Recombinomics Commentary 14:30
November 22, 2008
In addition, CDC performed antiviral resistance testing on one influenza A (H1N1), three influenza A (H3N2), and four influenza B viruses collected during September. All tested viruses are sensitive to both oseltamivir and zanamivir.
Three isolates from specimens collected during September were tested for adamantane resistance. The one influenza A (H1N1) virus tested and the two influenza A (H3N2) viruses tested were resistant to the adamantanes.
The above comments are from the week 46 influenza report from the CDC. Although the reporting on H1N1 is limited (the report cited 61 H1N1 isolates confirmed since October 1), data from last season and initial data from Canada and Europe paint a clear picture of H1N1 oseltamivir resistance at or near 100% in North America and Europe.
Last season the level of oseltamivir resistance in the United States was relatively low (near 10% of H1N1 isolates), which was due in part to clade 2C (Hong Kong) isolates which were negative for oseltamivir resistance (0 % in public sequences), but near 100% in adamantine resistance (M2 S31N).
The above comments indicate that the one H1N1 isolate collected in September was clade 2C, which is not surprising because most of the clade 2C isolates in the US last season were in the Pacific region, and most of the H1N1 reported for this season thus far was also in the Pacific region.
The above report includes the first oseltamivir resistant strain this season in the US, which is likely the Brisbane/59 sub-clade, which has H274Y but has a wild type M2 (adamantine sensitive). The October isolate, which is negative for H274Y, is likely clade 2C, but test results for M2 for this isolate have not been reported yet.
Thus, although only one of three H1N1 isolates in the US has H274Y, it is likely that only one of the three isolates is Brisbane/59 (it is unlikely that the “Brisbane/59 – like” antigen characterization distinguishes between clade 2B and clade 2C - both are called “Brisbane/59 – like”). Thus, although the antigenic characterization will not distinguish clade 2B from 2C, the resistance pattern will (clade 2B will have H274Y and S31, while clade 2C will have H274 and S31N).
However, this pattern may change because recent clade 2C sequences from Hong Kong had H274Y – the M2 sequence wasn’t released, so it is unclear if these isolates also had S31N). The 2008 Hong Kong sequences had evidence of reassortment and recombination between clade 2B and 2C. The HA sequence (2C) had a polymorphism that was among the newly acquired polymorphism in South Africa (2B), while one of the HA 2C isolates had an NA sequences that was the dominant 2B sub-clade.
Thus, at this time the limited data from the CDC is consistent with 100% H274Y levels in the Brisbane/59 strain, which is consistent with levels in Canada (1/1), England (12/13), Scotland (2/2) and Norway (1/1), although the Norway isolate had a likely origin in the US.
The US and Canada are both significantly lagging in the release of H274Y levels (the Canadian isolate was reported a month ago and the number of reported H274Y results of H1N1 isolates remains at one), which has delayed announcements on antiviral recommendations reflecting the true levels in Birsbane/59, which are at or near 100%. However, release of serotype data clear indicates that most isolates in the US are influenza A and the ratio of H1N1 to H3N2 is running near 5:1, signaling a high level of oseltamivir resistance overall.
Release of updated H274Y levels in H1N1 the US and Canada would be useful.
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