Increased Rates of Narcolepsy, Hypersomnia Linked to H1N1 Vaccine

Results of a recent population-based study published in Vaccine indicate a significant correlation between the H1N1 vaccine and both narcolepsy and hypersomnia.¹

Narcolepsy was a widely observed adverse effect of the H1N1 vaccine used in the 2009 influenza pandemic. A 2013 study in Sweden² reported that rates of narcolepsy were 25 times higher after vaccination than before.² Further investigations in Sweden, Finland, Denmark, Norway, Italy, the Netherlands, the United Kingdom, and Ireland all reported increases in narcolepsy associated with the vaccine, particularly among children and adolescents.^2-7

The current study,¹ led by Lill Trogstad, PhD, from the Norwegian Institute of Public Health in Nydalen, Norway, evaluated data collected from the Norwegian National Registry between October 1, 2009, and December 31, 2012 on 1,638,526 residents aged 3-29 years. Of that population, 687,982 (41.9%) were vaccinated during the pandemic, compared with 59,207 (3.6%) who had confirmed diagnoses of influenza during that period.

The investigators found that after influenza infection, the risk for narcolepsy was increased by 2- to 3-fold overall (adjusted hazard ratio [HR], 3.31; 95% CI, 1.01-10.79). The time between infection and onset of narcolepsy was 5 to 14 months.

Onset of narcolepsy occurred at a range of 1 to 28 months after vaccination, with a mean time of 7.6 months. Among those who were vaccinated, risk for narcolepsy was highest during the first 6 months after exposure to the vaccine (adjusted HR, 17.21; 95% CI, 6.28-47.14) compared with an HR of 8.71 (95% CI, 4.03-18.82) at 12 months and an HR of 5.53 (95% CI, 3.01-10.15) at the end of the 3-year follow-up period in 2012.

Rates of hypersomnia were also increased in the study cohort, but to a degree that was only significant in the 6-month period after exposure to influenza (adjusted HR, 1.54; 95% CI, 0.81-2.93), with a range of 2 to 35 months for the development of symptoms (mean, 20 months). The risk for hypersomnia associated with vaccination increased from exposure to the end of the study period (range, 1-37 months; mean, 22.5 months), with an adjusted HR of 1.83 (95% CI, 1.44-2.33).

Overall patterns indicated that narcolepsy increased most significantly during the first 6 months after either influenza infection or vaccination, with a decreasing risk during longer periods of exposure. Conversely, the risk for hypersomnia increased with longer duration of exposure. The HRs for narcolepsy and hypersomnia increased in periods of exposure to both infection and vaccination, which suggests a degree of synergy that could best be assessed in repeated exposure settings.

References

1. Trogstad L, Bakken IJ, Gunne N, et al. Narcolepsy and hypersomnia in Norwegian children and young adults following the influenza A(H1N1) 2009 pandemic. Vaccine. 2017;35:1879-1885. doi: 10.1016/j.vaccine.2017.02.053
2. Szakács A, Darin N, Hallböök T. Increased childhood incidence of narcolepsy in western Sweden after H1N1 influenza vaccination. Neurology. 2013;80:1315-1321. doi: 10.1212/WNL.0b013e31828ab26f
3. Bardage C, Persson I, Ørtquist Å, et al. Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in in Stockholm, Sweden. BMJ. 2011;343:d5956. doi: 10.1136/bmj.d5956
4. Nohynek H, Jokinen J, Partinen M, et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS ONE. 2012;7(3):e33536. doi: 10.1371/journal.pone.0033536
5. Wijnans L, Lecomte C, de Vries C, et al. The incidence of narcolepsy in Europe:before, during and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns. Vaccine. 2013;31:1246-1254. doi: 10.1016/j.vaccine.2012.12.015
6. O’Flanagan D, Barret AS, Foley M, et al. Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010. Euro Surveill. 2014;19(17):15-25. doi: 10.2807/1560-7917.ES2014.19.17.20789
7. Heier M, Gautvik KM, Wannag E, et al. Incidence of narcolepsy in children and adolescents after vaccination against H1N1 influenza A. Sleep Med. 2013;14:867-871. doi: 10.1016/j.sleep.2013.03.020