Project: Field evaluation of a point-of-care triage test for active tuberculosis

Acronym	Triage TB (Reference Number: RIA2018D-2499)
Duration	01/10/2019 - 30/09/2023
Project Topic	There is insufficient reduction in the number of tuberculosis (TB) cases to reach End TB Strategy milestones. Underdiagnosis leads to a 36% gap between reported and estimated cases. Current TB diagnostics are not accessible enough in high TB incidence, resource-limited areas. A point-of-care (POC), rapid, laboratory-free triage test for TB can potentially transform the TB diagnostic landscape. Overall objectives: to field-validate a point-of-care triage test for active TB. We have discovered host serum biosignatures in previous EDCTP-funded projects, which can be implemented on dipstick-type rapid POC tests. Multi-biomarker tests (MBT) are based on a rapid and quantitative POC platform, consisting of a single lateral flow (LF) strip, which measures individual concentrations of multiple biomarkers using upconverting reporter particles (UCP). The assay has proceeded to testing fingerstick capillary blood (FSB) and can be performed in a laboratory-free manner, yielding results within 30 minutes. Test sensitivity is >90% and specificity 75%, with a negative predictive value of 96%, suitable as rule-out test to identify those at highest risk for TB for confirmatory testing (i.e. avoiding up to 75% of negative GeneXpert tests). A triage test-aided and streamlined diagnostic process would yield results quickly, would lead to more appropriate GeneXpert use and would reduce transmission rates and subsequent morbidity and mortality. Achievement of objectives: We propose to validate the performance of the biosignature on samples from Asia, South America and Eastern Europe for universal applicability. We will also field-test out current best small signature MBT on 100 patients in Africa on FSB. Subsequently, the design-locked FSB MBT assay will be prospectively validated on samples from 600 newly recruited participants from Southern, West and East Africa in peripheral health care settings in a laboratory-free manner. The addition of FIND to our established TB diagnostic consortium adds exceptional assay development expertise and extensive know-how of the performance requirements and steps needed to enter the regulatory pathway for a new diagnostic and eventually for commercialization and delivery in low- and middle-income countries. The proposed work will also have strong capacity development and networking components for African scientists. Relevance to the call: Our proposal builds on extensive experience gained during previous EDCTP-funded projects, is based on strong biomarker data, an advanced user-friendly, rapid, multiplex test device and implementation expertise supported through EDCTP2. It addresses the important topic of a POC triage test for active TB to significantly speed up and streamline diagnostic approaches in resource-limited settings. Keywords: Tuberculosis, Diagnostics, Triage, host markers
Network	EDCTP2
Call	Diagnostic tools for poverty-related diseases

Project partner

Number	Name	Role	Country
1	Stellenbosch University	Coordinator	South Africa
2	ACADEMIC HOSPITAL LEIDEN	Partner	Netherlands
3	Foundation for Innovative New Diagnostics	Partner	Switzerland
4	LINQ Management GmbH	Partner	Germany
5	London School of Hygiene and Tropical Medicine	Partner	United Kingdom
6	Makerere University	Partner	Uganda