Defenseless Against Influenza

The World Health Organization announced mystifying news last week: The garden-variety influenza virus H1N1 that periodically besets the world, and is doing so this winter, seems to be developing a startling new resistance to Tamiflu (oseltamivir), the first and most important of antiviral drugs for influenza.That such a thing should happen is curious. No one bothers much with Tamiflu as a primary weapon of attack against the regular flu — at least not outside Japan, where aggressive marketing by a subsidiary of the global patent-holder, Hoffman-La Roche, has convinced the populace to more or less pop the stuff like candy. For flu programs in nursing homes and hospitals elsewhere, other antivirals come a lot cheaper and work just as well.

The problem is that the world, Canada included, has been counting on Tamiflu to come through in the event of a global epidemic of the H5N1 avian flu virus. This strategy always carried with it a high amount of uncertainty; the odd, surprising behaviour of H1N1 can only make matters worse.

It would not be such a great shock to see Tamiflu resistance develop in H1N1 because of overprescribing. Public health experts warned against this danger in 2005, when the drug was still scarce and patients panicked by headlines about avian flu were besieging their doctors. It was all too easy to imagine that jittery personal stockpilers of the drug might ransack their medical cabinets the instant they displayed any symptoms of flu or flu-like illness.

Yet according to the latest WHO report, the Tamiflu-resistant strain turns out to be most predominant in Europe, particularly Norway. It hasn’t been spotted at all in Tamiflu-crazy Japan, where one would expect to see it first if human irresponsibility were to blame. The organization cannot be sure that “selective drug pressure” bears no responsibility for this new clinical surprise, but none of the patients who were found to have the Tamiflu-resistant virus had taken the drug or been in contact with a user of it.

The implications for avian flu planning, the WHO says, are “uncertain” at this point. Avian flu has not yet begun to spread efficiently from human to human. Its mechanism of action on human victims is different enough from that of H1N1 that there remains hope that Tamiflu will be useful against H5N1. And in a way, physicians would be glad to have Tamiflu turn out to be useless against less threatening types of influenza, in order to reduce casual users’ price pressure on a drug that governments are only now topping up their stockpiles of. (Hoffman- La Roche actually issued a warning this week that it expects 2008 revenues from Tamiflu to be dramatically lower as the first desperate surge of government stockpiling finally ends.)

But the really frightening story lurking in the background is that no one is too sure whether Tamiflu will do any good at all against pandemic avian flu, which so far has an observed mortality rate of about 50% in humans who get it from working or living with poultry. If H5N1 mutates into a virus that readily jumps from human to human, unforeseeable changes will arise in the virus’ structure and activity. A layman can only be nervous at hearing that the world’s best scientists have apparently underestimated the ability of ordinary flu to outmanoeuvre our best flu drug.

And so far, real-world tests of Tamiflu against H5N1 have been disappointing. Indeed, there are critics who don’t consider its performance all that dazzling against any type of influenza at all. Vietnamese doctors who tried it with bird flu patients there, in the eye of the H5N1 storm, described it as “useless,” and some subvariants of H5N1 are already known to be Tamiflu-resistant. The WHO is now experimenting with tackling H5N1 by means of higher dosages — which, if it appears at all effective, will create another pell-mell stockpiling race amongst governments — and combining it with other drugs. Meanwhile, everyone is wondering what the ultimate shelf life of Tamiflu will turn out to be: It is still a new drug, and the known life span is just five years.

One day, perhaps, we will all be able to sleep easier knowing that the threat of viral pandemic is a thing of the past, thanks to an abundantly equipped arsenal of proven, broad-spectrum antivirals. But there are no magic bullets yet. We are still vulnerable, and our most important defences in the event of a catastrophe will, for now, remain those available to our ancestors: minimizing unnecessary interpersonal contact and practicing good hygiene.

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That IS bad news. Having an emergency supply of food and essential medications on hand just in case is a good idea.