Performance of 2 Finger-Stick Blood Tests to Triage Adults With Symptoms of Pulmonary Tuberculosis: A Prospective Multisite Diagnostic Accuracy Study

Abstract

Background: Non-sputum-based, point-of-care triage tests for pulmonary tuberculosis could enhance tuberculosis diagnostic programs. We assessed the diagnostic accuracy of 2 finger-stick blood tests: the Cepheid 3 gene host-response cartridge (Xpert-HR), which measures 3 host messenger RNA transcripts, and the 3-host protein multibiomarker test (MBT).

Methods: We performed a prospective diagnostic accuracy study of consecutive participants with symptoms compatible with pulmonary tuberculosis in The Gambia, South Africa, Uganda, and Vietnam. A composite reference standard for active pulmonary tuberculosis incorporated chest radiography, symptom resolution, and sputum microbiological test results. A training-test set approach was used to evaluate test cutoff specificities at 90% sensitivity.

Results: Between 1 November 2020 and 1 May 2023, we screened 1262 participants aged 12-70 years with cough lasting >2 weeks and another symptom suggestive of tuberculosis. Of those who were classifiable by reference tests, 1154 participants had evaluable Xpert-HR results and 961 had evaluable MBT results. Xpert-HR had an area under the receiver operating characteristic (AUROC) curve of 0.92 at a cutoff of -1.275 or below, with a sensitivity of 92.8%, specificity of 62.5%, positive predictive value of 47.9%, and negative predictive value of 95.9%. The MBT had an AUROC of 0.91 at a cutoff of ≥0.42, with a sensitivity of 91.4%, specificity of 73.2%, positive predictive value of 52.0%, and negative predictive value of 96.4%.

Conclusions: Our results show that both Xpert-HR and the MBT are promising non-sputum-based point-of-care tests. The MBT met the World Health Organization target product profile for a triage test, which suggests it should be further developed.

Keywords: Biomarkers; diagnosis; point-of-care; triage; tuberculosis.