Background: Timely and accurate identification of people with latent tuberculosis infection (LTBI) is important for\ncontrolling Mycobacterium tuberculosis (TB). There is no gold standard for diagnosis of LTBI. Screening tests such as\ninterferon gamma release assays (IGRAs) and tuberculin skin test (TST) provide indirect and imperfect information.\nThis systematic review compared two types of IGRAs QuantiFERON�®-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB\nwith TST for identification of LTBI by predicting progression to a diagnosis of active TB in three subgroups: children,\nimmunocompromised people, and those recently arrived from countries with high TB burden.\nMethods: Cohort studies were eligible for inclusion. We searched MEDLINE, EMBASE, the Cochrane Library and\nother databases from December 2009 to June 2015. One reviewer screened studies, extracted data, and assessed\nrisk of bias with cross checking by a second reviewer. Strength of association between test results and incidence\nof TB was summarised using cumulative incidence ratios (CIRs with 95% CIs). Summary effect measures: the ratio\nof CIRs (R-CIR) with 95% CIs. R-CIRs, were pooled using a random-effects model. Heterogeneity was assessed using\nChi-squared and I2 statistics.\nResults: Seventeen studies, mostly of moderate or high risk of bias (five in children, 10 in immunocompromised\npeople, and two in those recently arrived) were included. In children, while in two studies, there was no significant\ndifference between QFT-GIT and TST (â�¥5 mm) (pooled R-CIR = 1.11, 95% CI: 0.71, 1.74), two other studies showed\nQFT-GIT to outperform TST (â�¥10 mm) in identifying LTBI. In immunocompromised people, IGRA (T-SPOT.TB) was\nnot significant different from TST (â�¥10 mm) for identifying LTBI, (pooled R-CIR = 1.01, 95% CI: 0.65, 1.58). The forest\nplot of two studies in recently arrived people from countries with high TB burden demonstrated inconsistent\nfindings (high heterogeneity; I2 = 92%).\nConclusions: Prospective studies comparing IGRA testing against TST on the progression from LTBI to TB were\nsparse, and these results should be interpreted with caution due to uncertainty, risk of bias, and unexplained\nheterogeneity. Population-based studies with adequate sample size and follow-up are required to adequately\ncompare the performance of IGRA with TST in people at high risk of TB.
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