Improved Detection of Extrapulmonary and Paucibacillary Pulmonary Tuberculosis by Xpert MTB Host Response in a Tuberculosis Low-Endemic, High-Resource Setting.

BACKGROUND

The Xpert MTB Host Response (MTB-HR) assay has reached World Health Organization (WHO) test targets for pulmonary tuberculosis (PTB) with high bacillary loads. We investigated the contribution of MTB-HR as a nonsputum, near point-of-care diagnostic method in other prioritized groups, such as extrapulmonary tuberculosis (EPTB) and paucibacillary PTB.

METHODS

Individuals with presumed tuberculosis disease were prospectively included in Stockholm, Sweden (n = 307), and underwent MTB-HR venous and capillary testing in parallel. Clinical characterization was based on symptoms, microbiological results (microscopy, polymerase chain reaction [PCR], and culture), radiological assessment, and a panel of biochemical tests. Receiver operating characteristic analysis was performed to calculate cut-offs for maximized sensitivity and specificity, including WHO targets for screening and diagnostic tests.

RESULTS

MTB-HR performed equally well in microbiologically confirmed PTB (area under the curve [AUC], 0.84 [95% confidence interval {CI}, .78-.90]; n = 69) and EPTB (AUC, 0.82 [95% CI, .75-.90]; n = 34). Based on Youden index cut-offs, the negative predictive value (NPV) was high both in PCR-negative PTB (-1.27, NPV 94%) and in EPTB (-1.58, NPV 95%) and fulfilled the minimum target product profile sensitivity requirement for confirmed EPTB. In individuals without tuberculosis (n = 204), the majority had pulmonary infections. There was a close to perfect correlation between venous and capillary samples (r = 0.97, P < .001).

CONCLUSIONS

Capillary Xpert MTB-HR improves detection of sputum PCR-negative, culture-verified PTB and is promising as a rule-out test in EPTB. MTB-HR score and bacterial burden were highly correlated. We suggest a graded MTB-HR score as more clinically relevant than a binary result.