Potential risks associated with the proposed widespread use of Tamiflu.
Potential risks associated with the proposed widespread use of Tamiflu.
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DOI：
10.1289/ehp.9574
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发表时间：
2007-01
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
--
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大流行性流感的威胁使人们把注意力和资源集中在病毒监测、预防和遏制上。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大流行性流感感染。对这一策略长期有效性的一个主要关注是限制达菲耐药流感病毒株的发展。然而，一旦发生大流行，全球储存的数亿疗程的达菲将迅速部署。由于其明显的耐生物降解性和亲水性，奥司他韦羧酸盐（OC），达菲的活性抗病毒和代谢产物，预计进入接收河水从污水处理厂的活性形式。我们在这项研究中的目的是确定释放到美国和英国的OC的可能浓度。利用水文模型和当前关于流感大流行的进程和管理的假设，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，从而增加野禽中产生抗病毒耐药性和流感病毒之间遗传交换的风险。由于OC在污水处理厂中的明显不稳定性，在流感大流行期间达菲的广泛使用也对每个受影响国家的水道构成了潜在的重大、未定性的生态毒理学风险。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）进一步模拟人类和水禽经常密切接触的国家的集水区中可能的药物浓度，以及设想大量使用达菲的国家;和c）进一步表征在OC暴露的野禽中产生达菲抗性病毒的风险。
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 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.