Recombinomics: H1N1 Tamiflu Resistance In China Raises Concerns

Commentary

H1N1 Tamiflu Resistance In China Raises Concerns
Recombinomics Commentary 01:19
January 21, 2009

The Japan NIH has issued a report on H1N1 that included phylogenetic analysis of 33 of the 50 H274Y isolates reported to date in Japan. All 33 mapped into the sub-clade with D354G, which was in the dominant sub-clade with H274Y last season. However, this season the isolates in the United States emerged from a sub-clade within this dominant sub-clade, and all isolates had A193T on HA.

An earlier phylogenetic analysis from Japan had three isolates from a major outbreak in Sendai. Those sequences matched the dominant sub-clade from the United States, which had three receptor binding domain changes (G189V, A193T, H196R). The NA from those sequences had N28S which was seen in isolates from Yokohama and Sendai (see list below). Another grouping had two other NA polymorphisms, A86T and T339A (from Miyagi and Yamaguchi). Those changes matched A/Hawai/19/2008, which also had A193T.

The largest branch from Japan had isolates that did not have non-synonymous changes, but mapped on a branch with the above isolates, suggesting this branch (with isolates from Sapporo, Mie, Osaka, Sakai, Sopporo, Shiuoka, Kobe, and Hiroshima) also identified isolates with A193T on HA.

In addition, one isolate had N73K, which was in the major sub-clade from South Africa, which also had A193T. Thus, it appears that 31/33 of the isolates from Japan have HA A193T. The two exceptions were from Shiga.

Moreover, an isolate from China, A/Jilin-Chaoyang/1191/08, maps with the US isolates, suggesting this same sub-clade has spread to China. Another isolate from China, A/Beijing-Huairou/15/08, is closely related, raising concerns that H274Y levels in H1N1 in China are also near 100%.

The spread of resistant H1N1 to China raises concerns with regard to co-circulating H5N1. China has just reported four confirmed cases of H5N1 and four additional contacts are suspect cases. These patients, as well as contacts, are treated with oseltamivir, raising concerns that patients or contacts infected with H5N1 could also be infected with H1N1 with H274Y, which could lead to the emergence of H5N1 with H274Y.

Japan isolates (31/33)

N28S
Yokahama/95/08
Yokohama/96/08
Sendai/103/08
Sendai/104/08
Sendai/105/08
Sendai-H/2103/08
Texas/15/2008
Texas/16/2008
Texas/17/2008
Texas/18/2008
Pennsylvania/08/08
Pennsylvania/09/08
Hawaii/21/08

A86T T339A
Miyagi/35/08
Yamaguchi/26/08
Yamaguchi/27/08
Yamagichi/28/08
Hawaii/19/08

Related to above
Hiroshima/44/08
Hiroshima/45/08
Hiroshima/46/08
Hiroshima/48/08
Kobe/49/08
Mie/32/08
Osaka-C/39/08
Sakai/30/08
Sakai/47/08
Sapporo/63/08
Sapporo/64/08
Sapporo/66/08
Sapporo/68/08
Sapporo/70/08
Sapporo/72/08
Sapporo/80/08
Sapporo/83/08
Shizouka-C/51/08
Shizouka-C/54/08

N73K
Chiba/86/08
Johannesburg/12/2008
Johannesburg/14/2008
Johannesburg/33/2008
Johannesburg/35/2008
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