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Commentary
Fixing Tamiflu Resistance In pH1N1 In Japan
Recombinomics
Commentary 20:36
March 27, 2010
Similar levels may be circulating elsewhere. Recent reports from the US have cited the rapid appearance of H274Y in Tamiflu treated immune-compromised patients, and the rapid detection signals transmission of a minor sub-species which is quickly detected after the start of treatment. Similar reports have been made for contacts of H1N1 who became symptomatic 5-6 days after the start of prophylactic treatment. An even shorter time frame was reported for a patient treated in Singapore, where H274Y was detected 2-3 days after the start of treatment.
The sequences from Japan are widespread geographically and fall onto many branches of a phylogenetic tree. However, there is also clustering on some branches, signaling transmission. Transmission has also been reported in Vietnam, the US, and UK, signaling transmission at multiple levels (easily detectable, as well as minor species detected after the start of treatment).
However, the high rate of H274Y in 2010 isolates may signal the emergence of new variants which have less wild type competition because of increasing immunity in the target population. In the 2007/2008 season, H274Y levels in seasonal H1N1 varied, but in 2008 in the southern hemisphere one sub-clade emerged with H274Y, and the polymorphism became fixed in the 2008/2009 season. The large number of sub-clades that are now H274Y positive raise concerns that the fixing of H274Y in seasonal H1N1 will be repeated in pandemic H1N1 in the upcoming wave.
The latest sequences from Japan suggest that the fixing may already be well on its way.
A/NIIGATA/19/2010*
A/NIIGATA/16/2010*
A/YAMAGATA/29/2010*
A/KITAKYUSYU/4/2010*
A/FUKUOKA/1/2010*
A/WAKAYAMA-C/1/2010*
A/HIROSHIMA-C/1/2010
* = H274Y
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