Erasmus University Medical Center, Rotterdam, The Netherlands.
Vaccine. 2013 Feb 6;31(8):1246-54. doi: 10.1016/j.vaccine.2012.12.015. Epub 2012 Dec 16.
In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification.
We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom.
Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time.
The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.
2010 年 8 月，瑞典和芬兰报告了一种可能的关联，即接触 AS03 佐剂大流行性 A(H1N1)pdm09 疫苗与儿童和青少年发作性睡病的发生之间存在关联。针对这一信号，欧洲迅速评估了发作性睡病的基础发病率，以快速提供信号验证信息。
我们使用动态回顾性队列研究，使用六个国家（丹麦、芬兰、意大利、荷兰、瑞典和英国）的大型自动医疗保健数据库，评估 2000-2010 年期间的发作性睡病诊断率。
在近 2.8 亿人年的随访中，共发现 2608 例发作性睡病病例。汇总发病率为 0.93（95%CI：0.90-0.97）/10 万人年。15-30 岁（女性>男性）和 60 岁左右有高峰。在 5-19 岁年龄组中，与疫苗接种前相比，大流行性疫苗接种开始后发病率升高，丹麦的发病率比值（RR）为 1.9（95%CI：1.1-3.1），芬兰为 6.4（95%CI：4.2-9.7），瑞典为 7.5（95%CI：5.2-10.7）。荷兰的病例验证对随时间变化的发病率模式有显著影响。
本发病率研究的结果为人群水平的信号验证提供了有用的信息。在瑞典和芬兰观察到的大流行性疫苗接种开始后发作性睡病诊断增加的安全性信号，可以通过这种方法观察到。在其他国家，由于疫苗接种率在受影响的年龄组中较低，或未遵循流感 A(H1N1)pdm09 疫苗接种，未观察到发作性睡病诊断的增加。正在对这些国家进行病例水平分析，以更详细地验证信号。
