Tamiflu resistant flu viruses found in 9 European countries, Canada, U.S.

Feb. 7, 2008, Stockholm – Flu viruses resistant to the antiviral drug Tamiflu have been found in
nine of 17 European countries which submitted viruses for testing, the
European Centre for Disease Control says.

Approximately 14 per cent of H1N1 flu viruses checked carried the
resistance mutation, which has been shown in testing to dramatically
reduce a virus's susceptibility to the drug, the Stockholm-based agency
said in this week's issue of the electronic journal Eurosurveillance.

Surveillance done in previous years suggests under one per cent of flu viruses would be expected to be resistant to the drug.

International influenza experts are unsettled by the surprisingly high levels of resistance, found virtually exclusively, it seems, in viruses collected from people who had not taken oseltamivir, or Tamiflu.

It is known that a small proportion of people who take Tamiflu to combat influenza will shed viruses that are resistant to it. But it had been thought that viruses that acquired this resistance mutation, known as H274Y, would pay for that gain with a corresponding loss in their ability to transmit.

The thinking has been that if they developed in someone using Tamiflu, they would be unlikely to infect contacts of that person and start to circulate more widely because they would be too weak to compete with regular flu viruses in the race to infect other humans.

Finding these viruses in so many people who had not taken the drug suggests Tamiflu may be more vulnerable to the development of resistance than initially believed, experts fear.

“So far, there is no information that any of these viruses, in any country, has been obtained from a person who has either been treated or been in close contact with another individual who has been treated with oseltamivir,'' several senior European flu experts wrote in the Eurosurveillance article.

“We therefore conclude that the identification of these oseltamivir-resistant viruses as a substantial proportion of
circulating viruses, particularly in Norway, is the first clear  evidence that influenza A(H1N1) virus with the H274Y mutation can readily transmit between individuals.''

The cases aren't clustered, even within particular countries, the World Health Organization said in a  question-and-answer document posted on its website Thursday.

“Preliminary investigation so far suggests that most of the persons with resistant viruses were not in contact or linked in any known way.''

“Patients were not limited to a particular geographic location in a country. In general, patients in Norway were not known to have travelled to other countries before becoming ill. These findings are consistent with this virus strain circulating at community level in some European countries.''

Given the scarcity of flu antivirals -there are only four, and resistance to two older drugs is an even greater problem- influenza experts view this development with some concern.

“I really find it quite disturbing that there's now evidence of it (the resistant virus) spreading,'' said Jennifer
McKimm-Breschkin, a virologist with Australia's Commonwealth Science and Industrial Research Organization in Melbourne. McKimm-Breschkin was one of the scientists who developed Tamiflu's main competitor, zanamivir (Relenza).

The findings relate only to H1N1 viruses, which are one of two subtypes of influenza A viruses that regularly infect humans.

The same mutation has been found in three patients with H5N1avian flu who have been treated with Tamiflu, the WHO said, but it cautioned against concluding the rise of resistance in H1N1 viruses will translate to H5N1 viruses as well.

“The implications (for H5N1) are uncertain at this point,'' the Geneva-based agency stated. “Until we learn why the unexpected increase in oseltamivir resistance has occurred in H1N1 viruses, it is too early to know what, if any, potential there might be for a similar increase in resistance to occur in H5N1 viruses.''

The Eurosurveillance report reveals that most of the viruses have been found to date in Northern European countries. Resistant viruses have been found in Denmark (10 per cent), Finland (29 per cent), France (17 per cent), Germany (seven per cent), Netherlands (six per cent), Norway (70 per cent), Portugal (33 per cent), Sweden (eight
per cent) and the United Kingdom (six per cent).

Canada and the United States have also found these resistant viruses.

Nearly 10 per cent of the H1N1 viruses tested so far this flu season at the National Microbiology Laboratory in Winnipeg carry the resistance mutation. As of last week, the U.S. Centres for Disease Control had found it in 6.7 per cent of H1N1 viruses its laboratories had tested.

Paradoxically, officials in Japan have not found viruses with the resistance mutation this year, though 2.2 per cent of flu viruses in the 2005-06 flu season were resistant. Japan uses more Tamiflu than any other country in the world.

Public health officials in Europe and North America note that flu season has only recently started to get into full swing and the number of viruses tested so far is low – a fact which could over-inflate the incidence.

The resistant viruses have been isolated from both adults and children, ranging from one month old to 61 years old. The majority of people from whom the viruses were isolated were adults. To date there is no evidence the people who were infected with the resistant virus were any more ill than other flu patients.