title: Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis.
abstract: BACKGROUND
  Given the current lack of effective vaccines against TB, the accuracy of screening tests for determining or excluding latent TB infection (LTBI) is decisive in effective TB control. This meta-analysis critically appraises studies investigating the positive and the negative predictive value (PPV and NPV, respectively) from a test-determined LTBI state for progression to active TB of interferon-γ release assays (IGRAs) and the tuberculin skin test (TST).
  
  
  METHODS
  We searched MEDLINE, EMBASE, and Cochrane bibliographies for relevant articles. After qualitative evaluation, the PPV and NPV for progression of commercial and “in-house” IGRAs and the TST for persons not receiving preventive treatment in the context of the respective IGRA studies were pooled using both a fixed and a random-effect model. Weighted rates were calculated for all study populations and for groups solely at high risk of TB development.
  
  
  RESULTS
  The pooled PPV for progression for all studies using commercial IGRAs was 2.7% (95% CI, 2.3%-3.2%) compared with 1.5% (95% CI, 1.2%-1.7%) for the TST (P < .0001). PPV increased to 6.8% (95% CI, 5.6%-8.3%) and 2.4% (95% CI, 1.9%-2.9%) for the IGRAs and the TST, respectively, when only high-risk groups were considered (P < .0001). Pooled values of NPV for progression for both IGRAs and the TST were very high, at 99.7% (95% CI, 99.5%-99.8%) and 99.4% (95% CI, 99.2%-99.5%), respectively, although they were significantly higher for IGRAs (P < .01).
  
  
  CONCLUSIONS
  Commercial IGRAs have a higher PPV and NPV for progression to active TB compared with those of the TST, especially when performed in high-risk persons.
authors.affiliation: Department of Pulmonary Medicine, Medical School Hannover (MHH), Hannover, Institute for Health Service Research in Dermatology and Nursing, Hamburg, Germany. Electronic address: Diel.Roland@mh-hannover.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Diel
authors.affiliation: The German Central Committee Against Tuberculosis, Berlin, Institute for Health Service Research in Dermatology and Nursing, Hamburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Loddenkemper
authors.affiliation: University Medical Center Hamburg-Eppendorf, Institute for Health Service Research in Dermatology and Nursing, Hamburg, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Nienhaus
mesh_terms: D018450:Disease Progression; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000592:standards*; D055985:Latent Tuberculosis / Q000175:diagnosis*; D011237:Predictive Value of Tests; D012307:Risk Factors; D014374:Tuberculin Test / Q000592:standards*; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology