Search

Abstract: The neuraminidase inhibitors (NAIs) are an effective class of antiviral drugs for the treatment of influenza A and B infections. Until recently, only a low prevalence of NAI resistance (<1%) had been detected in circulating viruses. However, surveillance in Europe in late 2007 revealed significant numbers of A(H1N1) influenza strains with a H274Y neuraminidase mutation that were highly resistant to the NAI oseltamivir. We examined 264 A(H1N1) viruses collected in 2008 from South Africa, Oceania and SE Asia for their susceptibility to NAIs oseltamivir, zanamivir and peramivir in a fluorescence-based neuraminidase inhibition assay. Viruses with reduced oseltamivir susceptibility were further analysed by pyrosequencing assay. The frequency of the oseltamivir-resistant H274Y mutant increased significantly after May 2008, resulting in an overall proportion of 64% (168/264) resistance among A(H1N1) strains, although this subtype represented only 11.6% of all isolates received during 2008. H274Y mutant viruses demonstrated on average a 1466-fold reduction in oseltamivir susceptibility and 527-fold reduction in peramivir sensitivity compared to wild-type A(H1N1) viruses. The mutation had no impact on zanamivir susceptibility. Ongoing surveillance is essential to monitor how these strains may spread or persist in the future and to evaluate the effectiveness of treatments against them. [Copyright &y& Elsevier]

Australian lineages of avian influenza A viruses (AIVs) are thought to be phylogenetically distinct from those circulating in Eurasia and the Americas, suggesting the circulation of endemic viruses seeded by occasional introductions from other regions. However, processes underlying the introduction, evolution and maintenance of AIVs in Australia remain poorly understood. Waders (order Charadriiformes, family Scolopacidae) may play a unique role in the ecology and evolution of AIVs, particularly in Australia, where ducks, geese, and swans (order Anseriformes, family Anatidae) rarely undertake intercontinental migrations. Across a 5-year surveillance period (2011 to 2015), ruddy turnstones (Arenaria interpres) that "overwinter" during the Austral summer in southeastern Australia showed generally low levels of AIV prevalence (0 to 2%). However, in March 2014, we detected AIVs in 32% (95% confidence interval [CI], 25 to 39%) of individuals in a small, low-density, island population 90 km from the Australian mainland. This epizootic comprised three distinct AIV genotypes, each of which represent a unique reassortment of Australian-, recently introduced Eurasian-, and recently introduced American-lineage gene segments. Strikingly, the Australian-lineage gene segments showed high similarity to those of H10N7 viruses isolated in 2010 and 2012 from poultry outbreaks 900 to 1,500 km to the north. Together with the diverse geographic origins of the American and Eurasian gene segments, these findings suggest extensive circulation and reassortment of AIVs within Australian wild birds over vast geographic distances. Our findings indicate that long-term surveillance in waders may yield unique insights into AIV gene flow, especially in geographic regions like Oceania, where Anatidae species do not display regular inter- or intracontinental migration. [ABSTRACT FROM AUTHOR]

Influenza viruses collected from regions of Asia, Africa and Oceania between 2009 and 2012 were tested for their susceptibility to two new neuraminidase inhibitors, peramivir and laninamivir. All viruses tested had normal laninamivir inhibition. However, 3·2% (19/599) of A(H1N1)pdm09 viruses had highly reduced peramivir inhibition (due to H275Y NA mutation) and <1% (6/1238) of influenza B viruses had reduced or highly reduced peramivir inhibition, with single occurrence of variants containing I221T, A245T, K360E, A395E, D432G and a combined G145R+Y142H mutation. These data demonstrate that despite an increase in H275Y variants in 2011, there was no marked change in the frequency of peramivir- or laninamivir-resistant variants following the market release of the drugs in Japan in 2010.

Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.

During annual influenza epidemics, influenza B viruses frequently co-circulate with influenza A viruses and in some years, such as 2005, large outbreaks have occurred while in other years, the virus virtually disappears. Since 1987 there have been two lineages of influenza B viruses co-circulating in various countries and causing disease in humans. The proportions of these two lineages vary from year to year and country to country. For example, in 2005, the B/Victoria/2/87 lineage was predominant in New Zealand while in Australia the B/Yamagata/16/88 lineage was more common. Antigenic and genetic analysis has revealed gradual movement in the both lineages. Careful monitoring of the two virus lineages is important, as they are antigenically distinct. This is an important consideration for influenza vaccine formulation decisions, as only one influenza B component is traditionally included in the annual trivalent influenza vaccine.