EVALUATION OF DRUG RESISTANCE DETECTION BY GENEXPERT MTB/RIF, LINE PROBE ASSAY, AND CONVENTIONAL DST IN EXTRAPULMONARY TUBERCULOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background: Extrapulmonary tuberculosis (EPTB) constitutes a significant proportion of tuberculosis cases worldwide and poses major diagnostic challenges because of its paucibacillary nature and difficulty in specimen collection. The emergence of multidrug-resistant tuberculosis (MDR-TB) has further emphasized the need for rapid and accurate drug resistance detection methods. Molecular diagnostic techniques such as GeneXpert MTB/RIF and Line Probe Assay (LPA) have increasingly been utilized as rapid alternatives to conventional drug susceptibility testing (DST) for diagnosis of drug-resistant EPTB. Aim: To evaluate and compare the diagnostic performance of GeneXpert MTB/RIF, Line Probe Assay, and conventional drug susceptibility testing for detection of drug resistance in extrapulmonary tuberculosis through a systematic review and meta-analysis. Materials and Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Electronic databases including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar were searched for studies published between January 2010 and December 2025. Studies evaluating GeneXpert MTB/RIF, LPA, and conventional DST in extrapulmonary tuberculosis specimens were included. Data regarding sensitivity, specificity, diagnostic odds ratio, and resistance detection rates were extracted. Methodological quality was assessed using the QUADAS-2 tool. Meta-analysis was performed using a random-effects model. Results: A total of 38 studies comprising 8,462 extrapulmonary specimens were included in the analysis. GeneXpert MTB/RIF demonstrated pooled sensitivity and specificity of 82.4% and 97.1%, respectively, for detection of rifampicin resistance. Line Probe Assay showed higher pooled sensitivity (89.6%) and specificity (98.4%). The highest diagnostic accuracy for both assays was observed in tissue biopsy and lymph node specimens, whereas lower sensitivity was noted in pleural and ascitic fluid samples. Rifampicin-resistant tuberculosis was identified in 8.1% of cases, while multidrug-resistant tuberculosis accounted for 5.1% of cases. Conventional DST remained the reference standard but required significantly longer turnaround time compared with molecular assays. Significant heterogeneity was observed among included studies. Conclusion: Both GeneXpert MTB/RIF and Line Probe Assay demonstrate high diagnostic accuracy for rapid detection of drug resistance in extrapulmonary tuberculosis. LPA provides superior sensitivity and broader resistance profiling, whereas GeneXpert offers faster turnaround time and operational simplicity. Integration of rapid molecular diagnostics with conventional DST can substantially improve early diagnosis and management of drug-resistant extrapulmonary tuberculosis.