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Concerns of Increased H5N1 Transmission Efficiency in China
Recombinomics Commentary 14:55
January 26, 2009

The latest series of confirmed H5N1 cases in China indicate the H5N1 has achieved more efficient transmission to humans.  Two of the cases are linked to contacts who had bird flu symptoms.  In Beijing, a nurse recovered and test results have not been released.  In Hunan, the mother of the confirmed case (2F) died of pneumonia when the daughter developed symptoms.  Thus, in both clusters the index case died, but the contact survived.  This was also reported in the cluster in northern Vietnam.  The index case (13F) died of pneumonia, which her sister (8F) and neighbor (5M) survived.  The survival of these cluster members is consistent with human to human transmission, which involves a low viral load, leading to milder cases.

Milder cases in China and Vietnam (see updated map) remain a concern.  In China, all seven recent confirmed cases were admitted in critical condition.  One is recovering, one is stable, and the other five are dead.  This high case fatality rate suggests milder cases are not being detected / reported.

On the reporting front, the only H5N1 in poultry has been two outbreaks in Jiangsu in asymptomatic birds.  Although some of the recent human cases have been linked to poultry exposure, there has been an absence of linkages to dead, dying, or H5N1 confirmed poultry.

This lack of poultry links raises concerns that the poultry is asymptomatically infected, which can be due to a vaccine mismatch. The outbreak in Jiangsu was due to clade 7, which is not well matched to clade 1 or clade 2 vaccines.  The outbreak in Jiangsu was followed by new vaccinations of unaffected flocks.  This pattern is similar to the series of outbreaks in northern China in the 2005/2006.These poultry outbreaks were not well controlled, and at least some of these outbreaks also involved clade 7, which has been detected in northern China, as well as Hunan.  Moreover, it was recently detected in northern Vietnam and an isolate from Vietnam was recently selected as a human vaccine target, although no human vaccine against clade 7 is currently available.

Media reports in China have indicated A/Beijing/1/2009 was similar to H5N1 circulating in China between 2005-2008.  This would be consistent with clade 7, which was widely detected in 2005.  However, it also caused the first confirmed case in China, which was in Beijing in 2003.  Moreover, clade 2.3.4 has been linked to most reported H5N1 human cases in China and it also has been widely circulating between 2005-2008 and also has origins dating back to 2003, so the description of A/Beijing/1/2009 is ambiguous with regard to clade number.

Clade 7 has a large number of receptor binding domain changes flanking position 190, which is also true for the Tamiflu resistant H1N1 seasonal flu, which has spread throughout the northern hemisphere.

The co-circulation of clade 7 H5N1 and clade 2B H1N1 which has H274Y is an additional cause for concern, with regard to Tamiflu resistance on N and exchanges of receptor binding domain changes on H.

More information on the H5N1 clade linked to human cases in China and Vietnam would be useful as would release of H5N1 sequences from the recent cases in both countries.

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