Potential Risks Associated with the Proposed Widespread Use of Tamiflu

Abstract

BackgroundThe threat of pandemic influenza has focused attention and resources on virus surveillance, prevention, and containment. The World Health Organization has strongly recommended the use of the antiviral drug Tamiflu both to treat and prevent pandemic influenza infection. A major concern for the long-term efficacy of this strategy is to limit the development of Tamiflu-resistant influenza strains. However, in the event of a pandemic, hundreds of millions of courses of Tamiflu, stockpiled globally, will be rapidly deployed. Given its apparent resistance to biodegradation and hydrophilicity, oseltamivir carboxylate (OC), the active antiviral and metabolite of Tamiflu, is predicted to enter receiving riverwater from sewage treatment works in its active form.ObjectiveOur objective in this study was to determine the likely concentrations of OC released into U.S. and U.K. river catchments using hydrologic modeling and current assumptions about the course and management of an influenza pandemic.DiscussionWe predict that high concentrations of OC (micrograms per liter) capable of inhibiting influenza virus replication would be sustained for periods of several weeks, presenting an increased risk for the generation of antiviral resistance and genetic exchange between influenza viruses in wildfowl. Owing to the apparent recalcitrance of OC in sewage treatment works, widespread use of Tamiflu during an influenza pandemic also poses a potentially significant, uncharacterized, ecotoxicologic risk in each affected nation’s waterways.ConclusionTo gauge the hazard presented by Tamiflu use during a pandemic, we recommend a) direct measurement of Tamiflu persistence, biodegradation, and transformation in the environment; b) further modeling of likely drug concentrations in the catchments of countries where humans and waterfowl come into frequent close contact, and where significant Tamiflu deployment is envisaged; and c) further characterization of the risks of generating Tamiflu-resistant viruses in OC-exposed wildfowl.

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

“…Antiviral drugs are widely used in treatment and prophylaxis of various viral infections including influenza, hepatitis, herpes and HIV (De Clercq and Field, 2006;Kim et al, 2011;Kiso et al, 2004;Olsen et al, 2006;Singer et al, 2007). 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 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.…”

“…Studies about environmental toxicity of antiviral pharmaceuticals are so far mostly limited to oseltamivir and its active metabolite oseltamivir carboxylate (Singer et al, 2007(Singer et al, , 2008. Research reported rather high chronic no-observed effect concentration for oseltamivir and oseltamivir carboxylate (≥1 mg/L) based on ecotoxic tests using traditional aquatic organisms (Hutchinson et al, 2009;Straub, 2009).…”

Emerging Organic Contaminants in Groundwater

“…Other potential threats to surface water which have been identified are tamiflu and chemotherapy drugs, such as 5-fluorourcil, ifosfamide or cyclophosphamide [49][50][51][52] and illicit drugs such as cocaine and amphetamines [53][54].…”

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

“…The large load and high concentration of bioactive pharmaceuticals entering the wastewater and receiving rivers from widespread human consumption and excretion during a pandemic can potentially disrupt (micro)organisms through non-target effects [6][7][8][9][10][11][12] and cause the failure of wastewater treatment plants (WWTPs) to treat effluent to the required standard [13,14], hasten the generation of antiviral resistance in wildfowl and other influenza-susceptible organisms [15][16][17][18], and accelerate the generation and spread of (novel) antibiotic resistance in the environment [2,19,20].…”