Neuraminidase inhibitors for preventing and treating influenza in healthy adults

A class of drugs commonly used to treat typical influenza symptoms such as fever, headache and cough do not prevent people from becoming infected with the flu virus, a new review shows, although the use of these neuraminidase inhibitors (NIs) to check the spread of flu has been of interest to researchers.

Whether these antiviral drugs - including oseltamivir (or Tamiflu) and zanamivir (or Relenza) - would be effective in preventing spread in a pandemic or avian (bird) flu scenario is not clear, the authors stress.

"Because of their low effectiveness, NIs should not be used in routine seasonal influenza control," the authors write. "This review found that Nls are effective in preventing and treating the symptoms and complications of influenza but do not prevent infection or interrupt voidance of viruses from the nose."

Lead author Dr. Tom Jefferson of the Cochrane Collaboration vaccine program in Rome and a team of researchers analyzed four studies that used NIs for prevention, 13 that used NIs for treatment and four that studied infection after exposure to the flu virus.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The review only used studies with at least three-fourths of participants ages to 60 years old to exclude older participants, who are at higher risk of complications.

The researchers found that NIs had no effect in preventing flu. For relieving flu symptoms, oseltamivir at a dose of 75 mg daily was 61 percent effective or 73 percent at 150 mg daily; inhaled zanamivir at 10 mg daily was 62 percent effective.

In terms of symptom relief after exposure to the flu, oseltamivir was 68 percent to 89 percent effective for human contacts of flu-infected people; zanamivir had similar performance. Oseltamivir at 150 mg daily prevented lower respiratory tract complications.

The authors found side effects associated with NIs - oseltamivir caused nausea, vomiting and retching and zanamivir caused diarrhea.

Jefferson said that despite the results he did not wish to comment on national and global flu plans that suggest that NIs may be beneficial in helping the spread of avian or pandemic flu. "I am not in a position to comment specifically because I have not read the U.S. plan," Jefferson said.

"Current evidence from seasonal influenza trials led us to urge caution in making forecasts of possible impact of neuraminidase inhibitor use in any other epidemiological context," he added.

According to the World Health Organization, until a new flu virus strain actually emerges, "there is no direct evidence of the effectiveness of vaccine and antiviral drug prevention and treatment strategies for lowering mortality and morbidity, or for containing or delaying the spread of an influenza pandemic."

"NIs are not recommended for routine use in seasonal influenza," the authors conclude. "In exceptional circumstances they could be used as an adjunct to public health measures." They caution, however, "There is no evidence that NIs may be effective against bird flu. Because of their performance, NIs should not be used on their own, but alongside barrier (masks and gloves), personal hygiene and quarantine measures."

The authors call for "larger trials to assess the effects of NIs in epidemic influenza, especially their impact on complications and deaths," and for "further research on the possible effects of NIs on avian influenza subtypes."

Every year in the United States, 5 percent to 20 percent of the population gets the flu; more than 200,000 people are hospitalized from flu complications and about 36,000 people die from flu, according to the Centers for Disease Control and Prevention.

The review discloses that Dr. Jefferson was an ad hoc consultant for Hoffman LaRoche Ltd from 1988 to 1989.

By Lise Millay Stevens