Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vaccine in Quebec

PLoS One. 2014 Sep 29;9(9):e108489. doi: 10.1371/journal.pone.0108489. eCollection 2014.

Abstract

Context: An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.

Objective: To assess narcolepsy risk following administration of a similar vaccine in Quebec.

Design: Retrospective population-based study.

Setting: Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.

Population: Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.

Main outcome measures: Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method.

Results: A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12). RR was 2.07 (0.70-6.17) in the SCCS, and 1.48 (0.37-7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.

Conclusions: Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / adverse effects*
  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Drug Combinations
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / therapeutic use
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Narcolepsy / epidemiology*
  • Polysorbates / adverse effects*
  • Polysorbates / therapeutic use
  • Quebec / epidemiology
  • Retrospective Studies
  • Squalene / adverse effects*
  • Squalene / therapeutic use
  • Vaccination
  • Young Adult
  • alpha-Tocopherol / adverse effects*
  • alpha-Tocopherol / therapeutic use

Substances

  • Adjuvants, Immunologic
  • Drug Combinations
  • Influenza Vaccines
  • Polysorbates
  • Squalene
  • AS03 adjuvant
  • alpha-Tocopherol

Grants and funding

This study was funded by GlaxoSmithKline Biologicals. The sponsor had a role in the design of the study and provided comments on the first draft of the manuscript. It has, however, no role in the conduct of the study, collection, management, analysis of data, and preparation and approval of the final version of the manuscript.