Commentary
H1N1 Clade 2C Amantadine Resistance at 100% in United States?
Recombinomics Commentary 14:22
July 21, 2008
Adamantane resistance continues to be high among influenza A (H3N2) viruses with 524 (99.8%) of 525 influenza A (H3N2) viruses tested being resistant to the adamantanes. Adamantane resistance among influenza A (H1N1) viruses has been detected at a lower level. Of the 918 influenza A (H1N1) viruses tested, 98 (10.7%) were resistant to the adamantanes. None of the oseltamivir-resistant influenza A (H1N1) viruses identified during the 2007--08 season were resistant to adamantanes.
The above comments from the recent CDC MMWR report on influenza in the United States is confusing on the breakdown of H1N1 isolates in the past season. Although many of the earlier isolates were classified as Solomon Island/3 (clade 2A), phylogenetic analysis fails to identify any clade 2A isolates. Instead the isolates in the United States were either Brisbane/59 (clade 2B) or Hong Kong/2652 (clade 2C). Clade 2C isolates collected by the CDC was largely confined to western states, although isolates collected by the US Air Force in Georgia (age distribution suggests these isolates were from military personnel) were also clade 2C.
The frequency of CDC isolates approximates the 10% reported above for amantadine resistance (M2 S31N) in H1N1, suggesting that all clade 2C isolates are Amantadine resistance. This interpretation is support by the fact that all oseltamivir resistant (NA H274Y) samples in the United States in the past season were clade 2B.
Thus, the pattern of oseltamivir is breaking down along sub-clade lines. All H1N1 amantatine resistance in the US is clade 2C, and appears to be in virtually all Clade 2C isolates. Oseltamivir resistance is at a lower level (10-20%), but all H1N1 isolates with H274Y are Clade 2B. However, this number may increase because oseltamivir levels in South Africa have reached 100% (on first 23 samples tested), and none have amantadine resistance, suggesting all are clade 2B.
The above data raises concerns that H1N1 seasonal flu is evolving toward anti-viral resistance in all isolates, with clade 2B carrying resistance to oseltamivir, and clade 2C carrying resistance to the amantadines.
These dramatic increases in resistant reservoirs raises serious concerns about the utility of these anti-virals to control or blunt an H5N1 pandemic, were both H274Y and S31N have been reported previously.
Media Links
Recombinomics Presentations
Recombinomics Publications
Recombinomics Paper at Nature Precedings