Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France
Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France
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DOI：
10.1093/brain/awt187
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发表时间：
2013-08-01
期刊：
影响因子：
14.5
通讯作者：
Pariente, Antoine
中科院分区：
文献类型：
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作者：
Dauvilliers, Yves;Arnulf, Isabelle;Pariente, Antoine
在使用大流行性H1N1流感ASO 3佐剂疫苗的斯堪的纳维亚国家，发现儿童嗜睡症的发病率增加。在法国，使用含ASO 3佐剂和不含佐剂的疫苗开展了一项针对大流行性H1N1流感的疫苗接种运动。作为一项考虑所有类型发作性睡病的研究的一部分，我们调查了H1N1疫苗接种与儿童和成人发作性睡病伴癫痫发作之间的关联，并与匹配的对照组进行了比较;并根据H1N1疫苗接种暴露情况，比较了发作性睡病伴癫痫发作的表型。从法国14个专家中心纳入了发作性睡病-癫痫患者。诊断日期构成索引日期。独立专家使用布莱顿合作标准对病例进行了验证。根据年龄、性别和地理位置，最多有四名对照与病例单独匹配。进行了结构化电话访谈，以收集病史、既往感染和疫苗接种信息。纳入了85例发作性睡病-痉挛病例;根据合格性标准进一步排除了23例。在62例合格病例中，59例（64%男性，57.6%儿童）可与135例对照受试者匹配。H1N1疫苗接种与发作性睡病相关，18岁以下受试者的优势比为6.5（2.1-19.9），18岁及以上受试者为4.7（1.6-13.9）。考虑转诊诊断日期或症状发作日期作为索引日期的敏感性分析得出了类似的结果，仅关注ASO 3佐剂疫苗暴露的分析也是如此。当比较暴露于H1N1疫苗接种的发作性睡病-紧张症病例（n = 32;主要是AS 03佐剂疫苗，n = 28）与未暴露病例（n = 30）时，发现了轻微差异，包括暴露病例的诊断延迟较短和睡眠发作快速眼动期数量较多。感染史无差异。在这项亚组分析中，H1N1疫苗接种与法国儿童和成人发作性睡病的风险增加密切相关。即使像在每项观察性研究中一样，不能完全排除参与相关性的一些偏倚的可能性，但敏感性分析显示相关性很强，一项针对含ASO 3佐剂疫苗的特定分析发现了类似的增加。
An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged < 18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n = 32; mostly AS03-adjuvanted vaccine, n = 28) to non-exposed cases (n = 30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase.