DIAGNOSTIC PERFORMANCE OF MOLECULAR AND CONVENTIONAL METHODS FOR EXTRAPULMONARY TUBERCULOSIS DETECTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background: Extrapulmonary tuberculosis (EPTB) represents a significant proportion of the global tuberculosis burden and remains diagnostically challenging because of its paucibacillary nature, diverse clinical presentations, and difficulty in obtaining representative specimens. Conventional drug susceptibility testing (DST), Line Probe Assay (LPA), and GeneXpert MTB/RIF are widely used diagnostic modalities for tuberculosis detection and drug-resistance identification; however, their comparative diagnostic performance in EPTB remains incompletely understood. Aim: To compare the diagnostic accuracy of conventional DST, Line Probe Assay, and GeneXpert MTB/RIF in extrapulmonary tuberculosis through a systematic review and meta-analysis. Materials and Methods: A systematic search of PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases was performed for studies published between January 2010 and December 2025. Studies evaluating conventional DST, LPA, and/or GeneXpert MTB/RIF in extrapulmonary tuberculosis specimens were included. Data regarding sensitivity, specificity, diagnostic odds ratio (DOR), and turnaround time were extracted. Quality assessment was performed using the QUADAS-2 tool. A random-effects meta-analysis was conducted to calculate pooled estimates of diagnostic performance. Results: A total of 42 studies comprising 11,784 extrapulmonary specimens were included in the meta-analysis. GeneXpert MTB/RIF demonstrated the highest pooled sensitivity of 81.3% (95% CI: 76.4–85.2) and specificity of 97.8% (95% CI: 95.9–98.8), with an area under the summary receiver operating characteristic curve (AUC-SROC) of 0.93. Line Probe Assay showed pooled sensitivity and specificity of 74.6% and 98.5%, respectively, while conventional DST demonstrated lower pooled sensitivity of 61.8% despite maintaining highest specificity of 99.1%. Subgroup analysis revealed highest diagnostic accuracy of GeneXpert MTB/RIF in lymph node aspirates and tissue biopsy specimens. For rifampicin resistance detection, GeneXpert MTB/RIF demonstrated pooled sensitivity of 92.1% with significantly shorter turnaround time (~2 hours) compared with conventional DST (3–8 weeks). Moderate heterogeneity was observed across included studies. Conclusion: GeneXpert MTB/RIF demonstrated superior overall diagnostic performance compared with Line Probe Assay and conventional DST in extrapulmonary tuberculosis. Its rapid turnaround time, high sensitivity, and excellent specificity make it an effective frontline diagnostic tool for EPTB. Conventional DST remains essential for comprehensive phenotypic drug susceptibility assessment, while molecular assays substantially improve early diagnosis and therapeutic decision-making.