Head-to-head comparison of the diagnostic accuracy of Xpert MTB/RIF and Xpert MTB/RIF Ultra for tuberculosis: a meta-analysis

Background: Tuberculosis (TB) diagnosis has significantly improved since the introduction of the automated molecular test Xpert MTB/RIF (Xpert) and the new version Xpert MTB/RIF Ultra (Ultra) that detectMycobacterium tuberculosis. Due to the rapidly widespread use of Xpert and Ultra, we conducted a meta-analysis to compare the performances of Xpert and Ultra in diagnosing TB and discuss the advantages and limitations of these two tests. Methods: Web of Science, Medline (viaPubMed), Embase (viaOvidSP), the Cochrane Central Register of Controlled Trials and Google Scholar (up to April 2020) were searched for relevant studies. The diagnostic performance of Xpert and Ultra for TB was determined using a bivariate random-effects regression model. The sources of heterogeneity were exploredviameta-regression and subgroup analyses. Results: Of 19 studies that examined a total of 5855 samples, the pooled sensitivity and specificity of Xpert in TB diagnosis were 0.69 (95% CI: 0.57-0.78) and 0.99 (95% CI: 0.98-0.99), respectively. However, the pooled sensitivity and specificity of Ultra in TB diagnosis were 0.84 (95% CI: 0.76-0.90) and 0.97 (95% CI: 0.96-0.98), respectively. Regardless of whether the comparisons were indirect or direct, Ultra was consistently found to be more sensitive, but with slightly lower specificity than Xpert in diagnosing TB. Conclusions: Compared with Xpert, Ultra had higher sensitivity but slightly lower specificity for the diagnosis of TB disease. The excellent upgrade in sensitivity of the Ultra test was particularly relevant in subjects with paucibacillary TB including tuberculous pleurisy, tuberculous meningitis and paediatric TB.