European agencies find 14% of flu isolates are resistant to oseltamivir

BMJ 2008; 336 doi: (Published 07 February 2008) Cite this as: BMJ 2008;336:298
  1. Owen Dyer
  1. 1London

    European laboratories have detected an unusually high rate of resistance to the antiviral drug oseltamivir (Tamiflu) in random samples of seasonal influenza virus taken from around the continent.

    The European Centre for Disease Prevention and Control and other agencies reported last week that oseltamivir resistance had been detected in 59 of 437 influenza A (H1N1) isolates from around Europe, a rate of 14%. In previous years, resistance has generally been found in about 1% of isolates.

    The highest rate of resistance was found in samples from Norway, with 12 out of 16 tested isolates resistant to oseltamivir. Austria and Italy reported no resistant strains, whereas in Germany, the Netherlands and Sweden, the rate of resistance was less than 10%. Resistance was found in 17% of French samples tested.

    In Britain, the Health Protection Agency has reported finding oseltamivir resistance in eight of 162 isolates tested.

    Although resistance to oseltamivir has often developed in patients treated with the drug, the current increase in resistance is unusual because none of the patients who provided the samples had taken oseltamivir, said Gregory Hartl, WHO influenza spokesman.

    “When we looked at the cases in Norway, we found that none of these patients had taken oseltamivir, none had been in contact with each other, and in fact they come from different regions of the country,” he said. “For widespread resistance to crop up under these circumstances is something new, and we don’t yet understand what it signifies. A lot of people are working on answering that question right now.”

    A smaller but still unprecedented rate of oseltamivir resistance, about 6%, has also been found by the Centers for Disease Control and Prevention in the United States this year. But in Japan, where the drug is most widely used, no resistant cases have been found. No drug resistance has been reported in China, but isolates from the later part of the flu season have yet to be tested there.

    The resistant virus is believed to cause typical seasonal flu symptoms, and to be transmissible between humans. All of the resistant viruses have the same mutation, one which has been seen in patients treated with oseltamivir. Although this mutation has never been seen in H3N2 or type B influenza, it has been identified three times in patients with avian H5N1 influenza.

    Britain’s antiviral stockpile for a flu pandemic consists of enough doses of oseltamivir to treat a quarter of the population, a level of coverage that the government plans to double. For now, WHO, the UK Department of Health, other European health authorities, and the US health authorities all agree that there is no need to revise their pandemic flu preparations in the light of the new data.

    The resistant flu viruses detected to date remain susceptible to other antiviral drugs such as zanamivir, and the adamantane class. The flu vaccine’s effectiveness is unhindered by the mutation, and this year’s vaccine is a good match for most H1N1 strains currently circulating in Europe, according to WHO.

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