Interferon-gamma release assays for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis

Interferon -gamma release assays (IGRAs) provide a new diagnostic method for Mycobacterium tuberculosis (TB) infection. However, the diagnostic value of IGRAs for extrapulmonary TB (EPTB) has not been clarified. We searched several databases and selected papers with strict inclusion criteria, evaluated the evidence of commercially available IGRAs (QuantiFERON (R)-TB Gold QFT-G or QFT-GIT and T-SPOT (R).TB) on blood and the tuberculin skin test (TST) using random effects models. Twenty studies with 1711 patients were included. After excluding indeterminate results, pooled sensitivity for the diagnosis of EPTB was 72% [95% confidence interval (CI) 6579%] for QFT-G or GIT and 90% (95% CI, 8693%) for T-SPOT; in high-income countries the sensitivity of QFT-G or GIT (79%, 95% CI 7286%) was much higher than that (29%, 95% CI 1448%) in low/middle-income countries. Pooled specificity for EPTB was 82% (95% CI 7887%) for QFT-G or GIT and 68% (95% CI 6473%) for T-SPOT. Pooled sensitivity of TST from four studies in high-income countries was lower than that of IGRAs. T-SPOT was more sensitive in detecting EPTB than QFT-G or GIT and TST. However, both IGRAs and TST have similar specificity for EPTB. IGRAs have limited value as diagnostic tools to screen and rule out EPTB, especially in low/middle-income countries. The immune status of patients does not affect the diagnostic accuracy of IGRAs for EPTB.