Division of Molecular Biology and Human Genetics


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This project TMA2018SF-2470 is part of the EDCTP2 programme supported by the European Union​.

PROJE​CT: Evaluation of new biomarker-based approaches for improving the diagnosis of childhood tuberculous meningitis (TBMBIOMARKERS) 



Tuberculous meningitis (TBM) is the most common type of bacterial meningitis in the Western Cape. The tuberculosis (TB) incidence in South Africa has risen from 301 new cases/100,000 population in 1990 to 948 new cases/100,000 population in 2007. World-wide, the incidence of the disease has fallen by an average of 1.5% per year since 2000, but the incidence of the disease in South Africa is still 834 per 100, 000 population as indicated by recent World Health Organization (WHO) reports.

TBM represents the most severe manifestation of TB with high morbidity and mortality, despite adequate anti-TB therapy. This is mainly the result of delayed diagnosis and initiation of appropriate therapy. Despite ongoing research, early, cost-effective diagnostic tools are lacking. Demonstration of acid-fast bacilli and/or culture of Mycobacterium tuberculosis (Mtb) from cerebrospinal fluid (CSF) represents the gold standard for diagnosing TBM. Unfortunately, the sensitivity of both these tests is low. The diagnosis of TBM is therefore based on a combination of clinical, laboratory and radiological findings. 

In a recently patented and published study conducted by our research group, we investigated the usefulness of some of the host markers that we identified in our previous studies as diagnostic candidates for TBM. A three-marker CSF biosignature comprising of IL-13, VEGF and cathelicidin LL-37, diagnosed TBM with a sensitivity of 52%, specificity of 95%, with positive and negative predictive values of 91% and 66% respectively. However, none of these studies have been conducted specifically in children with TBM and it is not known, whether simple blood RNA signatures such as the ones already identified for pulmonary TB might be useful in this disease. 

The overall aim of the current study is therefore to assess the utility of ex vivo blood and CSF based host cytokine biomarkers and RNA transcripts as diagnostic tools for TBM. We are specifically validating the diagnostic accuracy of our previously established 3-marker TBM CSF biosignature as well as evaluating other new host markers which have shown potential in adult studies but which have not been investigated in children yet. 

At the conclusion of the study, the validated blood-based biosignatures shall be ready for incorporation into rapid, point-of-care diagnostic tools.