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November 02, 2005,
8:58 a.m.
Flummoxing the Flu
We need many parallel strategies.
Public-health experts have been saying for years that it's no longer a question if, but when, a flu pandemic will strike. Although we cannot predict with certainty how virulent or infectious the pandemic virus will be, it has the potential to be devastating not only to public health but also to the nation's economy — and so it has finally captured the attention of politicians.
President Bush on Tuesday disclosed the government's strategy for confronting the threat of an avian-flu pandemic, calling for $7.1 billion in emergency spending. Lacking many details, the president's plan apparently consists mainly of the stockpiling of reserves of antiviral medicines, and developing a new vaccine.
During the past several years, an especially virulent strain of avian flu has ravaged flocks of domesticated poultry in Asia and spread to migratory birds. Fortunately, it has been transmitted only rarely from birds to humans, and probably not at all between humans . . .yet. But flu virus mutates and shuffles genes readily, and virologists expect that sooner or later it will acquire the ability to spread from person to person, a potentially catastrophic event.
Why catastrophic? This avian-flu strain, designated H5N1, already has two of the three characteristics needed to cause a pandemic: It can jump from birds to humans and can produce a severe and often fatal illness; more than 60 human deaths have been attributed to H5N1. If additional genetic evolution makes the virus highly transmissible among humans — the third characteristic of a pandemic strain — a world-wide outbreak could become a reality. (The operative term here is highly transmissible; a flu virus that spreads as readily as the common cold would spell real trouble, but one that spreads less readily would be more manageable.)
Another reason for concern is that H5N1 is an extraordinarily deadly variant: The mortality rate for persons infected with the existing H5N1 appears to be around 50 percent, whereas the garden-variety annual flu bug kills fewer than one percent.
This gives us plenty to worry about. The acquisition of the genetic change(s) needed to become transmissible from human to human is a stochastic event — that is, it is essentially random, and therefore, quite literally unpredictable. However, the more viruses there are, the greater the chances that one will acquire the "open-sesame" genetic changes, either by mutation or by exchanging genes during simultaneous infection of a person or animal with H5N1 and another flu virus. And there is more H5N1 around every day: In recent months it has spread over much of Asia — from Japan to Indonesia — and into much of Russia, and during the past few weeks into Turkey, Romania, and Greece.
The United States is ill-prepared for a flu pandemic. Reserve capacity is grossly inadequate for vaccines, drugs and hospital beds. The best and most cost-effective intervention — prevention with a vaccine — presents many obstacles, technological, economic and logistical.
Anti-flu drugs exist but are not a panacea. Unlike vaccines, which confer long-term immunity after one or two doses, drugs need to be taken for long periods. The only drug that has been shown to prevent the flu is Tamiflu, the prophylactic dose of which is one tablet a day, the effect lasting only as long as one takes the drug. (The other major anti-flu medicine, Relenza, has only been shown to be effective to treat, but not prevent, flu.)
Historically, flu pandemics have come in two or three waves, lasting a total of 13-23 months. In other words, the need to take Tamiflu — by first responders, healthcare workers, and ordinary citizens — could go on for months and months, or even years. U.S. public-health officials have said they plan to buy 20 million doses of Tamiflu, but that would be enough to treat only 200,000 people (fewer than the number who would attend a seven-game World Series) for 100 days. And the retail price per pill is around $8, so the expense to treat that small number of people for that amount of time would be $160 million.
According to various models, in the absence of sufficient amounts of an effective vaccine — which is not yet within reach — to blunt a pandemic we would need to treat perhaps a third to a half of the population with Tamiflu. Do the math: 100 million people for 100 days equals 10 billion doses, at a retail cost of $80 billion, in order to blunt the pandemic's first wave.
Although President Bush and Health and Human Services Secretary Mike Leavitt are saying some of the right things about the need to prepare for the pandemic, if they or their staffs have done this sort of calculation, they give no sign of it. (Anyway, there is far too little Tamiflu to go around; the United States is far down on the first-come, first-served list of countries that have ordered it; and the manufacturer, Swiss-based Roche, suspended shipments to U.S wholesalers last week in order to forestall hoarding.)
Where do we go from here? During the Second World War, the Manhattan Project to build nuclear weapons simultaneously explored completely different ways to enrich for certain uranium isotopes, and in the end successfully produced one bomb that used uranium, a second that used plutonium. Similarly, in the face of a potentially cataclysmic pandemic, we need to undertake multiple, simultaneous approaches to both prophylaxis and treatment.
Grant-giving agencies should fund "proof of concept" research on cultured cells to supplant eggs for growing virus; and also on flu subunit vaccines, especially those that are "cross-subtype-specific" — that is, effective against many strains;