title: Interferon-γ release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States.
abstract: BACKGROUND
  IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs).
  
  
  OBJECTIVE
  Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs.
  
  
  METHODS
  A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011.
  
  
  RESULTS
  A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later.
  
  
  CONCLUSIONS
  Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.
authors.affiliation: 1 Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Dorman
authors.forename: Robert
authors.initials: R
authors.lastname: Belknap
authors.forename: Edward A
authors.initials: EA
authors.lastname: Graviss
authors.forename: Randall
authors.initials: R
authors.lastname: Reves
authors.forename: Neil
authors.initials: N
authors.lastname: Schluger
authors.forename: Paul
authors.initials: P
authors.lastname: Weinfurter
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.forename: Wendy
authors.initials: W
authors.lastname: Cronin
authors.forename: Yael
authors.initials: Y
authors.lastname: Hirsch-Moverman
authors.forename: Larry D
authors.initials: LD
authors.lastname: Teeter
authors.forename: Matthew
authors.initials: M
authors.lastname: Parker
authors.forename: Denise O
authors.initials: DO
authors.lastname: Garrett
authors.forename: Charles L
authors.initials: CL
authors.lastname: Daley
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D005189:False Positive Reactions; D005260:Female; D006282:Health Personnel; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000706:statistics & numerical data; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000706:statistics & numerical data; D014481:United States