title: Adverse events and association with age, sex and immunological parameters of Q fever vaccination in patients at risk for chronic Q fever in the Netherlands 2011.
abstract: BACKGROUND
  Following a large Q fever outbreak in the Netherlands, patients at risk for chronic Q fever received a whole-cell Q fever vaccine. Sensitized people were excluded based on pre-vaccination screening with skin test (ST) and serology. An investigational IFN-γ-production assay was added. No previous experience existed for Q fever vaccination in this patient risk-group with predefined cardiac valvular anomalies or aortic aneurysm/prosthesis and many co-morbidities. We studied the adverse events (AE) and their association with patient characteristics and immunological parameters.
  
  
  METHODS
  AE registration covered the week after skin test and 90 days following vaccination, with the use of diaries, interviews and spontaneous reports. Serious (S)AE were assessed immediately to ensure safety. We coded AE according to reported severity. Univariate and multivariate analysis addressed associations.
  
  
  RESULTS
  Pre-vaccination screening led to exclusion of 182 patients with positive serology and 207 patients with positive skin test-reading. The skin test did not lead to any causally related SAE. Subsequent vaccination of 1370 patients did not reveal unexpected AE; however, 80% of vaccinees reported local AE (in 26% of these pronounced or extensive). The two causally related SAE (0.1%) both concerned a persistent subcutaneous injection site mass. AE were more frequent in women, younger patients, and those without immunosuppressive co-morbidity/medication. The occurrence of local AE after skin test was associated with pre-vaccination positive serology and high IFN-γ production. This was also true for local AE following vaccination, with a strong association with local AE after skin test as well. The proportion of vaccinees with positive serology and positive IFN-γ values 6 months after vaccination was higher in those with local AE after skin test or after vaccination (non-significant, probably due to small numbers).
  
  
  CONCLUSIONS
  Q fever vaccination was safe but reactogenic in this high-risk patient-group. Rates of local AE were higher in women, younger age groups and in those with positive immunological parameters. Vaccinees with local AE after skin test or after vaccination appear to have more pronounced post-vaccination immune responses.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. teske.schoffelen@radboudumc.nl
authors.forename: Teske
authors.initials: T
authors.lastname: Schoffelen
authors.forename: Albert
authors.initials: A
authors.lastname: Wong
authors.forename: Hans C
authors.initials: HC
authors.lastname: Rümke
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Aura
authors.initials: A
authors.lastname: Timen
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Vermeer-de Bondt
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011778:Q Fever / Q000276:immunology / Q000517:prevention & control*; D012307:Risk Factors; D012737:Sex Factors; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014765:Viral Vaccines