Study calls for Tamiflu alternatives

Kawanza Newson

MILWAUKEE, Wis. (MCT) — Tamiflu-resistant strains of flu have been found in patients who haven’t taken the drug, suggesting the mutated virus is capable of spreading between humans, according to an international team of researchers that includes a University of Wisconsin-Madison scientist.

Experts say the study, which showed anti-viral resistance in the milder influenza B viruses, means that Tamiflu-resistant strains of other flu viruses, such as the more fatal avian flu, could spread between humans, too.

“This is a yellow caution light,” said William Schaffner, a flu expert and head of the preventive medicine department at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved in the study.

“We need to continue to be prudent in how we use these anti-viral drugs,” he said.

Schaffner said that overuse of anti-virals causes the viruses to mutate and become resistant to current medications. If the resistant viruses become more common, then new drugs will have to be developed to fight the flu, he said.

Influenza remains a major health problem in the United States, hospitalizing about 200,000 people a year and killing about 36,000.

Each year, health officials encourage patients — especially those in high-risk categories — to get flu shots for protection against the illness. But in January 2006, the CDC alerted doctors that the influenza A strain H3N2 was resistant to two commonly prescribed anti-virals — rimantadine and amantadine. For the first time, the agency urged them not to prescribe the drugs to their patients who had flu.

In the study, Madison virologist Yoshihiro Kawaoka and colleagues from the University of Tokyo obtained flu virus samples from 74 children who’d been treated with Tamiflu and 348 children and adults who were not treated during the 2004- `05 flu season in Japan. They were trying to determine if influenza B viruses were associated with Tamiflu resistance. Japan is known for its high use of anti-virals, though Kawaoka has said previously that use of the drugs is declining.

The researchers did identify a resistant virus in one child from the treated group. In addition, they also found seven people from the untreated group who also showed resistance, despite not ever taking Tamiflu. Although three patients likely became infected through sibling contact, the remaining four patients were likely infected elsewhere in the community.

“We don’t know how extensive that transmission is because we don’t know the history of those patients,” Kawaoka said in a statement. “But we do know that some of the patients in the study were not treated with Tamiflu, but shed Tamiflu-resistant viruses. If you find Tamiflu-resistant viruses in patients not treated with Tamiflu, and there is no animal reservoir for the virus, where else could they get it?”

But Kelly Henrickson, professor of pediatrics and an infectious disease expert at the Medical College of Wisconsin and Children’s Hospital of Wisconsin, said that the findings were not surprising and don’t warrant any changes in current clinical practice.

That’s because only one treated patient developed resistance to Tamiflu and it’s still unclear how patients in the untreated group developed resistance, he said.

“There’s nothing groundbreaking or shattering because it’s such a low level of resistance,” he said. “It’s reassuring that B doesn’t mutate as fast as A, but that’s what we already knew.”

The researchers acknowledge that the rate of resistance found in the treated patients, 1.4 percent, is much lower than the 5.5 percent to 18 percent rate seen among influenza A viruses, but say that any level of resistance is problematic.

If flu viruses manage to continually develop resistance, key lines of defense will have been effectively removed. More worrisome, said Kawaoka, is that the same resistance will emerge in influenza A viruses, which include highly pathogenic strains such as H5N1 avian influenza.

In a previous study, Kawaoka and colleagues had reported the discovery of a Vietnamese girl with a Tamiflu-resistant strain of the avian flu, raising concern about sole reliance on stockpiling the drug globally to fight a possible pandemic.

“There is an urgent need to develop new kinds of anti-virals,” he said.

Since 2003, the H5N1 strain has infected about 290 people, of those 170 have died. Most human cases have been linked to contact with sick birds, though the World Health Organization and others have warned that the virus could mutate into a form that spreads easily among humans, possibly triggering a global pandemic.

Experts have two concerns: the lack of a sufficient supply of vaccine and an increasing resistance to anti-virals used to treat a person infected with influenza.

“This reaffirms the importance of continuing the research to find vaccines for prevention,” Schaffner said. “If you have vaccines, then you limit the disease and you don’t need to treat as many people.”

Kawanza Newson