Improving technology to diagnose tuberculous meningitis: are we there yet?

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.