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H1N1 Tamiflu Resistance Levels Increase in Hong Kong
Recombinomics Commentary 14:58
November 28, 2008

CHP analysis of the July to September this year, 836 samples of influenza A H1N1 virus, there were 144 pairs of Tamiflu resistance

In the second quarter and first quarter of this year, only 15.7 and 11.8 percent of drug-resistant H1N1 samples.

H1N1 virus of amantadine resistance, from 16.9 percent in the first quarter of this year, surged to 70.5 percent in the third quarter.

The above translation describes increasing antiviral resistance in Hong Kong.  In the past few years the frequency of amantadine resistance (S31N) in clade 2C (Hong Kong strain) has been at 100%, so the increase from 16.9% to 70.5% in the first and third quarter of this year likely represents an increase in clade 2C levels.  Similarly, the increase in H274Y from 11.8% to 17.2% over the same period likely represents a significant increase in H274Y in clade 2B (Brisbane/59).

However, these increases may represent clade 2B acquiring S31N, and clade 2C acquiring H274Y via reassortment or recombination.  Three pairs of HA and NA sequences from Hong Kong were released.  All three had a clade 2C HA and also had H274Y in NA, but one of the NA sequences was 2B, indicating the H274Y in the clade 2C isolate,
A/HongKong/942/2008, was due to reassortment.  Similarly D354G, which is present on all public 2C NA sequences, is also on all 2B sequences from the dominant 2B sub-clade (which has now been found worldwide).

Thus, Hong Kong which has clade 2B and 2C co-circulating, may have higher levels of genetic exchanges that move resistance from one genetic background to another.  Last season clade 2B and 2C were co-circulating in Pacific region in the United States, but resistance exchanges were not reported (all H274Y was on clade 2B and all S31N was on clade 2C).  However, H274Y levels in the United States were low last season.

In contrast, the week 47 report from the CDC indicates 20/21 H1N1 isolates this season have H274Y and the majority of H1N1 isolates have been in the Pacific region, with highest levels in Hawaii raising the possibility that like Hong Kong, H274Y may have moved from clade 2B to clade 2C. 

Release of amantandine resistance levels for H274Y would help determine if this is the case, which can also be determined directly through phylogenetic analysis.  Therefore, release of these sequences or amantadine status would be useful.

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