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Can Tamiflu save us from bird flu?

02 June 2005 New Scientist news service

Debora Mackenzie

Amid ominous signs that H5N1 bird flu is acquiring the ability to spread more readily among people, many health authorities are pinning their hopes on Tamiflu, the only available antiviral drug known to block the replication of the virus. But can the drug really help stop an emerging flu pandemic?

Even if efforts to develop a vaccine are successful (New Scientist, 26 March, p 10), it could take many months to produce the billions of doses needed in the event of a pandemic. By then it might be too late. So in the meantime, the World Health Organization is stepping up its efforts to acquire a massive stockpile of Tamiflu (oseltamivir), which it hopes will at least slow any emerging flu pandemic.

“Last month the WHO reported that a patient in Vietnam was infected with a strain of H5N1 resistant to Tamiflu”

Recent cases of H5N1 in northern Vietnam have caused concern because of signs that the virus is changing. It has become less lethal and is occurring in larger clusters than past cases. Last month studies also revealed that the virus is diverging genetically.

Tamiflu can save lives if it is given early, no more than two days after symptoms first appear. But last month the WHO reported that a patient in Vietnam had a strain of H5N1 resistant to Tamiflu. So could the drug become useless before the pandemic even begins?

Luckily the resistant viruses may be poor at spreading, according to Fred Hayden of the University of Virginia, a leading expert on antiviral therapy. The mutation that made the Vietnam virus drug resistant also occurs in a normal human flu strain, making the virus a hundred times less contagious. In Japan, which uses Tamiflu for ordinary flu epidemics, the mutation appears in 16 per cent of treated children, yet such viruses almost never go on to infect others.

It is probable that the same will be true of any drug-resistant strains of H5N1. This assumption needs to be tested as soon as possible, Hayden says.

But even if Tamiflu remains effective in most cases, it might not be enough to stop a pandemic. The real difficulty with the WHO's antiviral plan, Hayden says, will be finding and treating all the cases and contacts in time. "But that doesn't mean we shouldn't try," he adds.

Ira Longini of Emory University in Atlanta, Georgia, says much depends on how fast the virus spreads. If each infected person passes the virus to fewer than two other people on average, then isolating and treating all cases and their contacts with antivirals could slow or even stop an epidemic, he calculates.

But health workers would not be able to keep up with the virus if sick people infect between two and three others, as happened in the 1918 flu pandemic. Drug stockpiles would still help save lives, Longini says, but would not halt the outbreak.

The best chance of the antiviral strategy succeeding will be in the early stages, when the virus might still spread slowly. The trouble, however, is that most stockpiles of Tamiflu are being acquired by rich countries in Europe and North America, not poor countries such as Vietnam, where any H5N1 pandemic is most likely to start.

What's more, Tamiflu is in short supply. Seventeen countries have ordered stockpiles of the drug from the Swiss company Roche, which holds the patent, and 10 more are said to be discussing purchases. The UK's order for 14.6 million five-day courses of treatment will take two years to fulfil, for instance. The drug is made from a plant in limited supply, and Roche is still trying to develop methods for synthesising it from scratch.

There are two other drugs that target the same enzyme as Tamiflu. But zanamivir (Relenza) must be taken by inhalation and is not widely available, while peramivir was dropped by US company Johnson & Johnson, which thought it unlikely to be profitable. BioCryst, the small Alabama firm that created peramivir, is still trying to find a new partner.

“Most stockpiles of Tamiflu are being acquired by rich countries, not the poor countries where a pandemic is most likely to start”

In Asia, H5N1 had already evolved resistance to another class of antivirals, including amantadine, by 2003. These resistant strains are just as deadly and contagious as non-resistant strains. "The Chinese have been incorporating amantadine in their chicken feed, so we have lost that as a treatment," says Robert Webster of St Jude Children's Research Hospital in Memphis, Tennessee. This also suggests that Chinese farmers have been fighting bird flu outbreaks since before 2003, although China officially reported its first outbreaks only last year.

“There is evidence that the H5N1 influenza virus strain - Avian Flu or Bird Flue - is susceptible to the Tamiflu antiviral drug. World governments are expanding stockpiles of Tamiflu against the contingency of a flu pandemic. With the increased demand for Tamiflu, we are offering Tamiflu for purchase online with free prescriptions to cope with shortages. Tamiflu can be prescribed without a physical examination. Consultations can now be done online for free. Protect your family against Avian or Bird Flue by ordering Tamiflu Influenza Vaccine online now. “

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