Bioscope ‘06

by  Dr. Barbara Price

          Avian Flu and Tamiflu: excreted and concentrated for resistance. Tamiflu, oseltamivir phosphate (OP), is converted by hepatic enzymes to oseltamivir carboxylate (OC), which works by binding the neuromindase so that it cannot act on infected cells to release replicated H5N1 viruses. This action contains the virus and permits the immune system to have a better chance to act on defeating the virus. A new study in the October issue of Environmental Health Perspectives discusses the probable effects of releasing OC in the environment during a possible pandemic. It is an interesting and thought provoking exercise in modeling.

          In the event of millions of people taking Tamiflu, according to the model, the amounts to be released will produce concentrations in the microgram per milliliter for up to several weeks. The current WHO strategy is to give all those over 1 year, 75 mg twice a day for 5 days. This may be supplemented with a prophylaxis dose of 75 mg once a day for 10 days and may be repeated for several weeks. In the event of a pandemic, this translates to up to 100 nanomolar in river and surface waters for one week, if one assumes the OC is used only by those being treated for actual infection and prophylactic treatment is not considered. Approximately 70 per cent of the tamiflu is excreted as OC in urine and approximately 10 per cent remains as OP, and is excreted fecally along with another 10 per cent OC. OC is resistant to biodegradation and thus will not be easily removed from sewage effluents by usual sewage treatment plants. Furthermore, the high water solubility (588 mg/mL @ 25°C) means that OC will not readily adsorb onto materials added to sewage and water treatment plants.

So what are the possible effects on waterfowl in these surface waters?

          Continuing the estimated release amounts and concentrations, the authors note that enough OC will get into waterfowl, and will concentrate in their intestines, to help selectively encourage the development of resistant strains of H5N1. The concentration of OC in waterfowl intestines could generate new strains incorporating Tamiflu-resistant NA genes and over time defeat the ability of OC to prevent the release of viral particles from infected cells. Although the authors examined river catchments in the UK and the USA, they note that these results have higher probabilities of concentrating OC in waterfowl in areas where humans and fowl are more intimately associated, such as in Southeast Asia. The authors recommend treating the urine and fecal material early in the waste stream, before the sewage treatment plants. However, the authors leave open the concern about how such treatment will work in rural areas of Southeast Asia, where even sewage treatment may be minimal.

"Potential Risks Associated with the Proposed Widespread Use of Tamiflu"
Andrew C. Singer, Miles A. Nunn, Ernest A. Gould and Andrew C. Johnson doi:10.1289/ehp.9574 (available at http://dx.doi.org/) Online 11 October 2006
http://www.ehponline.org/members/2006/9574/9574.pdf