17 October 2005

Doubts Over Effectiveness Of Tamiflu

by Kate Melville

Writing in the journal Nature, scientists from the University of Wisconsin-Madison, working with researchers in Asia, have reported a worrying finding regarding avian flu. It seems that the virus may already be altering itself to become resistant against the drug oseltamivir, marketed under the name Tamiflu.

A Vietnamese girl, provided with a prophylactic dose of the drug after experiencing mild influenza symptoms, subsequently developed a strain of the virus that was highly resistant to the drug. Tamiflu had previously been regarded as the best existing frontline defense against the much feared avian influenza pandemic. Tamiflu, used in combination with quarantine, was intended to slow the spread of the disease until a vaccine can be produced, which could take up to six months.

Recent reports indicate that governments around the world are stockpiling Tamiflu, with the U.S. government alone planning to increase its stockpile from 12 million to 81 million doses. "This is the first line of defense," said virologist Yoshihiro Kawaoka, a professor in the UW-Madison School of Veterinary Medicine. "It is the drug many countries are stockpiling, and the plan is to rely heavily on it."

Tamiflu works by binding to and inhibiting one of the surface enzymes the virus uses to exit infected cells. "The virus is still able to replicate inside a cell, but is unable to get out and infect other cells," explained Kawaoka.

While Kawaoka describes Tamiflu as an "amazing drug," he says it may be time to examine other options. The two other candidates for slowing the virus include derivatives of the compound adamantine, and the drug zanamivir. It's unlikely that adamantine based drugs would be effective as some flu viruses have already evolved resistance. The other drug, zanamivir, is effective, but is formulated as a powder and is more cumbersome to administer than the orally delivered Tamiflu.

Kawaoka said that even if Tamiflu remained effective, there may not be enough to go around given the stockpiling taking place. There is also a chance that this will equate to smaller doses being administered, which could accelerate the emergence of a virus resistant to the drug and hamper efforts to contain the spread of the disease.

Source: University of Wisconsin-Madison