Tamiflu resistance found in Japanese flu viruses

There is new and unwelcome evidence that flu viruses can develop partial resistance to the antiviral drugs Tamiflu and Relenza and spread from person to person.

Japanese researchers reported Tuesday that influenza B viruses recovered from several people who had not taken flu drugs were partially resistant to Tamiflu, Relenza or both, suggesting these less susceptible viruses were spreading at low levels in their communities.

It had been hoped that viruses that developed resistance to neuraminidase inhibitors — the drug class to which oseltamivir (Tamiflu) and zanamivir (Relenza) belong — would be so weakened by the mutations that make them resistant that they wouldn't be able to spread from person to person. This and other recent research suggests that's not the case.

But the new findings don't hint at whether increased use of the drugs against H5N1 avian flu — an influenza A subtype that many experts fear could cause a pandemic — will trigger increasing rates of drug resistance in those viruses, said an antiviral expert with the World Health Organization.

"I don't think this is a dire circumstance in terms of [all] influenza. I think you need to look at each virus type and subtype with the available evidence," Dr. Frederick Hayden, a scientist with the WHO's Global Influenza Program, said from Geneva.

Hayden noted that the mutations needed to confer resistance differ according to the type of influenza viruses and the drug. So the ease with which mutations develop in influenza B viruses doesn't portend how commonly resistance mutations will occur in influenza A viruses.

"I would not generalize the situation with influenza B to what might happen with influenza A viruses," he said. "So I don't think that this article really speaks to pandemic influenza or pandemic planning."

But Hayden and other scientists not involved in the study agreed this new evidence underscores how critical it is to keep an eye on flu viruses to see whether they are gaining resistance to the very few drugs available to treat them.

Need for new antivirals

"The emergence of drug resistant influenza B should draw attention to the importance of continual monitoring of strains over time and to the need for frequent rethinking of policies for use of antiviral drugs," antiviral experts Anne Moscona and Jennifer McKimm-Breschkin wrote in an editorial accompanying the article, published Wednesday in the Journal of the American Medical Association.

Moscona is an infectious diseases specialist at Cornell University's Weill Medical College in New York; McKimm-Breschkin is a chief research scientist at the Commonwealth Scientific and Industrial Research Organization, Australia's national science agency.

"While the news about resistance is not good and certainly calls into question some of the current assumptions about drug-resistant viruses, an effective response to this news can help contend with the new challenges of influenza," they said.

The findings also highlight the need for more antiviral drugs. Public health authorities concerned about a possible flu pandemic regularly bemoan the fact that there are only a handful of influenza drugs, two of which are essentially unusable because so many flu viruses are resistant to them. (Those drugs are amantadine and rimantadine.)

"There is urgent need to develop new kinds of antivirals," senior author Dr. Yoshihiro Kawaoka, who splits his time between the University of Wisconsin-Madison and the University of Tokyo, said in a release.

Season specific?

Kawaoka and his co-authors studied collected virus isolates from 74 children treated with antivirals and from 348 flu patients who didn't take the drugs during the 2004-05 influenza season in Japan, where neuraminidase inhibitors are more heavily used than anywhere else.

Seven of the untreated patients were infected with viruses that carried mutations that made them less vulnerable to one or the other or both neuraminidase inhibitors. Kawaoka and his colleagues concluded that three of those cases were likely infected by a sibling who had taken antivirals and who was shedding resistant viruses. Four people were likely infected in their communities.

"There may have been something about that particular season in terms of either natural variation in susceptibility patterns going on but also then potentially this low-level community transmission of variants with reduced susceptibility as well," he said.

© The Canadian Press, 2007