Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding.

Aims: We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF ("Xpert") and Xpert MTB/RIF Ultra ("Ultra") using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique.

Methods: Single respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificity their recategorisation to negative (in all and just among those previously treated individuals).

Results: 1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90-0.98) 0.88 (96% CI 0.82-0.93); p<0.001) and among smear-negative patients (0.84 (96% CI 0.71-0.93) 0.63 (96% CI 0.48-0.76)). Ultra's specificity was lower than Xpert's (0.96 (96% CI 0.95-0.97) 0.98 (96% CI 0.97-0.99); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI 0.22-0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12 out of 252) 2.7% (seven out of 252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort.

Conclusion: These results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios.