Not long ago, when infectious-disease specialist Connie Price saw a patient hospitalized with flu at Denver Health Medical Center, she had a powerful weapon at hand: a drug that could shorten the course of the illness and lessen its misery.
Now, the strength of that weapon, Tamiflu, has been undermined by a widely circulating flu strain, type A H1N1, that has developed the ability to resist the drug.
Even as this year's flu season winds down, doctors say the implications of the spread of drug-resistant flu strains could resonate in seasons to come, affecting treatment and highlighting the need for faster flu tests, new drugs and global monitoring of flu viruses.
Tamiflu, whose medical name is oseltamavir, is one of two drugs in a relatively new class of anti-flu medications that reduce the duration and severity of flu. Because it is easily taken in pill or liquid form, it quickly became the antiviral of choice for treating both seasonal flu and potential pandemic flu strains, such as H5N1, known as bird flu. Another drug in the same class is Relenza, or zanamavir, which has similar flu-fighting effects but is taken as an inhaled powder, which makes it difficult for some people to use, especially people who have lung problems such as asthma.
Stockpiling for pandemic
In recent years, because of rising concern about the potential for a flu pandemic, governments around the world have been stockpiling millions of doses of Tamiflu, along with smaller amounts of Relenza and older antivirals, amantadine and rimantadine.
Tamiflu still is effective against bird flu in most cases, though some variants show signs of reduced sensitivity, says Frederick Hayden of the Infectious Disease Society of America's Pandemic Flu Task Force. "It's important that we monitor susceptibility patterns, not only in humans but also in avian viruses."
Meanwhile, for doctors treating patients with regular flu, this season has been dizzyingly complicated. Type A H1N1 flu, the predominant strain circulating now, is the one resistant to Tamiflu; the two others in circulation, type A H3N2 and type B, are not.
Patients who have H1N1 flu can be treated with Relenza if they can inhale the medicine. If not, they can take amantadine or rimantadine. But if they have either of the other two flu strains, they can take only Tamiflu or Relenza, because H3N2 flu is resistant to amantadine and rimantadine, and those drugs don't work against type B flu.
The trouble is, most doctors don't know which flu strain is infecting their patients. The symptoms are the same. Rapid flu diagnostic tests may be able to tell if it's influenza A or B, but can't identify type A subtypes, such as H1N1 or H3N2. The gold-standard test, a viral culture, takes about a week to produce results.
Difficult choices
Price says that given the inability to quickly know exactly what flu strain is present, she issued a "blanket recommendation" for doctors treating patients with flu at her hospital. She advised them to use Relenza, if possible, and if not, to always combine Tamiflu with one of the older drugs, such as rimantadine.
That is "never desirable," she says, because it means some patients will be overmedicated and subject to drug side effects, such as nausea, loss of appetite, nervousness or dizziness.
The sickest patients who could benefit most from antiviral treatment, she says, are often those who are elderly or who have underlying health problems that put them at higher risk for flu complications. "Now, to give them two more drugs that may interact with other therapies, it makes it more complicated," to treat, Price says.
The U.S. Centers for Disease Control and Prevention says this has been a milder flu season than in previous years. But the most recent report shows flu is widespread in 30 states, and 32 children have died because of the flu since the season began last September. In the 2007-08 season, 88 children died of illnesses associated with flu.
Drugmakers are working on new antivirals, including a potent injectable that could be used for hospitalized patients. The drug, peramivir, developed by BioCryst with $102.6 million from the Department of Health and Human Services, "is a major public health priority," says Bill Sheridan, chief medical officer. Clinical trials are underway in Japan and the USA, but testing at least through next flu season is needed before the drug can be considered by the Food and Drug Administration.
Other medications are being developed, but they're not expected to be available for years, which leaves annual flu vaccination as the best defense, says Hayden, a flu researcher at the University of Virginia. "Make sure you get vaccinated," he says, "and use common sense in terms of reducing exposure to the virus."
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