Comparative evaluation of Xpert MTB/RIF and the new Xpert MTB/RIF ultra with respiratory and extra-pulmonary specimens for tuberculosis case detection in a low incidence setting

Background: The Xpert MTB/RIF assay (Xpert) is an automated molecular test for the detection of tuberculosis and rifampin resistance (RIF-R), but it lacks sensitivity in smear-negative samples and some limitations in determination of RIF-R have also been reported. The new Xpert MTB/RIF Ultra (Ultra) was developed to overcome these limitations. We aimed to compare Ultra and Xpert diagnostic accuracy setting culture and drug susceptibility testing as reference standards. Methods: A retrospective analysis was performed on 359 consecutive, respiratory (269) and extrapulmonary (90) specimens collected from 340 patients investigated for TB along a two-year period. Patients presenting at primary health-care centres and hospitals were recruited on the basis of symptoms and abnormal X-ray imaging. One-hundred seventy-four subjects were identified to have active tuberculosis by culture and 2 were MDR. Findings: Sensitivities of Ultra and Xpert were 87% and 75% for the 48 individuals with smear-negative and culture-positive respiratory TB (difference of 12%, 95% CI 3 to 21); 95% and 72% for the 40 individuals with smear-negative and culture-positive extrapulmonary disease (22%, 95% CI 10 to 34); and 95% and 86%, respectively, across all 174 individuals with culture-positive samples (8.5%, 95% CI 4.5 to 12.5). Specificities of Ultra and Xpert for tuberculosis case detection were 98% and 100% (–2.0%, 95% CI –4.3 to +0.3). Ultra and Xpert performed equal in detecting RIF-R. Interpretation: Sensitivity of Ultra was superior to that of Xpert in all categories of clinical samples. However, improved sensitivity was associated with a modest reduction in specificity. Keywords: Tuberculosis, Case detection, Nucleic acid amplification, Xpert MTB/RIF Ultra, Sensitivity, Specificit