Our project workplan will allow for refinement of a triage test for active TB, prior to the validation of the best locked-down signature on a point-of-care, lateral flow MBT format in primary health care clinics in Africa. The overall goal of the proposal is to refine, develop and validate a prototype point-of-care triage test for active TB that can be performed on finger stick blood (FSB) in a laboratory-free manner and that meets or exceeds WHO-endorsed target product profiles for such a triage test. To achieve this goal, the project work plan is divided into the following six work packages:
WP1 includes all activities to refine the biomarker signature on the MBT strip for global application. The work package also includes activities needed to identify potentially better performing biomarkers which can replace less contributing ones from the African biomarker signature established for MBT during ScreenTB. For this purpose, sera (provided by FIND) are available from cohorts of TB patients and ORD suggestive of TB collected outside Africa. Basic MBT strips comprising a 3-marker signature and strips with an expanded 6-marker African signature (used in ScreenTB) will be evaluated in parallel with ELISA and array technologies (Luminex and MSD). The smallest signature reaching 90%/70% Sn/Sp according to WHO TPP that can be implemented on the MBT platform will be locked down and appropriate MBT strips will be produced for evaluation in work package 2 in a large prospective study on fresh fingerstick blood.
WP2 will enrol adult participants who present at primary health care clinics in The Gambia, South Africa and Uganda, with symptoms compatible with active TB. The diagnostic performance of MBT tests will be compared to the final composite diagnostic gold standard of clinical findings, CXR, sputum microbiology (smear, GeneXpert and culture) and treatment response, according to established case definitions. The study will be a non-interventional clinical trial.
WP3 concerns clinical and laboratory data capturing into clinical trial databases, data management and analysis. State-of-the-art database practices are in place at all three African sites that participate in the clinical trial. There will be an emphasis on data security, integrity and participant confidentiality. Analysis of the new data sets derived from WP2 will focus on biomarker performance, including selection of the best global biosignatures and development of diagnostic algorithms that can be incorporated into the handheld readers to allow rapid determination of risk for active TB.
WP4 concerns capacity development and networking and will be interwoven with WP1 and WP2 activities. The focus will be on laboratory and clinical trial skills, exposure to assay development actions, formal degree courses (MSc and PhD students at the African sites) and skills workshops for both scientific as well as administrative staff. Mentoring and a focus on individual career development planning will support individuals to achieve their full potential. Students and study staff will be exposed to the multiple networks that the senior TriageTB investigators are already part of.
WP5 provides all necessary support to facilitate communication about the project, effective dissemination of its results, and will prepare the grounds for the optimal uptake and exploitation of project outcomes. Activities will include guidance regarding the final format of the multiplex test in view of global acceptance (WHO interface), future commercialization, upscaling, and involvement of potential manufacturers.
The aim of WP6 is the effective management of the project. It will include the implementation of all necessary support mechanisms to enable a smooth project workflow and ensure that all contractual commitments will be met in time.