Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A

Abstract

BackgroundFrom October 2009 to January 2010, approximately 470,000 children and adolescents in Norway ages 4–19years were vaccinated with Pandemrix® against influenza A (H1N1 subtype). The vaccination coverage in this age cohort was approximately 50%. ObjectivesOur study was performed to evaluate the possible association between Pandemrix® vaccination and narcolepsy in Norway. MethodsChildren and adolescents with sudden onset of excessive daytime sleepiness (EDS) and cataplexy occurring after the 2009–2010 vaccination period were registered by the National Institute of Public Health in cooperation with the Norwegian Resource Center for AD/HD, Tourette Syndrome, and Narcolepsy. ResultsFifty-eight vaccinated children and adolescents (35 girls, 23 boys) ages 4–19years (mean age, 10.5years) were diagnosed as new cases of confirmed narcolepsy and were included in our study during 2010 and 2011. Forty-two children had onset of symptoms within 6months after vaccination, with 12 of them having symptoms within the first 6weeks. All had EDS, 46 had documented cataplexy, 47 had mean sleep latency less than 8min, and 43 had two or more sleep-onset rapid eye movement sleep (SOREM) periods in multiple sleep latency tests (MSLT). Cerebrospinal fluid (CSF) hypocretin levels were measured in 41 patients, with low levels in all. Thirty seven patients that were analyzed had tissue type HLADQB1*0602. During the same period, 10 unvaccinated cases were reported (mean age, 12.5years). ConclusionThe data collected during 3years following vaccination showed a significantly increased risk for narcolepsy with cataplexy (P<.0001) and reduced CSF hypocretin levels in vaccinated children ages 4–19years the first year after Pandemrix® vaccination, with a minimum incidence of 10 of 100,000 individuals per year. The second year after vaccination, the incidence was 1.1 of 100,000 individuals per year, which was not significantly different from the incidence of 0.5–1 of 100,000 per year in unvaccinated children during the same period.