title: Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK.
abstract: BACKGROUND
  Over 70% of cervical cancers are related to human papillomavirus types 16 and 18. In 2008, the vaccine Cervarix, protecting against these two strains, was introduced into the routine UK immunisation programme for girls aged 12-13 years, with a catch-up in girls aged up to 18 years. As part of the risk management planning for this new campaign, the Medicines and Healthcare products Regulatory Agency (MHRA) anticipated a range of conditions, including chronic fatigue syndrome, which might be reported as adverse events in temporal association with the vaccine.
  
  
  METHODS
  Near-real time 'observed vs. expected' analyses were conducted comparing the number of reports of fatigue syndromes submitted via the MHRA's Yellow Card passive surveillance scheme to the expected number, using background rates calculated from the Clinical Practice Research Datalink (CPRD) and estimates of vaccination coverage. Subsequently, an ecological analysis and a self-controlled case series (SCCS), both using CPRD, compared the incidence rate of fatigue syndromes in girls before and after the start of the vaccination campaign and the risk in the year post-vaccination compared to other periods.
  
  
  RESULTS
  The number of spontaneous reports of chronic fatigue following Cervarix vaccination was consistent with estimated background rates even assuming low reporting. Ecological analyses suggested that there had been no change in the incidence of fatigue syndromes in girls aged 12-20 years after the introduction of the vaccination despite high uptake (IRR: 0.94, 95% CI: 0.78-1.14). The SCCS, including 187 girls, also showed no evidence of an increased risk of fatigue syndromes in the year post first vaccination (IRR: 1.07, 95% CI: 0.57-2.00, p=0.84).
  
  
  CONCLUSIONS
  The successful implementation of an enhanced pharmacovigilance plan provided immediate reassuring evidence that there was no association between vaccination with Cervarix and an increased risk of chronic fatigue syndromes. This has now also been further demonstrated in more comprehensive epidemiological studies.
authors.affiliation: Vigilance and Risk Management of Medicines, Medicines and Healthcare products Regulatory Agency, London, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Donegan
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Beau-Lejdstrom
authors.forename: Bridget
authors.initials: B
authors.lastname: King
authors.forename: Suzie
authors.initials: S
authors.lastname: Seabroke
authors.forename: Andrew
authors.initials: A
authors.lastname: Thomson
authors.forename: Philip
authors.initials: P
authors.lastname: Bryan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015673:Fatigue Syndrome, Chronic / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D018570:Risk Assessment; D006113:United Kingdom; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: Chronic fatigue syndrome; Human papillomavirus vaccine