Tamiflu-resistant strain found in Houston children
By ERIC BERGER
Copyright 2009 Houston Chronicle
Jan. 8, 2009, 11:27PM

A recently mutated strain of flu that resists the most commonly prescribed treatment has been found in Houston children.

Physicians have closely watched the development of this winter's U.S. flu season, because what appears to be the most widely circulating strain, H1N1, has developed resistance to Tamiflu, the leading antiviral drug.

Another leading antiviral drug — Relenza, a powder that must be inhaled — is effective against the strain but is not recommended for children under age 7.

For that reason, the U.S. Centers for Disease Control and Prevention recently issued an advisory recommending that doctors treat children with H1N1 with a combination of Tamiflu and an older drug, Flumadine, to which the strain is not resistant.

Although the existence of alternative therapies generally means there is no immediate danger to flu patients, infectious disease experts say the emergence of a widely circulating strain that resists Tamiflu highlights the vulnerability of the world's lean stock of antivirals.

"We definitely need to develop new treatments for influenza," said Dr. Paul Glezen, a flu expert at Baylor College of Medicine.

Glezen stressed that the H1N1 strain is among those protected by this year's flu vaccine. He urged those who have not received the vaccine to do so, because stockpiles remain available.

But with students back in school after the holiday break, Glezen said he expects the prevalence of the flu virus, which remains "sporadic" for much of the country, to increase. In Texas the virus is considered to have "local activity," which is a step up from sporadic.

Flu season typically peaks in February before ebbing in March.

"Flu is predictably unpredictable," said Dr. Gail Demm-ler, director of the Diagnostic Virology Laboratory at Texas Children's Hospital and a pediatrics professor at Baylor.

"Every year is unique. What we usually see is an increase of flu activity after the winter break," Demmler said. "Numberwise, looking through November and December, it seems to be a modest year. But honestly, it's still too early to tell how the season will go."


80 percent of flu type-A
Because this winter's flu season has likely not yet peaked, it's impossible to determine how prevalent H1N1 will become this year. It appears almost certain, however, that H1N1 will emerge as the most common strain in circulation.

According to the CDC's most recent report on U.S. activity, about 80 percent of the 45,000 flu specimens tested this winter have been type-A influenza. Although not all of these strains were sub-typed by scientists, H1N1 appears to account for about 90 percent of the type-A influenza in circulation. About 20 percent of the circulating flu is type-B.

The other circulating strains of type-A and type-B influenza are not resistant to Tamiflu.

Demmler said she sent specimens from the first two flu cases observed at Houston's Texas Children's Hospital to the CDC for testing in early December. The agency recently determined they were the H1N1 strain.

However, Demmler said she has since seen a "fair amount" of type B influenza in circulation among Houston children.


First detected in Norway
The emergence of a widely circulating strain that's resistant to Tamiflu has both surprised and perplexed infectious disease experts. Only about 2 percent of known strains, most of them rare, have previously been found to resist Tamiflu, which is manufactured by Roche.

Generally, if taken within 48 hours of the flu's onset, Tamiflu shortens the duration and severity of flu symptoms and reduces the chance that the ailment will spread to others.

Baylor's Glezen said it appears the H1N1 strain developed resistance spontaneously rather than because of Tamiflu use. That's because the new strains were first detected in Norway, where little Tamiflu is used.

Despite their effectiveness, antivirals such as Tamiflu are still not used widely in the United States, Glezen said. He estimated that just 5 percent of U.S. flu cases are treated with antivirals, partly because the ailment may not be diagnosed within two days of onset.


Fewer antivirals
This underuse has contributed to a dearth of antivirals in the drug development pipeline of pharmaceutical companies, he said, despite the fact that scientists knew influenza would eventually acquire resistance to existing drugs.

"The public uptake of antivirals has been so low there isn't a big incentive for pharmaceutical companies to develop new drugs," Glezen said. "At the same time — now more than ever — we need new drugs."

eric.berger@chron.com

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