Feasibility, accuracy, and effect of a rapid point-of-care serological test (SeroSelectTB) to identify presumptive pulmonary TB patients for confirmatory testing in Ethiopia, South Africa, and Tanzania: a multicenter, open-label, parallel-group, randomized, controlled trial.

Abstract

Background: The feasibility, accuracy and effect of a rapid point-of-care serological test, SeroSelectTB, was assessed to identify presumptive pulmonary tuberculosis (TB) patients at primary healthcare facilities in Ethiopia, South Africa, and Tanzania.

Methods: We conducted a multicenter, open-label, parallel-group, randomized controlled trial from 2020 through 2025. Adults were recruited at selected healthcare facilities with symptoms suggestive of active pulmonary TB. Eligible participants were randomized to standard-of-care (SOC, routine clinical investigation) or intervention (screening with SeroSelectTB) study arms. Our primary outcome was time-to-treatment initiation, calculated as the time from enrollment to treatment initiation. Data were analyzed using intention-to-treat. This trial was registered with Clinicaltrials.gov (NCT04752592) on 2 April 2021.

Findings: Between September 21, 2021, and June 19, 2025, 9097 presumptive pulmonary TB patients were randomly assigned to the SOC (n = 4545) and intervention (n = 4552) study arms. Pulmonary TB was confirmed in 1087 (11.5%) participants (SOC = 527; Intervention = 560). SeroSelectTB was associated with a shorter time-to-treatment initiation compared to SOC (crude hazard ratio (HR): 1.20; 95% CI: 1.06-1.35). The median time-to-treatment initiation among patients with confirmed TB in South Africa, Ethiopia, and Tanzania was 1, 3 and 3 days in the intervention arm compared to 2, 5, and 6 days in SOC arm, respectively. The SeroSelectTB sensitivity was 75.9% and specificity 49.5% in a high HIV setting, whereas sensitivity and specificity were 68.8% and 76.0% among HIV negative participants, respectively.

Interpretation: SeroSelectTB reduces the time-to-treatment initiation for pulmonary TB patients and could be considered for integration into TB testing algorithms at primary healthcare facilities. Rapid tests with a lower than optimal specificity can serve an important role as triage tools when adequate sensitivity is demonstrated.

Funding: This project (RIA2018D-2493, SeroSelectTB) is part of the EDCTP2 Programme supported by the European Union with funding from UK National Institute for Health and Care Research (NIHR). NIHR is funded by the Department of Health and Social Care. The NIHR Global Health Research portfolio supports high-quality applied health research for the direct and primary benefit of people in low- and middle-income countries, using international development funding from the UK Government. The views expressed in this publication are those of the authors and not necessarily those of the EDCTP, NIHR or the UK government.