Anti-Flu Drugs Losing Punch

April 3, 2007 — -- Tamiflu and Relenza, two anti-viral drugs commonly used to treat influenza, may be losing their effectiveness as the flu virus adapts, Japanese scientists report in a new study.

The study, published in the current issue of the Journal of the American Medical Association (JAMA), reports yet another obstacle in the fight against the flu.

The research suggests that scientists may have to find new ways to combat growing resistance to current flu treatments -- and possibly rethink the strategy for preventing a global flu pandemic.

There are three types of viruses that cause the flu: influenza types A, B and C. Drugs like Tamiflu, manufactured by Roche, and Relenza, manufactured by GlaxoSmithKline, are designed to fight the A and B types -- the two most responsible for yearly flu outbreaks.

According to the Centers for Disease Control and Prevention (CDC), about 36,000 people in the United States die every year from the flu.

Influenza A viruses -- among which is the H5N1 virus responsible for bird flu -- cause regular outbreaks of flu and can infect animals. Influenza B viruses are responsible for sporadic outbreaks of flu, while influenza C viruses rarely cause symptoms.

When an infectious agent such as a virus changes, or mutates, in such a way as to render a drug against it less effective, the virus is said to be drug-resistant.

The concept of flu resistance to anti-viral drugs is not new. While some influenza A viruses have already been found to be resistant to anti-viral agents, this report is the first to identify resistant strains of influenza B.

Approved by the U.S. Food and Drug Administration in 1999, Tamiflu and Relenza are relatively new additions to our armaments against the flu. They work by reducing the number of viruses released by infected cells. Fewer viruses means a lower chance of viral spread -- and a higher chance of survival for the infected individual.

Tamiflu is by far the more frequently used of the two anti-viral drugs, with more than 50 million patient treatments worldwide since its approval. Japan is the greatest user of medicines like Tamiflu, and more than 90 percent of all such prescriptions are for Tamiflu.

Resistant Viruses Just as Dangerous

Researchers had previously found some evidence that the mutations that make the flu virus resistant to drugs also lessens its ability to infect humans. The current study's findings suggest, however, that this is not always the case.

The resistant strains of influenza B identified in this study "cause infections with no difference in duration of symptoms, level of viral shedding, or clinical outcome," Dr. Anne Moscona, vice chair of research for pediatrics at New York Weill Cornell Medical Center, wrote in an accompanying editorial.

In other words, these resistant viruses make people just as sick. Furthermore, the resistant viruses seem to be passed readily from person to person -- not only within families, but also among community members.

Does this mean we can expect a pandemic of drug-resistant influenza B in the near future? Not necessarily.

While flu resistance is a concern, unlike influenza A, influenza B is "not likely to be spread pandemically," said Robert Garry, professor of microbiology and immunology at the Tulane University School of Medicine.

This is because influenza B viruses are not inherently programmed to result in pandemic spread in the same manner as influenza A viruses -- so it is unlikely that we need to prepare for a bird flu-like scare caused by influenza B.

Additionally, since this study was conducted in Japan, where Tamiflu use is much more common, "There are no immediate implications for anti-viral treatment in the U.S., but this is a yellow caution light," said Dr. William Schaffner, chair of the department of preventative medicine at the Vanderbilt University School of Medicine.

Resistance Still Rare, but Monitored

Though resistant strains of flu are being reported, resistance to Tamiflu is generally rare and is "continually and very closely monitored," according to Roche spokesperson Terry Hurley. He adds that anti-viral drugs such as Tamiflu are still "an essential part of any pandemic flu plan," and maintain their position as heavyweight fighters against flu.

Most importantly, the results of this study emphasize that anti-viral agents such as Tamiflu, Relenza and any other anti-viral drugs to be developed in the future should be used carefully in order to limit resistance.

And preventative measures, such as getting regular yearly flu shots, remain particularly important.

"The study reminds us that the treatment of influenza, although important, is not as effective as its prevention," Shaffner said. "We need to continue, indeed increase, research to create more effective influenza vaccines and improve methods of rapid vaccine production and delivery."