Drug-Resistant Flu Detected: Japanese strains appear transmissible

For the first time, researchers report drug resistance in type B influenza virus, which causes about 30 percent of flu cases in the United States. Furthermore, the researchers say that unlike a previously noted drug-resistant type A strain, this strain may jump from person to person.

“We’ve found a very clear case of resistance in the presence of antiviral drugs,” says Yoshihiro Kawaoka of the University of Tokyo and the University of Wisconsin–Madison.

Kawaoka’s team studied flu in children infected during a 2004–2005 type B outbreak in Japan. They collected viruses before and after the children had been treated with zanamivir or oseltamivir, two drugs more commonly prescribed in Japan than elsewhere.

While no virus displayed resistance before the drug treatment, a strain from one of 74 children showed resistance to oseltamivir after treatment. This strain harbored mutations in the gene for neuraminidase, the enzyme targeted by the antiviral drugs. Kawaoka says that there is a good chance that resistance arose because of the drug treatment.

The team also studied viruses from 348 ill but untreated adults and children. Seven patients carried drug-resistant viruses—a surprising find. “This is good evidence that the [resistant viruses are] circulating in the community,” Kawaoka says.

Three of the seven carriers may have caught the bug from siblings infected with a resistant strain. The other four probably caught it from nonfamily members in the community, the researchers say, although they acknowledge that the resistant bugs might have evolved spontaneously in the patients. All seven resistant strains carried mutations in the neuraminidase gene.

In 2004, the same research team found drug-resistant strains of the more common type A influenza in 18 children in Japan. The researchers found no evidence that those bugs could hop from person to person.

The new report suggests that drug-resistant type A strains could become transmissible, a scenario that worries Anne Moscona of the Weill Medical College of Cornell University in New York City.

In a commentary accompanying the Japanese report in the April 4 Journal of the American Medical Association, Moscona says that earlier laboratory and animal studies suggested that drug-resistant flu strains would be less infectious and less transmissible than normal strains. The new report, though, shows that “contrary to what had been hoped until now, some resistant variants are vigorous pathogens [that] may be here to stay,” Moscona says.

Japan’s reliance on antiviral medications makes the country an ideal breeding ground for drug-resistant flu strains, Kawaoka says. Both he and Moscona urge monitoring of seasonal outbreaks for further drug resistance and call for especially close scrutiny of any appearances of avian influenza, a type A virus.

“Influenza viruses evolve rapidly and nimbly,” Moscona says. She wants pharmaceutical companies to develop new drugs that target weak points on the influenza virus other than neuraminidase. She also says that policy makers and physicians should rethink their antiviral-medication policies to ensure that the drugs aren’t overused.