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No Amantadine Resistance Markers in Russian H5N1 Bird Flu
November 7, 2005
The M2 sequences from two H5N1 wild bird flu isolates from Russia ( A/duck/Novosibirsk/56/2005(H5N1) and A/grebe/Novosibirsk/29/2005(H5N1) ) have been made public at GenBank. These two sequences are exact matches of the sequences from Qinghai Lake. The M2 protein is the target of ion channel blocks in the amantadine family, including amantadine (Symmetrel) and rimantadine (Flumadine).
In southeast Asia all public M2 sequences from Vietnam, Thailand, Cambodia, Laos, and Malaysia, have two amantandine resistance markers (at positions 26 and 31). Consequently, H5N1 from this region is resistant to treatment with the Amantadines.
In contrast, the 16 sequences from Qinghai Lake did not have these changes, and therefore are expected to be sensitive to amatadines. The newly released sequences from Russia indicate that there isolates would also be treatable with the amantadines.
Concern has been expressed in the past about amantadine resisance in H5N1 in southeast Asia. However, H5N1 from China and Russia are greatly expanding the H5N1 global reach. Isolates have been identified in Turkey, Romania, and Croatia. These isolates are closely related to the China / Russia wild bird isolates described above, suggesting that the H5N1 in Europe is also sensitive to the amantadines.
The H5N1 in Europe is expected to migrate into the Middle East and Africa in the near term, and based on the above data, these isolates should also be sensitive to the amantdines.
Recently Canada has also announce the detection of H5 wild bird flu in British Columbia, Manitoba, and Quebec. Later this week, an announcement of a complete sero-type is expected. The high frequency of detection suggests some may be H5N1 although the domestic and wild birds in the areas where the H5 positive birds were found do not show evidence of disease.
In China there have been four recent H5N1 outbreaks and these infections may also be due to H5N1 wild bird flu. China has acknowledged that there may be human cases associated with these outbreaks, especially the outbreak in Hunan. Based on the above analysis, it seems likely that wild bird flu outbreaks in China will also be amantadine sensitive.