Risks of neurological and immune-related diseases, including narcolepsy, after vaccination with Pandemrix: a population- and registry-based cohort study with over 2 years of follow-up
Risks of neurological and immune-related diseases, including narcolepsy, after vaccination with Pandemrix: a population- and registry-based cohort study with over 2 years of follow-up
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DOI：
10.1111/joim.12150
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发表时间：
2014-02-01
影响因子：
11.1
通讯作者：
Feltelius, N.
中科院分区：
文献类型：
--
作者：
Persson, I.;Granath, F.;Feltelius, N.
目的调查接种Pandemrix疫苗与包括发作性睡病在内的特定神经系统和免疫相关疾病的风险之间的关系。设计基于人群的前瞻性队列研究，使用区域疫苗接种登记和国家卫生登记的数据。背景瑞典的七个医疗保健地区，占瑞典人口的61%。研究对象3347467名接种疫苗的人和2497572名未接种疫苗的人(接种覆盖率约为60%)在2009年至2011年期间进行了690万人年和600万人年的跟踪研究。主要结果衡量和分析首次记录的神经和免疫相关疾病的诊断。相对风险[风险比(HR)，95%可信区间(CI)]使用COX回归进行评估，并对协变量进行了调整。结果对于研究中的所有选定的神经和免疫相关结果，除了过敏性疫苗反应(我们验证了风险的预期增加)和发作性睡病外，HR接近1.0，始终低于1.3。我们观察到，在接种疫苗时，20岁的人被诊断为发作性睡病的风险增加了三倍(HR：2.92，95%CI：1.78-4.79；即每100000人年增加4例)，而在21至30岁的年轻人中，确诊为发作性睡病的风险增加了两倍(HR：2.18，95%CI：1.00-4.75)。在接种疫苗时，超额风险随年龄的增长而依次下降；40岁后风险没有增加。结论对于大量选定的神经系统和免疫相关疾病，我们既不能证实与Pandemrix的任何因果关系，也不能完全驳斥小的超额风险。我们证实了在20岁的人中诊断为发作性睡病的风险增加，并观察到在21至30岁的年轻人中也有风险增加的趋势。
ObjectivesTo investigate the association between vaccination with Pandemrix and risk of selected neurological and immune-related diseases including narcolepsy.DesignPopulation-based prospective cohort study using data from regional vaccination registries and national health registries.SettingSeven healthcare regions in Sweden comprising 61% of the Swedish population.SubjectsStudy population of 3347467 vaccinated and 2497572 nonvaccinated individuals (vaccination coverage approximate to 60%) followed between 2009 and 2011 for 6.9 million person-years after exposure and 6.0 million person-years without exposure.Main outcome measure and analysisFirst recorded diagnosis of neurological and immune-related diseases. Relative risks [hazard ratios (HRs) with 95% confidence intervals (CIs)] assessed using Cox regression, adjusted for covariates.ResultsFor all selected neurological and immune-related outcomes under study, other than allergic vaccine reactions (for which we verified an expected increase in risk) and narcolepsy, HRs were close to 1.0 and always below 1.3. We observed a three-fold increased risk of a diagnosis of narcolepsy (HR: 2.92, 95% CI: 1.78-4.79; that is, four additional cases per 100000 person-years) in individuals 20years of age at vaccination and a two-fold increase (HR: 2.18, 95% CI: 1.00-4.75) amongst young adults between 21 and 30years of age. The excess risk declined successively with increasing age at vaccination; no increase in risk was seen after 40years of age.ConclusionsFor a large number of selected neurological and immune-related diseases, we could neither confirm any causal association with Pandemrix nor refute entirely a small excess risk. We confirmed an increased risk for a diagnosis of narcolepsy in individuals 20years of age and observed a trend towards an increased risk also amongst young adults between 21 and 30years.