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

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.

[1]  Mats Tysklind,et al.  Screening of human antibiotic substances and determination of weekly mass flows in five sewage treatment plants in Sweden. , 2005, Environmental science & technology.

[2]  W. Arnold,et al.  Photodegradation of pharmaceuticals in the aquatic environment: A review , 2003, Aquatic Sciences.

[3]  J. Oxford,et al.  Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo. , 2002, Antiviral research.

[4]  W. Herron,et al.  Development of a high-performance liquid chromatographic-mass spectrometric assay for the specific and sensitive quantification of Ro 64-0802, an anti-influenza drug, and its pro-drug, oseltamivir, in human and animal plasma and urine. , 2000, Journal of chromatography. B, Biomedical sciences and applications.

[5]  Mats Tysklind,et al.  Behavior of fluoroquinolones and trimethoprim during mechanical, chemical, and active sludge treatment of sewage water and digestion of sludge. , 2006, Environmental science & technology.

[6]  F. Hayden,et al.  Neuraminidase Sequence Analysis and Susceptibilities of Influenza Virus Clinical Isolates to Zanamivir and Oseltamivir , 2003, Antimicrobial Agents and Chemotherapy.

[7]  A. Osterhaus,et al.  Global Patterns of Influenza A Virus in Wild Birds , 2006, Science.

[8]  D. Stallknecht,et al.  Host range of avian influenza virus in free-living birds , 2004, Veterinary Research Communications.

[9]  W. J. Bean,et al.  Intestinal influenza: Replication and characterization of influenza viruses in ducks , 1978, Virology.

[10]  J. McKimm-Breschkin,et al.  News about influenza B drug resistance that cannot be ignored. , 2007, JAMA.

[11]  Yoshihiro Kawaoka,et al.  oseltamivir: descriptive study , 2022 .

[12]  A. Amonsin,et al.  H5N1 Oseltamivir-resistance detection by real-time PCR using two high sensitivity labeled TaqMan probes , 2006, Journal of Virological Methods.

[13]  A. Moscona,et al.  Oseltamivir resistance--disabling our influenza defenses. , 2005, The New England journal of medicine.

[14]  Larisa V. Gubareva,et al.  Comparison of the Activities of Zanamivir, Oseltamivir, and RWJ-270201 against Clinical Isolates of Influenza Virus and Neuraminidase Inhibitor-Resistant Variants , 2001, Antimicrobial Agents and Chemotherapy.

[15]  Laurent Kaiser,et al.  Influenza virus neuraminidase inhibitors , 2000, The Lancet.

[16]  Adriano Joss,et al.  A rapid method to measure the solid-water distribution coefficient (Kd) for pharmaceuticals and musk fragrances in sewage sludge. , 2004, Water research.

[17]  Catherine Macken,et al.  Detection of Influenza Viruses Resistant to Neuraminidase Inhibitors in Global Surveillance during the First 3 Years of Their Use , 2006, Antimicrobial Agents and Chemotherapy.

[18]  Andrew C. Singer,et al.  Potential Risks Associated with the Proposed Widespread Use of Tamiflu , 2006, Environmental health perspectives.

[19]  M. Kiso,et al.  Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. , 2007, JAMA.

[20]  D. Stallknecht,et al.  Effects of pH, temperature, and salinity on persistence of avian influenza viruses in water. , 1990, Avian diseases.

[21]  A. Monto,et al.  Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. , 2004, The Journal of infectious diseases.

[22]  J. Oxford,et al.  Influenza A pandemics of the 20th century with special reference to 1918: virology, pathology and epidemiology , 2000, Reviews in medical virology.

[23]  D. Stallknecht,et al.  Persistence of avian influenza viruses in water. , 1990, Avian diseases.