TORONTO - Early signs from this flu season suggest doctors face a vexing dilemma in treating the illness.
Testing to date in Canada, the United States and Europe shows that nearly all H1N1 viruses are resistant to oseltamivir (sold as Tamiflu) and susceptible to the adamantane drugs, amantadine and rimantadine. The inverse is true for H3N2 viruses, which are universally resistant to the adamantanes and susceptible to oseltamivir.
Given that in reality little point-of-care testing is done to determine whether a patient actually has influenza, let alone which variety of the bug is behind the illness, the resistance situation could see doctors making choices that lead to treatment failure this season.
"This is a very challenging situation," Dr. Tim Uyeki, deputy chief of influenza surveillance and prevention for the U.S. Centers for Disease Control admitted about the bizarre resistance picture coming into focus in the early days of the flu season.
"It definitely adds to the complexity of trying to manage influenza," Dr. Maria Zambon, head of the respiratory viruses unit of Britain's Health Protection Agency, agreed in an interview.
In the face of these early results, the CDC issued a health alert Friday to bring the U.S. medical community up to speed and recommend changes in the usage of flu drugs for the time being.
The upshot? When in doubt -- and when the patient's age and health permits -- use the only other option, the drug zanamivir, which is sold under the brand name Relenza. So far, all influenza A viruses (H1N1 and H3N2 are subtypes of influenza A) as well as influenza B viruses seem to be susceptible to zanamivir.
Oseltamivir could be used in combination with one of the adamantane drugs, but should only be used alone when local surveillance shows the viruses circulating are likely to be H3N2 or influenza B, the CDC guidance says.
As U.S. surveillance suggests most disease there so far this season is being caused by the H1N1 viruses, zanamivir appears to be a better bet than oseltamivir -- or at least it is for patients who can use it. Zanamivir isn't licensed for use in children under seven years of age, and can't be used by people with chronic underlying airways disease or who can't manage the drug's inhalation device.
While they struggle to craft guidance for doctors, both the CDC and the Public Health Agency of Canada have a straightforward piece of advice for the public: Get a flu shot. This year's vaccine is well matched to the H1N1 viruses and the majority of H3N2 viruses currently making the rounds.
On the issue of antivirals, Canadian authorities aren't yet offering new treatment advice to the medical community in this country, though they are closely monitoring the situation, said Dr. Arlene King, director general for the Public Health Agency of Canada's centre for immunization and respiratory infectious diseases.
The National Microbiology Laboratory in Winnipeg has only tested 16 influenza viruses so far this season, finding all the H1N1s (three) resistant to oseltamivir and all the H3N2s (five) resistant to the adamantane drugs. The British Columbia Centre for Disease Control has tested another 19 H1N1 viruses, with 14 showing resistance and the results from the other five deemed inconclusive.
King said for now the recommendation is that doctors treating patients in long-term care facility outbreaks, for instance, should use oseltamivir. But they should be aware of the situation and be ready to shift gears.
"If physicians feel that treatment is merited, then they need to be obviously aware of this issue and should there be issues related to treatment failures, then they would have to consider other alternate drugs -- zanamivir being, of course, a good choice," she said.
In Europe, the resistance pattern looks identical to what's being seen in North America, said Zambon. But H3N2 viruses currently appear to be responsible for about 90 per cent of confirmed flu cases, leading European authorities to conclude oseltamivir will probably be effective in most situations.
In the first few years after oseltamivir's introduction to the market, it was thought drug resistance wasn't likely to pose too much of a problem for the drug. Laboratory testing suggested resistant viruses, if they developed, would be too weak to spread.
That theory proved far off the mark when earlier this year reports emerged from Europe of a new resistant strain of H1N1 viruses. The strain has disseminated widely and rapidly; 100 per cent of H1N1 viruses tested in South Africa during that country's recent winter carried the mutation that makes the viruses resistant.
In the face of this development, doctors who have already expressed skepticism over the merits of the available flu drugs may be even more reluctant to prescribe them in an out-patient setting or use them in hospitalized patients.
Experts, who feel the drugs are already underutilized, hope that isn't the case.
"I think that these recommendations are really meant to provide physicians with guidance on how they should use or could use antivirals," said Dr. Joe Bresee, the CDC's chief of influenza surveillance and prevention.
"So I really do hope these new recommendations won't scare anybody away from the use of antivirals but will in fact remind them about the value of use of antivirals and encourage them to use them appropriately."
