title: Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: a multinational self-controlled case series in Europe.
abstract: BACKGROUND
  The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1)pdm09 vaccination.
  
  
  METHODS
  A self-controlled case series (SCCS) analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1-4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI). Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS.
  
  
  RESULTS
  Three hundred and three (303) GBS and Miller Fisher syndrome cases were included. Ninety-nine (99) were exposed to A(H1N1)pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria). The unadjusted pooled RI for A(H1N1)pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI): 2.2-5.5), based on all countries. This lowered to 2.0 (95% CI: 1.2-3.1) after adjustment for calendartime and to 1.9 (95% CI: 1.1-3.2) when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom) we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month) to 1.4 (95% CI: 0.7-2.8), which is the main finding.
  
  
  CONCLUSIONS
  This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1)pdm09 vaccination (RI = 1.4 (95% CI: 0.7-2.8). Based on the upper limits of the pooled estimate we can rule out with 95% certainty that the number of excess GBS cases after influenza A(H1N1)pdm09 vaccination would be more than 3 per million vaccinated.
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Silvana
authors.initials: S
authors.lastname: Romio
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands ; Brighton Collaboration Foundation, Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weibel
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jeanne P
authors.initials: JP
authors.lastname: Dieleman
authors.affiliation: Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Henning K
authors.initials: HK
authors.lastname: Olberg
authors.affiliation: Department of Pharmacy & Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: Corinne S
authors.initials: CS
authors.lastname: de Vries
authors.affiliation: Department of Pharmacy & Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: Cormac
authors.initials: C
authors.lastname: Sammon
authors.affiliation: Health Protection Agency, London, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Mølgaard-Nielsen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
authors.affiliation: Department of Clinical Pharmacology, Toulouse University Hospital and Institut national de la santé et de la recherche médicale, Toulouse, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Lapeyre-Mestre
authors.affiliation: Department of Clinical Pharmacology, Toulouse University Hospital and Institut national de la santé et de la recherche médicale, Toulouse, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Sommet
authors.affiliation: French National Agency for Medicines and Health Products Safety, Saint Denis, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Saussier
authors.affiliation: Medical Doctor - Consultant, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Castot
authors.affiliation: Department of Vaccinology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
authors.forename: Harald
authors.initials: H
authors.lastname: Heijbel
authors.affiliation: Department Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Lisen
authors.initials: L
authors.lastname: Arnheim-Dahlström
authors.affiliation: Department Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Par
authors.initials: P
authors.lastname: Sparen
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Mees
authors.initials: M
authors.lastname: Mosseveld
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Schuemie
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Nicoline
authors.initials: N
authors.lastname: van der Maas
authors.affiliation: Departments of Neurology and Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Leino
authors.affiliation: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Terhi
authors.initials: T
authors.lastname: Kilpi
authors.affiliation: Department of Vaccines, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Jann
authors.initials: J
authors.lastname: Storsaeter
authors.affiliation: Surveillance and Response Support Unit, European Centre for Disease Prevention and Control, ECDC, Stockholm, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Johansen
authors.affiliation: Surveillance and Response Support Unit, European Centre for Disease Prevention and Control, ECDC, Stockholm, Sweden.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kramarz
authors.affiliation: Brighton Collaboration Foundation, Basel, Switzerland ; Department of Infectious Diseases and Vaccinology, University Children's Hospital, Basel, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Bonhoeffer
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020275:Guillain-Barre Syndrome / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D015994:Incidence; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011159:Population Surveillance; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; C556153:pandemrix