Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England

Sleep. 2016 May 1;39(5):1051-7. doi: 10.5665/sleep.5752.

Abstract

Study objectives: An increased risk of narcolepsy has been observed in children following ASO3-adjuvanted pandemic A/H1N1 2009 (Pandemrix) vaccine. We investigated whether this risk extends to adults in England.

Methods: Six adult sleep centers in England were visited between November 2012 and February 2014 and vaccination/clinical histories obtained from general practitioners. Suspected narcolepsy cases aged older than 17 y were selected. The risk of narcolepsy following Pandemrix was calculated using cases diagnosed by the time of the center visits and those with a diagnosis by November 30, 2011 after which there was increased awareness of the risk in children. The odds of vaccination in cases and in matched population data were compared using a case-coverage design.

Results: Of 1,446 possible cases identified, most had onset before 2009 or were clearly not narcolepsy. Of the 60 remaining cases, 20 were excluded after expert review, leaving 40 cases with narcolepsy; 5 had received Pandemrix between 3 and 18 mo before onset. All the vaccinated cases had cataplexy, two received a diagnosis by November 2011 and two were aged 40 y or older. The odds ratio for vaccination in cases compared to the population was 4.24 (95% confidence interval 1.45-12.38) using all cases and 9.06 (1.90-43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses.

Conclusions: We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design.

Keywords: Pandemrix; adult; case-coverage; narcolepsy; vaccination.

MeSH terms

  • Adjuvants, Immunologic*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cataplexy / diagnosis
  • Cataplexy / epidemiology
  • England / epidemiology
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control
  • Male
  • Middle Aged
  • Narcolepsy / diagnosis
  • Narcolepsy / epidemiology*
  • Odds Ratio
  • Pandemics
  • Reproducibility of Results
  • Research Design
  • Risk Assessment
  • Sleep
  • Vaccination / adverse effects*
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Influenza Vaccines
  • pandemrix