title: Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011.
abstract: Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited.
  
  
  
  We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009-10 MIV, 2010-11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls.
  
  
  
  Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009-10 MIV recipients and 2.80 million 2010-11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009-10 MIV/2010-11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59-3.99; risk difference = 0.93 per million doses, 95% CI, -0.71-5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60-16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49-26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior vaccination shorter than 6 weeks.
  
  
  
  After adjusting for antecedent infections, we found no evidence for an elevated GBS risk following 2009-10 MIV/2010-11 TIV influenza vaccines. However, the association between GBS and antecedent infection was strongly elevated.
authors.affiliation: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, United States of America.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Greene
authors.forename: Melisa D
authors.initials: MD
authors.lastname: Rett
authors.forename: Claudia
authors.initials: C
authors.lastname: Vellozzi
authors.forename: Lingling
authors.initials: L
authors.lastname: Li
authors.forename: Martin
authors.initials: M
authors.lastname: Kulldorff
authors.forename: S Michael
authors.initials: SM
authors.lastname: Marcy
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Daley
authors.forename: Edward A
authors.initials: EA
authors.lastname: Belongia
authors.forename: Roger
authors.initials: R
authors.lastname: Baxter
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Fireman
authors.forename: Michael L
authors.initials: ML
authors.lastname: Jackson
authors.forename: Saad B
authors.initials: SB
authors.lastname: Omer
authors.forename: James D
authors.initials: JD
authors.lastname: Nordin
authors.forename: Robert
authors.initials: R
authors.lastname: Jin
authors.forename: Eric S
authors.initials: ES
authors.lastname: Weintraub
authors.forename: Vinutha
authors.initials: V
authors.lastname: Vijayadeva
authors.forename: Grace M
authors.initials: GM
authors.lastname: Lee
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications*; D020275:Guillain-Barre Syndrome / Q000209:etiology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000150:complications*; D012449:Safety; D014611:Vaccination / Q000009:adverse effects*; D015164:Vaccines, Inactivated / Q000009:adverse effects
chemical_list: D000956:Antigens, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated