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Treatment and prevention of avian influenza

Iain Stephenson, MD, FRCP
Section Editor
Martin S Hirsch, MD
Deputy Editor
Anna R Thorner, MD


There have been five influenza pandemics during the past 100 years, and each has been caused by the emergence of a novel virus. In the 1957 and 1968 pandemics, the new viruses contained components of previous human as well as avian influenza viruses. The origin of the influenza virus responsible for the 1918 pandemic, which killed more people in a single year than the bubonic plague, remains uncertain, but it appears to have been an adapted avian influenza strain. The emergence of a novel H1N1 human-swine-avian reassortant virus in 2009 in North America started a new pandemic. (See "Epidemiology of pandemic H1N1 influenza ('swine influenza')".)

Sporadic transmission of avian influenza H5N1 to more than 850 humans since 2003 has prompted concerns that conditions are suitable for emergence of the next pandemic; the case-fatality rate is approximately 53 percent [1]. However, seroprevalence studies have found that some exposed individuals may have had a subclinical or mild infection, suggesting that the reported case-fatality rate may be an overestimate.

The treatment and prevention of H5N1 avian influenza will be reviewed here. The possible role of avian influenza vaccines, and the epidemiology, transmission, pathogenesis, clinical manifestations, and diagnosis of avian influenza are discussed separately. (See "Avian influenza vaccines" and "Epidemiology, transmission, and pathogenesis of avian influenza" and "Clinical manifestations and diagnosis of avian influenza".)

The novel avian influenza A H7N9 virus that emerged in 2013 in China is also presented separately. (See "Avian influenza A H7N9: Epidemiology, clinical manifestations, and diagnosis".)


Two classes of drugs are effective against influenza: adamantanes (amantadine and rimantadine, also known as M2 ion channel inhibitors) and neuraminidase inhibitors (oseltamivir and zanamivir). H5N1 viruses isolated in Thailand and Vietnam have amino acid substitutions within the M2 protein that confer resistance to amantadine and rimantadine [2]. However, these viruses are susceptible to the neuraminidase inhibitors [3].

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Literature review current through: Nov 2017. | This topic last updated: Dec 06, 2016.
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  1. World Health Organization. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003-2016. http://www.who.int/influenza/human_animal_interface/2016_10_03_tableH5N1.pdf?ua=1 (Accessed on December 02, 2016).
  2. Yen HL, Monto AS, Webster RG, Govorkova EA. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis 2005; 192:665.
  3. Li KS, Guan Y, Wang J, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 2004; 430:209.
  4. Adisasmito W, Chan PK, Lee N, et al. Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a Global Patient Registry. J Infect Dis 2010; 202:1154.
  5. Chan PK, Lee N, Zaman M, et al. Determinants of antiviral effectiveness in influenza virus A subtype H5N1. J Infect Dis 2012; 206:1359.
  6. Oner AF, Dogan N, Gasimov V, et al. H5N1 avian influenza in children. Clin Infect Dis 2012; 55:26.
  7. Govorkova EA, Leneva IA, Goloubeva OG, et al. Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob Agents Chemother 2001; 45:2723.
  8. Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med 2007; 357:1450.
  9. Herbreteau CH, Jacquot F, Rith S, et al. Specific polyclonal F(ab')2 neutralize a large panel of highly pathogenic avian influenza A viruses (H5N1) and control infection in mice. Immunotherapy 2014; 6:699.
  10. Bal C, Herbreteau CH, Buchy P, et al. Safety, potential efficacy, and pharmacokinetics of specific polyclonal immunoglobulin F(ab')₂ fragments against avian influenza A (H5N1) in healthy volunteers: a single-centre, randomised, double-blind, placebo-controlled, phase 1 study. Lancet Infect Dis 2015; 15:285.
  11. Chen Y, Qin K, Wu WL, et al. Broad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopes. J Infect Dis 2009; 199:49.
  12. Zheng Q, Xia L, Wu WL, et al. Properties and therapeutic efficacy of broadly reactive chimeric and humanized H5-specific monoclonal antibodies against H5N1 influenza viruses. Antimicrob Agents Chemother 2011; 55:1349.
  13. Sui J, Hwang WC, Perez S, et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 2009; 16:265.
  14. Ekiert DC, Bhabha G, Elsliger MA, et al. Antibody recognition of a highly conserved influenza virus epitope. Science 2009; 324:246.
  15. Ibañez LI, De Filette M, Hultberg A, et al. Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. J Infect Dis 2011; 203:1063.
  16. Holodniy M, Penzak SR, Straight TM, et al. Pharmacokinetics and tolerability of oseltamivir combined with probenecid. Antimicrob Agents Chemother 2008; 52:3013.
  17. Couch RB, Davis BR. Has oseltamivir been shown to be effective for treatment of H5N1 influenza? J Infect Dis 2010; 202:1149.
  18. WHO rapid advice guildelines on pharmacological management of humans infected with avian influenza A (H5N1) virus www.who.int/entity/medicines/publications/WHO_PSM_PAR_2006.6.pdf (Accessed on July 07, 2006).
  19. WHO. Clinical management of human infection with avian influenza A (H5N1) virus http://www.who.int/influenza/resources/documents/clinical_management_h5n1_15_08_2007/en/index.html (Accessed on October 18, 2011).
  20. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus, Abdel-Ghafar AN, Chotpitayasunondh T, et al. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 2008; 358:261.
  21. Liem NT, Tung CV, Hien ND, et al. Clinical features of human influenza A (H5N1) infection in Vietnam: 2004-2006. Clin Infect Dis 2009; 48:1639.
  22. Uyeki TM. Human infection with highly pathogenic avian influenza A (H5N1) virus: review of clinical issues. Clin Infect Dis 2009; 49:279.
  23. Kandun IN, Tresnaningsih E, Purba WH, et al. Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series. Lancet 2008; 372:744.
  24. de Jong MD, Simmons CP, Thanh TT, et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 2006; 12:1203.
  25. Tsiodras S, Mooney JD, Hatzakis A. Role of combination antiviral therapy in pandemic influenza and stockpiling implications. BMJ 2007; 334:293.
  26. Cheung CL, Rayner JM, Smith GJ, et al. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis 2006; 193:1626.
  27. Kandun IN, Wibisono H, Sedyaningsih ER, et al. Three Indonesian clusters of H5N1 virus infection in 2005. N Engl J Med 2006; 355:2186.
  28. Ward P, Small I, Smith J, et al. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother 2005; 55 Suppl 1:i5.
  29. Ong AK, Hayden FG. John F. Enders lecture 2006: antivirals for influenza. J Infect Dis 2007; 196:181.
  30. Mihajlovic ML, Mitrasinovic PM. Another look at the molecular mechanism of the resistance of H5N1 influenza A virus neuraminidase (NA) to oseltamivir (OTV). Biophys Chem 2008; 136:152.
  31. Moscona A. Oseltamivir resistance--disabling our influenza defenses. N Engl J Med 2005; 353:2633.
  32. de Jong MD, Tran TT, Truong HK, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005; 353:2667.
  33. Le QM, Kiso M, Someya K, et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature 2005; 437:1108.
  34. WHO diseases alert: 16 July 2004. Avian Influenza - Necessary precautions to prevent human infection of H5N1, need for virus sharing. www.who.int/csr/don/2004_07_16/en/ (Accessed on December 12, 2005).
  35. WHO interim protocol: rapid operations to contain the initial emergence of pandemic influenza. Updated October 2007. http://www.who.int/csr/disease/avian_influenza/guidelines/draftprotocol/en/ (Accessed on February 01, 2008).
  36. Apisarnthanarak A, Warren DK, Fraser VJ. Issues relevant to the adoption and modification of hospital infection-control recommendations for avian influenza (H5N1 infection) in developing countries. Clin Infect Dis 2007; 45:1338.
  37. Wang H, Feng Z, Shu Y, et al. Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Lancet 2008; 371:1427.
  38. Boltz DA, Rehg JE, McClaren J, et al. Oseltamivir prophylactic regimens prevent H5N1 influenza morbidity and mortality in a ferret model. J Infect Dis 2008; 197:1315.
  39. Sampathkumar P, Maki DG. Avian H5N1 influenza--are we inching closer to a global pandemic? Mayo Clin Proc 2005; 80:1552.
  40. US Department of Health and Human Services. National Strategy for Pandemic Influenza. http://www.whitehouse.gov/homeland/pandemic-influenza.html (Accessed on May 23, 2008).
  41. American College of Physicians, Barnitz L, Berkwits M. The health care response to pandemic influenza. Ann Intern Med 2006; 145:135.
  42. Monto AS, Whitley RJ. Seasonal and pandemic influenza: a 2007 update on challenges and solutions. Clin Infect Dis 2008; 46:1024.
  43. Liu M, Wood JM, Ellis T, et al. Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics. Virology 2003; 314:580.
  44. Longini IM Jr, Halloran ME, Nizam A, Yang Y. Containing pandemic influenza with antiviral agents. Am J Epidemiol 2004; 159:623.
  45. Brett AS, Zuger A. The run on tamiflu--should physicians prescribe on demand? N Engl J Med 2005; 353:2636.
  46. Gostin LO. Medical countermeasures for pandemic influenza: ethics and the law. JAMA 2006; 295:554.
  47. Fedson DS. Meeting the challenge of influenza pandemic preparedness in developing countries. Emerg Infect Dis 2009; 15:365.
  48. Bartlett JG. Planning for avian influenza. Ann Intern Med 2006; 145:141.
  49. British Infection Society, British Thoracic Society, Health Protection Agency. Pandemic flu: clinical management of patients with an influenza-like illness during an influenza pandemic. Provisional guidelines from the British Infection Society, British Thoracic Society, and Health Protection Agency in collaboration with the Department of Health. Thorax 2007; 62 Suppl 1:1.
  50. WHO interim protocol: rapid operations to contain the initial emergence of pandemic influenza. Updated October 2007. http://www.who.int/csr/disease/avian_influenza/guidelines/draftprotocol/en/ (Accessed on May 23, 2008).
  51. Monto AS. The risk of seasonal and pandemic influenza: prospects for control. Clin Infect Dis 2009; 48 Suppl 1:S20.
  52. Ferguson NM, Cummings DA, Fraser C, et al. Strategies for mitigating an influenza pandemic. Nature 2006; 442:448.
  53. Markel H, Lipman HB, Navarro JA, et al. Nonpharmaceutical interventions implemented by US cities during the 1918-1919 influenza pandemic. JAMA 2007; 298:644.
  54. Democratis J, Pareek M, Stephenson I. Use of neuraminidase inhibitors to combat pandemic influenza. J Antimicrob Chemother 2006; 58:911.
  55. Whitley RJ, Bartlett J, Hayden FG, et al. Seasonal and pandemic influenza: recommendations for preparedness in the United States. J Infect Dis 2006; 194 Suppl 2:S155.
  56. Mounier-Jack S, Coker RJ. How prepared is Europe for pandemic influenza? Analysis of national plans. Lancet 2006; 367:1405.
  57. Bartlett JG, Borio L. Healthcare epidemiology: the current status of planning for pandemic influenza and implications for health care planning in the United States. Clin Infect Dis 2008; 46:919.
  58. Oshitani H, Kamigaki T, Suzuki A. Major issues and challenges of influenza pandemic preparedness in developing countries. Emerg Infect Dis 2008; 14:875.
  59. Fineberg HV. Pandemic preparedness and response--lessons from the H1N1 influenza of 2009. N Engl J Med 2014; 370:1335.
  60. Fedson DS. How will physicians respond to the next influenza pandemic? Clin Infect Dis 2014; 58:233.