Project: Evaluation of new biomarker-based approaches for improving the diagnosis of childhood tuberculous meningitis

Acronym	TBMBIOMARKERS (Reference Number: TMA2018SF-2470)
Duration	01/11/2019 - 31/10/2024
Project Topic	The rapid diagnosis of tuberculosis (TB) in children remains a serious challenge owing to limitations in the existing diagnostic tests. TB meningitis (TBM), an extrapulmonary form of TB, is the most severe manifestation of paediatric TB. TBM results in high morbidity and mortality in children, despite the availability of chemotherapy, mainly due to diagnostic delay. Most tests required for proper TBM diagnosis including analysis of cerebrospinal fluid (CSF) and brain imaging are not available in resource-limited settings e.g., in most of Africa including South Africa. New tests for TBM are urgently needed. The main goal of this proposal is to develop a point-of-care (POC) diagnostic test for TBM, based on CSF and bloodbiomarkers. This will be done in collaboration with the Engineering Faculty at Stellenbosch University (SU). Aim 1: Evaluate the diagnostic potentials of 51 host inflammatory biomarkers that we recently identified in CSF and blood samples from children with suspected meningitis in a repository of 100 stored CSF and serum samples using a multiplex platform. After statistical analysis including multi-marker modelling by linear discriminant analysis, random forest, and other modelling techniques, we will select the best combination of up to four biomarkers for incorporation into the prototype diagnostic test (Aim 2). Aim 2: Incorporate the best performing CSF and serum biomarkers into a novel, patented biosensor-based POC diagnostic test, developed at the Engineering Faculty, SU. We will develop a multibiomarker prototype test for detecting up to 4 biomarkers in serum or CSF. Aim 3: Evaluate the newly developed POC test on 300 children prospectively. This will be done at the Tygerberg Academic Hospital. The diagnostic yield of the POC test will be compared to the routine diagnostic tests. This project will bring together a multidisciplinary team of engineers, paediatric neurologists, and immunologists and will train at least two Masters and two PhD students and will equip the applicant with important tools required for leading a multidisciplinary team, thus enabling him to grow as a research leader.
Network	EDCTP2
Call	Senior Fellowships 2018

Project partner

Number	Name	Role	Country
1	Stellenbosch University	Coordinator	South Africa