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Global Spread of H1N1 Tamiflu Resistance
Recombinomics Commentary 11:44
August 22, 2008
``The patients are from across the country, so the resistant strain is widespread,'' Terry Besselaar, director of South Africa's National Influenza Centre in Johannesburg, said in an e- mail today.
The above comments on Tamiflu (oseltamivir) resistance in H1N1 in South Africa represent a small subset of Tamiflu resistance spreading globally. Earlier reports on H1N1 in South Africa indicated that 23 of 23 H1N1 isolates had H274Y. Sequence data from these early isolates indicated all isolates were clade 2B (Brisbane/59), but the isolates fell into two sub-clades. The larger sub-clade had the same background as the dominant sequences in northern Europe and the United States reported in the 2007 / 2008 season. However, the South African isolates had a cluster of 5 polymorphisms on both sides of the receptor binding domain position 190 (using H3 numbers). One of the polymorphisms (G617A) was present on a subset of isolates from the United States and Europe. It had been in circulation in H1N1 isolates from the 1940’s. The polymorphism adjacent to this change (C610T) was also present on H1N1 isolates from the 1940’s, demonstrating sequential acquisition of adjacent polymorphisms via homologous recombination. These clustered changes will likely reduce the effectiveness of the northern hemisphere vaccine which will be introduced in the upcoming months and targets Brisbane/59.
However, H274Y is much more widespread the isolates in South Africa. All 10 of the H1N1 isolates from Australia this season also have H274Y. Similarly, recent data from a number of countries are reporting high frequencies of H274Y. Although the number of samples is low, H274Y is also being reported at 100% in Cameroon in west Africa and Montserrat in the Caribbean. High levels (5 of 8) are also being reported for the Seychelles off the coast of east Africa. Early reports on increased pneumonia rates have also been reported in nearby countries, including Zimbabwe in Africa as well as Honduras and Nicaragua in central America, raise concerns that these additional cases are also due to oseltamivir resistant H1N1.
The dramatic spread of H274Y is largely linked to its increased fixation on the Brisbane/59 strain which accounts for virtually all recent cases outside of Asia. H274Y was initially reported on New Caledonia (clade 1) in the United States and Hong Kong (clade 2C) in China, but the global spread has been fueled by clade 2B and involved multiple introductions. The initial sequence data from South Africa which has three non-synonymous changes flanking the receptor binding domain position 190 (N187S, G189A, A193T), raises concerns that the new northern hemisphere H1N1 vaccine will have limited utility, and Tamiflu resistance will continue on a global expansion.
Recombinomics Paper at Nature Precedings