Abstract
Although oseltamivir-resistant pandemic influenza A(H1N1)pdm09 is uncommon in immunocompetent individuals, a recent report from Newcastle, Australia, showed the first sustained community spread, from June to August 2011, of oseltamivir-resistant influenza A(H1N1)pdm09 virus carrying the H275Y neuraminidase (NA) mutation. To determine the frequency and the extent of this viral variant spread in the nearest major city to Newcastle, we performed a sequencebased genotypic assessment on samples from 143 oseltamivir untreated and 23 oseltamivir post-treatment individuals with influenza collected contemporaneously in Sydney, 120 km southwest of Newcastle. The detection of two of 143 (1.4%) community-derived samples containing H275Y suggests a low prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 virus in the general community and no convincing evidence of spread of the NA H275Y-bearing influenza A(H1N1)pdm09 virus. In oseltamivir treated patients, oseltamivir-resistant influenza A(H1N1)pdm09 virus continue to emerge with three of 23 (13%) post-treatment samples containing the H275Y mutation. The observation of signature mutations and distinct phylogenetic relationship in full-length sequences of haemagglutinin and neuraminidase genes derived from 2011 strains against 2009 strains indicates continued genetic evolution and antigenic drift of the influenza A(H1N1)pdm09 viruses circulating in Australia.
Highlights
The world has moved into the post-influenza pandemic period after 2009, local outbreaks and transmission of the pandemic influenza A(H1N1)pdm09 virus remained intense in the southern hemisphere 2011 winter [1].During the 2009 influenza pandemic, almost all tested influenza A(H1N1)pdm09 viruses remained susceptible to oseltamivir and zanamivir [2], but oseltamivirresistant variants bearing the H275Y neuraminidase (NA) mutation emerged from individuals receiving prophylaxis, and from immunocompromised patients receiving treatment [3,4,5]
A comparison of full-length HA and NA sequences derived from influenza A(H1N1)pdm09 viruses carrying NA H275Y mutation and five randomly selected wildtype influenza A(H1N1)pdm09 viruses collected during the same time period in Sydney showed closely related virus (99.65–100% HA nucleotide similarity and 99.22–100% NA nucleotide similarity), two additional NA amino acid substitutions, NA V83A, and NA E128G, were observed from two distinct strains (GenBank accession number: JQ624645 and JQ624650) (Figure 1A) in the NA H275Y-bearing influenza A(H1N1)
To determine the frequency and the extent of the spread of these oseltamivir-resistant influenza A(H1N1)pdm09 viruses in Sydney, Australia, the adjacent major city and transport hub, respiratory tract samples collected contemporaneously from influenza nucleic acid test (NAT) positive individuals were examined for the presence of the NA H275Y mutation
Summary
The world has moved into the post-influenza pandemic period after 2009, local outbreaks and transmission of the pandemic influenza A(H1N1)pdm virus remained intense in the southern hemisphere 2011 winter [1].During the 2009 influenza pandemic, almost all tested influenza A(H1N1)pdm viruses remained susceptible to oseltamivir and zanamivir [2], but oseltamivirresistant variants bearing the H275Y neuraminidase (NA) mutation emerged from individuals receiving prophylaxis, and from immunocompromised patients receiving treatment [3,4,5]. Oseltamivir-resistant influenza A(H1N1)pdm virus with the NA H275Y mutation may present equivalent viral fitness and transmissibility compared to wild-type viruses in animal models, indicating its potential transmission in the general community (similar to NA H275Ybearing seasonal influenza A(H1N1) viruses circulating prior to 2009) [6], others failed to confirm these results, and data derived from animal models may not be directly applicable to humans [7]. The detection of oseltamivir-resistant influenza A(H1N1)pdm virus in untreated individuals in the community remains uncommon (generally less than 1%) and transmission has been documented only in closed settings or where there is close contact with an infected individual [8,9,10]. A recent report of the first sustained community transmission of oseltamivir-resistant influenza A(H1N1)pdm viruses (detected in 16% of isolates), in Newcastle, Australia, between June and August 2011 [11], has highlighted the potential of widespread movement of oseltamivirresistant influenza A(H1N1)pdm virus
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