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Commentary

United States H1N1 With Tamflu and Adamantane Resistance
Recombinomics Commentary 19:03
January 16, 2009

The CDC flu report for week 1 describes antiviral resistance results on 15 additional H1N1 isolates.  As expected, all 15 have H274Y.  However, one of those 15 also has adamantine resistance.  H1N1 with resistance to both antivirals had been reported in isolates from Hong Kong last season.  However, these were clade 2C (Hong Kong/2652) isolates and all 2C isolates were adamantane resistant (S31N), and the acquisition of H274Y was not unexpected.

However, this season results from Japan and Korea indicate clade 2C isolates are rare, since almost all isolates have H274Y and are adamantine sensitive.  This pattern had also been observed in the United States.  Last season clade 2C was frequently detected in western states, and were most common in Hawaii.  Sequences from Hawaii were clade 2B and were from isolates that were adamantane sensitive, while clade 2C isoaltes were adamnatane resistant but oseltamivir sensitive.

The finding of adamantine resistance in an H1N1 that was oseltamivir resistance could represent a clade 2C isolate similar to those reported in Hong Kong.  Alternatively, this isolate could be clade 2B which has developed adamantine resistance due  to use of rimantadine in areas which had high levels of H1N1, which is the current situation in almost all areas of the United States.

The H1N1 is characterized as Brisbane/59-like, but those determinations are based on cross reactivity with ferret antisera, which varies from batch to batch.  A classification based on phylogenetic analysis would be more precise.  Last season all H1N1 in the US was Brisbane (clade 2B ) or Hong Kong (clade 2C), yet all were called Solomon Island-like (clade 2A) based on cross reactivities with ferret antisera directed against H1N1 grown in chicken eggs, which produced broad cross reactivities among all three clade 2 groupings, but antisera generated with H1N1 in mammalian cells produced activities which readily distinguished clade 2B from clade 2C or clade 2A.

Thus, it remains unclear if the H1N1 that is sensitive to oselatmivir and adamantanes is clade 2C, as had been seen previously in Hong Kong, or was clade 2B that had developed adamantine resistance, which had not been reported previously.

More information on the isolate with resistance to osletaminir and adamantanes would be useful.

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