Diagnostic and quantitative performance of the GeneXpert Mycobacterium tuberculosis/resistance to rifampin assay on pulmonary and extrapulmonary tuberculosis samples

Abstract

INTRODUCTION: No study has simultaneously assessed the diagnostic and quantitative performance of the GeneXpert Mycobacterium tuberculosis/resistance to rifampicin (MTB/RIF) assay on pulmonary and extrapulmonary samples processed in an Indian laboratory. We examined this to assess if GeneXpert can complement existing diagnostic facilities.METHODS: The performance of GeneXpert and acid-fast microscopy were evaluated against culture in 455 pulmonary and 69 extrapulmonary specimens. Their sensitivity, specificity, predictive values and area under the curve (AUC) were estimated. GeneXpert cycle threshold (Ct) cut-offs were also computed to assess their utility in predicting smear positivity and time to culture positivity (TTCP).RESULTS: GeneXpert was significantly more sensitive (100% vs. 84.4%; P < 0.001) and nearly as specific (94.8% vs. 96.7%; P = 0.344), with a greater AUC (0.97 vs. 0.91; P = 0.002) than acid-fast microscopy. It was sensitive and specific for pulmonary (100%; 94.1%) and extrapulmonary (100%; 96.5%) samples, and 100% sensitive for sputum, bronchoalveolar lavage (BAL), lymph node aspirates, pleural fluid, pus and urine. It detected smear-negative specimens with 100% sensitivity. GeneXpert Ct was inversely correlated with sputum smear grading (ρ = −0.66) and positively with TTCP (ρ =0.70). Mean Ct cut-offs of 21.4, 20.1 and 24.6 predicted smear positivity with maximum sensitivity and specificity in sputum, BAL and extrapulmonary samples, respectively. Rifampicin resistance was seen in 17% of samples.CONCLUSIONS: GeneXpert can be a reliable first-line diagnostic for both pulmonary and extrapulmonary samples. It can effectively detect smear-negative and paucibacillary patients, and estimate smear positivity and bacillary burden. This can help Indian laboratories to detect cases early and interrupt community transmission.