Oseltamivir in Environment May Spur Viral Resistance

Key Point

Oseltamivir’s concentration in certain environmental settings may lead to influenza viruses forming a resistance to the treatment.

Swedish researchers have discovered that oseltamivir (Tamiflu®) is not degraded during normal sewage treatment. Consequently, in countries where oseltamivir is used frequently, there is a risk that its concentration in natural waters might enable influenza viruses to develop a resistance to the treatment.

“That this substance is so difficult to break down means that it goes right through sewage treatment and out into surrounding waters,” said lead study author Jerker Fick, PhD, of the Department of Chemistry at Umeå University in Sweden. “Use of oseltamivir is low in most countries, but there are some exceptions, such as Japan, where a third of all influenza patients are treated with oseltamivir.”

As reported in the October PLoS ONE, Dr. Fick and colleagues conducted a series of batch experiments that simulated normal sewage treatment with oseltamivir present and recorded the ultraviolet spectra of the treatment. The investigators demonstrated that oseltamivir carboxylate, the active moiety of oseltamivir, is not removed in normal sewage water treatments and is not substantially degraded by ultraviolet light radiation, thus exposing the virtually unchanged active substance in waste water leaving sewage facilities.

“In some localities, wild ducks, domesticated ducks, poultry and humans all live in close proximity, transmit influenza viruses to each other, and conceivably ingest low concentrations of oseltamivir carboxylate in treated or untreated sewage water,” Dr. Fick and colleagues noted. “The water outside a sewage plant may comprise a particularly high risk microhabitat where ducks carrying a multitude of influenza virus strains encounter low levels of oseltamivir.” Viruses carried by wild ducks could then recombine with human viruses, thus creating new viruses resistant to oseltamivir.

Furthermore, the use of chicken manure as fertilizer in fish farming could expose ducks and other animals that frequent fishponds downstream from sewage outlets to highly pathogenic virus strains during an outbreak of avian influenza.

The investigators concluded that “ubiquitous use of oseltamivir may result in selection pressures in the environment that favor development of drug resistance. This raises the all-important question as to whether or not such a risk should be taken, or if a more restricted use of these agents should be advocated. This is an opinion shared by other researchers, and we would like to add that 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.”

Suggested Reading
Fick J, Lindberg RH, Tysklind M, et al. Antiviral oseltamivir is not removed or degraded in normal sewage water treatment: implications for development of resistance by influenza A virus. PLoS ONE. 2007;2(10):e986.

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