title: Comparing interferon-gamma release assays with tuberculin skin test for identifying latent tuberculosis infection that progresses to active tuberculosis: systematic review and meta-analysis.
abstract: Timely and accurate identification of people with latent tuberculosis infection (LTBI) is important for controlling Mycobacterium tuberculosis (TB). There is no gold standard for diagnosis of LTBI. Screening tests such as interferon gamma release assays (IGRAs) and tuberculin skin test (TST) provide indirect and imperfect information. This systematic review compared two types of IGRAs QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB with TST for identification of LTBI by predicting progression to a diagnosis of active TB in three subgroups: children, immunocompromised people, and those recently arrived from countries with high TB burden.
  
  
  
  Cohort studies were eligible for inclusion. We searched MEDLINE, EMBASE, the Cochrane Library and other databases from December 2009 to June 2015. One reviewer screened studies, extracted data, and assessed risk of bias with cross checking by a second reviewer. Strength of association between test results and incidence of TB was summarised using cumulative incidence ratios (CIRs with 95% CIs). Summary effect measures: the ratio of CIRs (R-CIR) with 95% CIs. R-CIRs, were pooled using a random-effects model. Heterogeneity was assessed using Chi-squared and I2statistics.
  
  
  
  Seventeen studies, mostly of moderate or high risk of bias (five in children, 10 in immunocompromised people, and two in those recently arrived) were included. In children, while in two studies, there was no significant difference between QFT-GIT and TST (≥5 mm) (pooled R-CIR = 1.11, 95% CI: 0.71, 1.74), two other studies showed QFT-GIT to outperform TST (≥10 mm) in identifying LTBI. In immunocompromised people, IGRA (T-SPOT.TB) was not significant different from TST (≥10 mm) for identifying LTBI, (pooled R-CIR = 1.01, 95% CI: 0.65, 1.58). The forest plot of two studies in recently arrived people from countries with high TB burden demonstrated inconsistent findings (high heterogeneity; I2= 92%).
  
  
  
  Prospective studies comparing IGRA testing against TST on the progression from LTBI to TB were sparse, and these results should be interpreted with caution due to uncertainty, risk of bias, and unexplained heterogeneity. Population-based studies with adequate sample size and follow-up are required to adequately compare the performance of IGRA with TST in people at high risk of TB.
authors.affiliation: Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. p.auguste@warwick.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Auguste
authors.affiliation: Evidence in Communicable Disease Epidemiology and Control, Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tsertsvadze
authors.affiliation: Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Pink
authors.affiliation: Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Court
authors.affiliation: Evidence in Communicable Disease Epidemiology and Control, Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Noel
authors.initials: N
authors.lastname: McCarthy
authors.affiliation: Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Sutcliffe
authors.affiliation: Warwick Evidence, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Aileen
authors.initials: A
authors.lastname: Clarke
mesh_terms: D000328:Adult; D002648:Child; D018450:Disease Progression; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D059425:Interferon-gamma Release Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D014374:Tuberculin Test / Q000379:methods*
keywords: Interferon gamma release assays; Latent tuberculosis infection; Systematic review; Tuberculin skin test