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Review
. 2017 Apr 20:10:121-134.
doi: 10.2147/IDR.S105473. eCollection 2017.

Drug resistance in influenza A virus: the epidemiology and management

Affiliations
Review

Drug resistance in influenza A virus: the epidemiology and management

Mazhar Hussain et al. Infect Drug Resist. .

Abstract

Influenza A virus (IAV) is the sole cause of the unpredictable influenza pandemics and deadly zoonotic outbreaks and constitutes at least half of the cause of regular annual influenza epidemics in humans. Two classes of anti-IAV drugs, adamantanes and neuraminidase (NA) inhibitors (NAIs) targeting the viral components M2 ion channel and NA, respectively, have been approved to treat IAV infections. However, IAV rapidly acquired resistance against both classes of drugs by mutating these viral components. The adamantane-resistant IAV has established itself in nature, and a majority of the IAV subtypes, especially the most common H1N1 and H3N2, circulating globally are resistant to adamantanes. Consequently, adamantanes have become practically obsolete as anti-IAV drugs. Similarly, up to 100% of the globally circulating IAV H1N1 subtypes were resistant to oseltamivir, the most commonly used NAI, until 2009. However, the 2009 pandemic IAV H1N1 subtype, which was sensitive to NAIs and has now become one of the dominant seasonal influenza virus strains, has replaced the pre-2009 oseltamivir-resistant H1N1 variants. This review traces the epidemiology of both adamantane- and NAI-resistant IAV subtypes since the approval of these drugs and highlights the susceptibility status of currently circulating IAV subtypes to NAIs. Further, it provides an overview of currently and soon to be available control measures to manage current and emerging drug-resistant IAV. Finally, this review outlines the research directions that should be undertaken to manage the circulation of IAV in intermediate hosts and develop effective and alternative anti-IAV therapies.

Keywords: M2 ion channel inhibitors; drug resistance; influenza A virus; neuraminidase inhibitors; oseltamivir; zanamivir.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The host range of influenza A virus. Notes: The IAV HA subtypes isolated from each host are mentioned in parenthesis. The significant interspecies IAV transmission is shown by solid (common) and dashed (sporadic) arrows. Abbreviations: IAV, influenza A virus; HA, hemagglutinin.

References

    1. Peasah SK, Azziz-Baumgartner E, Breese J, Meltzer MI, Widdowson MA. Influenza cost and cost-effectiveness studies globally – a review. Vaccine. 2013;31(46):5339–5348. - PubMed
    1. Cheng PY, Palekar R, Azziz-Baumgartner E, et al. Burden of influenza-associated deaths in the Americas, 2002-2008. Influenza Other Respir Viruses. 2015;9(suppl 1):13–21. - PMC - PubMed
    1. Kaczmarek MC, Ware RS, Coulthard MG, McEniery J, Lambert SB. Epidemiology of Australian influenza-related paediatric intensive care unit admissions, 1997-2013. PLoS One. 2016;11(3):e0152305. - PMC - PubMed
    1. Viboud C, Simonsen L, Fuentes R, Flores J, Miller MA, Chowell G. Global mortality impact of the 1957-1959 influenza pandemic. J Infect Dis. 2016;213(5):738–745. - PMC - PubMed
    1. Cooper BS, Kotirum S, Kulpeng W, et al. Mortality attributable to seasonal influenza A and B infections in Thailand, 2005-2009: a longitudinal study. Am J Epidemiol. 2015;181(11):898–907. - PMC - PubMed