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Commentary
XDR-pH1N1
Raises Pandemic Concerns NOT
Recombinomics
Commentary 02:22
August 26, 2010
On August 26 the CDC notified Recombinomics that the GISAID entry on antiviral resistance is in ERROR. A/Kansas/05/2010 is SENSITIVE to oseltamivir and Zanamivir.
The CDC released an NA sequence, A/Kansas/05/2010 yesterday. The associated characterization sheet indicated in vivo assays demonstrated resistance to oseltamivir (Tamiflu) and zamanivir (Relenza), representing the first reported example of Relenza resistance in pandemic H1N1. Moreover, since H274Y has been shown to previously inhibit oseltamivir and Peramivir, it is likely that the resistance to Relenza and Tamiflu extends to Peramivir. Although the M2 sequence was not released, it is also likely that the isolate also has S31N, conferring resistance to adamantines amantadine and rimantadine. Therefore, the above isolate is probably resistant to all five antivirals currently in use or approved for treatment of influenza A. Thus, Kansas/05/2010 has extensive drug resistance and should be called XDR-pH1N1.The NA sequence has two non-synonymous changes, S363N and I466M. Both changes have been reported previously in pandemic H1N1 (human and swine), as well as swine H1N1 (see S363N list here and I466M list here). Although these two markers are not widespread in influenza databases at Genbank and GISAID, most isolates do not include NA sequences and most are not tested in vivo for antiviral activity. Moreover, variants frequently arise when wild type sequences are at a low level.
An increase in frequency for this or these markers would significantly raise pandemic concerns, since none of the five current anti-virals are likely to be effective against this XDR-pH1N1.
Since both NA sequences released by the CDC today have I466M, it seems likely that this one change produces the XDR. More information on the testing and associated polymorphism(s) would be useful.
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