title: Challenges with QuantiFERON-TB Gold assay for large-scale, routine screening of U.S. healthcare workers.
abstract: BACKGROUND
  North American occupational health programs that switched from the tuberculin skin test (TST) to IFN-γ release assays for latent tuberculosis screening are reporting challenges with interpretation of serial testing results in healthcare workers (HCWs). However, limited data exist on the reproducibility of serial IFN-γ release assay results in low-risk HCWs.
  
  
  OBJECTIVE
  To evaluate the short-term reproducibility of QuantiFERON-TB Gold In-Tube (QFT) in a large cohort of HCWs and to define a QFT cutoff yielding a conversion rate equivalent to historical TST rates.
  
  
  METHODS
  We retrospectively evaluated the QFT results from HCWs with two or more QFT tests performed between June 2008 and July 2010 at an academic institution. Outcome measures were proportions of reproducibility, quantitative results, and conversion rates with alternate QFT cutoffs.
  
  
  RESULTS
  A total of 9,153 HCWs with two or more QFT tests were included in the analysis. Of 8,227 individuals with a negative result, 4.4% (n = 361) converted their QFT result over 2 years. A total of 261 (72.3%) of the HCWs with conversions underwent repeat short-term testing after the first positive result with 64.8% reverting (n = 169). An IFN-γ cutoff of 5.3 IU/ml or higher (manufacturer's cutoff is ≥0.35 IU/ml) yielded a conversion rate of 0.4%, equal to our institution's historical TST conversion rate.
  
  
  CONCLUSIONS
  The manufacturer's definition of QFT conversion results in an inflated conversion rate that is incompatible with our low-risk setting. A significantly higher QFT cutoff value is needed to match the historical TST conversion rate. Nonreproducible conversions in most converters suggested false-positive results.
authors: 1 Department of Medicine and.
authors: Madeline L
authors: ML
authors: Slater
authors: Gary
authors: G
authors: Welland
authors: Madhukar
authors: M
authors: Pai
authors: Julie
authors: J
authors: Parsonnet
authors: Niaz
authors: N
authors: Banaei
mesh_terms: D000328:Adult; D005189:False Positive Reactions; D005260:Female; D006282:Health Personnel; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008403:Mass Screening / Q000379:methods; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis; D014481:United States
references: Chest. 2012 Jul;142(1):63-75
references: 22490872
references: Int J Tuberc Lung Dis. 2007 Jun;11(6):593-605
references: 17519089
references: Int Arch Occup Environ Health. 2011 Apr;84(4):461-9
references: 20721576
references: J Clin Microbiol. 2011 Aug;49(8):3061-4
references: 21697332
references: MMWR Recomm Rep. 2005 Dec 16;54(RR-15):49-55
references: 16357824
references: Chest. 2012 Jul;142(1):55-62
references: 22796839
references: J Clin Microbiol. 2012 Sep;50(9):3105-7
references: 22785197
references: Clin Vaccine Immunol. 2011 Jul;18(7):1176-82
references: 21593237
references: Pulm Med. 2012;2012:291294
references: 23326660
references: Can Respir J. 2012 Mar-Apr;19(2):84-8
references: 22536576
references: PLoS One. 2013;8(1):e54748
references: 23382955
references: J Occup Med Toxicol. 2012 Jun 18;7(1):6
references: 22537915
references: J Occup Med Toxicol. 2013 Jan 28;8(1):1
references: 23356875
references: GMS Krankenhhyg Interdiszip. 2010 Sep 21;5(2):
references: 20941341
references: MMWR Recomm Rep. 2005 Dec 30;54(RR-17):1-141
references: 16382216
references: Thorax. 2012 Jan;67(1):62-70
references: 21228420
references: Am J Respir Crit Care Med. 2013 Jan 15;187(2):206-11
references: 23103734
references: Ann Intern Med. 2008 Aug 5;149(3):177-84
references: 18593687
references: MMWR Recomm Rep. 2010 Jun 25;59(RR-5):1-25
references: 20577159
references: Eur Respir J. 2010 Jun;35(6):1346-53
references: 19840963
references: Am J Respir Crit Care Med. 2012 Nov 15;186(10):1051-6
references: 22955316
references: PLoS One. 2009 Dec 30;4(12):e8517
references: 20041113
references: Lancet Infect Dis. 2012 Jan;12(1):45-55
references: 21846592
references: Ann Intern Med. 2007 Mar 6;146(5):340-54
references: 17339619
references: Epidemiol Infect. 2009 Dec;137(12):1691-8
references: 19426573
references: Clin Infect Dis. 2002 Oct 1;35(7):796-801
references: 12228815