We've known since January that most of the flu circulating this season is resistant to Tamiflu, an antiviral drug typically used against the infection. What remained a mystery was whether the resistant flu strain made people sicker than forms that respond to the treatment — and why the resistant strain surged this year, a worry for public health officials who stockpiled Tamiflu in the event of a flu pandemic stoked by avian influenza.

A study published today in the Journal of the American Medical Association indicates that Tamiflu-resistant flu does not make people any more or less sick. But researchers say they're still in dark as to why Tamiflu-resistant infections are on the rise. A whopping 98 percent of this year's circulating H1N1 flu strains are immune to Tamiflu, compared with only 12 percent during the 2007-2008 flu season.

"We don’t know what's physically happened to the virus to cause it to transmit more rapidly, but something has and even more so this year," says study author Nila Dharan, a fellow in the Centers for Disease Control and Prevention's (CDC) Epidemic Intelligence Service, which studies major disease outbreaks. Dharan tells ScientificAmerican.com that a spontaneous (natural) genetic mutation – and not overuse of Tamiflu — is to blame. She notes that additional structural changes to the virus (that scientists don’t completely understand) have enhanced the resistant strain's ability to grow and infect people.

The trend is alarming enough that Department of Health and Human Services (HHS) officials have been huddling for the past week to consider whether to adjust the composition of the federal pandemic flu drug stockpile, of which 40 million treatment courses (80 percent) is Tamiflu, says Robin Robinson, director of the Biomedical Advance Research and Development Authority (BARDA), an HHS arm that manages the stockpile.

Right now, the H5N1 subtype of avian flu isn’t resistant to Tamiflu, but the fear is that it could become so if it recombines with the Tamiflu-resistant H1N1 strain, Robinson says. There have been 409 human cases of avian flu, mostly in Asia, and 256 of those patients died since 2003, according to the World Health Organization (WHO). Symptoms include fever, cough, sore throat, muscle aches, eye infections, pneumonia and acute respiratory distress.

"It's cause for concern," Robinson says. "We need to talk seriously about what is in our stockpile and [whether] we need to change it. Right now the pandemic viruses are susceptible to Tamiflu. We want to follow this to make sure that it stays that way."

The CDC previously recommended that doctors give the antiviral drugs Relenza or Rimantidine to seasonal flu patients who do not respond to Tamiflu. Relenza accounts for 10 million treatment courses and Rimantidine for 2.8 million courses in the stockpile, Robinson says. He adds that authorities are set to decide by next month whether to reconfigure the stockpile. Officials also plan to test combination therapies of Tamiflu and Relenza in the U.S. and Asia against seasonal and bird flu.

Image of Tamiflu by Moriori via Wikimedia Commons