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Additional Spread of
In the United States
The above comments from the latest CDC update (week 34) describe two more cases of oseltamivir resistance in states that do their own antiviral resistance (CA, NY, WI). WI's week 34 report had no resistance in swine H1N1 and NY has not updated its site since the end of seasonal flu reporting in April, so it is likely that the two new cases are from California. California has already reported resistance in an H1N1 hospitalized case in northern California, and the CDC has not identified a Tamiflu linkage, raising concerns that the H1N1 in this case is evolutionarily fit. Moreover, the first evolutionarily fit pandemic H1N1 identified in Hong Kong was from a traveler from San Francisco, increasing concerns that evolutionarily fit H1N1 with H274Y is circulating in northern California. The latest two cases are also likely form California, and although the week 34 report indicated these new cases had a Tamiflu linkage, the relationship between the collection date of the H274Y positive samples and the start of Tamiflu treatment remains unclear.
These nine cases in the US are in addition to three cases in Japan, three in Hong Kong and at least one each from Denmark, Canada, Thailand, China, and Singapore. Thus, 20 cases have been made public, including at least two were evolutionarily fit.
Roche has recently issue a press release on reports of 13 Tamiflu resistant cases and noted that these cases were rare and expected because of prior Tamiflu resistant cases, including a rate of 4% in children. However, the cases in children were many years ago in Japan, where sub-optimal doses of Tamiflu were used to treat symptomatic children. Most of these children were infected with H3N2 and most resistance markers were not H274Y, These cases represented an usual set of circumstances which have not prodiced any recent cases. Indeed, there have been been no recent H3N2 cases resistant to Tamiflu, and all recent H1N1 cases (seasonal as well as pandemic) have involve just one change, H274Y. Moreover, the seasonal cases were almost exclusivekly in patients who had not been treated with Tamiflu.
The latest report from Hong Kong describes another case in a patient that had not received Tamiflu, and was presumably from a brother (32M), who was posiive for Tamiflu sensitive H1N1 three days earlier. The short time between the start of Tamiflu treatment and the appearance of resistance was similar to data fro Singapore. The rapid appearance of H274Y in patients being treated with Tamiflu is similar to the rapid appearance of resistance in patients on prophylactic Tamiflu, strongly supporting the silent spread of a sub-population with H274Y,
Thus, the detected H274Y is not due to de novo spontaneous appearances, but were linked to widespread pandemic H1N1 with H274Y.