Abstract
During the first year of the influenza A(H1N1) 2009 pandemic, unprecedented amounts of the neuraminidase inhibitors, predominantly oseltamivir, were used in economically developed countries for the treatment and prophylaxis of patients prior to the availability of a pandemic vaccine. Due to concerns about the development of resistance, over 1,400 influenza A(H1N1) 2009 viruses isolated from the Asia-Pacific region during the first year of the pandemic (March 2009 to March 2010) were analysed by phenotypic and genotypic assays to determine their susceptibility to the neuraminidase inhibitors. Amongst viruses submitted to the World Health Organization Collaborating Centre for Reference and Research in Melbourne, Australia,oseltamivir resistance was detected in 1.3% of influenza A(H1N1) 2009 strains from Australia and 3.1% of strains from Singapore, but none was detected in specimens received from other countries in Oceania or south-east Asia, or in east Asia. The overall frequency of oseltamivir resistance in the Asia-Pacific region was 16 of 1,488 (1.1%). No zanamivir-resistant viruses were detected. Of the 16 oseltamivir-resistant isolates detected, nine were from immunocompromised individuals undergoing oseltamivir treatment and three were from immunocompetent individuals undergoing oseltamivir treatment. Importantly, four oseltamivir-resistant strains were from immunocompetent individuals who had not been treated with oseltamivir, demonstrating limited low-level community transmission of oseltamivir-resistant strains. Even with increased use of oseltamivir during the pandemic, the frequency of resistance has been low, with little evidence of community-wide spread of the resistant strains. Nevertheless, prudent use of the neuraminidase inhibitors remains necessary, as does continued monitoring for drug-resistant influenza viruses.
Highlights
Neuraminidase inhibitors (NAIs) are designed to bind to the conserved neuraminidase (NA) enzymatic site of all influenza A and B viruses, inhibiting the normal function of the enzyme and preventing virus release from the host cell following replication [1]
Of the 1,146 cell culture-grown influenza A(H1N1)2009 influenza isolates tested for NAI susceptibility, nine demonstrated resistance to oseltamivir and none was resistant to zanamivir (Table 1)
The oseltamivir-resistant strains remained fully susceptible to zanamivir, but had peramivir IC50 values ranging from 30.6 nM to 42.0 nM, demonstrating an approximate 170-fold increase compared to the mean peramivir IC50 for fully susceptible influenza A(H1N1)2009 isolates (Table 2)
Summary
Neuraminidase inhibitors (NAIs) are designed to bind to the conserved neuraminidase (NA) enzymatic site of all influenza A and B viruses, inhibiting the normal function of the enzyme and preventing virus release from the host cell following replication [1]. The NAIs oseltamivir (Tamiflu, Hoffmann-La Roche) and zanamivir (Relenza, GlaxoSmithKline) have been available throughout the world for the treatment and prevention of influenza infections since 1999 Another NAI, peramivir (Biocryst), that has been under investigation as a parenteral formulation, was given emergency use authorisation in some countries such as the United States (US) and Australia during 2009, and in early 2010 was approved for use in Japan for the treatment of both uncomplicated and severe influenza infections [2,3]. In previous years the use of these drugs for the treatment of typical seasonal influenza has been greatest in Japan and the US, but has been very low in other parts of the world such as Australasia, southeast Asia and the South Pacific [4] Despite their relatively low usage for seasonal influenza and unknown effectiveness against potential pandemic strains, in the last decade many economically developed countries began stockpiling NAIs for use in the event of an influenza pandemic [5,6]. The influenza A(H1N1)2009 pandemic was the first influenza pandemic to have occurred since the NAIs became available
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