The premier flu-fighting drug is contaminating rivers downstream of sewage-treatment facilities, researchers in Japan confirm. The source: urinary excretion by people taking oseltamivir phosphate, best known as Tamiflu.

Concerns are now building that birds, which are natural influenza carriers, are being exposed to waterborne residues of Tamiflu’s active form and might develop and spread drug-resistant strains of seasonal and avian flu.

For their new study, Gopal Ghosh and his colleagues at Kyoto University sampled water discharged from three local sewage treatment plants and water at several points along two rivers into which the treated water flowed. Sampling started early in December 2008, as flu season got underway. The researchers sampled again at the height of the seasonal flu onslaught in early February and again as infection rates waned.

Tamiflu’s active form, oseltamivir carboxylate, or OC, turned up in the treated sewage on every occasion, the researchers report online Sept. 28 in Environmental Health Perspectives. Values were in the low nanograms-per-liter range during the first and last samplings, and reached a high of almost 300 ng/L at one outflow during the flu’s peak, a week when there were 1,738 recorded flu cases in Kyoto.

River residues showed up during only that second sampling — from low-nanogram levels at most sampling points to a high of 190 ng/L in a portion of the Nishitakase River where treated sewage accounts for 90 percent of the flow.

Computer modeling has shown that OC should survive sewage treatment, noted Wolf von Tümpling Jr. of the Helmholtz Center for Environmental Research, a federal institute in Magdeburg, Germany. Ghosh’s team is now the first to confirm this, he said. Von Tümpling’s own data show that once exposed to sunlight, OC will break down, albeit slowly. Concentrations would fall at best by half every three weeks, he said.

If correlations predicted by earlier studies are correct, concentrations measured at some river sites in the new Kyoto study seem “high enough to lead to antiviral resistance in waterfowl,” Ghosh says

And the Kyoto team didn’t test during a pandemic, when Tamiflu prescription rates might be 10 times higher, von Tümpling notes.

Indeed, the expected coinciding hits by seasonal and H1N1 swine flu this winter, could send Tamiflu use skyrocketing. In a July 14 letter, Food and Drug Administration deputy commissioner Joshua Sharfstein noted that “there is no adequate, approved and available alternative to the emergency use of certain oseltamivir phosphate products for the treatment and prophylaxis of influenza.”

Once ingested, virtually all Tamiflu will end up in the environment in the active form, noted environmental chemist Jerker Fick of Umeå University in Sweden. The reason: Tamiflu becomes active once the body converts it into a carboxylate form. Roughly 80 percent of an ingested dose becomes this OC, which the body eventually excretes. The body sheds the remaining 20 percent of Tamiflu in its original form, but this phosphate form is immediately turned into the active, carboxylate form when it reaches a water treatment plant, he said.

Two years ago, Fick’s team published data showing that most sewage-treatment technologies will remove “zero percent” of any OC present. And ducks love hanging out around warm, nutrient-rich outflows of treated water during winter-flu season. While sampling for waterborne OC last year in Japan, “I saw it myself,” he said.

If Tamiflu resistance does develop in exposed birds, the affected flu strains will probably be conventional seasonal and avian-flu strains, which claim thousands of lives each year, and not H1N1. That’s because H1N1 seems to bypass birds as it spreads among people, noted William Schaffner, chair of preventive medicine at the Vanderbilt University School of Medicine in Nashville, Tennessee.

He also notes that U.S. policy is more conservative than Japan’s when it comes to Tamiflu use. Federal guidelines, he said, recommend that “Tamiflu be reserved for treatment of the very sick and anyone who is immunocompromised.”

Image: Flickr/Karmor

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