Central nervous system (CNS) infections cause significant mortality and morbidity worldwide, especially in low- and middle-income countries (LMICs). Among all CNS infections, TB meningitis (TBM) is one of the most common causes of meningitis, with death or neurological disability recorded in half of all cases. However, the pathophysiology and causal factors of poor treatment outcomes in TBM remain unclear.

The “omics” revolution is one of the ways that can help reveal the mechanism underlying TB infection and identify biomarkers with diagnostic and therapeutic potential. Omics technologies have a broad range of studies and applications, including whole-genome or single-cell transcriptomics, single-cell RNA sequencing (scRNAseq), and metabolomics. Another potential adjunctive mode of diagnosing TBM is to detect antibodies (Abs) produced in the immune responses against Mtb antigen.

To improve our understanding of pathophysiology, diagnosis and treatment outcomes of TBM and other CNS infectious diseases, we propose to use new omics technologies, such as scRNAseq and metabolomics, and antibodies analysis in cerebrospinal fluid (CSF), urine and blood samples from TBM vs non-TBM patients admitted into the Hospital for Tropical Diseases, HCMC.

Primary objectives

To characterise cellular heterogeneity and the role of different cell populations in tuberculosis meningitis (TBM) and other central nervous system (CNS) infections pathophysiology and treatment outcomes.

Secondary objectives

– To identify urinary biomarkers by metabolomics from TBM and other CNS infections patients.

– To determine the aetiology of CNS infections by molecular biology and serological techniques

Methods

This is a 36-month prospective observational cohort study of consecutive adults admitted to the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, with suspected CNS infections.