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Resistance to Flu Drugs Mushrooming; Common Medicines Losing Strength to Stop Pandemic, Study Says

Posted on: Thursday, 22 September 2005, 15:00 CDT

Resistance to drugs commonly used to treat influenza has skyrocketed in the last 10 years, according to the most comprehensive study to date. The findings mean that it'll be even harder to stop the spread of the flu, putting the elderly and those with chronic illnesses at greater risk for complications, including death, from the virus.

And it highlights concerns about controlling a flu pandemic, were one to strike.

The research appeared Wednesday in the journal The Lancet.

Researchers from the U.S. Centers for Disease Control and Prevention and the Wisconsin State Laboratory of Hygiene report that viral resistance to a class of drugs called adamantanes, which includes amantadine and rimantadine, increased from 0.4% in 1994 to 12.3% in 2004.

The anti-viral drugs have been used to treat the flu and prevent its spread for more than 30 years. Amantadine is used to treat children, while rimantadine can be prescribed for both children and adults.

"We were alarmed to find such a dramatic increase in drug resistance in circulating human influenza viruses in recent years," said Rick Bright, a researcher at the CDC and an author of the report. "Our report has broad implications for agencies and governments planning to stockpile these drugs for epidemic and pandemic strains of influenza."

"With the increasing rates of resistance shown here, amantadine and rimantadine will probably no longer be effective for treatment and prophylaxis in the event of a pandemic outbreak of influenza," Bright said.

The news did not come as a surprise to Yoshihiro Kawaoka, a virologist and flu researcher at the University of Wisconsin- Madison and the University of Tokyo. He said researchers have known for some time that these drugs were showing resistance.

And Japan has sharply reduced its use, Kawaoka said.

He also said that with safer and more effective drugs available, such as Tamiflu, use of adamantanes in many parts of the world is diminishing.

Commonly used in Wisconsin

But because adamantanes are relatively inexpensive, they are still commonly prescribed in the United States. Amantadine and rimantadine are Medicaid's drugs of choice to treat flu in Wisconsin, according to the state's Department of Health and Family Services' Medicaid Preferred Drug List.

"In that context, this is an important drug," Kawaoka said.

For the study, the authors screened 7,000 influenza A viruses gathered from 1994 to 2005. They were looking for gene mutations known to be associated with adamantane resistance. They found that 6% of the viruses contained relevant mutations.

But it was the viruses collected from the last few years that were most telling: 82% of resistant viruses were found in samples collected since 2003. Of 636 viruses identified in the U.S. between October 2004 and March 2005, 15% showed resistance, up from 2% the year before.

The authors wrote that geographic analyses showed a "substantially rising percentage of drug-resistant" viruses isolated from the U.S., China, Hong Kong, Taiwan and South Korea.

And while the researchers focused on influenza A viruses of the H3N2 strain, their findings can be applied to the killer avian strain (H5N1) being monitored in Asia. The report noted that all human cases of the bird flu have been resistant.

The H5N1 strain of bird flu has killed at least 63 people and resulted in the deaths of tens of millions of birds since 2003.

Most human cases have been linked to contact with sick birds. But the World Health Organization has warned that the virus could mutate into a form that spreads easily among humans possibly triggering a global pandemic that could kill millions.

Scientists have said that it is impossible to predict when the virus might mutate into a form that spreads easily among people. But they have warned repeatedly that as ever more birds carry the virus and spread it to other species, notably pigs, it becomes more likely that the virus will adapt to people.

A top WHO official said Wednesday that the agency was prepared to begin distributing large-scale quantities of an anti-viral drug to treat bird flu in humans "if and when a pandemic starts."

Shigeru Omi, director for WHO's Western Pacific region, said at a WHO conference in New Caledonia that the U.N. agency was ready to open its stockpile of oseltamivir, or Tamiflu, to help avert a global pandemic of the disease.

Vaccine use suggested

Jeffrey Davis, Wisconsin's chief medical officer, said the state has an influenza pandemic plan, but that it's still a work in progress.

It places heavy emphasis on use of anti-viral drugs and other methods, such as isolation, to stop the flu from spreading.

But not knowing what Wisconsin will receive in terms of drug distribution, or how to get it here, poses a huge problem in ensuring preparedness, he said.

To complicate matters more, since amantadine and rimantadine resistance emerges quickly, other drugs such as Tamiflu must be stockpiled in abundance, too, he said.

And if resistance builds to other drugs, too?

"It's definitely a problem," he said.

"The question is, can this be reversed," Davis said. "Does it suggest that prudent use and control of products in the U.S. is an opportunity to do this?"

"We can minimize the use of anti-virals and therefore minimize the development of resistance to anti-virals by maximizing our use of vaccines before the season starts," said Geoffrey Swain, associate medical director at the Milwaukee Health Department.

Swain said that while facing a pandemic, it would be even more important for people to wash their hands and stay home if ill, particularly because vaccination would be impossible.

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The Associated Press contributed to this report.

Copyright 2005, Journal Sentinel Inc. All rights reserved. (Note: This notice does not apply to those news items already copyrighted and received through wire services or other media.)

Source: Milwaukee Journal Sentinel

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