H1N1 flu viruses growing more resistant to Tamiflu

Aug 25, 2008 (CIDRAP News) – With influenza season well under way in the southern hemisphere, one of the three kinds of seasonal influenza virus is becoming increasingly resistant to the antiviral drug oseltamivir (Tamiflu), the World Health Organization (WHO) reported last week.

Thirty-one percent (242 of 788) of influenza A/H1N1 isolates from 16 countries that were tested in recent months carried a mutation associated with oseltamivir resistance, the WHO said. In South Africa, all of the 107 isolates tested had this mutation, known as H274Y, the agency reported.

Other countries and areas that tested 10 or more isolates and found resistance included Australia, 100% (10 of 10 isolates); Ghana, 20% (2 of 10) Hong Kong, 17% (97 of 583); and Chile, 13% (4 of 32 isolates).

The findings strengthen a trend that that was first observed last January in Norway and subsequently in many other countries. Overall for the last quarter of 2007 and the first quarter of this year, 16% (1,182 of 7,528) of tested H1N1 isolates carried the resistance mutation, according to WHO figures. Resistance was found in 35 countries, mostly in the northern hemisphere, including in 12% of tested US isolates and 26% of tested Canadian isolates.

"What we're seeing is the evolution of the resistance gene and the distribution of it throughout the world," said Lance Jennings, a clinical virologist with the Canterbury District Health Board in Christchurch, New Zealand, and chair of the Asia-Pacific Advisory Committee on Influenza, as quoted in an Aug 22 Bloomberg News report.

In South Africa, Terry Besselaar, director of the National Influenza Centre in Johannesburg, said, "The patients are from across the country, so the resistant strain is widespread," according to the Bloomberg report.

The WHO said only 1 of the 107 patients in South Africa was taking oseltamivir, and no unusual clinical features or underlying conditions were found.

No increase in oseltamivir resistance has been reported in the other two types of seasonal flu viruses, A/H3N2 and B. Recent WHO updates have not indicated which types are most common overall in the southern hemisphere this season, but the Aug 20 statement said flu was widespread in New Zealand, with H3 and B viruses predominant. The statement also cited sporadic flu activity in Argentina, with H1 viruses most common.

Many countries have stockpiled oseltamivir, which is used to treat people infected with the H5N1 avian flu virus and is generally considered the most promising antiviral to use in case H5N1 evolves into a human pandemic strain. The WHO statement did not mention any reports of resistance to zanamivir (Relenza), the other drug in the neuraminidase inhibitor class.

A spokeswoman for Roche, the maker of Tamiflu, said H5N1 viruses remain sensitive to the drug, according to the Bloomberg report. The spokeswoman, Claudia Schmitt, said the company plans to conduct surveillance on resistant and susceptible flu viruses during the 2008-09 flu season.

In a summary of H1N1 resistance to oseltamivir in the the 2007-08 flu season, the WHO said in June that no link between "oseltamivir exposure and resistance at the individual patient level was noted."

The increasing oseltamivir resistance in H1N1 viruses has puzzled experts. In an editorial published by Eurosurveillance in January, authorities said resistant viruses with the H274Y mutation had been seen in previous flu seasons but were rare and did not spread easily. But the more recent H1N1 isolates with the mutation were "fitter" and were spreading in the community, they wrote.

A recent update by the European Centre for Disease Prevention and Control (ECDC) observed, "At this stage the significance of these [resistance] findings remains uncertain. The emergence of drug resistance in the context of limited drug use is unexpected, and the extent of future circulation is difficult to predict."

See also:

Jun 13 WHO statement on H1N1 oseltamivir resistance in 2007-08 season
http://www.who.int/influenza/patient_care/antivirals/oseltamivir_summary/en/

Feb 1 CIDRAP News story "Europe says Tamiflu-resistant virus seen in 9 countries"

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