H1N1 Tamiflu Resistance In Korea Raises Pandemic Concerns

Recombinomics Commentary 22:01
January 10, 2009

A/H1N1 17 16 (94.1%) Oseltamivir
A/H1N1 17 1 (5.9%) Amantadine

The above translation is from the Korean CDC report on antiviral resistance in Korea this season.. 16/17 H1N1 isolates were resistance to oseltamivir, while 1/17 was resistant to amantadine. These data indicate the H274Y levels in H1N1 were approaching 100%, as was seen in Japan.

In Japan, the H1N1 was sequenced and H274Y was identified in NA, while G189V, A193T, and H186R were identified in HA from three identical H1N1 isolates from Sendai, Japan. Those isolates were associated with the closing of 10 elementary schools and match H1N1 isolates from the United States (in HI, TX, PA). In the United States the level of H274Y was also approaching 100% (86/88).

These data indicate H274Y has become fixed throughout most if not all of the northern hemisphere. Resistance levels in Canada and Europe are also at or near 100%..

South Korea has issued an alert as ILI physician visits crossed baseline line levels in week 50. H1N1 levels exploded in weeks 51 and 52, suggesting that oseltamivir resistance was associated with an aggressive virus.

This dramatic increase in South Korea raises concerns of transfer of H274Y from H1N1 to H5N1. Two years ago there was a significant H5N1 outbreak in Korea at the end of 2006. That was followed by a larger outbreak in the spring of 2008. In the 2008 outbreak, one culler developed bird flu symptoms and was PCR H5 confirmed. This H5N1 history raises concerns of co-infections involving H5N1 and H1N1.

This concern extends to Japan, which has also had H5N1 outbreaks that coincided with outbreaks in South Korea. Japan is planning an aggressive H5N1 vaccine program for first responders which may be significantly expanded into the general population.

The high levels of H274Y in virtually all aggressive H1N1 in at least two countries in Asia with a history of H5N1 infections are causes for concern. Moreover, the H274Y levels in Korea and Japan suggest other countries in Asia, including China, have similar levels of H274Y, since last season Japan and South Korea had significant levels of clade 2C, which was adamantine resistant but oseltamivir sensitive.

The fixing of H274Y in H1N1 in Asia significantly increases pandemic concerns.