Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A.
Level 3 - non-randomized controlled study
Non-randomized population cohort surveillance study comparing vaccinated and unvaccinated incidence rates.
PubMed 23773727 · doi:10.1016/j.sleep.2013.03.020
What was done
National surveillance data were collected to evaluate the relationship between Pandemrix H1N1 influenza vaccination and new-onset narcolepsy among children and adolescents aged 4–19 years in Norway. The cohort included approximately 470,000 vaccinated individuals (~50% vaccine coverage) and their unvaccinated peers. Cases diagnosed in 2010 and 2011 with sudden excessive daytime sleepiness and cataplexy were evaluated through clinical testing, multiple sleep latency tests, cerebrospinal fluid (CSF) hypocretin measurements, and HLA typing.
What was found
Fifty-eight vaccinated cases (mean age 10.5 years) and 10 unvaccinated cases (mean age 12.5 years) were confirmed. Among vaccinated patients, 42 experienced symptom onset within 6 months (12 within 6 weeks). All 58 had excessive daytime sleepiness, 46 had cataplexy, 47 had mean sleep latency <8 minutes, 43 had ≥2 sleep-onset REM periods, all 41 tested had low CSF hypocretin levels, and all 37 tested were HLA-DQB1*0602 positive. In the first year post-vaccination, the risk of narcolepsy was significantly elevated (P < .0001) with a minimum incidence of 10 per 100,000 per year. In the second year, incidence fell to 1.1 per 100,000 per year, which did not significantly differ from unvaccinated baseline rates (0.5–1 per 100,000 per year).
Why it matters
This nationwide study confirms a strong, transient association between the AS03-adjuvanted H1N1 vaccine (Pandemrix) and hypocretin-deficient narcolepsy in children, with the elevated risk largely confined to the first year after immunization.
Limits
The abstract does not provide exact relative risk or hazard ratio point estimates with confidence intervals. Passive and registry-based surveillance carries risks of reporting and ascertainment bias, and unmeasured confounders inherent to observational vaccine safety surveillance could not be fully controlled.
Cited by
- supports A flu vaccine administered in Europe around 2009-2010 was found to be associated with an increased risk of narcolepsy, hypothesized to be caused by cross-reactivity against hypocretin-producing neurons.