Bird Flu Alarm

2006-01-19-Antiviral Drugs Weak Defense Against Bird Flu Pandemic, Study Finds

Understanding Avian Influenza

2006-01-19-Antiviral Drugs Weak Defense Against Bird Flu Pandemic, Study Finds


Tamiflu and Relenza, two antiviral drugs that have been the bulwark of the global defense against both human flu and avian flu, may not be enough to combat a lethal pandemic should one occur, researchers report.

The two drugs -- both members of the neuraminidase inhibitor class of antivirals -- appear to be ineffective against seasonal flu outbreaks and should only be used in the event of a serious epidemic or pandemic, the study authors report in the Jan. 19 online edition of The Lancet.


And even in the context of an epidemic or pandemic, these medications may simply not be enough on their own, the researchers say.


"If you're going to use these neuraminidase inhibitors, you shouldn't be using them as a single solution," said lead researcher Dr. Tom Jefferson, coordinator of the Cochrane Vaccines Field in Rome, Italy. "You should also use public health measures."


Such measures might include masks, gowns, gloves, quarantine and hand washing.


Two other drugs, amantadine and rimantadine, which belong to an older class of drugs known as M2 ion channel inhibitors, do not appear to be effective against influenza, they added.


The findings did not sit well with Tamiflu's maker, Roche, which announced this week that it would donate an additional 2 million treatment courses of the drug to the World Health Organization for regional stockpiling.


"Roche fundamentally disagrees with the conclusions reached by the authors that Tamiflu should not be used for the treatment of prevention of seasonal influenza," said company spokesman Terry Hurley. "The conclusion is at odds with the opinion of experts and regulatory authorities around the world."


"Regulatory authorities around the world, including the FDA, have approved Tamiflu for the treatment and prevention of influenza in patients one year [old] and above, confirming their confidence in the product for use in the control of influenza," he continued. Just last month, the FDA approved Tamiflu for the prevention of flu in children aged 1 to 12 years of age.


Hurley also asserted that recent animal data have shown Tamiflu to be effective against the H5N1 flu virus currently circulating in birds.


Influenza has become a mounting global concern. Not only does seasonal flu kill thousands of people worldwide, but the possibility of an avian flu pandemic has experts and civilians worried.


On Wednesday, 33 donor nations meeting in Beijing pledged $1.9 billion to help fight avian flu, which has killed at least 79 people in east Asia and Turkey.


Although vaccines are the first line of defense for seasonal human flu, antiviral drugs are playing a bigger and bigger role. In 2005, the World Health Organization encouraged countries to use antivirals during seasonal flu periods.


Such a strategy has a significant downside, however.


This past weekend, the U.S. Centers for Disease Control and Prevention ( CDC) recommended that neither amantadine or rimantadine be used to treat or prevent influenza A this season because of growing resistance to the drugs. Ninety one percent of samples tested by the CDC proved resistant to these two drugs, compared with only 11 percent last year, the Associated Press reported.


The agency has recommended that Relenza (zanamivir) or Tamiflu (oseltamivir) be used instead. But this presents a potential problem for management of an avian flu pandemic if it starts spreading from person to person. According to a recent report from the Associated Press, U.S. health officials had wanted to hold off using Tamiflu and Relenza now, so it would remain effective for such an eventuality.


In their study, Jefferson's team combined data from 51 trials that had already been conducted on both the older, M2 ion channel inhibitors and the newer neuraminidase inhibitors.


The Italian group found no evidence that either Relenza or Tamiflu were effective against avian flu.

"There are no comparative studies on avian flu. We're not saying drugs shouldn't be given. We just don't know," Jefferson said. "The jury is out."

Tamiflu was used in outbreaks in Southeast Asia but was not associated with any effect on mortality. This may have been because the drug was administered too late, however.

"After 72 hours, it's really too late. It really should be given 48 hours from when symptoms develop," Jefferson said. "They haven't been given a fair hearing."

The fact that Tamiflu and Relenza actually increase viral shedding from the nose could be particularly problematic in the event of a pandemic, the authors pointed out.

Both classes of drugs had some effect on preventing or easing symptoms of the seasonal human influenza A and B, but they did not prevent individuals from getting infected in the first place. None of the drugs had any effect on influenza-like illness, which is no surprise, as such illnesses are often caused by viruses other than influenza.

"This is not a surprise and people should not be prescribing them without an accurate diagnosis or a high clinical suspicion because they know that influenza is circulating in the community," Jefferson said. "The downside of that is the cost, creating resistance, adverse events and no effectiveness. It just doesn't work."

Roche stated that it has never advocated the use of Tamiflu for control of influenza-like symptoms.

The neuraminidase inhibitors also do not stop secretion of virus from the nose (which contributes to spread of the germ), but they do seem to prevent a number of complications of flu such as hospitalization from pneumonia and they did diminish household transmission.

Corroborating the recent CDC information, the authors also found that use of amantadine led quickly to the emergence of resistant strains. Both amantadine and rimantadine could cause adverse side effects such as nausea, insomnia and hallucinations, they added.

Understanding Avian Influenza