Systematic review of interferon-gamma release assays in tuberculosis: focus on likelihood ratios.

BACKGROUND Clinical roles of QuantiFERON-TB Gold (QFT-G)/Gold in-Tube (QFT-G-IT) and T-SPOT.TB in tuberculosis require clarification. METHODS MEDLINE and EMBASE were searched for relevant English papers. Summary estimates of likelihood ratios (LR) of QFT-G/QFT-G-IT and T-SPOT.TB for latent tuberculosis infection (LTBI) and tuberculosis disease in adults were obtained by bivariate and univariate random effects meta-analyses after assessing heterogeneity. Probable ranges of prevalence for LTBI and tuberculosis disease were estimated. Critical values of positive LR (PLR) and negative LR (NLR) corresponding to a 90% certainty threshold were calculated over probable prevalence ranges. It was considered reliable to rule in when the best estimated PLR exceeds the corresponding critical value and to rule out when the best estimated NLR is less than the corresponding critical value. RESULTS 35 studies involving predominantly immunocompetent adults were identified. Based on bivariate meta-analysis, PLR (95% CI) for LTBI were 7.9 (3.6 to 17.3) for T-SPOT.TB and 48.1 (19.7 to 117.6) and 10.8 (5.3 to 21.8) for QFT-G/QFT-G-IT based on Japanese and other studies, respectively. Corresponding NLR (95% CI) were 0.10 (0.06 to 0.18), 0.11 (0.07 to 0.18) and 0.23 (0.16 to 0.32). PLR (95% CI) for tuberculosis disease were 3.6 (2.3 to 5.6) for QFT-G, 2.1 (1.1 to 4.0) for QFT-G-IT and 4.7 (2.4 to 9.1) and 2.3 (1.3 to 4.0) for T-SPOT.TB based on studies with mean or median age >47. 1 years and < or = 47.1 years, respectively. Corresponding NLR (95% CI) were 0.18 (0.12 to 0.27), 0.38 (0.22 to 0.68), 0.11 (0.06 to 0.20) and 0.20 (0.10 to 0.40). Estimated prevalence ranges were 10-55% for LTBI and 40-60% for tuberculosis disease. CONCLUSIONS At a 90% certainty threshold, LTBI is best diagnosed by QFT-G/QFT-G-IT and excluded by T-SPOT.TB or QFT-G/QFT-G-IT; none can diagnose tuberculosis disease, whereas. T-SPOT.TB can exclude tuberculosis disease among middle-aged and older patients.