Department of Virology, ErasmusMC, Rotterdam, The Netherlands.
PLoS Pathog. 2013;9(5):e1003343. doi: 10.1371/journal.ppat.1003343. Epub 2013 May 23.
Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15%) cases with prolonged 2009 pandemic virus replication (longer than 14 days), despite antiviral therapy. In 5 out of these 11 (45%) cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y) 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.
免疫功能低下的个体往往比健康患者遭受更长时间的流感感染，并且并发症更严重。对于这些患者中感染时间延长和抗病毒治疗的效果知之甚少。在 ErasmusMC 收治的所有 189 例甲型流感病毒感染的免疫功能低下患者中，自 2009 年 H1N1 大流行开始以来，有 71 例住院。我们发现 11 例（15%）患者尽管接受了抗病毒治疗，但 2009 年大流行病毒复制时间延长（超过 14 天）。在这 11 例中的 5 例（45%）出现了奥司他韦耐药的 H275Y 病毒。鉴于研究免疫功能低下患者抗病毒疗效的固有困难，我们用野生型或奥司他韦耐药（H275Y）2009 年大流行病毒感染免疫功能低下的雪貂。所有雪貂均表现出延长的病毒脱落。在感染野生型病毒并接受奥司他韦治疗的动物中，在感染后一周内出现了 H275Y 耐药变异体。出人意料的是，奥司他韦治疗在感染耐药病毒的动物中仍具有部分保护作用。免疫功能低下的雪貂为研究新型抗病毒疗法的疗效提供了一种有吸引力的替代方法。
