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Resistance to Popular Influenza Drug May Be Higher Than Thought

If you come down with the flu, in addition to the added bed rest and fluids, your doctor will likely prescribe one of two possible medications: an M2 ion channel blocker or a neuraminidase inhibitor. The former prevents the virus from making copies of itself inside the cell, while the latter prevents new viruses from breaking free to infect other cells.

One of the benefits of neuraminidase inhibitors, such as zanamivir (Relenza) and oseltamivir (Tamiflu), is they work against both influenza A and B, whereas M2 inhibitors are only effective against influenza A. Also, the influenza virus appears to be less prone to becoming resistant to neuraminidase inhibitors than to M2 inhibitors.

Photo of Yoshihiro Kawaoka, D.V.M., Ph.D.
Yoshihiro Kawaoka, D.V.M., Ph.D.

"True," says NIAID-supported researcher Yoshihiro Kawaoka, D.V.M., Ph.D., on the subject of resistance, "but perhaps not as much as we'd originally thought." Dr. Kawaoka, a renowned virologist who holds professorships at the University of Wisconsin, Madison, and the University of Tokyo, recently studied the frequency with which the H3N2 influenza virus developed drug-resistant mutations in 50 Japanese children taking oseltamivir.

Analyzing the virus's gene sequences before and throughout treatment with oseltamivir, the researchers found mutations had occurred on the neuraminidase gene in nine, or 18 percent, of the children studied. All of the muta nts were resistant to the effects of oseltamivir. Earlier clinical trials had demonstrated oseltamivir-resistant mutations in only 4 percent of children ages 1 to 12 and in less than 1 percent of adults. (Resistance to the M2-inhibiting drugs amantadine and rimantadine are much higher, occurring in roughly 30 percent of patients who take those drugs. In another study, Dr. Kawaoka has shown that drug-resistant strains appeared in 80 percent of children taking amantadine.)

The researchers also found that some children who did not experience drug resistance continued spreading the flu virus, even after five days of treatment.

Dr. Kawaoka notes that younger children, who were probably exposed to influenza for the first or second time, developed more drug-resistant viruses than older children, who most likely possessed some pre-existing immunity against other strains. Because this scenario resembles that found during a flu pandemic, these findings could provide helpful insight into the use of neuraminidase inhibitors if a new pandemic should arise, he says.

Dr. Kawaoka's Web page

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Last Updated August 12, 2010