Thursday, December 22, 2005

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Why panics, pandemics, and policy don't mix

Concerns about a looming avian flu pandemic have prompted a lot of commentary and blog chatter over the past few months (including from yours truly) about whether governments are adequately pepared to combat an outbreak of avian influenza. However, panicked calls for governments to "do something" without contemplating the costs and risks that come with each strategy generally leads to bad policy.

Consider, for example, that many developed-country governments have been scrambling to load up on the drug Tamiflu as a way to treat the H5N1 variant of the bird flu. In the Financial Times, however, Andrew Jack explains why this might be a problem:

Fresh doubts were cast on the efficacy of Tamiflu as a treatment for bird flu on Wednesday night when one of the world’s most prestigious medical journals published new reports of resistance to the drug and deaths in patients in Vietnam.

Menno de Jong and colleagues from the hospital for tropical diseases in Ho Chi Minh City recorded in the New England Journal of Medicine that four out of eight patients suffering from the H5N1 flu strain and treated with Tamiflu had died, including two who developed resistance.

The reports increase suggested levels of resistance to nearly 10 per cent, or three out of the 31 known human cases of H5N1 treated with Tamiflu, which is marketed by Roche of Switzerland.

The study raises new questions about the drug, which more than 50 governments have ordered in significant quantities in recent months to stockpile as a potential prophylactic and treatment in the case of a flu pandemic.

An accompanying article in the journal reinforced calls for alternative approaches to treatment for a pandemic, including the stockpiling of the rival drug zanamivir, or Relenza.

Here's a link to the actual NEJM paper for all of the M.D.s in the house. Dr. Anne Moscona has a commentary on the paper in the NEJM that's worth reading for non-doctors as well. One disturbing implication:
It is therefore worrisome that personal stockpiling of oseltamivir [Tamiflu] is likely to lead to the use of insufficient doses or inadequate courses of therapy. Shortages during a pandemic would inspire sharing of personal supplies, resulting in inadequate treatment. Such undertreatment is of particular concern in children — the main source for the dissemination of influenza within the community, since they usually have higher viral loads than adults and excrete infectious virus for longer periods. The habit of stopping treatment prematurely when symptoms resolve (a well-established tendency with antibiotic therapy) could also lead to suboptimal treatment of influenza and promote the development of drug resistance....

Like any successful infectious agent, influenza virus will most likely evolve to evade any single drug. By targeting several points in the viral life cycle simultaneously with different drugs, we are more likely to discourage the emergence of viruses that can resist all drugs at once. But we currently rely solely on the neuraminidase inhibitors — and solely on oseltamivir in many situations, such as in patients who cannot use inhaled medication or in patients infected with H5N1 virus, in whom systemic drug levels may be important. We must not abrogate the usefulness of these drugs by exposing circulating influenza to them in such a way as to facilitate the selection of resistant viruses. The study by de Jong et al. confirms that oseltamivir-resistant H5N1 virus is now a reality. The need to learn more about how and when resistance to the neuraminidase inhibitors develops, while we focus on the development of new antiviral drugs, is pressing. This frightening report should inspire us to devise pandemic strategies that do not favor the development of oseltamivir-resistant strains. Improper use of personal stockpiles of oseltamivir may promote resistance, thereby lessening the usefulness of our frontline defense against influenza, and should be strongly discouraged. (emphasis added)

posted by Dan on 12.22.05 at 05:45 PM


I am both less worried and more worried than you are. We don't have a "frontline defense" in the first place. We never had a feasible plan for distributing tamiflu either. Resistance is a) expected, and b) a non-event; see the recent post over at Effect Measure for lots of technical details.

posted by: Tyler Cowen on 12.22.05 at 05:45 PM [permalink]

We couldn't have distributed the drug anyway. That happens when you eviscerate your public health infrastructure.

posted by: Matt Stoller on 12.22.05 at 05:45 PM [permalink]

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