In the years prior to 2013, avian influenza A H7 viruses were a cause of significant poultry mortality; however, human illness was generally mild. In March 2013, a novel influenza A(H7N9) virus emerged in China as an unexpected cause of severe human illness with 36% mortality. Chinese and other public health officials responded quickly, characterizing the virus and identifying more than 400 cases through use of new technologies and surveillance tools made possible by past preparedness and response efforts. Genetic sequencing, glycan-array receptor-binding assays, and ferret studies reveal the H7N9 virus to have increased binding to mammalian respiratory cells and to have mutations associated with higher virus replication rates and illness severity. New risk-assessment tools indicate H7N9 has the potential for further mammalian adaptation with possible human-to-human transmission. Vigilant virologic and epidemiologic surveillance is needed to monitor H7N9 and detect other unexpected novel influenza viruses that may emerge.


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Literature Cited

  1. Freidl G, Meijer A, de Bruin E. 1.  et al. 2014. Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1). Eurosurveillance 19:8–26 [Google Scholar]
  2. 2. World Health Organ 2014. Cumulative Cases of H5N1 Geneva: WHO http://www.who.int/influenza/human_animal_interface/EN_GIP_20140124CumulativeNumberH5N1cases.pdf?ua=1 [Google Scholar]
  3. Jernigan DB, Cox NJ. 3.  2013. Human influenza: one health, one world. Textbook of Influenza R Webster, A Monto, T Braciale, R Lamb 3–9 Hoboken, NJ: Wiley, 2nd ed.. [Google Scholar]
  4. Belser JA, Bridges CB, Katz JM, Tumpey TM. 4.  2009. Past, present, and possible future human infection with influenza virus A subtype H7. Emerg. Infect. Dis. 15:859–65 [Google Scholar]
  5. Fouchier RA, Schneeberger PM, Rozendaal FW. 5.  et al. 2004. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc. Natl. Acad. Sci. USA 101:1356–61 [Google Scholar]
  6. Tweed SA, Skowronski DM, David ST. 6.  et al. 2004. Human illness from avian influenza H7N3, British Columbia. Emerg. Infect. Dis. 10:2196–99 [Google Scholar]
  7. 7. World Health Organ., Glob. Alert Response 2013. Human Infection with Influenza A(H7N9) Virus in China. Geneva: WHO http://www.who.int/csr/don/2013_04_01/en/index.html [Google Scholar]
  8. Gao R1, Cao B, Hu Y. 8.  et al. 2013. Human infection with a novel avian-origin influenza A(H7N9) virus. N. Engl. J. Med. 368:1888–97 [Google Scholar]
  9. Lam TY, Wang J, Shen Y. 9.  et al. 2013. The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature 502:241–44 [Google Scholar]
  10. Lebarbenchon C, Brown JD, Stallknecht DE. 10.  2013. Evolution of influenza A virus H7 and N9 subtypes, Eastern Asia. Emerg. Infect. Dis. 19:1635–38 [Google Scholar]
  11. 11. Glob. Initiat. Shar. Avian Influenza Data 2014. The GISAID Initiative. Munich: GISAID http://platform.gisaid.org [Google Scholar]
  12. Guan Y, Shortridge KF, Krauss S, Webster RG. 12.  1999. Molecular characterization of H9N2 influenza viruses: Were they the donors of the “internal” genes of H5N1 viruses in Hong Kong?. Proc. Natl. Acad. Sci. USA 96:9363–67 [Google Scholar]
  13. Chen H, Yuan H, Gao R. 13.  et al. 2014. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet 383:714–21 [Google Scholar]
  14. Schrauwen EJ, Herfst S, Leijten LM. 14.  et al. 2012. The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets. J. Virol. 86:3975–84 [Google Scholar]
  15. Yang H1, Carney PJ, Chang JC. 15.  et al. 2013. Structural analysis of the hemagglutinin from the recent 2013 H7N9 influenza virus. J. Virol. 87:12433–46 [Google Scholar]
  16. Belser JA, Gustin KM, Pearce MB. 16.  et al. 2013. Pathogenesis and transmission of avian influenza A(H7N9) virus in ferrets and mice. Nature 501:556–59 [Google Scholar]
  17. Chen Y, Liang W, Yang S. 17.  et al. 2013. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet 381:1916–25 [Google Scholar]
  18. Gao Y, Zhang Y, Shinya K. 18.  et al. 2009. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLOS Pathog. 5:e1000709 [Google Scholar]
  19. Li Z, Chen H, Jiao P. 19.  et al. 2005. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J. Virol. 79:12058–64 [Google Scholar]
  20. Sleeman K, Guo Z, Barnes J. 20.  et al. 2013. R292K substitution and drug susceptibility of influenza A(H7N9) viruses. Emerg. Infect. Dis. 19:1521–24 [Google Scholar]
  21. Hai R, Schmolke M, Leyva-Grado VH. 21.  et al. 2013. Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility. Nat. Commun. 4:2854 [Google Scholar]
  22. Reed C, Katz JM, Hancock K. 22.  et al. 2012. Prevalence of seropositivity to pandemic influenza A/H1N1 virus in the United States following the 2009 pandemic. PLOS ONE 7:e48187 [Google Scholar]
  23. Xu C, Havers F, Wang L. 23.  et al. 2013. Monitoring avian influenza A(H7N9) virus through national influenza-like illness surveillance, China. Emerg. Infect. Dis. 19:1289–92 [Google Scholar]
  24. Xiang N, Havers F, Chen T. 24.  et al. 2013. Use of national pneumonia surveillance to describe influenza A(H7N9) virus epidemiology, China, 2004–2013. Emerg. Infect. Dis. 19:1784–90 [Google Scholar]
  25. Fung IC, Fu KW, Ying Y. 25.  et al. 2013. Chinese social media reaction to the MERS-CoV and avian influenza A(H7N9) outbreaks. Infect. Dis. Poverty 2:31 [Google Scholar]
  26. 26. Cent. Dis. Control Prev 2010. Estimates of deaths associated with seasonal influenza: United States, 1976–2007. Morb. Mortal. Wkly. Rep. 59:1057–62 [Google Scholar]
  27. Wang C, Yu H, Horby P. 27.  et al. 2014. Comparison of patients hospitalized with influenza A subtypes H7N9, H5N1, and 2009 pandemic H1N1. Clin. Infect. Dis. 58:1095–103 [Google Scholar]
  28. Fuller T, Havers F, Xu C. 28.  et al. 2014. Identifying areas with a high risk of human infection with the avian influenza A(H7N9) virus in East Asia. J. Infect. 69:174–81 [Google Scholar]
  29. Li Q, Zhou L, Zhou M. 29.  et al. 2014. Epidemiology of human infections with avian influenza A(H7N9) virus in China. N. Engl. J. Med. 370:520–32 [Google Scholar]
  30. Bai T, Zhou J, Shu Y. 30.  2013. Serologic study for influenza A(H7N9) among high-risk groups in China. N. Engl. J. Med. 368:2339–40 [Google Scholar]
  31. Wang X, Fang S, Lu X. 31.  et al. 2014. Seroprevalence to avian influenza A(H7N9) virus among poultry workers and the general population in southern China: a longitudinal study. Clin. Infect. Dis. 59:e76–83 [Google Scholar]
  32. 32. ChinaDaily 2014. H7N9 virus not detected in poultry farms: MOA. ChinaDaily updated Jan. 27. http://www.chinadaily.com.cn/china/2014-01/27/content_17261482.htm [Google Scholar]
  33. Wang C, Wang J, Su W. 33.  et al. 2014. Relationship between domestic and wild birds in live poultry market and a novel human H7N9 virus in China. J. Infect. Dis. 209:34–37 [Google Scholar]
  34. Qi J, Jiang D, Wang H. 34.  et al. 2014. Calculating the burden of disease of avian-origin H7N9 infections in China. BMJ Open 4:e004189 [Google Scholar]
  35. Wu Y, Gao G. 35.  2013. Lessons learnt from the human infections of avian-origin influenza A H7N9 virus: live free markets and human health. Sci. China Life Sci. 56:493–94 [Google Scholar]
  36. Yu H, Wu J, Cowling B. 36.  et al. 2014. Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. Lancet 383:541–48 [Google Scholar]
  37. Chowell G, Simonsen L, Towers S. 37.  et al. 2013. Transmission potential of influenza A/H7N9, February to May 2013, China. BMC Med. 11:214 [Google Scholar]
  38. 38. Cent. Dis. Control Prev 2012. Influenza Risk Assessment Tool. Atlanta, GA: CDC http://www.cdc.gov/flu/pandemic-resources/tools/risk-assessment.htm [Google Scholar]
  39. Trock SC, Burke SA, Cox NJ. 39.  2012. Development of an influenza virologic risk assessment tool. Avian Dis. 56:1058–61 [Google Scholar]
  40. Dormitzer PR, Suphaphiphat P, Gibson DG. 40.  et al. 2013. Synthetic generation of influenza vaccine viruses for rapid response to pandemics. Sci. Transl. Med. 5:185ra68 [Google Scholar]

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