title: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine.
abstract: BACKGROUND
  Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination.
  
  
  METHODS
  Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression.
  
  
  RESULTS
  The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91-1.04), while it was 2.04 (95% CI: 1.78-2.33) after being diagnosed with influenza infection during the peak pandemic period.
  
  
  CONCLUSIONS
  Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.
authors.affiliation: Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway. Electronic address: per.magnus@fhi.no.
authors.forename: Per
authors.initials: P
authors.lastname: Magnus
authors.affiliation: Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Gunnes
authors.affiliation: Journal of the Norwegian Medical Association, Oslo, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Tveito
authors.affiliation: Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Inger Johanne
authors.initials: IJ
authors.lastname: Bakken
authors.affiliation: Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Sara
authors.initials: S
authors.lastname: Ghaderi
authors.affiliation: Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stoltenberg
authors.affiliation: Center for Infection and Immunity, Columbia University, NY, NY, USA.
authors.forename: Mady
authors.initials: M
authors.lastname: Hornig
authors.affiliation: Center for Infection and Immunity, Columbia University, NY, NY, USA.
authors.forename: W Ian
authors.initials: WI
authors.lastname: Lipkin
authors.affiliation: Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Lill
authors.initials: L
authors.lastname: Trogstad
authors.affiliation: Norwegian Institute of Public Health, 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Siri E
authors.initials: SE
authors.lastname: Håberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D015673:Fatigue Syndrome, Chronic / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D007251:Influenza, Human / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines
keywords: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); Cohort; Influenza vaccine; Pandemic influenza