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|Paradigm Shift Intervention Monitoring||Audio: Apr21 Sep22
Resistant H1N1 in Taiwan Increases Concerns
The above comments on H1N1 in Taiwan supports data released yesterday by the NIH in Japan, which showed significant titer reductions in reference anti-sera activity against H1N1 isolates from recent patients at two medical centers in Japan. The titers were 4-8 fold lower than the Brisbane/59 isolate used in the current trivalent vaccine. In some cases the titer was 16-32 fold lower, indicating vaccine failure for many of the patients. The data from Taiwan reports similar results.
Moreover, the data from Japan showed that anti-sera directed against last year's vaccine target, Solomon Island/3, failed to produce detectable activity with the 2009 H1N1 isolates.
Japan has released a considerable amount of data on H1N1 isolates there. In the fall an outbreak in Sendai identified isolates which matched the major sub-clade circulating in the United States. These isolates had three characteristic HA polymorphisms, G189V, A193T, and H196R. A more comprehensive analysis was done on 33 H1N1 isolates, which again matched sequences in the United States, all of which had A193T. These changes around the receptor binding domain were likely responsible for the lower titers and vaccine failures.
Although A193T was present in the United States and Europe in late 2007 / early 2008, the vaccine target for this season does not have A193T. Moreover, the vaccine for the southern hemisphere also does not have A193T even though Tamiflu resistance last season was at 100% in South Africa and the dominant H1N1 also had A193T, suggesting that H1N1 with H274Y spread will continue to be facilitated by mismatch H1N1 vaccines in the upcoming flu season in the southern hemisphere.
These vaccine mismatches are cause for concern. Last season the H1N1 target was changed from New Caledonia (clade 1) to Solomon Islands (clade 2A). However, last season there was little Solomon Islands in circulation, because it had been replaced by Brisbane (clade 2B) and Hong Kong (clade 2C), although agencies in the US and Europe initially called all clade 2 sub-clades "Solomon Island -like." Later they began calling Brisbane "Brisbane-like", but the vaccine was a clear mismatch, which was demonstrated when appropriate reference anti-sera was used.
However, last season clade 2B acquired A193T from clade 2C, which created a new sub-clade which subsequently emerged in the southern and northern hemisphere, along with H274Y which was hitch-hiking with the dominant sub-clade, which is now not only Tamifu resistant because of H274Y on the NA, but also vaccine resistant because of the receptor binding domain changes on the HA.
The vaccine resistant H1N1 has exploded in Korea and Japan, resulting in school closing across Japan (see updated map) and a dramatic jump in doctor's visits in both countries. These jumps raise concerns of similar increases in countries where H1N1 is dominant, such as the United States and China. China spread creates additional concerns because of the increase in H5N1 human cases and reporting failures of H5N1 poultry cases. The human cases can lead to dual infections with Tamiflu resistant H1N1, leading to Tamiflu resistant H5N1 through recombination.