Commentary
H1N1
Tamflu Resistance Causes Concern in Japan
Recombinomics Commentary
22:02
January 13, 2009
The group will study epidemic situations in six or seven locations from Hokkaido to Kyushu, including Tottori Prefecture, where more than 30 percent of cases of influenza A virus subtype H1N1 were found to be resistant to Tamiflu.
The survey also will study causal associations between the occurrence of the resistant virus and the use of Tamiflu, and collect information on patients such as group infections in schools and households.
The group also will survey how antiflu drugs other than Tamiflu are used, and then will compile new treatment guidelines for the resistant virus.
According to the NIID, the drug-resistant virus this winter have been found in primary school-age patients in Miyagi and Shiga prefectures.
"We hope to find an appropriate way to use antiflu drugs as early as possible in preparation for further spread of the drug-resistant virus," a ministry official said.
The above comments describe a study of H1N1 Tamiflu resistance in Japan. As noted, there is a concern that use of Tamiflu to treat pandemic influenza, such as H5N1, might drive the H274Y in H1N1 seasonal flu onto the N1 in H5N1 pandemic flu. Both Japan and Korea have H1N1 Tamiflu resistance levels near 100% and both have had recent H5N1 outbreaks.
The report notes the earlier outbreaks in Sendai in the Mayagi prefecture and the subsequent outbreak in the Shiga prefecture. Both outbreaks involved Tamiflu resistant H1N1 and the sequences from the Sendai outbreaks match the sequences in the United States this season (in HI, TX, PA).
However, sequence analysis indicates that the H274Y outbreak had already started in 2006, as evidenced by H274Y in H1N1 in hosts not taking Tamiflu. These hosts were initially found in China, in patients infected with clade 2C (Hong Kong), which was followed by patients in the US and UK infected with clade 1 (New Caledonia) in 2007. Last season the initial cases were in Hawaii in patients infected with clade 2B (Brisbane), but the H274Y was subsequently acquired by another Brisbane sub-clade that spread H274Y at high frequencies in Norway, Russia, and France, and somewhat lower frequencies in other countries in Europe and North America.
H274Y levels rose to 100% in South Africa and were driven by A193T, which is in all isolates reported for this season in the United States and Japan. The fixing of H274Y was driven by recombination, which placed H274Y on multiple genetic backgrounds, which subsequently spread via hitch hiking with key changes on HA, which did not originate in Japan and were not linked to recent Tamiflu usage.
The linkage to Tamiflu usage goes back to Tamiflu blankets applied in northern Vietnam in 2005.
Media Links
Recombinomics Presentations
Recombinomics
Publications
Recombinomics
Paper
at Nature Precedings