Gillman Anna
Section for Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Zoonosis Science Centre, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden;
Infect Ecol Epidemiol. 2016 Oct 11;6:32870. doi: 10.3402/iee.v6.32870. eCollection 2016.
Oseltamivir is the best available anti-influenza drug and has therefore been stockpiled worldwide in large quantities as part of influenza pandemic preparedness planning. The active metabolite oseltamivir carboxylate (OC) is stable and is not removed by conventional sewage treatment. Active OC has been detected in river water at concentrations up to 0.86 µg/L. Although the natural reservoir hosts of influenza A virus (IAV) are wild waterfowl that reside in aquatic environments, the ecologic risks associated with environmental OC release and its potential to generate resistant viral variants among wild birds has largely been unknown. However, in recent years a number of mallard () studies have been conducted regarding the potential of avian IAVs to become resistant to OC in natural reservoir birds if these are drug exposed. Development of resistance to OC was observed both in Group 1 (N1) and Group 2 (N2, N9) neuraminidase subtypes, when infected ducks were exposed to OC at concentrations between 0.95 and 12 µg/L in their water. All resistant variants maintained replication and transmission between ducks during drug exposure. In an A(H1N1)/H274Y virus, the OC resistance mutation persisted without selective drug pressure, demonstrating the potential of an IAV with a permissive genetic background to acquire and maintain OC resistance, potentially allowing circulation of the resistant variant among wild birds. The experimental studies have improved the appreciation of the risks associated with the environmental release of OC related to resistance development of avian IAVs among wild birds. Combined with knowledge of efficient methods for improved sewage treatment, the observations warrant implementation of novel efficient wastewater treatment methods, rational use of anti-influenza drugs, and improved surveillance of IAV resistance in wild birds.
奥司他韦是现有的最佳抗流感药物，因此作为流感大流行防范计划的一部分，已在全球范围内大量储备。其活性代谢产物奥司他韦羧酸盐（OC）很稳定，不会被传统污水处理方法去除。在河水中已检测到活性OC，浓度高达0.86微克/升。虽然甲型流感病毒（IAV）的天然宿主是栖息在水生环境中的野生水禽，但与环境中OC释放相关的生态风险及其在野生鸟类中产生耐药病毒变体的可能性在很大程度上尚不清楚。然而，近年来针对野鸭开展了一些研究，探讨如果野生鸟类接触药物，禽IAV对OC产生耐药性的可能性。当感染的鸭子在水中接触浓度为0.95至12微克/升的OC时，在第1组（N1）和第2组（N2、N9）神经氨酸酶亚型中均观察到对OC的耐药性产生。所有耐药变体在药物暴露期间均保持在鸭子之间的复制和传播。在一种A（H1N1）/H274Y病毒中，OC耐药突变在没有选择性药物压力的情况下持续存在，表明具有允许遗传背景的IAV获得并维持OC耐药性的可能性，这可能使耐药变体在野生鸟类中传播。这些实验研究提高了人们对与环境中OC释放相关的风险的认识，这些风险与野生鸟类中禽IAV耐药性的发展有关。结合对改进污水处理有效方法的了解，这些观察结果促使人们采用新型高效的废水处理方法、合理使用抗流感药物，并加强对野生鸟类中IAV耐药性的监测。
