Diagnostic accuracy of the new Xpert MTB/RIF Ultra for tuberculosis disease: A preliminary systematic review and meta-analysis

Abstract

Objectives: The re-engineered Xpert MTB/RIF Ultra (Xpert Ultra) assay was developed due to the poor sensitivity of the Xpert MTB/RIF assay for the detection of tuberculosis (TB) in some conditions. This new assay has been recommended by the World Health Organization since 2017. A systematic review and meta-analysis was performed to assess the accuracy of Xpert Ultra for the detection of TB and rifampicin (RIF) resistance. Methods: The Medline (via PubMed), Embase (via OvidSP), ISI Web of Science, Cochrane Central Register of Controlled Trials, and Scopus databases were screened for original articles. Summary sensitivity and specificity were calculated with a bivariate mixed-effects model. A Fagan nomogram was used to assess the clinical utility. The sources of heterogeneity were investigated by meta-regression and subgroup analyses. Results: Sixteen studies were identified. The summary diagnostic accuracy of Xpert Ultra for the diagnosis of TB were as follows: sensitivity 87.2% (95% confidence interval (CI) 82.5–90.8%) and specificity 96.5% (95% CI 95.1–97.5%). For the detection of RIF resistance, sensitivity was 95.1% (95% CI 91.6–97.2%) and specificity was 98.9% (95% CI 97.6–99.5%). Meta-regression showed that the category of population, TB prevalence, reference standard, sample state, sample type, and study design attributed to the heterogeneity. Subgroup analyses found good performance of Xpert Ultra in settings with a low TB burden. Conclusions: As a rapid and highly sensitive test for the detection of TB and simultaneous detection of RIF resistance, Xpert Ultra exhibits a viable alternative in sensitivities in both pulmonary TB (PTB) and extrapulmonary TB (EPTB), which was proved to be higher than Xpert in the comparative analysis, and also shows a good performance in the detection of RIF resistance. Additional studies with comparative consistency tests are needed to precisely describe this finding for more forms of EPTB.