ABSTRACT
BACKGROUND: An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed. METHODS: A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24). RESULTS: A total of 497 participants, ages 6-83, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95%CI 28-37) when compared to Xpert MTB/RIF Ultra, 29% (95%CI 25-34) when compared to a bacteriological confirmation, and 22% (95%CI 18-26) when compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95%CI 74-89) when compared to Xpert MTB/RIF Ultra, 84% (95%CI 75-90) when compared to a bacteriological confirmation, and 54% (95%CI 44-64) when compared to a composite clinical diagnosis. CONCLUSIONS: While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.