protein when compared with that of the other Clade 2.3.2 viruses isolated between 2007 and 2011. More importantly, the sequence analysis of SW/SH/09 virus displayed the drug-resistant mutations on the matrix protein (M2) and neuraminidase (NA) genes.

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

    Directory of Open Access Journals (Sweden)

    Bertran Kateri

    2011-02-01

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

  2. 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.

  3. Avian Influenza (Bird Flu)

    Science.gov (United States)

    ... type="submit" value="Submit" /> Archived Flu Emails Influenza Types Seasonal Avian Swine Variant Pandemic Other Information on Avian Influenza Language: English (US) Español Recommend on Facebook Tweet ...

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Charles Nfon

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

  6. Characterisation and Identification of Avian Influenza Virus (AI

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2008-06-01

    Full Text Available Avian Influenza is caused by Influenza A virus which is a member of Orthomyxoviridae family. Influenza A virus is enveloped single stranded RNA with eight-segmented, negative polarity and filament or oval form, 50 – 120 by 200 – 300 nm diameters. Influenza A viruses have been found to infect birds, human, pig, horse and sometimes in the other mammalian such as seal and whale. The viruses are divided into different subtypes based on the antigenic protein which covers the virus surface i.e. Haemaglutinin (HA and Neuraminidase (NA. In addition, the nomenclature of subtype virus is based on HA and NA i.e HxNx, for example H5N1, H9N2 and the others. According to pathogenic, it could be divided into two distinct groups, they are Highly Pathogenic Avian Influenza (HPAI and Low Pathogenic Avian Influenza (LPAI. The Avian Influenza viruses have been continuously occurred and spread out in some continents such us America, Europe, Africa and Asian countries. The outbreak of Avian Influenza caused high mortality on birds and it has been reported that in human case Avian Influenza subtype H5N1 virus has caused several deaths. To anticipate this condition, an effort to prevent the transmission of Avian Influenza is needed. These strategic attempts include biosecurity, depopulation, vaccination, control of virus movement, monitoring and evaluation. Laboratory diagnostic plays an important role for successful prevention, control and eradication programs of Avian Influenza. Recently, there are two diagnostic methods for Avian Influenza. They are conventional (virological diagnosis and molecular methods. The conventional method is usually used for initial diagnostic of Avian Influenza. The conventional method takes more time and more costly, whereas the molecular method is more effective than conventional method. Based on the available diagnostic technique, basically diagnostic of Avian Influenza is done by serology test, isolation and identification as well

  7. Catalan family companies with high growth during the crisis period

    Directory of Open Access Journals (Sweden)

    Nuria Arimany-Serrat

    2016-11-01

    Full Text Available Purpose: This study aims to analyze the financial and economic health of the Catalan family companies with high growth during the crisis period (2008-2013, as an engine of job creation and economic development of the territory, identifying the economic and financial characteristics. Design/methodology/approach: The data used comes from the financial statements of the high growth Catalan companies during the crisis period of 2008-2013, in particular it collects a sample of the 140 high growth Catalan companies where a 70% of them are family businesses, there is a financial and economic analysis using descriptive statistics of these family businesses with a regression model to achieve results and conclusions. Findings: During the 2008-2013 crisis, Catalan family companies with high growth that are mostly small businesses have a good economic and financial health, with moderate innovation and a great potential for survival. Research limitations/implications: It would be convenient to make the same study in similar territories where most of the companies are family businesses, in order to compare the financial and economic analysis, valuing the impact of these companies in the business. Practical implications: It allows valuing the projection of these kinds of family companies, mostly in Catalonia, in a financial and economic level, identifying if they have a proper financial strategy. Social implications: The results show that these companies have great financial and economic health and have a better response during a crisis period. Originality / value: The study shows that family businesses have moderate indebtedness and acceptable rendibility in the crisis period, although, since they are small businesses the lack of innovation and patents can lead to future problems.

  8. Development of an influenza virus vaccine using the baculovirus-insect cell expression system : implications for pandemic preparedness

    NARCIS (Netherlands)

    Cox, M.M.J.

    2009-01-01

    Key word

    Influenza, rHA, vaccine, baculovirus, insect cells, production, pandemic preparedness

    Influenza (or flu) is a highly contagious, acute viral respiratory disease that occurs seasonally in most parts of the world and is caused by influenza viruses. Influenza

  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. Value innovation: the strategic logic of high growth.

    Science.gov (United States)

    Kim, W C; Mauborgne, R

    1997-01-01

    Why are some companies able to sustain high growth in revenues and profits--and others are not? To answer that question, the authors, both of INSEAD, spent five years studying more than 30 companies around the world. They found that the difference between the high-growth companies and their less successful competitors was in each group's assumptions about strategy. Managers of the less successful companies followed conventional strategic logic. Managers of the high-growth companies followed what the authors call the logic of value innovation. Conventional strategic logic and value innovation differ along the basic dimensions of strategy. Many companies take their industry's conditions as given; value innovators don't. Many companies let competitors set the parameters of their strategic thinking; value innovators do not use rivals as benchmarks. Rather than focus on the differences among customers, value innovators look for what customers value in common. Rather than view opportunities through the lens of existing assets and capabilities, value innovators ask, What if we start anew? The authors tell the story of the French hotelier Accor, which discarded the notion of what a hotel is supposed to look like in order to offer what most customers want: a good night's sleep at a low price. And Virgin Atlantic challenged industry conventions by eliminating first-class service and channeling savings into innovations for business-class passengers. Those companies didn't set out to build advantages over the competition, but they ended up achieving the greatest competitive advantages.

  11. 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)

  12. Movements of Wild Ruddy Shelducks in the Central Asian Flyway and Their Spatial Relationship to Outbreaks of Highly Pathogenic Avian Influenza H5N1

    Directory of Open Access Journals (Sweden)

    Scott H. Newman

    2013-09-01

    Full Text Available Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry and human health. Wild waterfowl are considered to be the reservoir for low pathogenic avian influenza viruses; however, relatively little is known about their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We studied movements of the ruddy shelduck (Tadorna ferruginea, a wild migratory waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined their migration with Brownian Bridge utilization distribution models and their breeding and wintering grounds with fixed kernel home ranges. We correlated their movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in the Central Asian Flyway. Our Akaike Information Criterion analysis indicated that outbreaks were correlated with land cover, latitude, and poultry density. Although shelduck movements were included in the top two models, they were not a top parameter selected in AICc stepwise regression results. However, timing of outbreaks suggested that outbreaks in the flyway began during the winter in poultry with spillover to wild birds during the spring migration. Thus, studies of the movement ecology of wild birds in areas with persistent HPAI H5N1 outbreaks may contribute to understanding their role in transmission of this disease.

  13. Movements of wild ruddy shelducks in the Central Asian Flyway and their spatial relationship to outbreaks of highly pathogenic avian influenza H5N1

    Science.gov (United States)

    Takekawa, John Y.; Prosser, Diann J.; Collins, Bridget M.; Douglas, David C.; Perry, William M.; Baoping, Yan; Luo, Ze; Hou, Yuansheng; Lei, Fumin; Li, Tianxian; Li, Yongdong; Newman, Scott H.

    2013-01-01

    Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry and human health. Wild waterfowl are considered to be the reservoir for low pathogenic avian influenza viruses; however, relatively little is known about their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We studied movements of the ruddy shelduck (Tadorna ferruginea), a wild migratory waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined their migration with Brownian Bridge utilization distribution models and their breeding and wintering grounds with fixed kernel home ranges. We correlated their movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in the Central Asian Flyway. Our Akaike Information Criterion analysis indicated that outbreaks were correlated with land cover, latitude, and poultry density. Although shelduck movements were included in the top two models, they were not a top parameter selected in AICc stepwise regression results. However, timing of outbreaks suggested that outbreaks in the flyway began during the winter in poultry with spillover to wild birds during the spring migration. Thus, studies of the movement ecology of wild birds in areas with persistent HPAI H5N1 outbreaks may contribute to understanding their role in transmission of this disease.

  14. Antigenic, genetic, and pathogenic characterization of H5N1 highly pathogenic avian influenza viruses isolated from dead whooper swans (Cygnus cygnus) found in northern Japan in 2008.

    Science.gov (United States)

    Okamatsu, Masatoshi; Tanaka, Tomohisa; Yamamoto, Naoki; Sakoda, Yoshihiro; Sasaki, Takashi; Tsuda, Yoshimi; Isoda, Norikazu; Kokumai, Norihide; Takada, Ayato; Umemura, Takashi; Kida, Hiroshi

    2010-12-01

    In April and May 2008, whooper swans (Cygnus cygnus) were found dead in Hokkaido in Japan. In this study, an adult whooper swan found dead beside Lake Saroma was pathologically examined and the identified H5N1 influenza virus isolates were genetically and antigenically analyzed. Pathological findings indicate that the swan died of severe congestive edema in the lungs. Phylogenetic analysis of the HA genes of the isolates revealed that they are the progeny viruses of isolates from poultry and wild birds in China, Russia, Korea, and Hong Kong. Antigenic analyses indicated that the viruses are distinguished from the H5N1 viruses isolated from wild birds and poultry before 2007. The chickens vaccinated with A/duck/Hokkaido/Vac-1/2004 (H5N1) survived for 14 days after challenge with A/whooper swan/Hokkaido/1/2008 (H5N1), although a small amount of the challenge virus was recovered from the tissues of the birds. These findings indicate that H5N1 highly pathogenic avian influenza viruses are circulating in wild birds in addition to domestic poultry in Asia and exhibit antigenic variation that may be due to vaccination.

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

    Directory of Open Access Journals (Sweden)

    Yi Jin

    2013-01-01

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

  16. Immune escape mutants of Highly Pathogenic Avian Influenza H5N1 selected using polyclonal sera: identification of key amino acids in the HA protein.

    Directory of Open Access Journals (Sweden)

    Ioannis Sitaras

    Full Text Available Evolution of Avian Influenza (AI viruses--especially of the Highly Pathogenic Avian Influenza (HPAI H5N1 subtype--is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1, using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.

  17. Control strategies against avian influenza

    Science.gov (United States)

    Since 1959, 40 epizootics of high pathogenicity avian influenza (HPAI) have occurred (Figure 1). Thirty-five of these epizootic HPAI viruses were geographically-limited (mostly to single countries), involved farm-to-farm spread and were eradicated from poultry by stamping-out programs; i.e. the HPAI...

  18. Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy

    Directory of Open Access Journals (Sweden)

    Urai Chaisri

    2018-01-01

    Full Text Available This narrative review article summarizes past and current technologies for generating antibodies for passive immunization/immunotherapy. Contemporary DNA and protein technologies have facilitated the development of engineered therapeutic monoclonal antibodies in a variety of formats according to the required effector functions. Chimeric, humanized, and human monoclonal antibodies to antigenic/epitopic myriads with less immunogenicity than animal-derived antibodies in human recipients can be produced in vitro. Immunotherapy with ready-to-use antibodies has gained wide acceptance as a powerful treatment against both infectious and noninfectious diseases. Influenza, a highly contagious disease, precipitates annual epidemics and occasional pandemics, resulting in high health and economic burden worldwide. Currently available drugs are becoming less and less effective against this rapidly mutating virus. Alternative treatment strategies are needed, particularly for individuals at high risk for severe morbidity. In a setting where vaccines are not yet protective or available, human antibodies that are broadly effective against various influenza subtypes could be highly efficacious in lowering morbidity and mortality and controlling unprecedented epidemic/pandemic. Prototypes of human single-chain antibodies to several conserved proteins of influenza virus with no Fc portion (hence, no ADE effect in recipients are available. These antibodies have high potential as a novel, safe, and effective anti-influenza agent.

  19. Vaccination using recombinants influenza and adenoviruses encoding amastigote surface protein-2 are highly effective on protection against Trypanosoma cruzi infection.

    Science.gov (United States)

    Barbosa, Rafael Polidoro Alves; Filho, Bruno Galvão; Dos Santos, Luara Isabela; Junior, Policarpo Ademar Sales; Marques, Pedro Elias; Pereira, Rafaela Vaz Sousa; Cara, Denise Carmona; Bruña-Romero, Oscar; Rodrigues, Maurício Martins; Gazzinelli, Ricardo Tostes; Machado, Alexandre Vieira

    2013-01-01

    In the present study we evaluated the protection raised by immunization with recombinant influenza viruses carrying sequences coding for polypeptides corresponding to medial and carboxi-terminal moieties of Trypanosoma cruzi ´s amastigote surface protein 2 (ASP2). Those viruses were used in sequential immunization with recombinant adenovirus (heterologous prime-boost immunization protocol) encoding the complete sequence of ASP2 (Ad-ASP2) in two mouse strains (C57BL/6 and C3H/He). The CD8 effector response elicited by this protocol was comparable to that observed in mice immunized twice with Ad-ASP2 and more robust than that observed in mice that were immunized once with Ad-ASP2. Whereas a single immunization with Ad-ASP2 sufficed to completely protect C57BL/6 mice, a higher survival rate was observed in C3H/He mice that were primed with recombinant influenza virus and boosted with Ad-ASP2 after being challenged with T. cruzi. Analyzing the phenotype of CD8+ T cells obtained from spleen of vaccinated C3H/He mice we observed that heterologous prime-boost immunization protocol elicited more CD8+ T cells specific for the immunodominant epitope as well as a higher number of CD8+ T cells producing TNF-α and IFN-γ and a higher mobilization of surface marker CD107a. Taken together, our results suggest that immunodominant subpopulations of CD8+ T elicited after immunization could be directly related to degree of protection achieved by different immunization protocols using different viral vectors. Overall, these results demonstrated the usefulness of recombinant influenza viruses in immunization protocols against Chagas Disease.

  20. The chest features of patients with the novel influenza type A H1N1 on high resolution CT

    International Nuclear Information System (INIS)

    Shi Yuxin; Li Shujuan; Zhou Su; Shi Suodi; Zhang Zhiyong

    2010-01-01

    Objective: To explore the chest features of patients with the novel influenza type A H1N1 on HRCT. Methods: One hundred and seventy-two chest HRCT examinations on 163 cases with Influenza type A H1N1 (9 cases were reexamed) were retrospectively analyzed using standard pulmonary window and mediastinal window, respectively. HRCT imaging appearances were summarized. Results: Ninety-seven cases showed normal on chest HRCT, while the others showed abnormalities of parenchymal and interstitial. Among them, HRCT identified ground-glass opacity in 35 cases (53.0%), centrilobular nodules in 30 cases (45.5%), thickening of intralobular septa in 31 cases (47.0%), intralobular thin reticulation and micro-nodule in 8 cases (12.1%), single-lobular inflammation in 19 cases (28.8%), consolidation of lung (the large consolidation and multiple small consolidations) in 15 cases (22.7%), pulmonary atelectasis in 3 cases (4.5%), and irregular lines in 2 cases (3.0%). Pleurisy was also revealed including 8 cases with right pleurisy, 5 cases with left pleurisy, 5 cases with left pleurisy, and 19 cases with bilateral pleurisy. Mediastinal and axillary lymphadenopathy were found in 7 cases, who were spared of pleural effusion. All above abnormalities resolved quickly after anti-virus treatment. Conclusion: Parenchymal and interstitial abnormalities, mediastinum and axillary fossa lymphadenopathy, and pleural effusion were the common findings on HRCT in patients with Influenza type A H1N1, which were similar to those of other viral pneumonia. (authors)

  1. Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas.

    Science.gov (United States)

    Thacker, Eileen; Janke, Bruce

    2008-02-15

    Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic.

  2. Efficacy of single dose of a bivalent vaccine containing inactivated Newcastle disease virus and reassortant highly pathogenic avian influenza H5N1 virus against lethal HPAI and NDV infection in chickens.

    Directory of Open Access Journals (Sweden)

    Dong-Hun Lee

    Full Text Available Highly pathogenic avian influenza (HPAI and Newcastle disease (ND are 2 devastating diseases of poultry, which cause great economic losses to the poultry industry. In the present study, we developed a bivalent vaccine containing antigens of inactivated ND and reassortant HPAI H5N1 viruses as a candidate poultry vaccine, and we evaluated its immunogenicity and protective efficacy in specific pathogen-free chickens. The 6:2 reassortant H5N1 vaccine strain containing the surface genes of the A/Chicken/Korea/ES/2003(H5N1 virus was successfully generated by reverse genetics. A polybasic cleavage site of the hemagglutinin segment was replaced by a monobasic cleavage site. We characterized the reverse genetics-derived reassortant HPAI H5N1 clade 2.5 vaccine strain by evaluating its growth kinetics in eggs, minimum effective dose in chickens, and cross-clade immunogenicity against HPAI clade 1 and 2. The bivalent vaccine was prepared by emulsifying inactivated ND (La Sota strain and reassortant HPAI viruses with Montanide ISA 70 adjuvant. A single immunization with this vaccine induced high levels of hemagglutination-inhibiting antibody titers and protected chickens against a lethal challenge with the wild-type HPAI and ND viruses. Our results demonstrate that the bivalent, inactivated vaccine developed in this study is a promising approach for the control of both HPAI H5N1 and ND viral infections.

  3. High speed diesel consumption and economic growth in India

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Sajal [Management Development Institute (MDI), Gurgaon 122001 (India)

    2010-04-15

    This study probes the long-term equilibrium relationship among High Speed Diesel (HSD) consumption, real GDP and price of HSD in India using autoregressive distributed lag (ARDL) bounds testing approach of cointegration for the time span 1972-1973 to 2005-2006. Empirical results reveal that the series are cointegrated and long term income elasticity for HSD demand in India is 1.27 while that for short-run is 0.46. Both long-run and short-run price elasticities are found to be statistically insignificant. The study also establishes a short-run bi-directional causality between economic growth and HSD consumption and the existence of a long-run unidirectional causality running from economic growth to HSD consumption. Finally, a set of policy prescriptions have been suggested to reduce the consumption of HSD, which should have no adverse impact on economy in the long-run. (author)

  4. Spatial distribution and risk factors of influenza in Jiangsu province, China, based on geographical information system

    Directory of Open Access Journals (Sweden)

    Jia-Cheng Zhang

    2014-05-01

    Full Text Available Influenza poses a constant, heavy burden on society. Recent research has focused on ecological factors associated with influenza incidence and has also studied influenza with respect to its geographic spread at different scales. This research explores the temporal and spatial parameters of influenza and identifies factors influencing its transmission. A spatial autocorrelation analysis, a spatial-temporal cluster analysis and a spatial regression analysis of influenza rates, carried out in Jiangsu province from 2004 to 2011, found that influenza rates to be spatially dependent in 2004, 2005, 2006 and 2008. South-western districts consistently revealed hotspots of high-incidence influenza. The regression analysis indicates that railways, rivers and lakes are important predictive environmental variables for influenza risk. A better understanding of the epidemic pattern and ecological factors associated with pandemic influenza should benefit public health officials with respect to prevention and controlling measures during future epidemics.

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

    Science.gov (United States)

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

  6. On the role of vaccine dose and antigenic distance in the transmission dynamics of Highly Pathogenic Avian Influenza (HPAI) H5N1 virus and its selected mutants in vaccinated animals

    NARCIS (Netherlands)

    Sitaras, Ioannis

    2017-01-01

    Influenza virus infections can cause high morbidity and mortality rates among animals and humans, and result in staggering direct and indirect financial losses amounting to billions of US dollars. Ever since it emerged in 1996 in Guangdong province, People’s Republic of China, one particular

  7. Antibody titer has positive predictive value for vaccine protection against challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian influenza viruses from Indonesia

    Science.gov (United States)

    Beginning with Hong Kong in 2002, vaccines have been used as part of an integrated control strategy in 14 countries/regions to protect poultry against H5N1 high pathogenicity avian influenza (HPAI). H5N1 HPAI was first reported in Indonesia in 2003 and vaccination was initiated the following year. ...

  8. Evaluation of the U.S. Department of Agriculture's egg pasteurization processes on the inactivation of high pathogenicity avian influenza virus and velogenic Newcastle disease virus in processed egg products

    Science.gov (United States)

    High pathogenicity avian influenza virus (HPAIV) A/chicken/Pennsylvania/1370/1983 (H5N2), and velogenic Newcastle disease virus (vNDV) AMPV-1/California/212676/2002 were inoculated into various egg products then heat treated at various temperatures for 0 to 30 min to determine thermal inactivation p...

  9. Optimisation Of Volvariella volvacea Spawn Production For High Mycelia Growth

    International Nuclear Information System (INIS)

    Nie, H.J.; Azhar Mohamad; Joyce, Y.S.M.; Muhamad Najmi Moin

    2016-01-01

    Volvariella volvacea is a tropical mushroom cultivated throughout the world mostly in Asia and Europe for its taste, nutrition, fast growing nature and simple method of cultivation. It is also widely cultivated in Malaysia and known locally as Paddy Straw Mushroom. Growers strive to obtain high quality mushroom spawn to achieve high production. High quality spawn with fast mycelia growth are achieved through strain selection and optimisation of seedling production conditions. This study aims to optimise spawn production through 3 studies along the production main stages. Firstly, comparisons were made between agar media. Mycelia grown on Malt Extract Agar (MEA) covered the agar plates 2 days faster than Potato Dextrose Agar (PDA) grown mycelia. The next stage is of mother grain spawn production by inoculating a bag of grains from mycelia agar plugs. Bags are then sealed with caps. The amount of aeration for grain spawn were studied by using two types of caps. Caps with hole allowed more aeration compared to caps without holes. Study determined bags with more aeration colonised grains 2 days faster than bags with lesser aeration. For the final stage of producing planting spawn, the growth on paddy straw substrate with and without kapok (10 %) were evaluated. Results revealed mycelia fully colonised the substrate bags without kapok 1-2 days faster than substrate bags with kapok. These findings contribute in achieving production of high quality Volvariella volvacea spawn. (author)

  10. Bulge Growth Through Disc Instabilities in High-Redshift Galaxies

    Science.gov (United States)

    Bournaud, Frédéric

    The role of disc instabilities, such as bars and spiral arms, and the associated resonances, in growing bulges in the inner regions of disc galaxies have long been studied in the low-redshift nearby Universe. There it has long been probed observationally, in particular through peanut-shaped bulges (Chap. 14 10.1007/978-3-319-19378-6_14"). This secular growth of bulges in modern disc galaxies is driven by weak, non-axisymmetric instabilities: it mostly produces pseudobulges at slow rates and with long star-formation timescales. Disc instabilities at high redshift (z > 1) in moderate-mass to massive galaxies (1010 to a few 1011 M⊙ of stars) are very different from those found in modern spiral galaxies. High-redshift discs are globally unstable and fragment into giant clumps containing 108-9 M⊙ of gas and stars each, which results in highly irregular galaxy morphologies. The clumps and other features associated to the violent instability drive disc evolution and bulge growth through various mechanisms on short timescales. The giant clumps can migrate inward and coalesce into the bulge in a few 108 years. The instability in the very turbulent media drives intense gas inflows toward the bulge and nuclear region. Thick discs and supermassive black holes can grow concurrently as a result of the violent instability. This chapter reviews the properties of high-redshift disc instabilities, the evolution of giant clumps and other features associated to the instability, and the resulting growth of bulges and associated sub-galactic components.

  11. Rapid detection of the avian influenza virus H5N1 subtype in Egypt

    African Journals Online (AJOL)

    Dr

    highly pathogenic avian influenza virus subtype H5N1 in Egypt is threatening poultry and ... Key words: Avian influenza virus, H5N1, fluorescent antibody enzyme-linked immunosorbent assay (ELISA) ..... poultry and is potentially zoonotic.

  12. Helium solubility and bubble growth in metals under high pressure

    International Nuclear Information System (INIS)

    Laakmann, J.

    1985-07-01

    Helium solubility and bubble growth in metals under high pressure polycrystals and single crystals of gold were heated in helium at temperatures between 475 K and 1250 K in a pressure regime of 200 to 2700 bar to measure the solubility of helium in gold. After quenching to room temperature the helium content, measured by mass spectrometry, showed the following properties: 1) A linear dependence of the He solubility on pressure. 2) Thinning of the specimen reduces the helium content by a factor 10 to 100 but does not change the linear pressure dependence. 3) The thermal release of He from thinned polycrystals and single crystals occurs mainly in a single peak at 500 K. 4) The He concentration of the thinned single crystals was lower by a factor of 10 to 50 than that of the thinned polycrystals. 5) The He solubility in single crystals can be described by an enthalpy of solution Hsub(s)sup(f) = 0.85 +- 0.7 eV and a non-configurational entropy of Ssub(s)sup(f) between 0 k and 1 k (k: Boltzmann-constant). In order to measure the pressure dependence of helium bubble growth in nickel polycrystal Ni-foils were α-implanted to a helium content of 130 appm. The evaluation of the size distribution of the helium bubbles after heat treatments shows 1) The helium content of the observable bubbles - assumed to be in equilibrium - equals the amount of helium implanted into the specimen. 2) The activation energy for the growth of helium bubbles is 1.25 +- 0.3 eV. The comparison of specimen which had been heated at low pressures up to 10 bar with others heated at 2500-2700 bar does not show an unequivocal pressure dependence for helium bubble growth. (orig./IHOE) [de

  13. A simple Pichia pastoris fermentation and downstream processing strategy for making recombinant pandemic Swine Origin Influenza a virus Hemagglutinin protein.

    Science.gov (United States)

    Athmaram, T N; Singh, Anil Kumar; Saraswat, Shweta; Srivastava, Saurabh; Misra, Princi; Kameswara Rao, M; Gopalan, N; Rao, P V L

    2013-02-01

    The present Influenza vaccine manufacturing process has posed a clear impediment to initiation of rapid mass vaccination against spreading pandemic influenza. New vaccine strategies are therefore needed that can accelerate the vaccine production. Pichia offers several advantages for rapid and economical bulk production of recombinant proteins and, hence, can be attractive alternative for producing an effective influenza HA based subunit vaccine. The recombinant Pichia harboring the transgene was subjected to fed-batch fermentation at 10 L scale. A simple fermentation and downstream processing strategy is developed for high-yield secretory expression of the recombinant Hemagglutinin protein of pandemic Swine Origin Influenza A virus using Pichia pastoris via fed-batch fermentation. Expression and purification were optimized and the expressed recombinant Hemagglutinin protein was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blot and MALDI-TOF analysis. In this paper, we describe a fed-batch fermentation protocol for the secreted production of Swine Influenza A Hemagglutinin protein in the P. pastoris GS115 strain. We have shown that there is a clear relationship between product yield and specific growth rate. The fed-batch fermentation and downstream processing methods optimized in the present study have immense practical application for high-level production of the recombinant H1N1 HA protein in a cost effective way using P. pastoris.

  14. Isolation and Characterization of Avian Influenza Viruses, Including Highly Pathogenic H5N1, from Poultry in Live Bird Markets in Hanoi, Vietnam, in 2001

    Science.gov (United States)

    Nguyen, Doan C.; Uyeki, Timothy M.; Jadhao, Samadhan; Maines, Taronna; Shaw, Michael; Matsuoka, Yumiko; Smith, Catherine; Rowe, Thomas; Lu, Xiuhua; Hall, Henrietta; Xu, Xiyan; Balish, Amanda; Klimov, Alexander; Tumpey, Terrence M.; Swayne, David E.; Huynh, Lien P. T.; Nghiem, Ha K.; Nguyen, Hanh H. T.; Hoang, Long T.; Cox, Nancy J.; Katz, Jacqueline M.

    2005-01-01

    Since 1997, outbreaks of highly pathogenic (HP) H5N1 and circulation of H9N2 viruses among domestic poultry in Asia have posed a threat to public health. To better understand the extent of transmission of avian influenza viruses (AIV) to humans in Asia, we conducted a cross-sectional virologic study in live bird markets (LBM) in Hanoi, Vietnam, in October 2001. Specimens from 189 birds and 18 environmental samples were collected at 10 LBM. Four influenza A viruses of the H4N6 (n = 1), H5N2 (n = 1), and H9N3 (n = 2) subtypes were isolated from healthy ducks for an isolation frequency of over 30% from this species. Two H5N1 viruses were isolated from healthy geese. The hemagglutinin (HA) genes of these H5N1 viruses possessed multiple basic amino acid motifs at the cleavage site, were HP for experimentally infected chickens, and were thus characterized as HP AIV. These HA genes shared high amino acid identities with genes of other H5N1 viruses isolated in Asia during this period, but they were genetically distinct from those of H5N1 viruses isolated from poultry and humans in Vietnam during the early 2004 outbreaks. These viruses were not highly virulent for experimentally infected ducks, mice, or ferrets. These results establish that HP H5N1 viruses with properties similar to viruses isolated in Hong Kong and mainland China circulated in Vietnam as early as 2001, suggest a common source for H5N1 viruses circulating in these Asian countries, and provide a framework to better understand the recent widespread emergence of HP H5N1 viruses in Asia. PMID:15767421

  15. H5N2 Highly Pathogenic Avian Influenza Viruses from the US 2014-2015 outbreak have an unusually long pre-clinical period in turkeys.

    Science.gov (United States)

    Spackman, Erica; Pantin-Jackwood, Mary J; Kapczynski, Darrell R; Swayne, David E; Suarez, David L

    2016-11-22

    From December 2014 through June 2015, the US experienced the most costly highly pathogenic avian influenza (HPAI) outbreak to date. Most cases in commercial poultry were caused by an H5N2 strain which was a reassortant with 5 Eurasian lineage genes, including a clade 2.3.4.4 goose/Guangdong/1996 lineage hemagglutinin, and 3 genes from North American wild waterfowl low pathogenicity avian influenza viruses. The outbreak primarily affected turkeys and table-egg layer type chickens. Three isolates were selected for characterization in turkeys: the US index isolate from December 2014 (A/northern pintail/WA/40964/2014), and two poultry isolates from April 2015 (A/chicken/IA/13388/2015 and A/turkey/MN/12528/2015). Four week old broad-breasted white turkeys were inoculated with one of three doses (10 2 , 10 4 or 10 6 50% egg infectious doses [EID 50 ] per bird) of each of the isolates to evaluate infectious dose and pathogenesis. The mean bird infectious dose of A/northern pintail/WA/40964/2014 and A/turkey/MN/12528/2015 was 10 5 EID 50 per bird, but was 10 3 EID 50 per bird for A/chicken/IA/13388/2015, suggesting the latter had greater adaptation to gallinaceous birds. All three isolates had unusually long mean death time of 5.3-5.9 days post challenge, and the primary clinical signs were severe lethargy and neurological signs which started no more than 24 h before death (the average pre-clinical period was 4 days). Infected turkeys also shed high levels of virus by both the oropharyngeal and cloacal routes. The unusually long mean death times, high levels of virus in feces, and increased adaptation of the later viruses may have contributed to the rapid spread of the virus during the peak of the outbreak.

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

    Directory of Open Access Journals (Sweden)

    Kateri Bertran

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

  17. 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

  18. Protective efficacy of Newcastle disease virus expressing soluble trimeric hemagglutinin against highly pathogenic H5N1 influenza in chickens and mice.

    Directory of Open Access Journals (Sweden)

    Lisette A H M Cornelissen

    Full Text Available BACKGROUND: Highly pathogenic avian influenza virus (HPAIV causes a highly contagious often fatal disease in poultry, resulting in significant economic losses in the poultry industry. HPAIV H5N1 also poses a major public health threat as it can be transmitted directly from infected poultry to humans. One effective way to combat avian influenza with pandemic potential is through the vaccination of poultry. Several live vaccines based on attenuated Newcastle disease virus (NDV that express influenza hemagglutinin (HA have been developed to protect chickens or mammalian species against HPAIV. However, the zoonotic potential of NDV raises safety concerns regarding the use of live NDV recombinants, as the incorporation of a heterologous attachment protein may result in the generation of NDV with altered tropism and/or pathogenicity. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we generated recombinant NDVs expressing either full length, membrane-anchored HA of the H5 subtype (NDV-H5 or a soluble trimeric form thereof (NDV-sH5(3. A single intramuscular immunization with NDV-sH5(3 or NDV-H5 fully protected chickens against disease after a lethal challenge with H5N1 and reduced levels of virus shedding in tracheal and cloacal swabs. NDV-sH5(3 was less protective than NDV-H5 (50% vs 80% protection when administered via the respiratory tract. The NDV-sH5(3 was ineffective in mice, regardless of whether administered oculonasally or intramuscularly. In this species, NDV-H5 induced protective immunity against HPAIV H5N1, but only after oculonasal administration, despite the poor H5-specific serum antibody response it elicited. CONCLUSIONS/SIGNIFICANCE: Although NDV expressing membrane anchored H5 in general provided better protection than its counterpart expressing soluble H5, chickens could be fully protected against a lethal challenge with H5N1 by using the latter NDV vector. This study thus provides proof of concept for the use of recombinant

  19. 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

  20. Immunogenicity and Clinical Efficacy of Influenza Vaccination In Pregnancy

    Directory of Open Access Journals (Sweden)

    Alexander W Kay

    2015-06-01

    Full Text Available Pregnant women are at high risk from influenza due to disproportionate morbidity, mortality, and adverse pregnancy outcomes following infection. As such, they are classified as a high priority group for vaccination. However, changes in the maternal immune system required to accommodate the allogeneic fetus may alter the immunogenicity of influenza vaccines. A large number of studies have evaluated the safety of the influenza vaccine. Here, we will review available studies on the immunogenicity and efficacy of the influenza vaccine during pregnancy, focusing on both humoral and cellular immunity.

  1. New reassortant and enzootic European swine influenza 1 viruses transmits efficiently through direct contact in the ferret model

    DEFF Research Database (Denmark)

    Fobian, Kristina; P. Fabrizio, Thomas; Yoon, Sun-Woo

    2015-01-01

    The reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in Europe. The pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of European pigs...... with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2 and two were new reassortants, one with avian-like H1...... and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titers in nasal wash- and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via the airborne route. Growth kinetics...

  2. Genetic and phylogenetic characterizations of a novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea.

    Science.gov (United States)

    Kim, Young-Il; Park, Su-Jin; Kwon, Hyeok-Il; Kim, Eun-Ha; Si, Young-Jae; Jeong, Ju-Hwan; Lee, In-Won; Nguyen, Hiep Dinh; Kwon, Jin-Jung; Choi, Won Suk; Song, Min-Suk; Kim, Chul-Joong; Choi, Young-Ki

    2017-09-01

    During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2010-02-01

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

  4. Standardization of an inactivated H17N1 avian influenza vaccine and efficacy against A/Chicken/Italy/13474/99 high-pathogenicity virus infection.

    Science.gov (United States)

    Di Trani, L; Cordioli, P; Falcone, E; Lombardi, G; Moreno, A; Sala, G; Tollis, M

    2003-01-01

    The minimum requirements for assessing the immunogenicity of an experimental avian influenza (AI) vaccine prepared from inactivated A/Turkey/Italy/2676/99 (H7N1) low-pathogenicity (LP) AI (LPAI) virus were determined in chickens of different ages. A correlation between the amount of hemagglutinin (HA) per dose of vaccine and the protection against clinical signs of disease and infection by A/Chicken/Italy/13474/99 highly pathogenic (HP) AI (HPAI) virus was established. Depending on the vaccination schedule, one or two administrations of 0.5 microg of hemagglutinin protected chickens against clinical signs and death and completely prevented virus shedding from birds challenged at different times after vaccination.

  5. Avian Influenza Virus (H5N1): a Threat to Human Health

    OpenAIRE

    Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

    2007-01-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, ...

  6. Mathematical Assessment of Canada’s Pandemic Influenza Preparedness Plan

    Directory of Open Access Journals (Sweden)

    Abba B Gumel

    2008-01-01

    Full Text Available OBJECTIVE: The presence of the highly pathogenic avian H5N1 virus in wild bird populations in several regions of the world, together with recurrent cases of H5N1 influenza arising primarily from direct contact with poultry, have highlighted the urgent need for prepared-ness and coordinated global strategies to effectively combat a potential influenza pandemic. The purpose of the present study was to evaluate the Canadian pandemic influenza preparedness plan.

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

    Science.gov (United States)

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

    2008-03-01

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

  8. Heterologous prime-boost immunization of Newcastle disease virus vectored vaccines protected broiler chickens against highly pathogenic avian influenza and Newcastle disease viruses.

    Science.gov (United States)

    Kim, Shin-Hee; Samal, Siba K

    2017-07-24

    Avian Influenza virus (AIV) is an important pathogen for both human and animal health. There is a great need to develop a safe and effective vaccine for AI infections in the field. Live-attenuated Newcastle disease virus (NDV) vectored AI vaccines have shown to be effective, but preexisting antibodies to the vaccine vector can affect the protective efficacy of the vaccine in the field. To improve the efficacy of AI vaccine, we generated a novel vectored vaccine by using a chimeric NDV vector that is serologically distant from NDV. In this study, the protective efficacy of our vaccines was evaluated by using H5N1 highly pathogenic avian influenza virus (HPAIV) strain A/Vietnam/1203/2004, a prototype strain for vaccine development. The vaccine viruses were three chimeric NDVs expressing the hemagglutinin (HA) protein in combination with the neuraminidase (NA) protein, matrix 1 protein, or nonstructural 1 protein. Comparison of their protective efficacy between a single and prime-boost immunizations indicated that prime immunization of 1-day-old SPF chicks with our vaccine viruses followed by boosting with the conventional NDV vector strain LaSota expressing the HA protein provided complete protection of chickens against mortality, clinical signs and virus shedding. Further verification of our heterologous prime-boost immunization using commercial broiler chickens suggested that a sequential immunization of chickens with chimeric NDV vector expressing the HA and NA proteins following the boost with NDV vector expressing the HA protein can be a promising strategy for the field vaccination against HPAIVs and against highly virulent NDVs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Low- and High-Pathogenic Avian Influenza H5 and H7 Spread Risk Assessment Within and Between Australian Commercial Chicken Farms.

    Science.gov (United States)

    Scott, Angela Bullanday; Toribio, Jenny-Ann L M L; Singh, Mini; Groves, Peter; Barnes, Belinda; Glass, Kathryn; Moloney, Barbara; Black, Amanda; Hernandez-Jover, Marta

    2018-01-01

    This study quantified and compared the probability of avian influenza (AI) spread within and between Australian commercial chicken farms via specified spread pathways using scenario tree mathematical modeling. Input values for the models were sourced from scientific literature, expert opinion, and a farm survey conducted during 2015 and 2016 on Australian commercial chicken farms located in New South Wales (NSW) and Queensland. Outputs from the models indicate that the probability of no establishment of infection in a shed is the most likely end-point after exposure and infection of low-pathogenic avian influenza (LPAI) in one chicken for all farm types (non-free range meat chicken, free range meat chicken, cage layer, barn layer, and free range layer farms). If LPAI infection is established in a shed, LPAI is more likely to spread to other sheds and beyond the index farm due to a relatively low probability of detection and reporting during LPAI infection compared to high-pathogenic avian influenza (HPAI) infection. Among farm types, the median probability for HPAI spread between sheds and between farms is higher for layer farms (0.0019, 0.0016, and 0.0031 for cage, barn, and free range layer, respectively) than meat chicken farms (0.00025 and 0.00043 for barn and free range meat chicken, respectively) due to a higher probability of mutation in layer birds, which relates to their longer production cycle. The pathway of LPAI spread between sheds with the highest average median probability was spread via equipment (0.015; 5-95%, 0.0058-0.036) and for HPAI spread between farms, the pathway with the highest average median probability was spread via egg trays (3.70 × 10 -5 ; 5-95%, 1.47 × 10 -6 -0.00034). As the spread model did not explicitly consider volume and frequency of the spread pathways, these results provide a comparison of spread probabilities per pathway. These findings highlight the importance of performing biosecurity practices to limit spread of

  10. Low- and High-Pathogenic Avian Influenza H5 and H7 Spread Risk Assessment Within and Between Australian Commercial Chicken Farms

    Science.gov (United States)

    Scott, Angela Bullanday; Toribio, Jenny-Ann L. M. L.; Singh, Mini; Groves, Peter; Barnes, Belinda; Glass, Kathryn; Moloney, Barbara; Black, Amanda; Hernandez-Jover, Marta

    2018-01-01

    This study quantified and compared the probability of avian influenza (AI) spread within and between Australian commercial chicken farms via specified spread pathways using scenario tree mathematical modeling. Input values for the models were sourced from scientific literature, expert opinion, and a farm survey conducted during 2015 and 2016 on Australian commercial chicken farms located in New South Wales (NSW) and Queensland. Outputs from the models indicate that the probability of no establishment of infection in a shed is the most likely end-point after exposure and infection of low-pathogenic avian influenza (LPAI) in one chicken for all farm types (non-free range meat chicken, free range meat chicken, cage layer, barn layer, and free range layer farms). If LPAI infection is established in a shed, LPAI is more likely to spread to other sheds and beyond the index farm due to a relatively low probability of detection and reporting during LPAI infection compared to high-pathogenic avian influenza (HPAI) infection. Among farm types, the median probability for HPAI spread between sheds and between farms is higher for layer farms (0.0019, 0.0016, and 0.0031 for cage, barn, and free range layer, respectively) than meat chicken farms (0.00025 and 0.00043 for barn and free range meat chicken, respectively) due to a higher probability of mutation in layer birds, which relates to their longer production cycle. The pathway of LPAI spread between sheds with the highest average median probability was spread via equipment (0.015; 5–95%, 0.0058–0.036) and for HPAI spread between farms, the pathway with the highest average median probability was spread via egg trays (3.70 × 10−5; 5–95%, 1.47 × 10−6–0.00034). As the spread model did not explicitly consider volume and frequency of the spread pathways, these results provide a comparison of spread probabilities per pathway. These findings highlight the importance of performing biosecurity practices to limit

  11. Low- and High-Pathogenic Avian Influenza H5 and H7 Spread Risk Assessment Within and Between Australian Commercial Chicken Farms

    Directory of Open Access Journals (Sweden)

    Angela Bullanday Scott

    2018-04-01

    Full Text Available This study quantified and compared the probability of avian influenza (AI spread within and between Australian commercial chicken farms via specified spread pathways using scenario tree mathematical modeling. Input values for the models were sourced from scientific literature, expert opinion, and a farm survey conducted during 2015 and 2016 on Australian commercial chicken farms located in New South Wales (NSW and Queensland. Outputs from the models indicate that the probability of no establishment of infection in a shed is the most likely end-point after exposure and infection of low-pathogenic avian influenza (LPAI in one chicken for all farm types (non-free range meat chicken, free range meat chicken, cage layer, barn layer, and free range layer farms. If LPAI infection is established in a shed, LPAI is more likely to spread to other sheds and beyond the index farm due to a relatively low probability of detection and reporting during LPAI infection compared to high-pathogenic avian influenza (HPAI infection. Among farm types, the median probability for HPAI spread between sheds and between farms is higher for layer farms (0.0019, 0.0016, and 0.0031 for cage, barn, and free range layer, respectively than meat chicken farms (0.00025 and 0.00043 for barn and free range meat chicken, respectively due to a higher probability of mutation in layer birds, which relates to their longer production cycle. The pathway of LPAI spread between sheds with the highest average median probability was spread via equipment (0.015; 5–95%, 0.0058–0.036 and for HPAI spread between farms, the pathway with the highest average median probability was spread via egg trays (3.70 × 10−5; 5–95%, 1.47 × 10−6–0.00034. As the spread model did not explicitly consider volume and frequency of the spread pathways, these results provide a comparison of spread probabilities per pathway. These findings highlight the importance of performing biosecurity practices

  12. A novel small molecule inhibitor of influenza A viruses that targets polymerase function and indirectly induces interferon.

    Directory of Open Access Journals (Sweden)

    Mila Brum Ortigoza

    Full Text Available Influenza viruses continue to pose a major public health threat worldwide and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. The antiviral cytokine, interferon (IFN is an essential mediator of the innate immune response and influenza viruses, like many viruses, have evolved strategies to evade this response, resulting in increased replication and enhanced pathogenicity. A cell-based assay that monitors IFN production was developed and applied in a high-throughput compound screen to identify molecules that restore the IFN response to influenza virus infected cells. We report the identification of compound ASN2, which induces IFN only in the presence of influenza virus infection. ASN2 preferentially inhibits the growth of influenza A viruses, including the 1918 H1N1, 1968 H3N2 and 2009 H1N1 pandemic strains and avian H5N1 virus. In vivo, ASN2 partially protects mice challenged with a lethal dose of influenza A virus. Surprisingly, we found that the antiviral activity of ASN2 is not dependent on IFN production and signaling. Rather, its IFN-inducing property appears to be an indirect effect resulting from ASN2-mediated inhibition of viral polymerase function, and subsequent loss of the expression of the viral IFN antagonist, NS1. Moreover, we identified a single amino acid mutation at position 499 of the influenza virus PB1 protein that confers resistance to ASN2, suggesting that PB1 is the direct target. This two-pronged antiviral mechanism, consisting of direct inhibition of virus replication and simultaneous activation of the host innate immune response, is a unique property not previously described for any single antiviral molecule.

  13. The evolving history of influenza viruses and influenza vaccines.

    Science.gov (United States)

    Hannoun, Claude

    2013-09-01

    The isolation of influenza virus 80 years ago in 1933 very quickly led to the development of the first generation of live-attenuated vaccines. The first inactivated influenza vaccine was monovalent (influenza A). In 1942, a bivalent vaccine was produced after the discovery of influenza B. It was later discovered that influenza viruses mutated leading to antigenic changes. Since 1973, the WHO has issued annual recommendations for the composition of the influenza vaccine based on results from surveillance systems that identify currently circulating strains. In 1978, the first trivalent vaccine included two influenza A strains and one influenza B strain. Currently, there are two influenza B lineages circulating; in the latest WHO recommendations, it is suggested that a second B strain could be added to give a quadrivalent vaccine. The history of influenza vaccine and the associated technology shows how the vaccine has evolved to match the evolution of influenza viruses.

  14. Secondary Bacterial Infections Associated with Influenza Pandemics

    Science.gov (United States)

    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

  15. Secondary Bacterial Infections Associated with Influenza Pandemics

    Directory of Open Access Journals (Sweden)

    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.

  16. Potent peptidic fusion inhibitors of influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

    2017-09-28

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

  17. Uptake of the Influenza Vaccination in Pregnancy

    LENUS (Irish Health Repository)

    Crosby, DA

    2016-09-01

    Influenza is caused by a highly infectious RNA virus, which usually occurs in a seasonal pattern with epidemics in the winter months. The objective of this study was to determine the uptake of the influenza vaccine in a pregnant population and ascertain the reasons why some women did not receive it. A prospective cohort study was conducted over a two-week period in January 2016 in the National Maternity Hospital Dublin, a tertiary referral maternity hospital delivering over 9000 infants per year. There were 504 women studied over the 2-week period. Overall, 197(39.1%) women received the vaccine at a mean gestational age 20.9 weeks (SD 7.0). Given the increased rates of influenza in the community and the associated implications for mother and infant, it is important that pregnant women are educated regarding the risks of influenza in pregnancy and encourage this cohort to be vaccinated.

  18. Suspension culture process for H9N2 avian influenza virus (strain Re-2).

    Science.gov (United States)

    Wang, Honglin; Guo, Suying; Li, Zhenguang; Xu, Xiaoqin; Shao, Zexiang; Song, Guicai

    2017-10-01

    H9N2 avian influenza virus has caused huge economic loss for the Chinese poultry industry since it was first identified. Vaccination is frequently used as a control method for the disease. Meanwhile suspension culture has become an important tool for the development of influenza vaccines. To optimize the suspension culture conditions for the avian influenza H9N2 virus (Re-2 strain) in Madin-Darby Canine Kidney (MDCK) cells, we studied the culture conditions for cell growth and proliferation parameters for H9N2 virus replication. MDCK cells were successfully cultured in suspension, from a small scale to industrial levels of production, with passage time and initial cell density being optimized. The influence of pH on the culture process in the reactor has been discussed and the process parameters for industrial production were explored via amplification of the 650L reactor. Subsequently, we cultivated cells at high cell density and harvested high amounts of virus, reaching 10log2 (1:1024). Furthermore an animal experiment was conducted to detect antibody. Compared to the chicken embryo virus vaccine, virus cultured from MDCK suspension cells can produce a higher amount of antibodies. The suspension culture process is simple and cost efficient, thus providing a solid foundation for the realization of large-scale avian influenza vaccine production.

  19. Neuroinvasion of the highly pathogenic influenza virus H7N1 is caused by disruption of the blood brain barrier in an avian model.

    Directory of Open Access Journals (Sweden)

    Aida J Chaves

    Full Text Available Influenza A virus (IAV causes central nervous system (CNS lesions in avian and mammalian species, including humans. However, the mechanism used by IAV to invade the brain has not been determined. In the current work, we used chickens infected with a highly pathogenic avian influenza (HPAI virus as a model to elucidate the mechanism of entry of IAV into the brain. The permeability of the BBB was evaluated in fifteen-day-old H7N1-infected and non-infected chickens using three different methods: (i detecting Evans blue (EB extravasation into the brain, (ii determining the leakage of the serum protein immunoglobulin Y (IgY into the brain and (iii assessing the stability of the tight-junction (TJ proteins zonula occludens-1 and claudin-1 in the chicken brain at 6, 12, 18, 24, 36 and 48 hours post-inoculation (hpi. The onset of the induced viremia was evaluated by quantitative real time RT-PCR (RT-qPCR at the same time points. Viral RNA was detected from 18 hpi onward in blood samples, whereas IAV antigen was detected at 24 hpi in brain tissue samples. EB and IgY extravasation and loss of integrity of the TJs associated with the presence of viral antigen was first observed at 36 and 48 hpi in the telencephalic pallium and cerebellum. Our data suggest that the mechanism of entry of the H7N1 HPAI into the brain includes infection of the endothelial cells at early stages (24 hpi with subsequent disruption of the TJs of the BBB and leakage of virus and serum proteins into the adjacent neuroparenchyma.

  20. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection.

    Science.gov (United States)

    Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A

    2016-06-08

    Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Highly pathogenic avian influenza virus subtype H5N1 in Africa: a comprehensive phylogenetic analysis and molecular characterization of isolates.

    Directory of Open Access Journals (Sweden)

    Giovanni Cattoli

    Full Text Available Highly pathogenic avian influenza virus A/H5N1 was first officially reported in Africa in early 2006. Since the first outbreak in Nigeria, this virus spread rapidly to other African countries. From its emergence to early 2008, 11 African countries experienced A/H5N1 outbreaks in poultry and human cases were also reported in three of these countries. At present, little is known of the epidemiology and molecular evolution of A/H5N1 viruses in Africa. We have generated 494 full gene sequences from 67 African isolates and applied molecular analysis tools to a total of 1,152 A/H5N1 sequences obtained from viruses isolated in Africa, Europe and the Middle East between 2006 and early 2008. Detailed phylogenetic analyses of the 8 gene viral segments confirmed that 3 distinct sublineages were introduced, which have persisted and spread across the continent over this 2-year period. Additionally, our molecular epidemiological studies highlighted the association between genetic clustering and area of origin in a majority of cases. Molecular signatures unique to strains isolated in selected areas also gave us a clearer picture of the spread of A/H5N1 viruses across the continent. Mutations described as typical of human influenza viruses in the genes coding for internal proteins or associated with host adaptation and increased resistance to antiviral drugs have also been detected in the genes coding for transmembrane proteins. These findings raise concern for the possible human health risk presented by viruses with these genetic properties and highlight the need for increased efforts to monitor the evolution of A/H5N1 viruses across the African continent. They further stress how imperative it is to implement sustainable control strategies to improve animal and public health at a global level.

  2. Persistence of highly pathogenic avian influenza virus (H7N1) in infected chickens: feather as a suitable sample for diagnosis.

    Science.gov (United States)

    Busquets, Núria; Abad, F Xavier; Alba, Anna; Dolz, Roser; Allepuz, Alberto; Rivas, Raquel; Ramis, Antonio; Darji, Ayub; Majó, Natàlia

    2010-09-01

    Selection of an ideal sample is a vital element in early detection of influenza infection. Rapid identification of infectious individuals or animals is crucial not only for avian influenza virus (AIV) surveillance programmes, but also for treatment and containment strategies. This study used a combination of quantitative real-time RT-PCR with an internal positive control and a cell-titration system to examine the presence of virus in different samples during active experimental AIV infection and its persistence in the infected carcasses. Oropharyngeal/cloacal swabs as well as feather pulp and blood samples were collected from 15-day-old chicks infected with H7N1 highly pathogenic AIV (HPAIV) and the kinetics of virus shedding during active infection were evaluated. Additionally, several samples (muscle, skin, brain, feather pulp and oropharyngeal and cloacal swabs) were examined to assess the persistence of virus in the HPAIV-infected carcasses. Based on the results, feather pulp was found to be the best sample to detect and isolate HPAIV from infected chicks from 24 h after inoculation onwards. Kinetic studies on the persistence of virus in infected carcasses revealed that tissues such as muscle could potentially transmit infectious virus for 3 days post-mortem (p.m.), whilst other tissues such as skin, feather pulp and brain retained their infectivity for as long as 5-6 days p.m. at environmental temperature (22-23 degrees C). These results strongly favour feather as a useful sample for HPAIV diagnosis in infected chickens as well as in carcasses.

  3. siRNA for Influenza Therapy

    Directory of Open Access Journals (Sweden)

    Sailen Barik

    2010-07-01

    Full Text Available Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world's population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA, has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here.

  4. siRNA for Influenza Therapy.

    Science.gov (United States)

    Barik, Sailen

    2010-07-01

    Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world's population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA), has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here.

  5. [History of pandemic influenza in Japan].

    Science.gov (United States)

    Matsumoto, Keizo

    2010-09-01

    In Japan, influenza like epidemics were described many times since Heian era. However, Spanish flu as the modern medicine invaded Japan in 1918, thus almost infected 390,000 patients died with associated pneumonia. After the discovery of influenza virus in 1933, Japan experienced pandemic influenza--Asian flu(H2N2) in 1957. After about 10 years, Hong Kong flu (H3N2) came to Japan at 1968. However, we had many reliable antibiotics but had not any antiviral drug at the early time. After year 2000, we fortunately obtained reliable three antiviral drugs such as amantadine, oseltamivir and zanamivir. Moreover, very useful rapid test kits for influenza A and B viruses were developed and used in Japan. 2009 H1N1 influenza epidemic occured in Japan after the great epidemic in Mexico and North America but elderly patient was few. With together, host conditions regarding with high risk are changing. Lessons from past several pandemic influenza are those that many issues for changing high risk conditions, viral genetic changes, developing antiviral agents, developing new useful vaccins and determinating bacterial secondary pathogens are important.

  6. Influenza vaccines: from whole virus preparations to recombinant protein technology.

    Science.gov (United States)

    Huber, Victor C

    2014-01-01

    Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.

  7. High-oxygen and high-carbon dioxide containing atmospheres inhibit growth of food associated moulds

    NARCIS (Netherlands)

    Hoogerwerf, S.W.; Kets, E.P.W.; Dijksterhuis, J.

    2002-01-01

    Aims: The objective of this study was to determine the relationship between the growth of three foodborne fungi and high-oxygen modified atmosphere. Methods and Results: Petri dishes were incubated in a series of connected flasks, which were placed in a climatized room and flushed continuously with

  8. The novel human influenza A(H7N9) virus is naturally adapted to efficient growth in human lung tissue.

    Science.gov (United States)

    Knepper, Jessica; Schierhorn, Kristina L; Becher, Anne; Budt, Matthias; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Gruber, Achim D; Suttorp, Norbert; Schweiger, Brunhilde; Hippenstiel, Stefan; Hocke, Andreas C; Wolff, Thorsten

    2013-10-08

    A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients. Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to

  9. Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

    DEFF Research Database (Denmark)

    Fordyce, Sarah Louise; Bragstad, Karoline; Pedersen, Svend Stenvang

    2013-01-01

    Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly res...

  10. Avian influenza virus (H5N1): a threat to human health

    NARCIS (Netherlands)

    Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

    2007-01-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes.

  11. 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.

  12. 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.

  13. Establishment and evaluation of a theater influenza monitoring platform.

    Science.gov (United States)

    Wang, Jian; Yang, Hui-Suo; Deng, Bing; Shi, Meng-Jing; Li, Xiang-Da; Nian, Qing-Gong; Song, Wen-Jing; Bing, Feng; Li, Qing-Feng

    2017-11-20

    Influenza is an acute respiratory infectious disease with a high incidence rate in the Chinese army, which directly disturbs military training and affects soldiers' health. Influenza surveillance systems are widely used around the world and play an important role in influenza epidemic prevention and control. As a theater centers for disease prevention and control, we established an influenza monitoring platform (IMP) in 2014 to strengthen the monitoring of influenza-like illness and influenza virus infection. In this study, we introduced the constitution, influenza virus detection, and quality control for an IMP. The monitoring effect was also evaluated by comparing the monitoring data with data from national influenza surveillance systems. The experiences and problems associated with the platform also were summarized. A theater IMP was established based on 3 levels of medical units, including monitoring sites, testing laboratories and a checking laboratory. A series of measures were taken to guarantee the quality of monitoring, such as technical training, a unified process, sufficient supervision and timely communication. The platform has run smoothly for 3 monitoring years to date. In the 2014-2015 and 2016-2017 monitoring years, sample amount coincided with that obtained from the National Influenza Surveillance program. In the 2015-2016 monitoring year, due to the strict prevention and control measures, an influenza epidemic peak was avoided in monitoring units, and the monitoring data did not coincide with that of the National Influenza Surveillance program. Several problems, including insufficient attention, unreasonable administrative intervention or subordination relationships, and the necessity of detection in monitoring sites were still observed. A theater IMP was established rationally and played a deserved role in the prevention and control of influenza. However, several problems remain to be solved.

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

    Science.gov (United States)

    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

  15. High Yield Chemical Vapor Deposition Growth of High Quality Large-Area AB Stacked Bilayer Graphene

    Science.gov (United States)

    Liu, Lixin; Zhou, Hailong; Cheng, Rui; Yu, Woo Jong; Liu, Yuan; Chen, Yu; Shaw, Jonathan; Zhong, Xing; Huang, Yu; Duan, Xiangfeng

    2012-01-01

    Bernal stacked (AB stacked) bilayer graphene is of significant interest for functional electronic and photonic devices due to the feasibility to continuously tune its band gap with a vertical electrical field. Mechanical exfoliation can be used to produce AB stacked bilayer graphene flakes but typically with the sizes limited to a few micrometers. Chemical vapor deposition (CVD) has been recently explored for the synthesis of bilayer graphene but usually with limited coverage and a mixture of AB and randomly stacked structures. Herein we report a rational approach to produce large-area high quality AB stacked bilayer graphene. We show that the self-limiting effect of graphene growth on Cu foil can be broken by using a high H2/CH4 ratio in a low pressure CVD process to enable the continued growth of bilayer graphene. A high temperature and low pressure nucleation step is found to be critical for the formation of bilayer graphene nuclei with high AB stacking ratio. A rational design of a two-step CVD process is developed for the growth of bilayer graphene with high AB stacking ratio (up to 90 %) and high coverage (up to 99 %). The electrical transport studies demonstrated that devices made of the as-grown bilayer graphene exhibit typical characteristics of AB stacked bilayer graphene with the highest carrier mobility exceeding 4,000 cm2/V·s at room temperature, comparable to that of the exfoliated bilayer graphene. PMID:22906199

  16. Fibroblast activation protein is dispensable in the anti-influenza immune response in mice.

    Directory of Open Access Journals (Sweden)

    Sioh-Yang Tan

    Full Text Available Fibroblast activation protein alpha (FAP is a unique dual peptidase of the S9B serine protease family, being capable of both dipeptidyl peptidase and endopeptidase activities. FAP is expressed at low level in healthy adult organs including the pancreas, cervix, uterus, submaxillary gland and the skin, and highly upregulated in embryogenesis, chronic inflammation and tissue remodelling. It is also expressed by cancer-associated stromal fibroblasts in more than 90% of epithelial tumours. FAP has enzymatic and non-enzymatic functions in the growth, immunosuppression, invasion and cell signalling of tumour cells. FAP deficient mice are fertile and viable with no gross abnormality, but little data exist on the role of FAP in the immune system. FAP is upregulated in association with microbial stimulation and chronic inflammation, but its function in infection remains unknown. We showed that major populations of immune cells including CD4+ and CD8+ T cells, B cells, dendritic cells and neutrophils are generated and maintained normally in FAP knockout mice. Upon intranasal challenge with influenza virus, FAP mRNA was increased in the lungs and lung-draining lymph nodes. Nonetheless, FAP deficient mice showed similar pathologic kinetics to wildtype controls, and were capable of supporting normal anti-influenza T and B cell responses. There was no evidence of compensatory upregulation of other DPP4 family members in influenza-infected FAP-deficient mice. FAP appears to be dispensable in anti-influenza adaptive immunity.

  17. Influenza A Subtyping

    Science.gov (United States)

    Kaul, Karen L.; Mangold, Kathy A.; Du, Hongyan; Pesavento, Kristen M.; Nawrocki, John; Nowak, Jan A.

    2010-01-01

    Influenza virus subtyping has emerged as a critical tool in the diagnosis of influenza. Antiviral resistance is present in the majority of seasonal H1N1 influenza A infections, with association of viral strain type and antiviral resistance. Influenza A virus subtypes can be reliably distinguished by examining conserved sequences in the matrix protein gene. We describe our experience with an assay for influenza A subtyping based on matrix gene sequences. Viral RNA was prepared from nasopharyngeal swab samples, and real-time RT-PCR detection of influenza A and B was performed using a laboratory developed analyte-specific reagent-based assay that targets a conserved region of the influenza A matrix protein gene. FluA-positive samples were analyzed using a second RT-PCR assay targeting the matrix protein gene to distinguish seasonal influenza subtypes based on differential melting of fluorescence resonance energy transfer probes. The novel H1N1 influenza strain responsible for the 2009 pandemic showed a melting profile distinct from that of seasonal H1N1 or H3N2 and compatible with the predicted melting temperature based on the published novel H1N1 matrix gene sequence. Validation by comparison with the Centers for Disease Control and Prevention real-time RT-PCR for swine influenza A (novel H1N1) test showed this assay to be both rapid and reliable (>99% sensitive and specific) in the identification of the novel H1N1 influenza A virus strain. PMID:20595627

  18. Mild to moderate influenza activity in Europe and the detection of novel A (H1N2) and B viruses during the winter of 2001-02.

    NARCIS (Netherlands)

    Paget, W.J.; Meerhoff, T.J.; Goddard, N.L.

    2002-01-01

    Influenza activity in Europe during the 2001-02 influenza season was mild to moderate. Compared to historical data, the intensity was low in six countries, medium in eleven and high in one country (Spain). The dominant virus circulating in Europe was influenza A(H3N2). Two novel influenza virus

  19. The safety and immunogenicity of influenza vaccine in children with asthma in Mexico.

    Science.gov (United States)

    Pedroza, Alvaro; Huerta, José G; Garcia, Maria de la Luz; Rojas, Arsheli; López-Martínez, Irma; Penagos, Martín; Franco-Paredes, Carlos; Deroche, Christele; Mascareñas, Cesar

    2009-07-01

    The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations. We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population. The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients. Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.

  20. Anti-influenza drugs: the development of sialidase inhibitors.

    Science.gov (United States)

    von Itzstein, Mark; Thomson, Robin

    2009-01-01

    Viruses, particularly those that are harmful to humans, are the 'silent terrorists' of the twenty-first century. Well over four million humans die per annum as a result of viral infections alone. The scourge of influenza virus has plagued mankind throughout the ages. The fact that new viral strains emerge on a regular basis, particularly out of Asia, establishes a continual socio-economic threat to mankind. The arrival of the highly pathogenic avian influenza H5N1 heightened the threat of a potential human pandemic to the point where many countries have put in place 'preparedness plans' to defend against such an outcome. The discovery of the first designer influenza virus sialidase inhibitor and anti-influenza drug Relenza, and subsequently Tamiflu, has now inspired a number of continuing efforts towards the discovery of next generation anti-influenza drugs. Such drugs may act as 'first-line-of-defence' against the spread of influenza infection and buy time for necessary vaccine development particularly in a human pandemic setting. Furthermore, the fact that influenza virus can develop resistance to therapeutics makes these continuing efforts extremely important. An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter.

  1. The role of influenza, RSV and other common respiratory viruses in severe acute respiratory infections and influenza-like illness in a population with a high HIV sero-prevalence, South Africa 2012-2015.

    Science.gov (United States)

    Pretorius, Marthi A; Tempia, Stefano; Walaza, Sibongile; Cohen, Adam L; Moyes, Jocelyn; Variava, Ebrahim; Dawood, Halima; Seleka, Mpho; Hellferscee, Orienka; Treurnicht, Florette; Cohen, Cheryl; Venter, Marietjie

    2016-02-01

    Viruses detected in patients with acute respiratory infections may be the cause of illness or asymptomatic shedding. To estimate the attributable fraction (AF) and the detection rate attributable to illness for each of the different respiratory viruses We compared the prevalence of 10 common respiratory viruses (influenza A and B viruses, parainfluenza virus 1-3; respiratory syncytial virus (RSV); adenovirus, rhinovirus, human metapneumovirus (hMPV) and enterovirus) in both HIV positive and negative patients hospitalized with severe acute respiratory illness (SARI), outpatients with influenza-like illness (ILI), and control subjects who did not report any febrile, respiratory or gastrointestinal illness during 2012-2015 in South Africa. We enrolled 1959 SARI, 3784 ILI and 1793 controls with a HIV sero-prevalence of 26%, 30% and 43%, respectively. Influenza virus (AF: 86.3%; 95%CI: 77.7-91.6%), hMPV (AF: 85.6%; 95%CI: 72.0-92.6%), and RSV (AF: 83.7%; 95%CI: 77.5-88.2%) infections were associated with severe disease., while rhinovirus (AF: 46.9%; 95%CI: 37.6-56.5%) and adenovirus (AF: 36.4%; 95%CI: 20.6-49.0%) were only moderately associated. Influenza, RSV and hMPV can be considered pathogens if detected in ILI and SARI while rhinovirus and adenovirus were commonly identified in controls suggesting that they may cause only a proportion of clinical disease observed in positive patients. Nonetheless, they may be important contributors to disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Avian influenza virus

    Science.gov (United States)

    Avian influenza virus (AIV) is type A influenza that is adapted to avian host species. Although the virus can be isolated from numerous avian species, the natural host reservoir species are dabbling ducks, shorebirds and gulls. Domestic poultry species (poultry being defined as birds that are rais...

  3. ADULT INFLUENZA VACCINATION GUIDELINE

    African Journals Online (AJOL)

    Infections with the influenza virus and Streptococcus pneumoniae are associated with ... .well as the potential benefit and the safety of the vaccine ..... 4.6 Antiviral agents for influenza A2 ... persons who are to travel to other areas, e.g. northern.

  4. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

    Science.gov (United States)

    van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

    2010-04-01

    Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

  5. Avian Influenza: Potential Impact on Sub-Saharan Military Populations with High Rates of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

    National Research Council Canada - National Science Library

    Feldman, Robert L; Nickell, Kent

    2007-01-01

    ...)/acquired immunodeficiency syndrome. With the arrival of avian influenza in Africa, the potential exists that some of those soldiers might also become infected with H5N1, the virus responsible for the disease...

  6. Cell culture based production of avian influenza vaccines

    NARCIS (Netherlands)

    Wielink, van R.

    2012-01-01

    Vaccination of poultry can be used as a tool to control outbreaks of avian influenza, including that of highly pathogenic H5 and H7 strains. Influenza vaccines are traditionally produced in embryonated chicken eggs. Continuous cell lines have been suggested as an alternative substrate to produce

  7. Detecting emerging transmissibility of avian influenza virus in human households

    NARCIS (Netherlands)

    Boven, M. van; Koopmans, M.; Du Ry van Beest Holle, M.; Meijer, Adam; Klinkenberg, D.; Donnelly, C.A.; Heesterbeek, J.A.P.

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore,

  8. Detecting emerging transmissibility of avian influenza virus in human households

    NARCIS (Netherlands)

    Boven, van R.M.; Koopmans, M.; Du Ry Beest Holle, van M.; Meijer, A.; Klinkenberg, D.; Donnelly, C.; Heesterbeek, J.A.P.

    2007-01-01

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore,

  9. The pathogenesis of H7N8 low and highly pathogenic avian influenza viruses from the United States 2016 outbreak in chickens, turkeys and mallards.

    Directory of Open Access Journals (Sweden)

    Mary J Pantin-Jackwood

    Full Text Available In January 2016, a combined outbreak of highly pathogenic (HP avian influenza virus (AIV and low pathogenicity (LP AIV occurred in commercial turkeys in the state of Indiana, United States. Genetically, the viruses were highly similar, belonged to the North American wild bird lineage, and had not been previously detected in poultry. In order to understand the pathobiology of the H7N8 LPAIV and HPAIV, infectivity, transmission and pathogenicity studies were conducted in chickens, turkeys, and mallards. Among the three species the lowest mean infectious dose for both the LP and HP phenotype was for turkeys, and also disease from the LPAIV was only observed with turkeys. Furthermore, although the HPAIV was lethal for both chickens and turkeys, clinical signs caused by the HPAIV isolate differed between the two species; neurological signs were only observed in turkeys. Mallards could be infected with and transmit both viruses to contacts, but neither caused clinical disease. Interestingly, with all three species, the mean infectious dose of the HP isolate was at least ten times lower than that of the LP isolate. This study corroborates the high susceptibility of turkeys to AIV as well as a pathobiology that is different from chickens. Further, this study demonstrates that mallards can be asymptomatically infected with HP and LP AIV from gallinaceous poultry and may not just be involved in transmitting AIV to them.

  10. The pathogenesis of H7N8 low and highly pathogenic avian influenza viruses from the United States 2016 outbreak in chickens, turkeys and mallards

    Science.gov (United States)

    Pantin-Jackwood, Mary J.; Stephens, Christopher B.; Bertran, Kateri; Swayne, David E.

    2017-01-01

    In January 2016, a combined outbreak of highly pathogenic (HP) avian influenza virus (AIV) and low pathogenicity (LP) AIV occurred in commercial turkeys in the state of Indiana, United States. Genetically, the viruses were highly similar, belonged to the North American wild bird lineage, and had not been previously detected in poultry. In order to understand the pathobiology of the H7N8 LPAIV and HPAIV, infectivity, transmission and pathogenicity studies were conducted in chickens, turkeys, and mallards. Among the three species the lowest mean infectious dose for both the LP and HP phenotype was for turkeys, and also disease from the LPAIV was only observed with turkeys. Furthermore, although the HPAIV was lethal for both chickens and turkeys, clinical signs caused by the HPAIV isolate differed between the two species; neurological signs were only observed in turkeys. Mallards could be infected with and transmit both viruses to contacts, but neither caused clinical disease. Interestingly, with all three species, the mean infectious dose of the HP isolate was at least ten times lower than that of the LP isolate. This study corroborates the high susceptibility of turkeys to AIV as well as a pathobiology that is different from chickens. Further, this study demonstrates that mallards can be asymptomatically infected with HP and LP AIV from gallinaceous poultry and may not just be involved in transmitting AIV to them. PMID:28481948

  11. Bacterially produced recombinant influenza vaccines based on virus-like particles.

    Directory of Open Access Journals (Sweden)

    Andrea Jegerlehner

    Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.

  12. Growth

    Science.gov (United States)

    John R. Jones; George A. Schier

    1985-01-01

    This chapter considers aspen growth as a process, and discusses some characteristics of the growth and development of trees and stands. For the most part, factors affecting growth are discussed elsewhere, particularly in the GENETICS AND VARIATION chapter and in chapters in PART 11. ECOLOGY. Aspen growth as it relates to wood production is examined in the WOOD RESOURCE...

  13. Simplifying influenza vaccination during pandemics : sublingual priming and intramuscular boosting of immune responses with heterologous whole inactivated influenza vaccine

    NARCIS (Netherlands)

    Murugappan, Senthil; Patil, Harshad P; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

    2014-01-01

    The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been

  14. High-Level Systemic Expression of Conserved Influenza Epitope in Plants on the Surface of Rod-Shaped Chimeric Particles

    Directory of Open Access Journals (Sweden)

    Natalia V. Petukhova

    2014-04-01

    Full Text Available Recombinant viruses based on the cDNA copy of the tobacco mosaic virus (TMV genome carrying different versions of the conserved M2e epitope from influenza virus A cloned into the coat protein (CP gene were obtained and partially characterized by our group previously; cysteines in the human consensus M2e sequence were changed to serine residues. This work intends to show some biological properties of these viruses following plant infections. Agroinfiltration experiments on Nicotiana benthamiana confirmed the efficient systemic expression of M2e peptides, and two point amino acid substitutions in recombinant CPs significantly influenced the symptoms and development of viral infections. Joint expression of RNA interference suppressor protein p19 from tomato bushy stunt virus (TBSV did not affect the accumulation of CP-M2e-ser recombinant protein in non-inoculated leaves. RT-PCR analysis of RNA isolated from either infected leaves or purified TMV-M2e particles proved the genetic stability of TMV‑based viral vectors. Immunoelectron microscopy of crude plant extracts demonstrated that foreign epitopes are located on the surface of chimeric virions. The rod‑shaped geometry of plant-produced M2e epitopes is different from the icosahedral or helical filamentous arrangement of M2e antigens on the carrier virus-like particles (VLP described earlier. Thereby, we created a simple and efficient system that employs agrobacteria and plant viral vectors in order to produce a candidate broad-spectrum flu vaccine.

  15. Growth of high-temperature superconductor crystals from flux

    International Nuclear Information System (INIS)

    Demianets, L.N.; Bykov, A.B.; Melnikov, O.K.; Stishov, S.M.

    1991-01-01

    Crystallization of high-temperature superconductors was studied in La-Sr-Cu-O, Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O systems. Platelet crystals YBa 2 Cu 3 Osub(6.5+x) were obtained by spontaneous crystallization from homogeneous nonstoichiometric melts enriched in barium and copper oxides. Lasub(2-x)Sr x CuO 4 was prepared by slow cooling of melts enriched in copper oxide. Bi 2 (Sr, Ca)sub(n+1)Cu n O y , (n=1;2) was obtained by melting zone travelling. The crystals show transition to superconducting state at T=93K, ΔT 0.2-0.5 K (Y, Ba cuprate), T=87K, ΔT 2K (Bi, Sr, Ca-cuprate). La, Sr-cuprate single crystals obtained by Czochralski method did not show transition to superconducting state. For flux-grown crystals T c was 5-26 K depending on the composition, growth and heat treatment. The short characterization of some accessory phases (Ba 3 Y 2 Cu 3 PtO 10 , Casub(1.75)Srsub(1.5)Cusub(0.75)PtO 6 , BaCuO 2 , Ba 41 Cu 44 O 84 Cl 2 ) is reported. (author). 15 ref s., 8 figs

  16. Stockpiling Ventilators for Influenza Pandemics.

    Science.gov (United States)

    Huang, Hsin-Chan; Araz, Ozgur M; Morton, David P; Johnson, Gregory P; Damien, Paul; Clements, Bruce; Meyers, Lauren Ancel

    2017-06-01

    In preparing for influenza pandemics, public health agencies stockpile critical medical resources. Determining appropriate quantities and locations for such resources can be challenging, given the considerable uncertainty in the timing and severity of future pandemics. We introduce a method for optimizing stockpiles of mechanical ventilators, which are critical for treating hospitalized influenza patients in respiratory failure. As a case study, we consider the US state of Texas during mild, moderate, and severe pandemics. Optimal allocations prioritize local over central storage, even though the latter can be deployed adaptively, on the basis of real-time needs. This prioritization stems from high geographic correlations and the slightly lower treatment success assumed for centrally stockpiled ventilators. We developed our model and analysis in collaboration with academic researchers and a state public health agency and incorporated it into a Web-based decision-support tool for pandemic preparedness and response.

  17. Infectivity, transmission and pathogenicity of H5 highly pathogenic avian influenza clade 2.3.4.4 (H5N8 and H5N2) United States index viruses in Pekin ducks and Chinese geese

    Science.gov (United States)

    In late 2014, a H5N8 highly pathogenic avian influenza (HPAI) virus, clade 2.3.4.4, spread by migratory birds into North America mixing with low pathogenicity AI viruses to produce a H5N2 HPAI virus. The H5N8 and H5N2 HPAI viruses were detected initially in wild waterfowl and backyard birds, and lat...

  18. High frequency chest wall oscillation plus Mechanical In-Exsufflation in Duchenne muscular dystrophy with respiratory complications related to pandemic Influenza A/H1N1

    Directory of Open Access Journals (Sweden)

    G. Crescimanno

    2010-11-01

    Full Text Available Two young boys with Duchenne muscular dystrophy, who had contracted 2009 pandemic influenza A/H1N1 (pH1N1, had been treated with antibiotics and steroids without significant improvement. One of them showed severe scoliosis. After hospitalization chest CT scan revealed extensive pulmonary bilateral segmental atelectasis. Their clinical and radiological findings rapidly improved when a sequential respiratory physiotherapy protocol was adopted that consisted of the application of multiple sessions of high-frequency chest wall oscillations each one followed by mechanically assisted coughing manoeuvres. The protocol was well tolerated, effective, easy to apply and special positioning was not required. Fifteen days after treatment initiation both patients clinically recovered. This treatment can be very helpful for neuromuscular patients, particularly when scoliosis prevents conventional respiratory physiotherapy. Resumo: Duas crianças do sexo masculino com distrofia muscular de Duchenne que contraíram o vírus da gripe pandémica A/H1N1(pH1N1 de 2009 foram tratados com antibióticos e esteróides sem melhoria significativa.Um deles revelou escoliose severa. Depois da hospitalização, um TAC ao peito revelou uma atelectasia pulmonar segmentar bilateral extensa. Os seus resultados clínicos e radiológicos melhoraram rapidamente quando foi adoptado um tratamento de fisioterapia respiratória sequencial, consistente na aplicação de múltiplas sessões de oscilações torácicas de alta frequência, cada uma seguida por exercícios de tosse mecanicamente assistidos. O tratamento foi bem tolerado, eficaz e fácil de aplicar, sendo que não foi necessário um posicionamento especial. Quinze dias depois do início do tratamento, ambos os pacientes se encontravam clinicamente recuperados. Este tratamento pode ser muito útil em pacientes com doenças neuromusculares, particularmente quando a escoliose

  19. High frequency chest wall oscillation plus Mechanical In-Exsufflation in Duchenne muscular dystrophy with respiratory complications related to pandemic Influenza A/H1N1

    Directory of Open Access Journals (Sweden)

    G. Crescimanno

    2010-11-01

    Full Text Available Two young boys with Duchenne muscular dystrophy, who had contracted 2009 pandemic influenza A/H1N1 (pH1N1, had been treated with antibiotics and steroids without significant improvement. One of them showed severe scoliosis. After hospitalization chest CT scan revealed extensive pulmonary bilateral segmental atelectasis. Their clinical and radiological findings rapidly improved when a sequential respiratory physiotherapy protocol was adopted that consisted of the application of multiple sessions of high-frequency chest wall oscillations, each one followed by mechanically assisted coughing manoeuvres. The protocol was well tolerated, effective, easy to apply and special positioning was not required. Fifteen days after treatment initiation both patients clinically recovered. This treatment can be very helpful for neuromuscular patients, particularly when scoliosis prevents conventional respiratory physiotherapy. Resumo: Duas crianças do sexo masculino com distrofia muscular de Duchenne que contraíram o vírus da gripe pandémica A/H1N1(pH1N1 de 2009 foram tratados com antibióticos e esteróides sem melhoria significativa.Um deles revelou escoliose severa. Depois da hospitalização, um TAC ao peito revelou uma atelectasia pulmonar segmentar bilateral extensa. Os seus resultados clínicos e radiológicos melhoraram rapidamente quando foi adoptado um tratamento de fisioterapia respiratória sequencial, consistente na aplicação de múltiplas sessões de oscilações torácicas de alta frequência, cada uma seguida por exercícios de tosse mecanicamente assistidos. O tratamento foi bem tolerado, eficaz e fácil de aplicar, sendo que não foi necessário um posicionamento especial. Quinze dias depois do início do tratamento, ambos os pacientes se encontravam clinicamente recuperados. Este tratamento pode ser muito útil em pacientes com doenças neuromusculares, particularmente quando a escoliose

  20. Intranasal immunization of baculovirus displayed hemagglutinin confers complete protection against mouse adapted highly pathogenic H7N7 reassortant influenza virus.

    Directory of Open Access Journals (Sweden)

    Subaschandrabose Rajesh Kumar

    Full Text Available BACKGROUND: Avian influenza A H7N7 virus poses a pandemic threat to human health because of its ability for direct transmission from domestic poultry to humans and from human to human. The wide zoonotic potential of H7N7 combined with an antiviral immunity inhibition similar to pandemic 1918 H1N1 and 2009 H1N1 influenza viruses is disconcerting and increases the risk of a putative H7N7 pandemic in the future, underlining the urgent need for vaccine development against this virus. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we developed a recombinant vaccine by expressing the H7N7-HA protein on the surface of baculovirus (Bac-HA. The protective efficacy of the live Bac-HA vaccine construct was evaluated in a mouse model by challenging mice immunized intranasally (i.n. or subcutaneously (s.c. with high pathogenic mouse adapted H7N7 reassorted strain. Although s.c. injection of live Bac-HA induced higher specific IgG than i.n. immunization, the later resulted in an elevated neutralization titer. Interestingly, 100% protection from the lethal viral challenge was only observed for the mice immunized intranasally with live Bac-HA, whereas no protection was achieved in any other s.c. or i.n. immunized mice groups. In addition, we also observed higher mucosal IgA as well as increased IFN-γ and IL-4 responses in the splenocytes of the surviving mice coupled with a reduced viral titer and diminished histopathological signs in the lungs. CONCLUSION: Our results indicated that protection from high pathogenic H7N7 (NL/219/03 virus requires both mucosal and systemic immune responses in mice. The balance between Th1 and Th2 cytokines is also required for the protection against the H7N7 pathogen. Intranasal administration of live Bac-HA induced all these immune responses and protected the mice from lethal viral challenge. Therefore, live Bac-HA is an effective vaccine candidate against H7N7 viral infections.

  1. Experimental infection with highly pathogenic H5N8 avian influenza viruses in the Mandarin duck (Aix galericulata) and domestic pigeon (Columba livia domestica).

    Science.gov (United States)

    Kwon, Jung-Hoon; Noh, Yun Kyung; Lee, Dong-Hun; Yuk, Seong-Su; Erdene-Ochir, Tseren-Ochir; Noh, Jin-Yong; Hong, Woo-Tack; Jeong, Jei-Hyun; Jeong, Sol; Gwon, Gyeong-Bin; Song, Chang-Seon; Nahm, Sang-Soep

    2017-05-01

    Wild birds play a major role in the evolution, maintenance, and dissemination of highly pathogenic avian influenza viruses (HPAIV). Sub-clinical infection with HPAI in resident wild birds could be a source of dissemination of HPAIV and continuous outbreaks. In this study, the pathogenicity and infectivity of two strains of H5N8 clade 2.3.4.4 virus were evaluated in the Mandarin duck (Aix galericulata) and domestic pigeon (Columba livia domestica). None of the birds experimentally infected with H5N8 viruses showed clinical signs or mortality. The H5N8 viruses efficiently replicated in the virus-inoculated Mandarin ducks and transmitted to co-housed Mandarin ducks. Although relatively high levels of viral shedding were noted in pigeons, viral shedding was not detected in some of the pigeons and the shedding period was relatively short. Furthermore, the infection was not transmitted to co-housed pigeons. Immunohistochemical examination revealed the presence of HPAIV in multiple organs of the infected birds. Histopathological evaluation showed the presence of inflammatory responses primarily in HPAIV-positive organs. Our results indicate that Mandarin ducks and pigeons can be infected with H5N8 HPAIV without exhibiting clinical signs; thus, they may be potential healthy reservoirs of the H5N8 HPAIV. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. First introduction of highly pathogenic H5NI avian influenza A viruses in wild and domestic birds in Denmark, Northern Europe

    DEFF Research Database (Denmark)

    Bragstad, K.; Jørgensen, Poul Henrik; Handberg, Kurt

    2007-01-01

    Background: Since 2005 highly pathogenic ( HP) avian influenza A H5N1 viruses have spread from Asia to Africa and Europe infecting poultry, humans and wild birds. HP H5N1 virus was isolated in Denmark for the first time in March 2006. A total of 44 wild birds were found positive for the HP H5N1...... infection. In addition, one case was reported in a backyard poultry flock. Results: Full-genome characterisation of nine isolates revealed that the Danish H5N1 viruses were highly similar to German H5N1 isolates in all genes from the same time period. The haemagglutinin gene grouped phylogenetically in H5...... clade 2 subclade 2 and closest relatives besides the German isolates were isolates from Croatia in 2005, Nigeria and Niger in 2006 and isolates from Astrakhan in Russia 2006. The German and Danish isolates shared unique substitutions in the NA, PB1 and NS2 proteins. Conclusion: The first case of HP H5N1...

  3. A pseudovirus-based hemagglutination-inhibition assay as a rapid, highly sensitive, and specific assay for detecting avian influenza A (H7N9 antibodies

    Directory of Open Access Journals (Sweden)

    Anli Zhang

    2015-06-01

    Full Text Available Background Increased surveillance of avian-origin influenza A (H7N9 virus infection is critical to assess the risk of new outbreaks in China. A high-throughput assay with a good safety profile, sensitivity, and specificity is urgently needed. Methods We used a hemagglutination-inhibition (HI assay based on an H7N9-enveloped pseudovirus to assess serum neutralization antibodies level in 40 H7N9 positive sera and 40 H7N9 negative sera and compared the efficacy of the assay with traditional HI test and micro-neutralization (MN test. Results Spearman’s rank correlation coefficient analysis showed pseudovirus HI (PHI titers correlated well with both HI titers and MN titers. Receiver operating characteristic (ROC curves test revealed using a PHI cut-off titer of 10, the sensitivity and specificity reached 1.0. Conclusions PHI can be used in H7N9-related serological studies. This assay is high-throughput, very sensitive and specific, and cost effective.

  4. Thermal inactivation of H5N2 high-pathogenicity avian influenza virus in dried egg white with 7.5% moisture.

    Science.gov (United States)

    Thomas, Colleen; Swayne, David E

    2009-09-01

    High-pathogenicity avian influenza viruses (HPAIV) cause severe systemic disease with high mortality in chickens. Isolation of HPAIV from the internal contents of chicken eggs has been reported, and this is cause for concern because HPAIV can be spread by movement of poultry products during marketing and trade activity. This study presents thermal inactivation data for the HPAIV strain A/chicken/PA/1370/83 (H5N2) (PA/83) in dried egg white with a moisture content (7.5%) similar to that found in commercially available spray-dried egg white products. The 95% upper confidence limits for D-values calculated from linear regression of the survival curves at 54.4, 60.0, 65.5, and 71.1 degrees C were 475.4, 192.2, 141.0, and 50.1 min, respectively. The line equation y = [0.05494 x degrees C] + 5.5693 (root mean square error = 0.0711) was obtained by linear regression of experimental D-values versus temperature. Conservative predictions based on the thermal inactivation data suggest that standard industry pasteurization protocols would be very effective for HPAIV inactivation in dried egg white. For example, these calculations predict that a 7-log reduction would take only 2.6 days at 54.4 degrees C.

  5. Risk factors for the introduction of high pathogenicity Avian Influenza virus into poultry farms during the epidemic in the Netherlands in 2003.

    Science.gov (United States)

    Thomas, M E; Bouma, A; Ekker, H M; Fonken, A J M; Stegeman, J A; Nielen, M

    2005-06-10

    An epidemic of high pathogenicity Avian Influenza (HPAI) occurred in the Netherlands in 2003. A census survey of 173 infected and 401 uninfected commercial poultry farms was carried out to identify factors associated with the introduction of the HPAI virus into poultry farms. Data on farm size, production characteristics, type of housing, presence of cattle and pigs were gathered by the National Inspection Service for Livestock and Meat from all farms included in this study. For each risk factor (RF) available for analysis, the Mantel-Haenszel odds ratio was calculated (stratified on farm size and housing type). We found an increased risk of HPAI virus introduction in layer finisher type poultry: OR = 2.05 (95% confidence interval, CI = 1.29-3.27). An explanation for this increased risk is the high number of contacts between these farms, especially via cardboard egg trays used for removal of eggs during the epidemic. Our analysis did not indicate significant differences between the infected and uninfected farms with regard to housing type, presence of cattle or pigs. Since layer finisher type farms are assumed to be at higher risk for HPAI virus introduction, more specific control measures might be applied in future outbreaks.

  6. Chimeric avian paramyxovirus-based vector immunization against highly pathogenic avian influenza followed by conventional Newcastle disease vaccination eliminates lack of protection from virulent ND virus

    Directory of Open Access Journals (Sweden)

    C. Steglich

    2014-01-01

    Full Text Available Recently, we described a chimeric, hemagglutinin of highly pathogenic avian influenza virus (HPAIV H5 expressing Newcastle disease virus (NDV-based vector vaccine (chNDVFHNPMV8H5 in which NDV envelope glycoproteins were replaced by those of avian paramyxovirus-8 (APMV-8. This chimeric vaccine induced solid protection against lethal HPAIV H5N1 even in chickens with maternal antibodies against NDV (MDA+. However, due to the absence of the major NDV immunogens it failed to induce protection against Newcastle disease (ND. Here, we report on protection of MDA+ chickens against HPAI H5N1 and ND, by vaccination with chNDVFHNPMV8H5 either on day 1 or day seven after hatch, and subsequent immunization with live attenuated NDV seven days later. Vaccination was well tolerated and three weeks after immunization, challenge infections with highly pathogenic NDV as well as HPAIV H5N1 were carried out. All animals remained healthy without exhibiting any clinical signs, whereas non-vaccinated animals showed morbidity and mortality. Therefore, vaccination with chNDVFHNPMV8H5 can be followed by NDV vaccination to protect chickens from HPAIV as well as NDV, indicating that the antibody response against chNDVFHNPMV8H5 does not interfere with live ND vaccination.

  7. Quantitative assessment of a spatial multicriteria model for highly pathogenic avian influenza H5N1 in Thailand, and application in Cambodia

    Science.gov (United States)

    Paul, Mathilde C.; Goutard, Flavie L.; Roulleau, Floriane; Holl, Davun; Thanapongtharm, Weerapong; Roger, François L.; Tran, Annelise

    2016-01-01

    The Highly Pathogenic Avian Influenza H5N1 (HPAI) virus is now considered endemic in several Asian countries. In Cambodia, the virus has been circulating in the poultry population since 2004, with a dramatic effect on farmers’ livelihoods and public health. In Thailand, surveillance and control are still important to prevent any new H5N1 incursion. Risk mapping can contribute effectively to disease surveillance and control systems, but is a very challenging task in the absence of reliable disease data. In this work, we used spatial multicriteria decision analysis (MCDA) to produce risk maps for HPAI H5N1 in poultry. We aimed to i) evaluate the performance of the MCDA approach to predict areas suitable for H5N1 based on a dataset from Thailand, comparing the predictive capacities of two sources of a priori knowledge (literature and experts), and ii) apply the best method to produce a risk map for H5N1 in poultry in Cambodia. Our results showed that the expert-based model had a very high predictive capacity in Thailand (AUC = 0.97). Applied in Cambodia, MCDA mapping made it possible to identify hotspots suitable for HPAI H5N1 in the Tonlé Sap watershed, around the cities of Battambang and Kampong Cham, and along the Vietnamese border. PMID:27489997

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

    Directory of Open Access Journals (Sweden)

    Jeffrey S Hall

    2009-10-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  10. Emerging highly pathogenic H5 avian influenza viruses in France during winter 2015/16: phylogenetic analyses and markers for zoonotic potential.

    Science.gov (United States)

    Briand, François-Xavier; Schmitz, Audrey; Ogor, Katell; Le Prioux, Aurélie; Guillou-Cloarec, Cécile; Guillemoto, Carole; Allée, Chantal; Le Bras, Marie-Odile; Hirchaud, Edouard; Quenault, Hélène; Touzain, Fabrice; Cherbonnel-Pansart, Martine; Lemaitre, Evelyne; Courtillon, Céline; Gares, Hélène; Daniel, Patrick; Fediaevsky, Alexandre; Massin, Pascale; Blanchard, Yannick; Eterradossi, Nicolas; van der Werf, Sylvie; Jestin, Véronique; Niqueux, Eric

    2017-03-02

    Several new highly pathogenic (HP) H5 avian influenza virus (AIV) have been detected in poultry farms from south-western France since November 2015, among which an HP H5N1. The zoonotic potential and origin of these AIVs immediately became matters of concern. One virus of each subtype H5N1 (150169a), H5N2 (150233) and H5N9 (150236) was characterised. All proved highly pathogenic for poultry as demonstrated molecularly by the presence of a polybasic cleavage site in their HA protein - with a sequence (HQRRKR/GLF) previously unknown among avian H5 HPAI viruses - or experimentally by the in vivo demonstration of an intravenous pathogenicity index of 2.9 for the H5N1 HP isolate. Phylogenetic analyses based on the full genomes obtained by NGS confirmed that the eight viral segments of the three isolates were all part of avian Eurasian phylogenetic lineage but differed from the Gs/Gd/1/96-like lineage. The study of the genetic characteristics at specific amino acid positions relevant for modulating the adaptation to and the virulence for mammals showed that presently, these viruses possess most molecular features characteristic of AIV and lack some major characteristics required for efficient respiratory transmission to or between humans. The three isolates are therefore predicted to have no significant pandemic potential. This article is copyright of The Authors, 2017.

  11. Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

    Science.gov (United States)

    Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

    2016-08-01

    The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration.

  12. The 1918–1920 influenza pandemic in Peru

    Science.gov (United States)

    Chowell, G.; Viboud, C.; Simonsen, L.; Miller, M.A.; Hurtado, J.; Soto, G.; Vargas, R.; Guzman, M.A.; Ulloa, M.; Munayco, C.V.

    2011-01-01

    Background Increasing our knowledge of past influenza pandemic patterns in different regions of the world is crucial to guide preparedness plans against future influenza pandemics. Here, we undertook extensive archival collection efforts from 3 representative cities of Peru (Lima in the central coast, Iquitos in the northeastern Amazon region, Ica in the southern coast) to characterize the age and geographic patterns of the 1918–1920 influenza pandemic in this country. Materials and Methods We analyzed historical documents describing the 1918–1920 influenza pandemic in Peru and retrieved individual mortality records from local provincial archives for quantitative analysis. We applied seasonal excess mortality models to daily and monthly respiratory mortality rates for 1917–1920 and quantified transmissibility estimates based on the daily growth rate in respiratory deaths. Results A total of 52,739 individual mortality records were inspected from local provincial archives. We found evidence for an initial mild pandemic wave during July-September 1918 in Lima, identified a synchronized severe pandemic wave of respiratory mortality in all three locations in Peru during November 1918-February 1919, and a severe pandemic wave during January 1920- March 1920 in Lima and July-October 1920 in Ica. There was no recrudescent pandemic wave in 1920 in Iquitos. Remarkably, Lima experienced the brunt of the 1918–20 excess mortality impact during the 1920 recrudescent wave, with all age groups experiencing an increase in all cause excess mortality from 1918–19 to 1920. Middle age groups experienced the highest excess mortality impact, relative to baseline levels, in the 1918–19 and 1920 pandemic waves. Cumulative excess mortality rates for the 1918–20 pandemic period were higher in Iquitos (2.9%) than Lima (1.6%). The mean reproduction number for Lima was estimated in the range 1.3–1.5. Conclusions We identified synchronized pandemic waves of intense excess

  13. Prospects of HA-Based Universal Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Anwar M. Hashem

    2015-01-01

    Full Text Available Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs. Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA. Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs.

  14. Quantification of the effect of vaccination on transmission of avian influenza (H7N7) in chickens

    NARCIS (Netherlands)

    Goot, van der A.J.; Koch, G.; Jong, de M.C.M.; Boven, van R.M.

    2005-01-01

    Recent outbreaks of highly pathogenic avian influenza (HPAI) viruses in poultry and their threatening zoonotic consequences emphasize the need for effective control measures. Although vaccination of poultry against avian influenza provides a potentially attractive control measure, little is known

  15. Establishing seasonal and alert influenza thresholds in Cambodia using the WHO method: implications for effective utilization of influenza surveillance in the tropics and subtropics.

    Science.gov (United States)

    Ly, Sovann; Arashiro, Takeshi; Ieng, Vanra; Tsuyuoka, Reiko; Parry, Amy; Horwood, Paul; Heng, Seng; Hamid, Sarah; Vandemaele, Katelijn; Chin, Savuth; Sar, Borann; Arima, Yuzo

    2017-01-01

    To establish seasonal and alert thresholds and transmission intensity categories for influenza to provide timely triggers for preventive measures or upscaling control measures in Cambodia. Using Cambodia's influenza-like illness (ILI) and laboratory-confirmed influenza surveillance data from 2009 to 2015, three parameters were assessed to monitor influenza activity: the proportion of ILI patients among all outpatients, proportion of ILI samples positive for influenza and the product of the two. With these parameters, four threshold levels (seasonal, moderate, high and alert) were established and transmission intensity was categorized based on a World Health Organization alignment method. Parameters were compared against their respective thresholds. Distinct seasonality was observed using the two parameters that incorporated laboratory data. Thresholds established using the composite parameter, combining syndromic and laboratory data, had the least number of false alarms in declaring season onset and were most useful in monitoring intensity. Unlike in temperate regions, the syndromic parameter was less useful in monitoring influenza activity or for setting thresholds. Influenza thresholds based on appropriate parameters have the potential to provide timely triggers for public health measures in a tropical country where monitoring and assessing influenza activity has been challenging. Based on these findings, the Ministry of Health plans to raise general awareness regarding influenza among the medical community and the general public. Our findings have important implications for countries in the tropics/subtropics and in resource-limited settings, and categorized transmission intensity can be used to assess severity of potential pandemic influenza as well as seasonal influenza.

  16. 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.

  17. Influenza seasonality in Madagascar: the mysterious African free-runner.

    Science.gov (United States)

    Alonso, Wladimir Jimenez; Guillebaud, Julia; Viboud, Cecile; Razanajatovo, Norosoa Harline; Orelle, Arnaud; Zhou, Steven Zhixiang; Randrianasolo, Laurence; Heraud, Jean-Michel

    2015-05-01

    The seasonal drivers of influenza activity remain debated in tropical settings where epidemics are not clearly phased. Antananarivo is a particularly interesting case study because it is in Madagascar, an island situated in the tropics and with quantifiable connectivity levels to other countries. We aimed at disentangling the role of environmental forcing and population fluxes on influenza seasonality in Madagascar. We compiled weekly counts of laboratory-confirmed influenza-positive specimens for the period 2002 to 2012 collected in Antananarivo, with data available from sub-Saharan countries and countries contributing most foreign travelers to Madagascar. Daily climate indicators were compiled for the study period. Overall, influenza activity detected in Antananarivo predated that identified in temperate Northern Hemisphere locations. This activity presented poor temporal matching with viral activity in other countries from the African continent or countries highly connected to Madagascar excepted for A(H1N1)pdm09. Influenza detection in Antananarivo was not associated with travel activity and, although it was positively correlated with all climatic variables studied, such association was weak. The timing of influenza activity in Antananarivo is irregular, is not driven by climate, and does not align with that of countries in geographic proximity or highly connected to Madagascar. This work opens fresh questions regarding the drivers of influenza seasonality globally particularly in mid-latitude and less-connected regions to tailor vaccine strategies locally. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2017-09-15

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

  19. Pandemic influenza: certain uncertainties

    Science.gov (United States)

    Morens, David M.; Taubenberger, Jeffery K.

    2011-01-01

    SUMMARY For at least five centuries, major epidemics and pandemics of influenza have occurred unexpectedly and at irregular intervals. Despite the modern notion that pandemic influenza is a distinct phenomenon obeying such constant (if incompletely understood) rules such as dramatic genetic change, cyclicity, “wave” patterning, virus replacement, and predictable epidemic behavior, much evidence suggests the opposite. Although there is much that we know about pandemic influenza, there appears to be much more that we do not know. Pandemics arise as a result of various genetic mechanisms, have no predictable patterns of mortality among different age groups, and vary greatly in how and when they arise and recur. Some are followed by new pandemics, whereas others fade gradually or abruptly into long-term endemicity. Human influenza pandemics have been caused by viruses that evolved singly or in co-circulation with other pandemic virus descendants and often have involved significant transmission between, or establishment of, viral reservoirs within other animal hosts. In recent decades, pandemic influenza has continued to produce numerous unanticipated events that expose fundamental gaps in scientific knowledge. Influenza pandemics appear to be not a single phenomenon but a heterogeneous collection of viral evolutionary events whose similarities are overshadowed by important differences, the determinants of which remain poorly understood. These uncertainties make it difficult to predict influenza pandemics and, therefore, to adequately plan to prevent them. PMID:21706672

  20. CD206+ Cell Number Differentiates Influenza A (H1N1pdm09 from Seasonal Influenza A Virus in Fatal Cases

    Directory of Open Access Journals (Sweden)

    Heidi G. Rodriguez-Ramirez

    2014-01-01

    Full Text Available In 2009, a new influenza A (H1N1 virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1pdm09. Cytokines (inflammatory and anti-inflammatory and cellular markers (macrophages and lymphocytes subpopulation markers were analyzed in lung tissue from both influenza A (H1N1pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1pdm09 and seasonal cases when compared with healthy lung tissue (P<0.05. Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1pdm09 and seasonal influenza virus (P<0.05. Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung were found in influenza A (H1N1pdm09 when compared with seasonal influenza virus (P<0.05, and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1pdm09 (P<0.05. In conclusion, CD206+ cells differentiate between influenza A (H1N1pdm09 and seasonal influenza virus in lung tissue of fatal cases.

  1. Growth rate of sheep fed high fat ration

    Directory of Open Access Journals (Sweden)

    Darwinsyah Lubis

    1998-10-01

    Full Text Available Incorporating high amount of fats into the ration for ruminants will affect the rumen microbes adversely and will reducefiber digestion potential. To correct such negative effects, the free fatty acids used for feed should be bond with Ca++, so it canpassing through the rumen savely (rumen by-pass fat. To test the Ca-fat utilization biologically, 20 growing male Garut shee pwere used and fed with 4 type of isocaloric-isoprotein concentrate feed which were allotted based on a randomized block desig nwith 5 replications. The concentrate (C-A was a positive control diet, while C-B was substituted with 10% free fatty acids (negative control, C-C was substituted with 10% Ca-fat, and C-D with 15% Ca-fat. The concentrate feed was fed at 500 g/d, while forage (King grass was 4 kg/d. Results of the experiment showed that the negative effect of free fatty acids can be corrected if it was given in the form of Ca-fat. Growth rate curve indicating a good growing pattern, with average daily gain was 100.18, 87.68, 112.86, and 115.00 g/d (P0.05. Carcass production was relatively good, where for C-A, C-B, C-C, and C-D were 14.84, 14.68, 16.34, and 15.72 kg (P<0.05 respectively, with final live weights of 34.00, 31.74, 34.58, and 34.30 kg (P<0.05. It can be concluded that Ca-fat (rumen by-pass fat can be used as an energy source component for growing sheep diet, and give the best result at 10% substitution rate in concentrate feed.

  2. Influenza A induced cellular signal transduction pathways

    Science.gov (United States)

    Michael, Paul; Brabant, Danielle; Bleiblo, Farag; Ramana, Chilakamarti V.; Rutherford, Michael; Khurana, Sandhya; Tai, T.C.; Kumar, Anand

    2013-01-01

    Influenza A is a negative sense single stranded RNA virus that belongs to the Orthomyxoviridae Family. This enveloped virus contains 8 segments of viral RNA which encodes 11 viral proteins. Influenza A infects humans and is the causative agent of the flu. Annually it infects approximately 5% to 15% of the population world wide and results in an estimated 250,000 to 500,000 deaths a year. The nature of influenza A replication results in a high mutation rate which results in the need for seasonal vaccinations. In addition the zoonotic nature of the influenza virus allows for recombination of viral segments from different strains creating new variants that have not been encountered before. This type of mutation is the method by which pandemic strains of the flu arises. Infection with influenza results in a respiratory illness that for most individuals is self limiting. However in susceptible populations which include individuals with pre-existing pulmonary or cardiac conditions, the very young and the elderly fatal complications may arise. The most serious of these is the development of viral pneumonia which may be accompanied by secondary bacterial infections. Progression of pneumonia leads to the development of acute respiratory distress syndrome (ARDS), acute lung injury (ALI) and potentially respiratory failure. This progression is a combined effect of the host immune system response to influenza infection and the viral infection itself. This review will focus on molecular aspects of viral replication in alveolar cells and their response to infection. The response of select innate immune cells and their contribution to viral clearance and lung epithelial damage will also be discussed. Molecular aspects of antiviral response in the cells in particular the protein kinase RNA dependent response, and the oligoadenylate synthetase RNAse L system in relation to influenza infection. PMID:23977434

  3. 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.

  4. Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses.

    Science.gov (United States)

    Pantin-Jackwood, Mary J; Costa-Hurtado, Mar; Miller, Patti J; Afonso, Claudio L; Spackman, Erica; Kapczynski, Darrell R; Shepherd, Eric; Smith, Diane; Swayne, David E

    2015-05-15

    Infections with avian influenza viruses (AIV) of low and high pathogenicity (LP and HP) and Newcastle disease virus (NDV) are commonly reported in domestic ducks in many parts of the world. However, it is not clear if co-infections with these viruses affect the severity of the diseases they produce, the amount of virus shed, and transmission of the viruses. In this study we infected domestic ducks with a virulent NDV virus (vNDV) and either a LPAIV or a HPAIV by giving the viruses individually, simultaneously, or sequentially two days apart. No clinical signs were observed in ducks infected or co-infected with vNDV and LPAIV, but co-infection decreased the number of ducks shedding vNDV and the amount of virus shed (Pducks inoculated with only LPAIV compared to ducks co-infected with vNDV. Ducks that received the HPAIV with the vNDV simultaneously survived fewer days (Pducks that received the vNDV two days before the HPAIV. Co-infection also reduced transmission of vNDV to naïve contact ducks housed with the inoculated ducks. In conclusion, domestic ducks can become co-infected with vNDV and LPAIV with no effect on clinical signs but with reduction of virus shedding and transmission. These findings indicate that infection with one virus can interfere with replication of another, modifying the pathogenesis and transmission of the viruses. Published by Elsevier B.V.

  5. Evolutionary genetics of highly pathogenic H5N1 avian influenza viruses isolated from whooper swans in northern Japan in 2008.

    Science.gov (United States)

    Usui, Tatsufumi; Yamaguchi, Tsuyoshi; Ito, Hiroshi; Ozaki, Hiroichi; Murase, Toshiyuki; Ito, Toshihiro

    2009-12-01

    In April and May 2008, highly pathogenic avian influenza viruses subtype H5N1 were isolated from dead or moribund whooper swans in Aomori, Akita and Hokkaido prefectures in northern Japan. To trace the genetic lineage of the isolates, the nucleotide sequences of all eight genes were determined and phylogenetically analyzed. The Japanese strains were nearly identical to chicken viruses isolated in Russia in April 2008 and closely related to viruses isolated from dead wild birds in Hong Kong in 2007-2008. Their HA genes clustered in clade 2.3.2. On the other hand, NA and the other internal genes were closely related to those of clade 2.3.4 viruses (genotype V) whose NP genes originated from an HA clade 2.3.2 virus. In conclusion, the H5N1 viruses isolated in Japan, Russia and Hong Kong were derived from a common ancestor virus belonging to genotype V that was generated from genetic reassortment events between viruses of HA clades 2.3.2 and 2.3.4.

  6. Efficacy of two H5N9-inactivated vaccines against challenge with a recent H5N1 highly pathogenic avian influenza isolate from a chicken in Thailand.

    Science.gov (United States)

    Bublot, Michel; Le Gros, François-Xavier; Nieddu, Daniela; Pritchard, Nikki; Mickle, Thomas R; Swayne, David E

    2007-03-01

    The objective of this study was to compare the efficacy of two avian influenza (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68 H5N9; H5N9-WI) or a Eurasian isolate (A/chicken/Italy/22A/98 H5N9; H5N9-It). Three-week-old specific pathogen-free chickens were vaccinated once and challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2 days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It, respectively, were protected against morbidity and mortality. Both vaccines prevented cloacal shedding and significantly reduced oral shedding of the challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were placed in contact with the directly challenged birds 18 hr after challenge. All unvaccinated chickens in contact with unvaccinated challenged birds died within 3 days after contact, whereas unvaccinated chickens in contact with vaccinated challenged birds either showed a significantly delayed mortality or did not become infected. All vaccinated contacts were protected against clinical signs, and most chickens did not shed detectable amount of HPAI virus. Altogether, these data indicate that both vaccines protected very well against morbidity and mortality and reduced or prevented shedding induced by direct or contact exposure to Asian H5N1 HPAI virus.

  7. Overview of incursions of Asian H5N1 subtype highly pathogenic avian influenza virus into Great Britain, 2005-2008.

    Science.gov (United States)

    Alexander, Dennis J; Manvell, Ruth J; Irvine, Richard; Londt, Brandon Z; Cox, Bill; Ceeraz, Vanessa; Banks, Jill; Browna, Ian H

    2010-03-01

    Since 2005 there have been five incursions into Great Britain of highly pathogenic avian influenza (HPAI) viruses of subtype H5N1 related to the ongoing global epizootic. The first incursion occurred in October 2005 in birds held in quarantine after importation from Taiwan. Two incursions related to wild birds: one involved a single dead whooper swan found in March 2006 in the sea off the east coast of Scotland, and the other involved 10 mute swans and a Canada goose found dead over the period extending from late December 2007 to late February 2008 on or close to a swannery on the south coast of England. The other two outbreaks occurred in commercial poultry in January 2007 and November 2007, both in the county of Suffolk. The first of these poultry outbreaks occurred on a large turkey farm, and there was no further spread. The second outbreak occurred on a free-range farm rearing turkeys, ducks, and geese and spread to birds on a second turkey farm that was culled as a dangerous contact. Viruses isolated from these five outbreaks were confirmed to be Asian H5N1 HPAI viruses; the quarantine outbreak was attributed to a clade 2.3 virus and the other four to clade 2.2 viruses. This article describes the outbreaks, their control, and the possible origins of the responsible viruses.

  8. Pathogenicity of Genetically Similar, H5N1 Highly Pathogenic Avian Influenza Virus Strains in Chicken and the Differences in Sensitivity among Different Chicken Breeds

    Science.gov (United States)

    Matsuu, Aya; Kobayashi, Tomoko; Patchimasiri, Tuangthong; Shiina, Takashi; Suzuki, Shingo; Chaichoune, Kridsada; Ratanakorn, Parntep; Hiromoto, Yasuaki; Abe, Haruka; Parchariyanon, Sujira; Saito, Takehiko

    2016-01-01

    Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV. PMID:27078641

  9. Highly Pathogenic Avian Influenza A(H5N1) Viruses at the Animal-Human Interface in Vietnam, 2003-2010.

    Science.gov (United States)

    Creanga, Adrian; Hang, Nguyen Le Khanh; Cuong, Vuong Duc; Nguyen, Ha T; Phuong, Hoang Vu Mai; Thanh, Le Thi; Thach, Nguyen Co; Hien, Pham Thi; Tung, Nguyen; Jang, Yunho; Balish, Amanda; Dang, Nguyen Hoang; Duong, Mai Thuy; Huong, Ngo Thu; Hoa, Do Ngoc; Tho, Nguyen Dang; Klimov, Alexander; Kapella, Bryan K; Gubareva, Larisa; Kile, James C; Hien, Nguyen Tran; Mai, Le Quynh; Davis, C Todd

    2017-09-15

    Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Impact of the implementation of rest days in live bird markets on the dynamics of H5N1 highly pathogenic avian influenza.

    Science.gov (United States)

    Fournié, G; Guitian, F J; Mangtani, P; Ghani, A C

    2011-08-07

    Live bird markets (LBMs) act as a network 'hub' and potential reservoir of infection for domestic poultry. They may therefore be responsible for sustaining H5N1 highly pathogenic avian influenza (HPAI) virus circulation within the poultry sector, and thus a suitable target for implementing control strategies. We developed a stochastic transmission model to understand how market functioning impacts on the transmission dynamics. We then investigated the potential for rest days-periods during which markets are emptied and disinfected-to modulate the dynamics of H5N1 HPAI within the poultry sector using a stochastic meta-population model. Our results suggest that under plausible parameter scenarios, HPAI H5N1 could be sustained silently within LBMs with the time spent by poultry in markets and the frequency of introduction of new susceptible birds' dominant factors determining sustained silent spread. Compared with interventions applied in farms (i.e. stamping out, vaccination), our model shows that frequent rest days are an effective means to reduce HPAI transmission. Furthermore, our model predicts that full market closure would be only slightly more effective than rest days to reduce transmission. Strategies applied within markets could thus help to control transmission of the disease.

  11. Mitigation strategies to reduce the generation and transmission of airborne highly pathogenic avian influenza virus particles during processing of infected poultry.

    Science.gov (United States)

    Bertran, Kateri; Clark, Andrew; Swayne, David E

    2018-06-08

    Airborne transmission of H5N1 highly pathogenic avian influenza (HPAI) viruses has occurred among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry, and such transmission has been experimentally reproduced. In this study, we investigated simple, practical changes in the processing of H5N1 virus-infected chickens to reduce infectious airborne particles and their transmission. Our findings suggest that containing the birds during the killing and bleeding first step by using a disposable plastic bag, a commonly available cooking pot widely used in Egypt (halla), or a bucket significantly reduces generation of infectious airborne particles and transmission to ferrets. Similarly, lack of infectious airborne particles was observed when processing vaccinated chickens that had been challenged with HPAI virus. Moreover, the use of a mechanical defeatherer significantly increased total number of particles in the air compared to manual defeathering. This study confirms that simple changes in poultry processing can efficiently mitigate generation of infectious airborne particles and their transmission to humans. Published by Elsevier GmbH.

  12. Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus.

    Science.gov (United States)

    Li, Sumei; Jia, Xiuhua; Shen, Xintian; Wei, Zhuwen; Jiang, Zhiyan; Liao, Yixian; Guo, Yiming; Zheng, Xiaojun; Zhong, Guohua; Song, Gaopeng

    2017-08-15

    Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC 50 values of 4.05μM and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3β- to 3α-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Counteracting structural errors in ensemble forecast of influenza outbreaks.

    Science.gov (United States)

    Pei, Sen; Shaman, Jeffrey

    2017-10-13

    For influenza forecasts generated using dynamical models, forecast inaccuracy is partly attributable to the nonlinear growth of error. As a consequence, quantification of the nonlinear error structure in current forecast models is needed so that this growth can be corrected and forecast skill improved. Here, we inspect the error growth of a compartmental influenza model and find that a robust error structure arises naturally from the nonlinear model dynamics. By counteracting these structural errors, diagnosed using error breeding, we develop a new forecast approach that combines dynamical error correction and statistical filtering techniques. In retrospective forecasts of historical influenza outbreaks for 95 US cities from 2003 to 2014, overall forecast accuracy for outbreak peak timing, peak intensity and attack rate, are substantially improved for predicted lead times up to 10 weeks. This error growth correction method can be generalized to improve the forecast accuracy of other infectious disease dynamical models.Inaccuracy of influenza forecasts based on dynamical models is partly due to nonlinear error growth. Here the authors address the error structure of a compartmental influenza model, and develop a new improved forecast approach combining dynamical error correction and statistical filtering techniques.

  14. [Influenza surveillance in nine consecutive seasons, 2003-2012: results from National Influenza Reference Laboratory, Istanbul Faculty Of Medicine, Turkey].

    Science.gov (United States)

    Akçay Ciblak, Meral; Kanturvardar Tütenyurd, Melis; Asar, Serkan; Tulunoğlu, Merve; Fındıkçı, Nurcihan; Badur, Selim

    2012-10-01

    Influenza is a public health problem that affects 5-20% of the world population annually causing high morbidity and mortality especially in risk groups. In addition to determining prevention and treatment strategies with vaccines and antivirals, surveillance data plays an important role in combat against influenza. Surveillance provides valuable data on characteristics of influenza activity, on types, sub-types, antigenic properties and antiviral resistance profile of circulating viruses in a given region. The first influenza surveillance was initiated as a pilot study in 2003 by now named National Influenza Reference Laboratory, Istanbul Faculty of Medicine. Surveillance was launched at national level by Ministry of Health in 2004 and two National Influenza Laboratories, one in Istanbul and the other in Ankara, have been conducting surveillance in Turkey. Surveillance data obtained for nine consecutive years, 2003-2012, by National Influenza Reference Laboratory in Istanbul Faculty of Medicine have been summarized in this report. During 2003-2012 influenza surveillance seasons, a total of 11.077 nasal swabs collected in viral transport medium were sent to the National Influenza Reference Laboratory, Istanbul for analysis. Immun-capture ELISA followed by MDCK cell culture was used for detection of influenza viruses before 2009 and real-time RT-PCR was used thereafter. Antigenic characterizations were done by hemagglutination inhibition assay with the reactives supplied by World Health Organization. Analysis of the results showed that influenza B viruses have entered the circulation in 2005-2006 seasons, and have contributed to the epidemics at increasing rates every year except in the 2009 pandemic season. Influenza B Victoria and Yamagata lineages were cocirculating for two seasons. For other seasons either lineage was in circulation. Antigenic characterization revealed that circulating B viruses matched the vaccine composition either partially or totally for only

  15. Mortality Associated With Seasonal and Pandemic Influenza Among Pregnant and Nonpregnant Women of Childbearing Age in a High-HIV-Prevalence Setting-South Africa, 1999-2009.

    Science.gov (United States)

    Tempia, Stefano; Walaza, Sibongile; Cohen, Adam L; von Mollendorf, Claire; Moyes, Jocelyn; McAnerney, Johanna M; Cohen, Cheryl

    2015-10-01

    Information on the mortality burden associated with seasonal and pandemic influenza virus infection among pregnant women is scarce in most settings, particularly in sub-Saharan Africa where pregnancy and maternal mortality rates as well as human immunodeficiency virus (HIV) prevalence are elevated. We used an ecological study design to estimate the seasonal and A(H1N1)pdm09 influenza-associated mortality among pregnant and nonpregnant women of childbearing age (15-49 years) by HIV serostatus during 1999-2009 in South Africa. Mortality rates were expressed per 100 000 person-years. During 1999-2009, the estimated mean annual seasonal influenza-associated mortality rates were 12.6 (123 deaths) and 7.3 (914 deaths) among pregnant and nonpregnant women, respectively. Among pregnant women, the estimated mean annual seasonal influenza-associated mortality rates were 74.9 (109 deaths) among HIV-infected and 1.5 (14 deaths) among HIV-uninfected individuals. Among nonpregnant women, the estimated mean annual seasonal influenza-associated mortality rate was 41.2 (824 deaths) among HIV-infected and 0.9 (90 deaths) among HIV-uninfected individuals. Pregnant women experienced an increased risk of seasonal influenza-associated mortality compared with nonpregnant women (relative risk [RR], 2.8; 95% confidence interval [CI], 1.7-3.9). In 2009, the estimated influenza A(H1N1)pdm09-associated mortality rates were 19.3 (181 deaths) and 9.4 (1189 deaths) among pregnant and nonpregnant women, respectively (RR, 3.2; 95% CI, 2.3-4.1). Among women of childbearing age, the majority of estimated seasonal influenza-associated deaths occurred in HIV-infected individuals. Pregnant women experienced an increased risk of death associated with seasonal and A(H1N1)pdm09 influenza infection compared with nonpregnant women. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. 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.

  17. 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.

  18. Geographical and Historical Patterns in the Emergences of Novel Highly Pathogenic Avian Influenza (HPAI H5 and H7 Viruses in Poultry

    Directory of Open Access Journals (Sweden)

    Madhur S. Dhingra

    2018-06-01

    Full Text Available Over the years, the emergence of novel H5 and H7 highly pathogenic avian influenza viruses (HPAI has been taking place through two main mechanisms: first, the conversion of a low pathogenic into a highly pathogenic virus, and second, the reassortment between different genetic segments of low and highly pathogenic viruses already in circulation. We investigated and summarized the literature on emerging HPAI H5 and H7 viruses with the aim of building a spatio-temporal database of all these recorded conversions and reassortments events. We subsequently mapped the spatio-temporal distribution of known emergence events, as well as the species and production systems that they were associated with, the aim being to establish their main characteristics. From 1959 onwards, we identified a total of 39 independent H7 and H5 LPAI to HPAI conversion events. All but two of these events were reported in commercial poultry production systems, and a majority of these events took place in high-income countries. In contrast, a total of 127 reassortments have been reported from 1983 to 2015, which predominantly took place in countries with poultry production systems transitioning from backyard to intensive production systems. Those systems are characterized by several co-circulating viruses, multiple host species, regular contact points in live bird markets, limited biosecurity within value chains, and frequent vaccination campaigns that impose selection pressures for emergence of novel reassortants. We conclude that novel HPAI emergences by these two mechanisms occur in different ecological niches, with different viral, environmental and host associated factors, which has implications in early detection and management and mitigation of the risk of emergence of novel HPAI viruses.

  19. High Resolution N-Body Simulations of Terrestrial Planet Growth

    Science.gov (United States)

    Clark Wallace, Spencer; Quinn, Thomas R.

    2018-04-01

    We investigate planetesimal accretion with a direct N-body simulation of an annulus at 1 AU around a 1 M_sun star. The planetesimal ring, which initially contains N = 106 bodies is evolved through the runaway growth stage into the phase of oligarchic growth. We find that the mass distribution of planetesimals develops a bump around 1022 g shortly after the oligarchs form. This feature is absent in previous lower resolution studies. We find that this bump marks a boundary between growth modes. Below the bump mass, planetesimals are packed tightly enough together to populate first order mean motion resonances with the oligarchs. These resonances act to heat the tightly packed, low mass planetesimals, inhibiting their growth. We examine the eccentricity evolution of a dynamically hot planetary embryo embedded in an annulus of planetesimals and find that dynamical friction acts more strongly on the embryo when the planetesimals are finely resolved. This effect disappears when the annulus is made narrow enough to exclude most of the mean motion resonances. Additionally, we find that the 1022 g bump is significantly less prominent when we follow planetesimal growth with a skinny annulus.This feature, which is reminiscent of the power law break seen in the size distribution of asteroid belt objects may be an important clue for constraining the initial size of planetesimals in planet formation models.

  20. Rheumatoid arthritis and the incidence of influenza and influenza-related complications: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Blumentals William A

    2012-08-01

    Full Text Available Abstract Background Patients with rheumatoid arthritis (RA are known to be at increased risk of infection, particularly if they are taking drugs with immunomodulatory effects. There is a need for more information on the risk of influenza in patients with RA. Methods A retrospective cohort study was carried out using data gathered from a large US commercial health insurance database (Thomson Reuters Medstat MarketScan from 1 January 2000 to 31 December 2007. Patients were ≥18 years of age, with at least two RA claims diagnoses. The database was scanned for incidence of seasonal influenza and its complications on or up to 30 days after an influenza diagnosis in RA patients and matched controls. Other factors accounted for included medical conditions, use of disease-modifying anti-rheumatic drugs (DMARDs, use of biological agents, influenza vaccination and high- or low-dose corticosteroids. Incidence rate ratios (IRRs were calculated for influenza and its complications in patients with RA. Results 46,030 patients with RA and a matching number of controls had a median age of 57 years. The incidence of influenza was higher in RA patients than in controls (409.33 vs 306.12 cases per 100,000 patient-years, and there was a 2.75-fold increase in incidence of complications in RA. Presence or absence of DMARDs or biologics had no significant effect. The adjusted IRR of influenza was statistically significant in patients aged 60–69 years, and especially among men. A significantly increased rate of influenza complications was observed in women and in both genders combined (but not in men only when all age groups were combined. In general, the risk of influenza complications was similar in RA patients not receiving DMARDs or biologics to that in all RA patients. Pneumonia rates were significantly higher in women with RA. Rates of stroke/myocardial infarction (MI were higher in men, although statistical significance was borderline. Conclusions RA is

  1. Avian influenza A (H5N1)

    NARCIS (Netherlands)

    de Jong, Menno D.; Hien, Tran Tinh

    2006-01-01

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

  2. New reassortant and enzootic European swine influenza viruses transmit efficiently through direct contact in the ferret model.

    Science.gov (United States)

    Fobian, Kristina; Fabrizio, Thomas P; Yoon, Sun-Woo; Hansen, Mette Sif; Webby, Richard J; Larsen, Lars E

    2015-07-01

    The reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in Europe. The pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of European pigs with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2, and two were new reassortants, one with avian-like H1 and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titres in nasal wash and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via the airborne route. Growth kinetics using a differentiated human bronchial epithelial cell line showed that all four viruses were able to replicate to high titres. Further, the viruses revealed preferential binding to the 2,6-α-silalylated glycans and investigation of the antiviral susceptibility of the viruses revealed that all were sensitive to neuraminidase inhibitors. These findings suggested that these viruses have the potential to infect humans and further underline the need for continued surveillance as well as biological characterization of new influenza A viruses.

  3. High mortality and poor growth of green mussels, Perna viridis, in high chlorophyll- a environment

    Science.gov (United States)

    Soon, Tan Kar; Denil, Delta Jenetty; Ransangan, Julian

    2016-03-01

    The current study was carried out from May 2014 to April 2015 to estimate the stock status of P. viridis in Marudu Bay. The gonad development was monitored by histological examination, while the population parameters including asymptotic length ( L ∞), growth coefficient ( K), mortality rate ( Z, F and M), exploitation level ( E) and recruitment of P. viridis were estimated using the lengthfrequency data. Results of the current study demonstrated that P. viridis in Marudu Bay spawned throughout the year with two major peaks, one in April to May and another one in October to December. The recruitment pattern was continuous with the peak in May to June 2014, which corresponded to the first spawning peak in April. However, no significant recruitment was observed from the second spawning peak due to the difference in spawning timing between male and female populations. The estimated asymptotic length ( L ∞), growth coefficient ( K), total mortality ( Z), natural mortality ( M), fishing mortality ( F) and growth performance ( φ) of P. viridis in Marudu Bay were estimate to be 117 mm, 0.97 yr-1, 4.39 yr-1, 1.23 yr-1, 3.16 yr-1 and 4.123, respectively. The exponent b of the lengthweight relationship was 2.4 and exploitation level ( E) was 0.72. The high mortality, low condition indices and negative allometric of P. viridis in Marudu Bay is caused by a lack of suitable food in the surrounding water.

  4. The Survey and Analysis of Excellent Senior High School Physics Teachers' Professional Growth Actuality

    Science.gov (United States)

    Sun, Haibin; Liu, Tingting

    2010-01-01

    Excellent senior high school physics teachers are the backbone power in the new course reform of physics in China. The excellent senior high school physics teachers' professional growth actuality in Shandong is surveyed in this article by the self-made "Questionnaire of Excellent Senior High School Physics Teachers' Professional Growth",…

  5. Influenza and IBD

    Science.gov (United States)

    ... to person worldwide, most likely in a similar fashion to regular seasonal influenza viruses. For the this ... endorsement of a particular individual, group, company or product. Related Resources Order Patient Brochures Education & Support for ...

  6. Avian Influenza in Birds

    Science.gov (United States)

    ... the United States Department of Agriculture’s Animal and Plant Health Inspection Service . Surveillance for Avian Influenza CDC, ... maintained by: Office of the Associate Director for Communication, Digital Media Branch, Division of Public Affairs Email ...

  7. Vaccination against seasonal influenza

    CERN Multimedia

    DG Unit

    2009-01-01

    As every year, the Medical Service is taking part in the campaign to promote vaccination against seasonal influenza. Vaccination against seasonal influenza is especially recommended for people suffering from chronic lung, cardio-vascular or kidney conditions or diabetes, for those recovering from a serious illness or surgical operation and for everyone over the age of 65. The influenza virus is transmitted by air and contact with contaminated surfaces, hence the importance of washing hands regularly with soap and / or disinfection using a hydro-alcoholic solution. From the onset of symptoms (fever> 38°, chills, cough, muscle aches and / or joint pain, fatigue) you are strongly recommended to stay at home to avoid spreading the virus. In the present context of the influenza A (H1N1) pandemic, it is important to dissociate these two illnesses and emphasise that the two viruses and the vaccines used to combat them are quite different and that protection against one will not pr...

  8. Vírus influenza

    Directory of Open Access Journals (Sweden)

    Fernanda de-Paris

    2013-06-01

    Full Text Available Um dos registros mais antigos da gripe descrita como doença é de autoria de Hipócrates, em meados do ano 412 a.C. Desta forma, seu agente etiológico, o vírus influenza, tem circulação entre a população humana há muito tempo.  Entretanto, o primeiro isolamento do vírus influenza humano ocorreu somente em 1933, realizado por Smith, Andrewes e Laidlaw, pesquisadores do “National Institute for Medical Research” – Londres. Este vírus isolado foi considerado o primeiro vírus influenza humano e denominado de “influenza A”.

  9. Rivers and flooded areas identified by medium-resolution remote sensing improve risk prediction of the highly pathogenic avian influenza H5N1 in Thailand

    Directory of Open Access Journals (Sweden)

    Weerapong Thanapongtharm

    2013-11-01

    Full Text Available Thailand experienced several epidemic waves of the highly pathogenic avian influenza (HPAI H5N1 between 2004 and 2005. This study investigated the role of water in the landscape, which has not been previously assessed because of a lack of high-resolution information on the distribution of flooded land at the time of the epidemic. Nine Landsat 7- Enhanced Thematic Mapper Plus scenes covering 174,610 km2 were processed using k-means unsupervised classification to map the distribution of flooded areas as well as permanent lakes and reservoirs at the time of the main epidemic HPAI H5N1 wave of October 2004. These variables, together with other factors previously identified as significantly associated with risk, were entered into an autologistic regression model in order to quantify the gain in risk explanation over previously published models. We found that, in addition to other factors previously identified as associated with risk, the proportion of land covered by flooding along with expansion of rivers and streams, derived from an existing, sub-district level (administrative level no. 3 geographical information system database, was a highly significant risk factor in this 2004 HPAI epidemic. These results suggest that water-borne transmission could have partly contributed to the spread of HPAI H5N1 during the epidemic. Future work stemming from these results should involve studies where the actual distribution of small canals, rivers, ponds, rice paddy fields and farms are mapped and tested against farm-level data with respect to HPAI H5N1.

  10. Spatial transmission of H5N6 highly pathogenic avian influenza viruses among wild birds in Ibaraki Prefecture, Japan, 2016-2017.

    Science.gov (United States)

    Tsunekuni, Ryota; Yaguchi, Yuji; Kashima, Yuki; Yamashita, Kaoru; Takemae, Nobuhiro; Mine, Junki; Tanikawa, Taichiro; Uchida, Yuko; Saito, Takehiko

    2018-05-01

    From 29 November 2016 to 24 January 2017, sixty-three cases of H5N6 highly pathogenic avian influenza virus (HPAIV) infections were detected in wild birds in Ibaraki Prefecture, Japan. Here, we analyzed the genetic, temporal, and geographic correlations of these 63 HPAIVs to elucidate their dissemination throughout the prefecture. Full-genome sequence analysis of the Ibaraki isolates showed that 7 segments (PB2, PB1, PA, HA, NP, NA, NS) were derived from G1.1.9 strains while the M segment was from G1.1 strains; both groups of strains circulated in south China. Pathological studies revealed severe systemic infection in dead swans (the majority of dead birds and the only species necropsied), thus indicating high susceptibility to H5N6 HPAIVs. Coalescent phylogenetic analysis using the 7 G1.1.9-derived segments enabled detailed analysis of the short-term evolution of these highly homologous HPAIVs. This analysis revealed that the H5N6 HPAIVs isolated from wild birds in Ibaraki Prefecture were divided into 7 groups. Spatial analysis demonstrated that most of the cases concentrated around Senba Lake originated from a single source, and progeny viruses were transmitted to other locations after the infection expanded in mute swans. In contrast, within just a 5-km radius of the area in which cases were concentrated, three different intrusions of H5N6 HPAIVs were evident. Multi-segment analysis of short-term evolution showed that not only was the invading virus spread throughout Ibaraki Prefecture but also that, despite the small size of this region, multiple invasions had occurred during winter 2016-2017.

  11. Survival of influenza virus on banknotes.

    Science.gov (United States)

    Thomas, Yves; Vogel, Guido; Wunderli, Werner; Suter, Patricia; Witschi, Mark; Koch, Daniel; Tapparel, Caroline; Kaiser, Laurent

    2008-05-01

    Successful control of a viral disease requires knowledge of the different vectors that could promote its transmission among hosts. We assessed the survival of human influenza viruses on banknotes given that billions of these notes are exchanged daily worldwide. Banknotes were experimentally contaminated with representative influenza virus subtypes at various concentrations, and survival was tested after different time periods. Influenza A viruses tested by cell culture survived up to 3 days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase