Singer Andrew C, Nunn Miles A, Gould Ernest A, Johnson Andrew C
Center for Ecology & Hydrology, Oxford, United Kingdom.
Environ Health Perspect. 2007 Jan;115(1):102-6. doi: 10.1289/ehp.9574.
The 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.
Our 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.
We 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.
To 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 dose contact, and where significant Tamiflu deployment is envisaged; and c) further characterization of the risks of generating Tamiflu-resistant viruses in OC-exposed wildfowl.
甲型流感大流行的威胁使人们将注意力和资源集中在病毒监测、预防和控制上。世界卫生组织强烈建议使用抗病毒药物达菲来治疗和预防甲型流感大流行感染。该策略长期疗效的一个主要担忧是限制对达菲耐药的流感毒株的出现。然而,在大流行发生时,全球储备的数亿疗程的达菲将迅速投入使用。鉴于其对生物降解的明显抗性和亲水性,达菲的活性抗病毒代谢产物奥司他韦羧酸盐(OC)预计将以其活性形式从污水处理厂进入接纳河流。
我们在本研究中的目的是利用水文模型以及当前关于甲型流感大流行过程和管理的假设,确定释放到美国和英国河流集水区中的OC可能浓度。
我们预测,能够抑制流感病毒复制的高浓度OC(微克/升)将持续数周,这增加了野生禽类中产生抗病毒抗性以及流感病毒之间发生基因交换的风险。由于OC在污水处理厂中明显具有难降解性,在甲型流感大流行期间广泛使用达菲也会在每个受影响国家的水道中带来潜在的重大、未明确的生态毒理学风险。
为了评估在大流行期间使用达菲所带来的危害,我们建议:a)直接测量达菲在环境中的持久性、生物降解和转化;b)对人类与水禽频繁接触且预计会大量使用达菲的国家的集水区中可能的药物浓度进行进一步建模;c)进一步明确在接触OC的野生禽类中产生达菲耐药病毒的风险。