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Drug resistance in influenza A virus: the epidemiology and management
Authors Hussain M, Galvin HD, Haw TY, Nutsford AN, Husain M
Received 1 March 2017
Accepted for publication 28 March 2017
Published 20 April 2017 Volume 2017:10 Pages 121—134
DOI https://doi.org/10.2147/IDR.S105473
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Suresh Antony
Mazhar Hussain, Henry D Galvin,* Tatt Y Haw,* Ashley N Nutsford,* Matloob Husain
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
*These authors contributed equally to this work
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: influenza A virus, drug resistance, M2 ion channel inhibitors, neuraminidase inhibitors, oseltamivir, zanamivir
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