Interferon-Gamma Release Assays Versus Tuberculin Skin Test for Active Tuberculosis Diagnosis: A Systematic Review and Diagnostic Meta-Analysis

Background: The world health goal of eliminating tuberculosis (TB) is heavily hinged on timely and efficient diagnosis and treatment. The interferon-γ release assays (I.G.R.A.s) can diagnose Mycobacterium tuberculosis infection and offer an alternative to the centuries-old tuberculin skin test (T.S.T.). Yet there is disagreement over replacing the T.S.T. with I.G.R.A.s as a standard tool. Objective: We aim to assess the diagnostic ability of I.G.R.A.s compared with T.S.T. for detecting active TB cases. Methods: A systematic review identified relevant studies from four databases. In the diagnostic meta-analysis conducted with OpenMeta Analyst software, we calculated the sensitivity (SN) and specificity (SP) for active TB detection via I.G.R.A. and T.S.T. methods compared to TB culture. Results included pooled estimates for SN and SP with 95% confidence intervals (CI), stratified by age, immunity, I.G.R.A. type, and T.S.T. cut-off. Results: Our meta-analysis revealed that TB diagnosis using T.S.T. showed an SN of 72.4% and SP of 79.3%, while I.G.R.A. demonstrated higher accuracy with an SN of 78.9% and SP of 85.7%. Subgroup analysis by age indicated that I.G.R.A. consistently outperformed T.S.T. in both adult and pediatric populations. Among immunocompromised individuals, T.S.T. had low SN (23%) but high SP (91.2%), whereas I.G.R.A. had higher SN (65.6%) but lower SP (81.9%). Immunocompetent subjects showed that T.S.T. had SN of 72% and SP of 87.3%, while I.G.R.A. had higher SN (82.9%) and SP (89.1%). Evaluation by I.G.R.A. type revealed that T-SPOT.GIT demonstrated a higher SN but lower SP compared to QFT-GIT. Assessing T.S.T. cut-offs, SP was highest (88.8%) at ≥15 mm, while SN peaked (71.6%) at ≥5 mm. Conclusions: I.G.R.A. consistently showed higher diagnostic accuracy than T.S.T. across most studied subgroups, indicating its potential superiority in active TB diagnosis.