Avian influenza A H7N9: Treatment and prevention
- Anna R Thorner, MD
Anna R Thorner, MD
- Deputy Editor — Infectious Diseases
- Assistant Professor of Medicine, Part-time
- Harvard Medical School
In late March and April 2013, human cases of severe pneumonia caused by novel avian influenza A H7N9 infection in China were reported to the World Health Organization [1-7]. The number of new cases in the first wave peaked in April and then decreased , likely related, at least in part, to implementation of control strategies including closure of live bird markets and increased public awareness. A rise in the number of cases occurred in late 2013 and early 2014, late 2014 and early 2015, and late 2016 and early 2017, coinciding with influenza season . Cases continue to be detected [10,11].
The treatment and prevention of avian influenza A H7N9 infections will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of avian influenza A H7N9 infections are discussed separately. (See "Avian influenza A H7N9: Epidemiology, clinical manifestations, and diagnosis".)
Other avian influenza viruses (eg, H5N1 influenza) and seasonal influenza viruses are also reviewed separately. (See "Epidemiology, transmission, and pathogenesis of avian influenza" and "Clinical manifestations and diagnosis of avian influenza" and "Treatment and prevention of avian influenza" and "Avian influenza vaccines" and "Epidemiology of influenza" and "Clinical manifestations of seasonal influenza in adults" and "Diagnosis of seasonal influenza in adults" and "Seasonal influenza in children: Clinical features and diagnosis" and "Treatment of seasonal influenza in adults" and "Seasonal influenza in children: Prevention and treatment with antiviral drugs" and "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines".)
Avian influenza A H7N9 virus appears to be resistant to the adamantanes (amantadine and rimantadine) but currently susceptible to the neuraminidase inhibitors (oseltamivir and zanamivir) [5,12,13]. However, an arginine-to-lysine mutation at position 292 of the neuraminidase protein has been detected in several clinical isolates [4,5,14-16]. This mutation has been associated with in vitro resistance to neuraminidase inhibitors in another N9 influenza virus .
The United States Centers for Disease Control and Prevention (CDC) released updated treatment guidelines for avian influenza A H7N9 infection on September 30, 2013 . The recommendations below are in accordance with the CDC’s guidelines. Clinicians should check the CDC website for updated recommendations.
- World Health Organization. Global alert and response. H7N9 avian influenza human infections in China. http://www.who.int/csr/don/2013_04_01/en/index.html (Accessed on April 03, 2013).
- World Health Organization. Global alert and response. Human infection with influenza A(H7N9) virus in China - update. http://www.who.int/csr/don/2013_04_04/en/index.html (Accessed on April 04, 2013).
- World Health Organization. Global alert and response. Human infection with influenza A(H7N9) in China – update. http://www.who.int/csr/don/2013_04_03/en/index.html (Accessed on April 03, 2013).
- Gao R, Cao B, Hu Y, et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 2013; 368:1888.
- Uyeki TM, Cox NJ. Global concerns regarding novel influenza A (H7N9) virus infections. N Engl J Med 2013; 368:1862.
- Li Q, Zhou L, Zhou M, et al. Epidemiology of human infections with avian influenza A(H7N9) virus in China. N Engl J Med 2014; 370:520.
- Centers for Disease Control and Prevention (CDC). Emergence of avian influenza A(H7N9) virus causing severe human illness - China, February-April 2013. MMWR Morb Mortal Wkly Rep 2013; 62:366.
- Cowling BJ, Jin L, Lau EH, et al. Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratory-confirmed cases. Lancet 2013; 382:129.
- World Health Organization. Influenza at the human-animal interface. Summary and assessment, 4 October to 21 November 2016. http://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_11_15_2016.pdf?ua=1 (Accessed on November 30, 2016).
- Xiang N, Li X, Ren R, et al. Assessing Change in Avian Influenza A(H7N9) Virus Infections During the Fourth Epidemic - China, September 2015-August 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1390.
- World Health Organization. Human infection with avian influenza A(H7N9) virus – China. http://www.who.int/csr/don/17-january-2017-ah7n9- (Accessed on January 17, 2017).
- Zhou J, Wang D, Gao R, et al. Biological features of novel avian influenza A (H7N9) virus. Nature 2013; 499:500.
- Baranovich T, Burnham AJ, Marathe BM, et al. The neuraminidase inhibitor oseltamivir is effective against A/Anhui/1/2013 (H7N9) influenza virus in a mouse model of acute respiratory distress syndrome. J Infect Dis 2014; 209:1343.
- Kageyama T, Fujisaki S, Takashita E, et al. Genetic analysis of novel avian A(H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro Surveill 2013; 18:20453.
- Hu Y, Lu S, Song Z, et al. Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. Lancet 2013; 381:2273.
- Lin PH, Chao TL, Kuo SW, et al. Virological, serological, and antiviral studies in an imported human case of avian influenza A(H7N9) virus in Taiwan. Clin Infect Dis 2014; 58:242.
- Centers for Disease Control and Prevention. Interim guidance on the use of antiviral agents for treatment of human infections with avian influenza A (H7N9) virus. http://www.cdc.gov/flu/avianflu/h7n9-antiviral-treatment.htm (Accessed on October 14, 2013).
- From SARS to H7N9: will history repeat itself? Lancet 2013; 381:1333.
- Gao HN, Lu HZ, Cao B, et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med 2013; 368:2277.
- Hay AJ, Hayden FG. Oseltamivir resistance during treatment of H7N9 infection. Lancet 2013; 381:2230.
- Zürcher T, Yates PJ, Daly J, et al. Mutations conferring zanamivir resistance in human influenza virus N2 neuraminidases compromise virus fitness and are not stably maintained in vitro. J Antimicrob Chemother 2006; 58:723.
- Marjuki H, Mishin VP, Chesnokov AP, et al. Characterization of drug-resistant influenza A(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan. J Infect Dis 2015; 211:249.
- World Health Organization. Analysis of recent scientific information on avian influenza A(H7N9) virus - 10 February 2017. http://www.who.int/influenza/human_animal_interface/avian_influenza/riskassessment_AH7N9_201702/en/ (Accessed on February 15, 2017).
- Marjuki H, Mishin VP, Chesnokov AP, et al. An investigational antiviral drug, DAS181, effectively inhibits replication of zoonotic influenza A virus subtype H7N9 and protects mice from lethality. J Infect Dis 2014; 210:435.
- Wang Y. The H7N9 influenza virus in China--changes since SARS. N Engl J Med 2013; 368:2348.
- Wu S, Wu F, He J. Emerging risk of H7N9 influenza in China. Lancet 2013; 381:1539.
- Yu H, Wu JT, Cowling BJ, et al. Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. Lancet 2014; 383:541.
- Xu J, Lu S, Wang H, Chen C. Reducing exposure to avian influenza H7N9. Lancet 2013; 381:1815.
- Lee SS, Wong NS, Leung CC. Exposure to avian influenza H7N9 in farms and wet markets. Lancet 2013; 381:1815.
- Fournié G, Pfeiffer DU. Can closure of live poultry markets halt the spread of H7N9? Lancet 2014; 383:496.
- Centers for Disease Control and Prevention. Interim guidance for infection control within healthcare settings when caring for patients with confirmed, probable, or cases under investigation of avian influenza A(H7N9) virus infection. http://www.cdc.gov/flu/avianflu/h7n9-infection-control.htm (Accessed on April 30, 2013).
- Centers for Disease Control and Prevention. Interim risk assessment and biosafety level recommendations for working with influenza A(H7N9) viruses. http://www.cdc.gov/flu/avianflu/h7n9/risk-assessment.htm (Accessed on June 10, 2013).
- Centers for Disease Control and Prevention. Interim guidance on the use of antiviral medications for chemoprophylaxis of close contacts of persons with avian influenza A (H7N9) virus infection. http://www.cdc.gov/flu/avianflu/h7n9-av-chemoprophylaxis-guidance.htm (Accessed on October 14, 2013).
- Centers for Disease Control and Prevention. Additional H7N9 cases reported in China; CDC receives H7N9 virus isolate. http://www.cdc.gov/flu/spotlights/h7n9-cases-china.htm (Accessed on April 15, 2013).
- Centers for Disease Control and Prevention. H7N9 situation and CDC response update. http://www.cdc.gov/flu/spotlights/h7n9-cdc-response.htm (Accessed on May 17, 2013).
- World Health Organization. WHO provisional recommendation on influenza A(H7N9) vaccine virus. http://www.who.int/influenza/human_animal_interface/influenza_h7n9/ProvisionalRecommendation_H7N9_31May13.pdf (Accessed on June 07, 2013).
- Osterholm MT, Ballering KS, Kelley NS. Major challenges in providing an effective and timely pandemic vaccine for influenza A(H7N9). JAMA 2013; 309:2557.
- World Health Organization. Overview of the emergence and characteristics of the avian influenza A(H7N9) virus. http://www.who.int/influenza/human_animal_interface/influenza_h7n9/WHO_H7N9_review_31May13.pdf (Accessed on June 06, 2013).
- Khazeni N, Hutton DW, Collins CI, et al. Health and economic benefits of early vaccination and nonpharmaceutical interventions for a human influenza A (H7N9) pandemic: a modeling study. Ann Intern Med 2014; 160:684.
- Fries LF, Smith GE, Glenn GM. A recombinant viruslike particle influenza A (H7N9) vaccine. N Engl J Med 2013; 369:2564.
- Mulligan MJ, Bernstein DI, Winokur P, et al. Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant: a randomized clinical trial. JAMA 2014; 312:1409.
- Jackson LA, Campbell JD, Frey SE, et al. Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without AS03 and MF59 Adjuvants on Immune Response: A Randomized Clinical Trial. JAMA 2015; 314:237.
- Madan A, Segall N, Ferguson M, et al. Immunogenicity and Safety of an AS03-Adjuvanted H7N9 Pandemic Influenza Vaccine in a Randomized Trial in Healthy Adults. J Infect Dis 2016; 214:1717.
- Sobhanie M, Matsuoka Y, Jegaskanda S, et al. Evaluation of the Safety and Immunogenicity of a Candidate Pandemic Live Attenuated Influenza Vaccine (pLAIV) Against Influenza A(H7N9). J Infect Dis 2016; 213:922.
- World Health Organization. Global alert and response. Human infection with influenza A(H7N9) virus in China - update. http://www.who.int/csr/don/2013_04_15/en/index.html (Accessed on April 16, 2013).
- Centers for Disease Control and Prevention. Travelers' Health - Avian flu (H7N9) in China. http://wwwnc.cdc.gov/travel/notices/watch/avian-flu-h7n9-china.htm (Accessed on April 23, 2013).
- World Health Organization. Influenza at the human-animal interface. Summary and assessment, 22 November to 19 December 2016. http://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_12_19_2016.pdf?ua=1 (Accessed on January 17, 2017).
- Yu H, Cowling BJ, Feng L, et al. Human infection with avian influenza A H7N9 virus: an assessment of clinical severity. Lancet 2013; 382:138.
- General recommendations
- Hospitalized patients
- - Dosing
- - Duration
- Uncomplicated illness in outpatients
- - Dosing
- - Duration
- Neuraminidase inhibitor resistance
- Infection control
- Postexposure prophylaxis
- Treatment of symptomatic close contacts
- Patients who develop symptoms after use of an antiviral agent
- Follow-up of close contacts
- Vaccine development
- Travel information
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS