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 ... 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.

The idea is simply to "detect the first clusters quickly and then slow or squelch the emerging virus by blanketing the outbreak area with antivirals" (Scientific American).

But for this strategy to work, a lot of things have to fall into place. For one thing:

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.
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Interestingly, in the other article linked above, Dr. Longini postulates that the rate of secondary infection, or "reproduction number", must be less than 1.4 for this strategy to be fully effective. Furthermore,

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. link

Another problem is availability:

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.link

So there is not enough of Tamiflu to go around, and what there is is not being stockpiled where it can do the most good.

The challenge to the rich countries is thus two-fold:

1. Are they prepared to use their stockpiles to hem in an outbreak (instead of reserving their stockpiles for medical and other "essential" personnel, and


2. Will they be couragous enough to deploy their stockpiles where there would be the greatest chance of containing an outbreak (conceivably in the face of media-amplified scaremongering demagogues at home)?

Oh, and speaking of rich countries, there's one more thing a well-financed government could do:

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

I submit that it would be in the public interest for a government to offer some form of financial support to any pharmaceutical company interested in manufacturing this antiviral compound.

But even if all these obstacles can be overcome and the global health establishment can get its act together, containment of H5N1 is still not a sure thing. One uncertainty factor is the speed of contagion, mentioned above. Another is the mutability of the virus itself:

[L]ast 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?

Fortunately, experts seem to regard this a low-level threat:

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.

Note that this conclusion is ultimately an inference, and not a proven fact. But then, everything about the potential avian flu pandemic - both the strategies and the pandemic itself - represents nothing more (or less) than the best guesses of a lot of skilled and dedicated - but human - experts.

So what's the bottom line? Bird flu ain't beat - we won't even get close to that until vaccines come on line, and that is most likely a year or two down the road. But strategies are emerging that are making it increasingly likely that we will at least avoid the worst-case scenarios.

Or not. But as virologist Fred Hayden of the University of Virginia says, "That doesn't mean we shouldn't try." link