title: The incidence of narcolepsy in Europe: before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns.
abstract: BACKGROUND
  In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification.
  
  
  METHODS
  We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom.
  
  
  RESULTS
  Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time.
  
  
  CONCLUSIONS
  The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.
authors.affiliation: Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Leonoor
authors.initials: L
authors.lastname: Wijnans
authors.forename: Coralie
authors.initials: C
authors.lastname: Lecomte
authors.forename: Corinne
authors.initials: C
authors.lastname: de Vries
authors.forename: Daniel
authors.initials: D
authors.lastname: Weibel
authors.forename: Cormac
authors.initials: C
authors.lastname: Sammon
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.forename: Ditte
authors.initials: D
authors.lastname: Mølgaard-Nielsen
authors.forename: Harald
authors.initials: H
authors.lastname: Heijbel
authors.forename: Lisen Arnheim
authors.initials: LA
authors.lastname: Dahlström
authors.forename: Jonas
authors.initials: J
authors.lastname: Hallgren
authors.forename: Par
authors.initials: P
authors.lastname: Sparen
authors.forename: Poul
authors.initials: P
authors.lastname: Jennum
authors.forename: Mees
authors.initials: M
authors.lastname: Mosseveld
authors.forename: Martijn
authors.initials: M
authors.lastname: Schuemie
authors.forename: Nicoline
authors.initials: N
authors.lastname: van der Maas
authors.forename: Markku
authors.initials: M
authors.lastname: Partinen
authors.forename: Silvana
authors.initials: S
authors.lastname: Romio
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.forename: Carmela
authors.initials: C
authors.lastname: Santuccio
authors.forename: Angelo
authors.initials: A
authors.lastname: Menna
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Plazzi
authors.forename: Keivan Kaveh
authors.initials: KK
authors.lastname: Moghadam
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ferro
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Lammers
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Overeem
authors.forename: Kari
authors.initials: K
authors.lastname: Johansen
authors.forename: Piotr
authors.initials: P
authors.lastname: Kramarz
authors.forename: Jan
authors.initials: J
authors.lastname: Bonhoeffer
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000453:epidemiology*; D012189:Retrospective Studies; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines