title: Specific interferon γ detection for the diagnosis of previous Q fever.
abstract: BACKGROUND
  Current practice for diagnosis of Q fever, caused by the intracellular pathogen Coxiella burnetii, relies mainly on serology and, in prevaccination assessment, on skin tests (STs), which both have drawbacks. In this study, C. burnetii-specific interferon γ (IFN-γ) production was used as a new diagnostic tool for previous Q fever, circumventing most of these drawbacks. Our aim was to compare this test to serology and ST.
  
  
  METHODS
  One thousand five hundred twenty-five individuals from an endemic area with a risk for chronic Q fever were enrolled. IFN-γ production was measured after in vitro stimulation of whole blood with C. burnetii antigens. Various formats using different C. burnetii antigens were tested. Serology and ST were performed in all individuals.
  
  
  RESULTS
  In all assay formats, C. burnetii-specific IFN-γ production was higher (P < .0001) in seropositive or ST-positive subjects than in seronegative and ST-negative subjects. Whole blood incubated for 24 hours with C. burnetii Nine Mile showed optimal performance. After excluding subjects with equivocal serology and/or borderline ST results, IFN-γ production was 449 ± 82 pg/mL in the positive individuals (n = 219) but only 21 ± 3 pg/mL in negative subjects (n = 908). Using Bayesian analysis, sensitivity and specificity (87.0% and 90.2%, respectively) were similar to the combination of serology and ST (83.0% and 95.6%, respectively). Agreement with the combination of serology and ST was moderate (84% concordance; κ = 0.542).
  
  
  CONCLUSIONS
  Specific IFN-γ detection is a novel diagnostic assay for previous C. burnetii infection and shows similar performance and practical advantages over serology and ST. Future studies to investigate the clinical value in practice are warranted.
authors: Department of Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, The Netherlands.
authors: Teske
authors: T
authors: Schoffelen
authors: Leo A B
authors: LA
authors: Joosten
authors: Tineke
authors: T
authors: Herremans
authors: Anton F J
authors: AF
authors: de Haan
authors: Anne
authors: A
authors: Ammerdorffer
authors: Hans C
authors: HC
authors: Rümke
authors: Clementine J
authors: CJ
authors: Wijkmans
authors: Hendrik I Jan
authors: HI
authors: Roest
authors: Mihai G
authors: MG
authors: Netea
authors: Jos W M
authors: JW
authors: van der Meer
authors: Tom
authors: T
authors: Sprong
authors: Marcel
authors: M
authors: van Deuren
mesh_terms: D000368:Aged; D001431:Bacteriological Techniques / Q000379:methods; D016997:Coxiella burnetii / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis* / Q000276:immunology; D059425:Interferon-gamma Release Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011778:Q Fever / Q000175:diagnosis* / Q000276:immunology; D012372:ROC Curve; D015203:Reproducibility of Results; D012698:Serologic Tests / Q000379:methods; D012882:Skin Tests / Q000379:methods; D018709:Statistics, Nonparametric
chemical_list: D007371:Interferon-gamma
keywords: Coxiella burnetii; Q fever; interferon γ; serology; skin test