Abstract
Two Dutch travellers were infected with oseltamivir-resistant influenza A(H1N1)pdm09 viruses with an H275Y neuraminidase substitution in early August 2012. Both cases were probably infected during separate holidays at the Catalonian coast (Spain). No epidemiological connection between the two cases was found, and neither of them was treated with oseltamivir before specimen collection. Genetic analysis of the neuraminidase gene revealed the presence of previously described permissive mutations that may increase the likelihood of such strains emerging and spreading widely.
Highlights
Screening for antiviral resistance in influenza viruses has become important in recent years
In the Netherlands, year-round surveillance for influenza antiviral resistance is based on respiratory specimens collected by the Dutch Sentinel General Practice Network of the NIVEL Netherlands Institute for Health Services Research from patients presenting with influenza-like illness (ILI) or another acute respiratory infection (ARI), and on influenza virus isolates or influenza virus positive clinical specimens sent to the Dutch National Influenza Centre on a voluntary basis by all diagnostic laboratories in the Netherlands [17]
The Dutch and Perth viruses from 2012 carry NA substitutions, V241I, N369K and N386S, that potentially facilitate accommodation of the H275Y substitution, as did the 2011 Australian oseltamivir-resistant cluster of viruses, the HA genes from these two groups form separate genetic clusters (Figure)
Summary
Screening for antiviral resistance in influenza viruses has become important in recent years. Likewise in Europe, many countries began conducting antiviral susceptibility monitoring in 2005/06 with the support from the two collaborating European Union (EU)-funded projects European Surveillance Network for Vigilance against Viral Resistance (VIRGIL) and European Influenza Surveillance Scheme (EISS) [4] With this monitoring system in place, the EISS network in Europe was able to rapidly detect and monitor the emergence and spread of oseltamivir-resistant former seasonal influenza A(H1N1) viruses in the community [6,7,8]. In the Netherlands, only 20 NA H275Y cases infected with oseltamivir-resistant influenza A(H1N1)pdm virus were detected during the 2009/10 pandemic, matching the low proportions of such viruses detected world-wide [12,13] Most of these cases involved immunocompromised patients undergoing prolonged oseltamivir treatment, with no further transmission, reflecting the poor fitness of the resistant viruses. It was hypothesised that other mutations in the NA genes of these viruses that potentially facilitate accommodation of the H275Y substitution had enabled the virus to retain fitness when the H275Y substitution was obtained [15]
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