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M2 Markers Signal Poor H5N1 Surveillance in Southeast Asia

Recombinomics Commentary

August 24, 2005

The paper "Evolution of H5N1 Avian Influenza Viruses in Asia" was published ahead of the October, 2005 publication by the WHO Global Influenza Surveillance Network.  The publication in Emerging Infectious Diseases was accompanied by the release of sequence data from a number of isolates from Laos, Cambodia, Malaysia, Thailand, and Vietnam that were collected in 2004. These M2 sequences are now publicly available at Loa Alamos National Labs.


Prior sequences from Vietnam and Thailand had demonstrated that the M2 protein had two polymorphisms in the ion channel.  Mutations in this region are often associated with resistance to amantadines, and isolates from Vietnam and Thailand had been shown to be resistant to amantadines in laboratory tests.

The M2 sequence of the isolates above, all have the same two polymorphisms L26I and S31N.  The presence of both of the changes was limited to isolates from Vietnam and Thailand and correlated with the ability to cause disease in humans.

All of the newly released sequences from Vietnam, Thailand, Cambodia, Laos, and Malaysia have these two polymorphisms, suggesting the isolates could cause H5N1 infections in humans.  However, in 2004 only infections in Vietnam and Thailand were reported.  Cambodia reported fatal infection s in 2005, while Laos and Malaysia have never reported human infections.  Similarly, Thailand reported no human infections in 2005, although the H5N1 bird infections were widely reported in 2004 and 2005.

The close relationship between the isolates from Vietnam, Thailand, Laos, Cambodia, and Malaysia was also seen in the HA and NA genes as shown in the phylogenetic trees in the above publication.

The lack of reported human infections in these countries in 2004 and/or 2005 raise serious questions about human surveillance in these countries.  Recent models have suggested that H5N1 could be contained if certain criteria were met, including rapid identification of human cases.

The failure to report any human cases in the above countries raises serious doubts about the surveillance networks in these countries.  The potential for human infections is likely to be increased in the upcoming months, as H5N1 wild bird flu migrates to southeast Asia.  H5N1 is already endemic in the region, and the newly arriving sequences will offer many opportunities for dual infections, recombination, and additional human cases.

The scandalously poor surveillance in 2004 and 2005 offers little indication that human cases in southeast Asia will be effectively identified.

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