Antiviral Oseltamivir Is not Removed or Degraded in Normal Sewage Water Treatment: Implications for Development of Resistance by Influenza A Virus

Abstract

Oseltamivir is the main antiviral for treatment and prevention of pandemic influenza. The increase in oseltamivir resistance reported recently has therefore sparked a debate on how to use oseltamivir in non pandemic influenza and the risks associated with wide spread use during a pandemic. Several questions have been asked about the fate of oseltamivir in the sewage treatment plants and in the environment. We have assessed the fate of oseltamivir and discuss the implications of environmental residues of oseltamivir regarding the occurrence of resistance. A series of batch experiments that simulated normal sewage treatment with oseltamivir present was conducted and the UV-spectra of oseltamivir were recorded. Findings: Our experiments show that the active moiety of oseltamivir is not removed in normal sewage water treatments and is not degraded substantially by UV light radiation, and that the active substance is released in waste water leaving the plant. Our conclusion is that a ubiquitous use of oseltamivir may result in selection pressures in the environment that favor development of drug-resistance.

Profile and behavior of antiviral drugs in aquatic environments of the Pearl River Delta, China

“…Ganciclovir and ribavirin were below the quantification limits in the influent, whereas the other antivirals were not detected in the wastewater (Table S1, Supporting material). This result was quite different from previous reports for wastewater in Japan and Europe in which oseltamivir and oseltamivir acid were frequently detected (Fick et al, 2007;Ghosh et al, 2009Ghosh et al, , 2010aPrasse et al, 2010;Soderstrom et al, 2009;Singer et al, 2008;Slater et al, 2011). In addition, abacavir, lamivudine, nevirapine, penciclovir, stavudine, and zidovudine were detected at several to hundreds of ng L −1 in the wastewater of Germany (Prasse et al, 2010) whereas the concentrations of lamivudine and nevirapine were approximately 1 μg L −1 in treated wastewater in Kenya (Koreje et al, 2012).…”

“…As many other pharmaceuticals, antiviral drugs may not be completely metabolized by treated human and animals and are subsequently excreted and discharged into wastewaters (Fick et al, 2007;Ghosh et al, 2010a,b;Renner, 2007;Soderstrom et al, 2009). As a result, antiviral pharmaceuticals may find their way to the environment if they are not effectively eliminated during wastewater treatment (Accinelli et al, 2010a,b;Fick et al, 2007;Ellis, 2010;Singer et al, 2007Singer et al, , 2008.…”

“…There have been reports about occurrence of oseltamivir and oseltamivir carboxylate in wastewater and river water of Japan and Europe at tens of ng L −1 to low μg L −1 levels (Azuma et al, 2012;Ellis, 2010;Fick et al, 2007;Ghosh et al, 2009;Leknes et al, 2012;Prasse et al, 2010;Soderstrom et al, 2009;Takanami et al, 2010). Prasse et al (2010Prasse et al ( , 2011 have also reported the presence of other antivirals, including acyclovir and its metabolite carboxy-acyclovir, zidovudine, lamivudine, abacavir, and penciclovir in wastewater, river water, and even groundwater in Germany.…”

Assessment of Domestic Wastewater Disposal in Some Selected Wards of Maiduguri Metropolis, Borno State, Nigeria

“…(Table S2 in File S1) [1,25,35-39]. The maximum concentration The persistence of OC in the Oxford WWTP is consistent with many reports in the literature that document minimal loss of OC in laboratory and field studies [13,35,37,38,40]. However, the extent of OC loss seen in the Benson WWTP (approximately 50%), was well above the range reported for WWTP not using ozonation, but it is consistent with the removal efficiency reported in WWTPs with ozonation in Germany, where elimination of OC was reported to be 59% [25], and Japan, where loss was between 30-40% [38].…”

Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards

“…There is, however, accumulating evidence that waterfowl can be exposed to NAIs in the environment, which may cause selection of resistant IAV variants in the natural reservoir. OC, the drug primarily studied, is inefficiently removed by conventional sewage water treatment (16,17). Consequently, OC can be discharged to water environments where waterfowl reside, and OC concentrations as high as 865 ng/liter have been detected in surface water (18)(19)(20).…”