Evaluating the Cepheid Xpert TB/LTBI Research-Use-Only Assay for Detection of Active and Latent <i>Mycobacterium tuberculosis</i> Infection

BACKGROUND: Accurate non-sputum tests are essential for improving tuberculosis (TB) detection. We report the first evaluation of the Xpert TB/LTBI assay (research-use-only, Cepheid, USA), which detects nine Mycobacterium tuberculosis antigen-stimulated mRNA targets from blood. METHODS: We enrolled individuals ≥12 years with presumptive TB from clinics in Uganda and Vietnam. All participants underwent sputum- (liquid culture; Xpert MTB/RIF Ultra) and blood-based (Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]) testing. Participants were classified as having active TB (positive sputum results), latent TB infection (LTBI; positive QFT-Plus with negative sputum results), or no TB infection. Diagnostic accuracy for active TB (primary analysis) and of a two-step algorithm that first predicted TB infection (active TB or LTBI) and then distinguished active TB from LTBI was assessed using logistic regression and receiver operating characteristic analysis. RESULTS: Among 214 participants included, 56.5% were male, 9.3% were living with HIV, 29.0% had active TB, and 31.8% had LTBI. Xpert TB/LTBI area under the curve (AUC) was 0.92 (95% CI 0.88-0.96) for identifying active TB, and sensitivity was 93.5% (95% CI 84.6-97.5) and specificity 76.3% (95% CI 69.0-82.4) at a cut-point that achieved ≥90% sensitivity. In the two-step algorithm, Xpert TB/LTBI had high accuracy for identifying TB infection in the first step, but accuracy was lower for distinguishing active TB from LTBI in the second step. CONCLUSIONS: Xpert TB/LTBI exceeded World Health Organization (WHO)-recommended minimum accuracy targets for a TB screening test. However, further refinement is needed to improve its ability to distinguish active TB from LTBI.