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Widespread and Common Tamiflu Resistance in Japan
Recombinomics Commentary 19:29
February 26, 2010

The Japan NIID released sequences (at GISAID) from 13 recent isolates in Japan which were collected between November, 2009 and January, 2010.  Ten of the thirteen were Tamiflu resistant because of H274Y.  The geographic locations were diverse and the sequences fell onto multiple branches of  a phylogenetic tree indicating they were independently introduced, while those clustered were also transmitting.  The independent introductions and transmission were reported previously, but not at this high frequency of 77% (10/13).

Although A/Wakayama-C/1/2010 represents the first reported sequence from a 2010 isolate with H274Y, the large number of such sequences in December collections suggests H274Y is currently widespread in Japan.  Earlier sequences created a trend of an increasing frequency of reported sequences with H274Y, but the latest report suggests that the trend is quickly moving toward fixing H274Y in pandemic H1N1, as was seen in seasonal flu.

H274Y produces resistance in Tamiflu as well as Peramivir, which leaves Relenza as the only approved antiviral unaffected by H274Y or S31N in M2.  The recent reports of increased H1N1 activity on Region 4, as well as increased absenteeism in schools, raise concerns of a new wave of H1N1.  Each of the prior pandemics last century had a winter/spring wave which followed a fall wave, and the emerging pandemic displaced the existing influenza A seasonal flu.  The latest week flu report by the CDC (week 7) had no detection of seasonal H1N1 or H3N2, supporting a repeat of patterns seen in the past three pandemics.

The trend of increasing frequencies of H274Y in isolates in Japan, coupled with reports of low reactor recombinants, raises concerns that the winter/spring wave will be more difficult to manage.

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