Commentary
H1N1 Tamiflu Resistance Emergence and Evolution
Recombinomics Commentary 16:41
September 2, 2008
The recent reports from South Africa and Australia have increased concerns that H1N1 oseltamivir resistance (H274Y) is becoming widespread during the current flu season in the southern hemisphere. Similarly, the recent HA sequences released by the US Air Force surveillance program has raised concerns that H274Y is also becoming dominant in the Americas.
Tamiflu resistance can be assessed indirectly through phyogenetic analysis of HA sequences which include sequences from isolates known to contain H274Y. In the United States, there is a dominant HA sequence associated with H274Y on NA. The 2008 sequences from the Air Force, A/New JerseyAF1291/2008 and A/Texas/AF1960/2008 both map to this branch, indicating the isolates are likely to contain H274Y. Similarly, another branch has H274Y positive isolates from Wyoming and Arizona, indicating the co-mapping sequence from A/Oklahoma/AF1901/2008, is also from an isolate positive for H274Y. Another branch has H274Y positive sequences from Illinois, Indiana, and Minnesota, indicating A/Alabama/AF1952/2008 is also H274Y positive. Yet another branch, which has A/Paris/1208/2008, also has the five recent isolates from Guatemala and Honduras, raising concerns that H274Y is present at high frequencies in H1N1 isolates in North America.
These isolates from Honduras and Guatemala are closely related to each other ands the French isolate, and were collected in June and July, raising concerns that this sub-clade is gaining dominance. Moreover, the other isolates above demonstrate how the established sub-clades continue to increase in number and increasing geographic reach. This was also seen in the sequences from South Africa, as well as phylogenetic analysis of isolates from Japan.
These new branches with H274Y isolates support new acquisitions of H274Y onto various genetic backgrounds, raising concerns that the dramatic increase of H274Y levels in H1N1 seasonal flu, which may be linked to the vaccine mismatch, will lead to transfer of H274Y onto new backgrounds via recombination, in addition to backgrounds that evolve from existing sequences.
The genetic background jumping was seen in prior seasons. H274Y was first reported on a Hong Kong (clade 2C) background in China in the 2005/2006 season, which was followed by New Caledonia (clade 1 in 2006/2007). The first reported cases on the Brisbane (clade 2B) background were in 2007 in Hawaii, which was followed by acquisition by the dominant B sub-clade in the United States and northern Europe.
The above expansion was in patients who were not taking Tamiflu, raising concerns that the fixing of H274Y in H1N1 will continue to increase, as seen in recent isolates from South Africa and Australia, as well as likely acquisitions in the Americas.
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