Web Exclusive: Cause for loss of flu medication efficacy identified

Scientists may have identified over-use by human influenza patients as potential cause of reduced efficacy of oseltamivir (Tamiflu).

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Drug molecules accumulating in water supplies (via sewage) through excessive use by the human population is nothing new. For example, sex changes in fish have been ascribed to hormones originating from birth control pills. According to research in Sweden, there are real fears that accumulation of oseltamivir (trade name: Tamiflu) in water supplies could jeopardise future efficacy in the event of a human flu pandemic originating in the H5N1 highly pathogenic avian influenza (AI) virus.

Swedish scientists led by Jerker Fick, a chemist at Umea University, assessed the persistence of oseltamivir in water taken from three phases in a standard sewage system. First phase was raw sewage water, second was water filtered and treated with chemicals and the third water sourced from ‘activated sludge’, in which microbes are used to digest waste material. Oseltamivir survived all three processes, clearly indicating that it will be present in waste water exiting sewage plants.

Implications are that over-use of the drug could raise concentration to a level that exerts selection pressure on H5N1 causing development of strains which are resistant.

Waterfowl – widely regarded as one of the key causes of AI virus spread – are commonly found near sewage outlets, especially ducks such as mallards that forage for food in such situations. Furthermore, what happens if drinker water supplies to poultry farms were to contain relatively high concentrations of drugs used to combat flu viruses in humans?

“Biggest threat is that resistance will become common among low pathogenic influenza viruses carried by wild ducks,” said the paper’s co-author, Bjoern Olsen, professor of infectious diseases at the University of Uppsala and University of Kalmar.

These avian viruses could then recombine with ordinary human flu viruses, creating new strains that are resistant to Tamiflu. “Antiviral medicines such as Tamiflu must be used with care and only when the medical situation justifies it,” warned Professor Olsen. “Otherwise, there is a risk that they will be ineffective when most needed, such as during the next influenza pandemic.”

All eyes are apparently on Japan. The paper quotes figures from Swiss company Roche (manufacturer of Tamiflu), estimating that out of 16 million Japanese who fell ill with flu in the 2004-5 influenza season, six million received the drug.

At such dosages, say the Swedish researchers, amount of Tamiflu released into the Japanese environment is roughly equivalent to what is predicted in areas where the drug would be used in a pandemic. Japan has a high rate of emerging resistance to Tamiflu, claimed the research paper.
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