Sturkenboom Miriam C J M
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Vaccine. 2015 Jun 8;33 Suppl 2:B6-B13. doi: 10.1016/j.vaccine.2015.03.026.
A safety signal around Pandemrix, an AS03 adjuvanted influenza A(H1N1) pdm09 vaccine potentially causing narcolepsy in children and adolescents became public in August 2010, long after cessation of the influenza A(H1N1) pdm09 campaigns in Europe. The signal originated from Finland and Sweden, two countries with school based pandemic vaccination campaigns, with high vaccine coverage, and vaccinations being provided at the peak of the circulating wild virus. Since the announcement awareness grew in Europe, with extensive public media dissemination and regulatory actions. This resulted in a steep increase in the spontaneous reports of exposed cases, a decrease in diagnostic lag times of this rare, underdiagnosed disease and finally victim compensation. The signaling countries conducted rapid risk assessment studies to quantify the signal to the best of their abilities, in the midst of the public awareness, most of which could not distinguish between a vaccine and an awareness effect. Due to the strong but variable associations from the epidemiological studies, the search for biological mechanisms started. Currently it is not yet understood how Pandemrix might cause narcolepsy, and whether it would be specific to Pandemrix. The paper describes the current evidence and puts forward the questions that remain to be answered, which are relevant for future pandemic preparedness when adjuvants may be used for dose sparing.
2010年8月，一种AS03佐剂的甲型H1N1pdm09流感疫苗“盼尔来福”（Pandemrix）可能导致儿童和青少年发作性睡病的安全信号被公开，此时欧洲甲型H1N1pdm09流感疫苗接种活动早已结束。该信号源自芬兰和瑞典，这两个国家开展了以学校为基础的大流行疫苗接种活动，疫苗接种率高，且在野生病毒传播高峰期进行接种。自该信号公布以来，随着广泛的公共媒体传播和监管行动，欧洲的关注度不断提高。这导致暴露病例的自发报告急剧增加，这种罕见的、诊断不足的疾病的诊断滞后时间缩短，最终实现了受害者赔偿。在公众关注度较高的情况下，发出信号的国家尽最大能力开展了快速风险评估研究，以量化该信号，其中大多数研究无法区分疫苗和关注度的影响。由于流行病学研究的关联很强但存在差异，因此开始寻找生物学机制。目前尚不清楚“盼尔来福”如何导致发作性睡病，以及它是否是“盼尔来福”所特有的。本文描述了当前的证据，并提出了有待回答的问题，这些问题对于未来在可能使用佐剂来节省剂量的大流行防范工作具有相关性。
