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Potential risks associated with the proposed widespread use of Tamiflu

机译:拟议广泛使用达菲的潜在风险

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摘要

Background: 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.ududObjective: 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.ududDiscussion: 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.ududConclusion: 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.
机译:背景:大流行性流感的威胁已将注意力和资源集中在病毒的监视,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大流行性流感感染。此策略的长期有效性的主要问题是限制耐达菲的流感病毒株的发展。但是,一旦发生大流行,将迅速部署全球储备的数亿疗程的达菲。由于其对生物降解和亲水性具有明显的抵抗力,预计奥司他韦羧酸盐(OC)是达菲的活性抗病毒和代谢产物,预计将以其活性形式进入污水处理厂接收的河水中。 ud ud目的:本研究的目的是为了使用水文模型和关于流感大流行的过程和管理的当前假设,确定释放到美国和英国河流集水区的OC的可能浓度。 ud ud讨论:我们预测能够抑制流感的高浓度OC(每升微克)病毒复制将持续数周,这增加了野生禽流感病毒之间产生抗病毒抗性和基因交换的风险。由于污水处理厂中OC的明显顽强性,在流感大流行期间广泛使用达菲还会在每个受影响国家的水道中造成潜在的重大未表征的生态毒理学风险。 ud ud结论:评估达菲在使用过程中的危害对于大流行,我们建议a)直接测量达菲的持久性,生物降解和环境转化; b)在人类和水禽经常密切接触,并计划大量部署达菲的国家的流域,进一步模拟可能的药物浓度; c)进一步表征暴露于OC的野禽中产生耐达菲的病毒的风险。

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