Our project workplan was designed to 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 was 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 was divided into the following six work packages:
WP1 included all activities to refine the biomarker signature on the MBT strip for global application. The work package also covered 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) were 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) were evaluated in parallel with ELISA and array technologies (Luminex and MSD). The smallest signature reaching 90%/70% Sn/Sp according to WHO TPP was to be implemented on the MBT platform and appropriate MBT strips were produced for evaluation in work package 2 in a large prospective study on fresh fingerstick blood.
WP2 enrolled 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 were 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 was a non-interventional clinical trial.
WP3 concerned clinical and laboratory data capturing into clinical trial databases, data management and analysis. State-of-the-art database practices were in place at all three African sites that participate in the clinical trial. There was an emphasis on data security, integrity and participant confidentiality. Analysis of the new data sets derived from WP2 focused on biomarker performance, including selection of the best global biosignatures and development of diagnostic algorithms to be incorporated into the handheld readers to allow rapid determination of risk for active TB.
WP4 concerned capacity development and networking and was interwoven with WP1 and WP2 activities. The focus was 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 supported individuals to achieve their full potential. Students and study staff were exposed to the multiple networks that the senior TriageTB investigators were already part of.
WP5 supported and facilitated communication about the project, dissemination of its results, and helped prepare the grounds for the optimal uptake and exploitation of project outcomes. Activities included 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 was the effective management of the project. It included the implementation of all necessary support mechanisms to enable a smooth project workflow and ensured that all contractual commitments were met in time.
