A group of Swedish scientists have discovered that the active metabolite of Roche's Tamiflu (oseltamivir) is not removed or degraded during normal sewage treatment, according to an article in the journal PLoS ONE. Increasing concentrations in natural water can create drug resistant flu viruses, and increases the risk that viruses infecting humans could become resistant to the drug. It is widely known that excessive prescribing of some drugs, such as antivirals or antibiotics, can cause the pathogen to defend itself and mutate, which then leads to it becoming resistant to the drug. Similarly it is accepted that the waste products of pharmaceutical manufacturing must be carefully controlled to minimise impact on the environment. However, what is less often discussed is when the worlds of environmental waste and drug resistance collide. If a drug, or more specifically its active metabolite, is secreted by the body unchanged, the only barrier to prevent levels of the drug building up in the environment is a sewage treatment plant. The question is, what if that barrier fails too - what are the consequences in terms of drug resistance? This is the question that Björn Olsen, Professor of Infectious Diseases with the Uppsala University and the University of Kalmar, and his colleagues set out to answer. "Antiviral medicines such as Tamiflu must be used with care and only when the medical situation justifies it," he cautioned. "Otherwise there is a risk that they will be ineffective when most needed, such as during the next influenza pandemic." Tamiflu is degraded to its active part, oseltamivir carboxylate, before being secreted by the body. This molecule is a viral neuraminidase inhibitor. Through binding to the target, it prevents the protein from breaking up host cell receptors and so reduces the number of new virus particles from the infected cell In order to test whether this metabolite is removed by sewage treatment, the group set up a number of experiments using three different water solutions to represent each of the three phases in sewage treatment. The team found that the drug passes through the treatment process virtually unchanged. "That this substance is so difficult to break down means that it goes right through sewage treatment and out into surrounding waters," says Dr Jerker Fick from Umeå University, who is lead author on the paper. Although the use of Tamiflu is low in most countries, there are exceptions. In Japan, for example, a third of all influenza patients are treated with the drug, according to Fick. Influenza viruses are common among certain waterfowl, especially dabbling ducks such as mallards. These ducks often forage for food in water near sewage outlets and can potentially encounter oseltamivir in concentrations high enough to develop resistance in the viruses they carry. These viruses could then recombine with viruses that infect humans to create new viruses that are resistant to the antiviral drugs currently available. The potential risks seem to be real; studies have shown that, so far, most Tamiflu-resistant strains have been detected in patients not treated with the drug, according to Fick. Whether or not this is down to environmental levels of the drug or viral transmission from treated patients is not yet clear. "[However] the effects of pharmaceuticals continuously released into the environment should not be underestimated and certainly investigated carefully before widespread use of a drug is encouraged," wrote Fick.