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Additional Worldwide Fixing of H1N1 Tamiflu Resistance
Recombinomics Commentary 21:36
October 19, 2008

In South Africa, a total of 306 A(H1N1) viruses have been isolated during the 2008 influenza season as of 6 October.

Of those, 225 isolates have been tested for oseltamivir resistance by the National Institute of Communicable Diseases (NICD) and 100% were found to be resistant to oseltamivir by genotypic analysis

In Australia, 47 of 59, Argentina, 15 of 33, Chile, 10 of 79, Kenya, 1 of 4, New Caledonia, 7 of 7, New Zealand, 2 of 2, and Uruguay 13 of 16 A(H1N1) viruses analysed showed the specific neuraminidase mutation (H274Y) associated with oseltamivir resistance, respectively.

WHO has also received reports from NICs in other parts of the world; in Algeria, 4 of 13, Canada, 1of 2, Ghana 5 of 13, Guatemala, 4 of 5, Honduras, 5 of 8, Ivory Coast, 2 of 5, the Netherlands, 1 of 2, Nigeria, 1 of 1, Senegal 10 of 10 and the United States of America, 3 of 7 A(H1N1) viruses tested were found to be resistant, respectively.

The above comments describe a global expansion of H274Y in H1N1.  In South Africa, where the dominant HA sequence has acquired five changes in proximity to position 190 (H3 numbering), 225/225 sequenced isolates have H274Y in NA.  Other countries at 100% oseltamivir resistance include New Caledonia (7/7), New Zealand (2/2), Nigeria (1/1), Senegal (10/10).  Countries with resistance at 50% or higher include Australia (47/59), Uraguay (13/26), and Canada (1/2), indicating the resistance is spreading worldwide.

Recent HA sequences from Kenya have two tandem changes, G604A and G605A, which are present in the South African and Seychelles isolates, signaling additional recombination.  Two adjacent tandem changes (C610T and G617A) match H1N1 from the 1940’s, while the fifth change (A599G) is in a recent clade 2C isolate from Hong Kong.  Four of the five changes produce non-synonymous changes flanking the receptor binding domain position at 190 (N187S, G189N, A193T).

The sequences with the cluster of changes evolved from the Brisbane/59 sub-clade that was dominant in northern Europe in 2007/2008.  The result from South Africa suggests this sub-clade continues to evolve and expand. Some countries still have other H1N1 sub-clade in circulation, but the countries reporting H274Y levels at or near 100% of H1N1 isolates suggests this change will soon be fixed in H1N1 worldwide.

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