Diagnostic Accuracy Of The Xpert (R) Mtb/Rif Cycle Threshold Level To Predict Smear Positivity: A Meta-Analysis

SETTING: Xpert (R) MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, C-T) correlates with the bacillary burden.OBJECTIVE: To investigate the association between Xpert C-T values and smear status through a systematic review and individual-level data meta-analysis.DESIGN: Studies on the association between C-T values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated.RESULTS: Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off C-T values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%C1 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples.CONCLUSION: Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off C-T values of 27.7 or 31.8 would not replace smear microscopy. How C-T values compare with smear microscopy in predicting infectiousness remains to be seen.