TORONTO - Canada's National Microbiology Laboratory is reporting a high level of Tamiflu resistance among H1N1 viruses circulating so far this flu season in this country, one of a number of labs to see a phenomenon that is unsettling influenza experts.
Nearly 10 per cent of H1N1 viruses tested so far this year by the Winnipeg lab are resistant to the drug, a cornerstone of pandemic planning for many countries around the globe. In the past, fewer than one per cent of circulating human flu viruses were thought to be resistant to Tamiflu.
"That's quite a surprise," the lab's scientific director, Dr. Frank Plummer, said, noting the resistance mutation spotted in the Winnipeg testing is the same one that has been reported over the past few days from Norway, several other European countries and the United States.
Eight of 81 H1N1 viruses tested carry the H274Y mutation - one each from British Columbia and Newfoundland and Labrador, and six from Ontario. Plummer said that total includes one virus (from British Columbia) recovered from a child who is believed to have been infected in Sudan.
His surprise is shared by experts with the World Health Organization's Global Influenza Program, which convened a teleconference of about 50 scientists from leading influenza laboratories around the world Tuesday to try to get a handle on how far this virus has spread, how common it is in places where it is being found and what is driving the spread.
Dr. Frederick Hayden, a leading antiviral expert working at the WHO, said the resistance virus has been reported over a broad geographic range, both in terms of countries and within countries themselves.
"We do know that again within the countries that have the information, it's not just focal pockets. There are multiple sites, for example, within France or within Norway where this has been detected," he said from Geneva.
The United States has reported that 5.5 per cent of tested H1N1 viruses there are resistant to the drug. European countries known to have found resistant viruses include Norway, Denmark, France and the United Kingdom. Hayden suggested more countries have found these viruses, but said he wasn't at liberty to name names.
Perplexingly, Japan - the country that uses more Tamiflu by far than any other in the world - has not found any of these resistant viruses this flu season, Hayden said.
Reports worldwide still number in the "few dozens." But that is enough to send up red flags, especially given that in all of the cases where details are known, people who caught the virus hadn't taken Tamiflu.
It wouldn't be startling to see people who've used the drug shedding viruses that are resistant to it. Like antibiotic resistance, resistance to antiviral drugs can develop in people who use them, though rates of drug-triggered resistance are low with Tamiflu.
But it had been thought that viruses that acquired this H274Y resistance mutation would pay for that gain with a corresponding loss in their ability to transmit. The belief was that if they developed in someone using Tamiflu, they would be unlikely to infect contacts of that person and start to circulate more widely - in essence, that they would be too weak to compete with regular flu viruses in the race to infect human respiratory tracts.
These recent findings suggest the drug is more vulnerable to the development of drug resistance than had been previously thought, experts fear.
"This mutation is not going to affect the fitness of the viruses as much as we thought," said Jennifer McKimm-Breschkin, a virologist with Australia's Commonwealth Science and Industrial Research Organization in Melbourne.
McKimm-Breschkin was one of the scientists involved in the discovery of Tamiflu's competitor, Relenza. Though the two drugs are in the same class, Relenza is still effective against viruses with the H274Y mutation.
"We're now seeing the ability of this virus that we thought would not have the ability to compete (with unmutated viruses) spreading globally," she said, suggesting that doesn't bode well if H5N1 avian flu starts a pandemic. The same mutation creates Tamiflu resistance in H5N1 viruses.
Hayden said the appearance of resistant H1N1 viruses across such a broad expanse "does raise a lot of questions."
Dr. Joe Bresee, chief of flu epidemiology and prevention at the U.S. Centers for Disease Control, questioned Monday whether there was a true rise in the number of resistant viruses.
Bresee cautioned that increased influenza surveillance prompted by concerns over the H5N1 virus may be turning a spotlight on something that always existed but went unnoticed in the past.
Hayden disagreed, saying an international network of antiviral experts has been watching for this resistance pattern but it has only been found rarely.
"Basically it was present at very low frequencies, less than a half per cent. In most studies, (it was) not even detected. So I think this is a new phenomenon and one that we need to understand better."
He said work is already underway to try to catalogue cases and to sequence resistant viruses to see if their genomes hold clues to how the resistance arose.
