Abstract
To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay. The total frequency of ORVs was 2.6% (45/1,734) during the 2007-08 season and 99.7% (1,477/1,482) during the 2008-09 season, indicating a marked increase in ORVs in Japan during 1 influenza season. The NA gene of ORVs in the 2007-08 season fell into 2 distinct lineages by D354G substitution, whereas that of ORVs in the 2008-09 season fell into 1 lineage. NA inhibition assay and M2 sequencing showed that almost all the ORVs were sensitive to zanamivir and amantadine. The hemagglutination inhibition test showed that ORVs were antigenetically similar to the 2008-09 vaccine strain A/Brisbane/59/2007. Our data indicate that the current vaccine or zanamivir and amantadine are effective against recent ORVs, but continuous surveillance remains necessary.
Highlights
To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay
In response to public health concerns about ORVs, the World Health Organization (WHO) directed Global Influenza Surveillance Network laboratories to intensify neuraminidase inhibitors (NAIs) surveillance and announced regularly updated summaries of ORV data collected from each laboratory on its website [16]
To estimate the frequency of influenza A (H1N1) ORVs in each prefecture of Japan, 1,734 isolates during the 2007–08 season and 1,482 isolates during the 2008–09 season were collected from all prefectures and examined by NA sequencing to detect the H275Y mutation in NA protein
Summary
To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay. At the beginning of the 2007–08 influenza season, detection of a substantially increased number of oseltamivir-resistant influenza viruses A (H1N1) (ORVs) was reported, mainly in countries in Europe where the prevalence varies, with the highest levels in Norway (67%) and France (47%) [11,12,13,14]. These viruses showed a specific NA mutation with a histidine-to-tyrosine substitution at the aa 275 position (N1 numbering, H275Y), conferring highlevel resistance to oseltamivir. The total frequencies were 2.6% in the 2007–08 season and 99.7% in the 2008–09 season, indicating that ORVs increased dramatically in Japan
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