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Commentary

Early Emergence of H1N1 in the United States
Recombinomics Commentary 13:19
November 08, 2008

The week 44 influenza report by the CDC this season had much in common with the week 44 report for last season.  Most of the confirmed influenza cases were influenza A, most of the sub-typed influenza A isolates were H1N1, and most of the H1 was in the western (Pacific) region.

Last season the first US isolates with H274Y were in Hawaii and collected on October 22.  Although these isolates were Brisbane/59, they were not the dominant sub-clade, which was confirmed with isolates in Arizona collected in early December.  In the US, the overall frequency of H274Y was lower than many countries in Europe, in part because many of the isolates in the western US (especially Hawaii) were clade 2C (Hong Kong), and no H274Y was reported in clade 2C isolates in the US (although H274Y positives were reported in China as early as mid-2006).

The dominant sub-clade with H274Y was more dominant in several European countries, including Norway and France, where frequencies approached 50% of H1N1 isolates. However, this level approached or reached 100% in the summer of 2008.  Most notable was South Africa, were 225/225 isolates were H274Y positive.  The positives were dominated by a version of H1N1 that had acquired a number of changes clustered around the receptor binding domain, which raised concerns that the current vaccine, which targets Brisbane/59, will have reduced efficacy.

Moreover, recent isolates from Hong Kong raise concerns that the levels of H274Y may be increasing in clade 2C.  Three sets of HA and NA sequences from isolates collected in late spring or the summer of 2008 were H274Y positive and these isolates had evidence of exchange of genetic information between clade 2B and 2C.  One of the isolates had a clade 2C HA and a clade 2B NA, indicating it was a reassortant.  Similarly, one of the changes near the receptor binding domain in the South African sequences is also on the HA of clade 2C.  Thus, the sequences from Hong Kong raise concerns regarding H274Y in clade 2C, and the H274Y positive sub-clade may appear in the western US early in the season.

Early indications from the UK and Canada also raise concerns regarding H274Y, since the first H1N1 isolate in Canada and the first 3 isolates in UK were Tamiflu (oseltamivir) resistant, suggesting early H1N1 isolates in the US may be clade 2B and clade 2C, but both sub-clades may have high levels of H274Y.

The CDC week 44 report was silent on H274Y levels, which may trail sub-type data.  However, HA and NA sequences from early H1N1 isolates in the US would be useful.

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