Improving Technology to Diagnose Tuberculous Meningitis: Are We There Yet?

Abstract

Diagnosis of tuberculous meningitis (TBM) remains challenging due to a paucity of high-performance diagnostics. Even those that have reasonable sensitivity are not adequate to 'rule out' TBM. Therefore, a combination of clinical factors alongside microbiological, molecular, and radiological investigations are utilized, depending on availability. A low threshold for starting empiric therapy in the appropriate clinical scenario remains crucial for good outcomes in many cases. Herein, we review the current TBM diagnostics landscape with a focus on limitations frequently encountered, such as diagnostic test performance, cost, laboratory infrastructure, and clinical expertise. Though molecular technologies, particularly GeneXpert MTB/Rif Ultra, have been a step forward, diagnosis of TBM remains difficult. We also provide an overview of promising technologies, such as cerebrospinal fluid (CSF) lactate, a new lipoarabinomannan test (FujiLAM), metagenomic next-generation sequencing, and transcriptomics that may further improve our TBM diagnostic capacity and lead to better outcomes.

Keywords: TB meningitis; cerebrospinal fluid; diagnostic testing; molecular testing; tuberculosis; tuberculous meningitis.

Figure 1

Brain magnetic resonance imaging (MRI) for tuberculous meningitis (TBM) diagnosis. These are selected images from a brain MRI obtained from a patient with definite TBM showing cerebral space occupying lesions (tuberculomas) in the brainstem (A–C) and frontal lobe along with white matter ischemic changes (B).