By the Rivers of Tamiflu

9 January 2007 (All day)

The antiviral drug Tamiflu may save many lives if the world faces an influenza pandemic. But widespread use could inadvertently create new hazards, according to a new study. Significant amounts of the drug would be excreted, then flushed down toilets and end up in surface water, where it might trigger resistance in flu-infected water birds or pose unknown environmental threats. Although the researchers don't argue against the use of Tamiflu, they say the risks of its use on a large scale should be better studied.

Many countries have amassed stockpiles of Tamiflu (also known as oseltamivir) for the first phase of a flu pandemic, such as a bird flu outbreak, when vaccines will likely be unavailable (ScienceNOW, 21 December 2005). After absorption in the gastrointestinal tract, oseltamivir is converted into oseltamivir carboxylate (OC), the compound that actually thwarts the virus. Most of the OC eventually leaves the human body unaltered; according to estimates, roughly 70% is excreted into the urine and some 20% into the feces. Not very much is known about the speed with which Tamiflu breaks down in the environment, says Andrew Singer of the Centre for Ecology & Hydrology in Oxford, U.K., but the data that exist, as well as what's known about a related drug, zanamivir, suggest that it's quite persistent.

Singer and his colleagues built a model to predict the resulting concentrations in rivers. They used existing data on water flow, surface area, and population for five river catchments in the United Kingdom and 11 in the United States, as well as epidemiological data from a recent flu pandemic model (with two rates of viral spread), to calculate the expected OC concentration in river water during the months after a pandemic breaks loose.

The levels vary widely by river catchment, the team reports in the January issue of Environmental Health Perspectives. But in many cases, it reached 1 nanomolar (nM, or 6 × 1014 molecules per liter), a concentration at which OC blocks virus reproduction, for a month or more, Singer says. In a few, drier catchments, such as the Lower Colorado, the concentration got as high as 50 nM for several weeks. These numbers are conservative, Singer adds, because the team assumed that only infected people would get oseltamivir. In reality, many healthy people may use the drug prophylactically as well.

The levels could trigger resistance in influenza-infected birds, Singer says, which could theoretically lead to a "second wave" of a slightly different pandemic strain. What's more, many species have the neuraminidase enzyme that OC inhibits--including some bacteria--so there may well be a much broader, as-yet-unknown ecological impact, he says.

A spokesperson for Roche disputes the findings, however. Zanamivir, on which some of the assumptions are based, is more stable in water than OC is, which biased the results, she says. What's more, even if OC concentrations are high, the drug doesn't easily make its way to the tissues in birds where virus replication takes place, which makes it "highly unlikely that resistance would be provoked." The spokesperson declined to make available Roche's own ecological assessment of Tamiflu.

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