title: Comparison of two interferon-gamma assays and tuberculin skin test for tracing tuberculosis contacts.
abstract: BACKGROUND
  The tuberculin skin test (TST) has low specificity. QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB are based on interferon (IFN)-gamma responses to Mycobacterium tuberculosis-specific antigens. A novel in-tube format of QFT-G (QFT-GIT) offers logistical advantages.
  
  
  OBJECTIVE
  To compare TST, QFT-GIT, and T-SPOT.TB in bacillus Calmette-Guérin unvaccinated contacts and correlate results with measures of recent exposure.
  
  
  METHODS
  When a supermarket employee with smear-positive tuberculosis had infected most close contacts, a contact investigation among more than 20,000 customers was performed. We recruited subjects randomly on the day of TST administration (n = 469) and subjects with TST of more than 0 mm on the day of TST reading (n = 316). QFT-GIT and T-SPOT.TB were performed. Demographic data and measures of exposure were collected. TST results were analyzed at a cutoff of 10 or 15 mm. Blood tests were interpreted following the manufacturers' criteria and by varying cutoff levels.
  
  
  RESULTS
  Among 785 study participants, TST results were associated with age, whereas positive IFN-gamma responses were significantly associated with cumulative shopping time, most markedly for QFT-GIT. Among participants with a TST of 15 mm or greater, sensitivity of QFT-GIT and T-SPOT.TB was 42.2 and 51.3%, respectively. Interassay agreement was 89.6% (kappa = 0.59). By varying cutoff values, agreement between the IFN-gamma assays was optimal at 93.6% (kappa = 0.71) using a cutoff of 0.20 IU/ml for QFT-GIT and 13 spots for T-SPOT.TB.
  
  
  CONCLUSIONS
  Blood test results were associated with exposure, whereas the TST was not. A possible lack of sensitivity of IFN-gamma assays in detecting individuals with TST of 15 mm or greater, despite negative bacillus Calmette-Guérin vaccination status, warrants further investigation into alternative cutoff values.
authors.affiliation: Leiden University Medical Center, Infectious Diseases, Leiden, The Netherlands.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Arend
authors.forename: Steven F T
authors.initials: SF
authors.lastname: Thijsen
authors.forename: Eliane M S
authors.initials: EM
authors.lastname: Leyten
authors.forename: John J M
authors.initials: JJ
authors.lastname: Bouwman
authors.forename: Willeke P J
authors.initials: WP
authors.lastname: Franken
authors.forename: Ben F P J
authors.initials: BF
authors.lastname: Koster
authors.forename: Frank G J
authors.initials: FG
authors.lastname: Cobelens
authors.forename: Arend-Jan
authors.initials: AJ
authors.lastname: van Houte
authors.forename: Ailko W J
authors.initials: AW
authors.lastname: Bossink
mesh_terms: D000328:Adult; D000367:Age Factors; D016358:Contact Tracing; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000635:transmission*
chemical_list: D007371:Interferon-gamma