Diagnostic Accuracy of Xpert MTB/RIF and Line Probe Assays for Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

Abstract

Background: Rapid and accurate detection of drug-resistant tuberculosis (DR-TB) is essential to guide effective therapy and prevent transmission. Molecular assays such as Xpert MTB/RIF and Line Probe Assays (LPAs) are widely implemented for detecting Mycobacterium tuberculosis complex and mutations associated with rifampicin (RIF) and isoniazid (INH) resistance. Despite their widespread use, variations in diagnostic performance across settings warrant a comprehensive synthesis of global evidence.

Methods: A systematic review and meta-analysis were conducted according to PRISMA-DTA guidelines. Electronic databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched from inception to March 2024. Studies evaluating Xpert MTB/RIF or LPAs against a reference standard (phenotypic drug susceptibility testing or gene sequencing) were included. Two reviewers independently assessed study quality using QUADAS-2 and extracted data to construct 2×2 tables. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios (DORs) were calculated using a bivariate random-effects model, and HSROC curves were generated to summarize diagnostic performance.

Results: Seventy-four studies encompassing 39,184 clinical specimens were included. For Xpert MTB/RIF, the pooled sensitivity and specificity for RIF resistance detection were 93.1% (95% CI: 90.4–95.1) and 98.0% (95% CI: 96.2–98.9), respectively (AUC = 0.989). For LPAs, pooled sensitivity and specificity for RIF resistance were 89.7% (95% CI: 86.2–92.5) and 97.8% (95% CI: 95.6–98.9), while for INH resistance they were 88.9% (95% CI: 85.3–91.8) and 97.1% (95% CI: 94.8–98.5) (AUC = 0.982). Both assays exhibited excellent specificity and high diagnostic accuracy, with minimal publication bias.

Conclusion: Both Xpert MTB/RIF and LPAs demonstrate excellent diagnostic accuracy for detecting drug-resistant tuberculosis. Xpert provides rapid, near-patient detection of rifampicin resistance, while LPAs offer broader profiling by simultaneously identifying isoniazid resistance. Integrating both assays within national diagnostic algorithms can enhance early detection, optimize treatment initiation, and strengthen global DR-TB control efforts.