Meningitis

Helicobacter pylori

Intensive care medicine

Metabolite

Biology

Mycobacterium tuberculosis

Clinical trial

Clarithromycin

Rifabutin

Immunology

Pediatrics

Bioinformatics

Metabolome

Tuberculosis

Internal medicine

Medicine

Tuberculous meningitis

GeneXpert MTB/RIF

Metabolomics

Pathology

The Lancet Neurology

<h2>Summary</h2> Tuberculous meningitis is a devastating brain infection that is caused by <i>Mycobacterium tuberculosis</i> and is notoriously difficult to diagnose and treat. New technologies characterising the transcriptome, proteome, and metabolome have identified new molecules and pathways associated with tuberculous meningitis severity and poor outcomes that could offer novel diagnostic and therapeutic targets. The next-generation GeneXpert MTB/RIF Ultra assay, when used on CSF, offers diagnostic sensitivity for tuberculous meningitis of approximately 70%, although it is not widely available and a negative result cannot rule out tuberculous meningitis. Small trials indicate that clinical outcomes might be improved with increased doses of rifampicin, the addition of linezolid or fluoroquinolones to standard antituberculosis therapy, or treatment with adjunctive aspirin combined with corticosteroids. Large phase 3 clinical trials are underway worldwide to address these and other questions concerning the optimal management of tuberculous meningitis; these studies also form a platform for studying pathogenesis and identifying novel diagnostic and treatment strategies, by allowing the implementation of new genomic, transcriptomic, proteomic, and metabolomic technologies in nested substudies.

Tuberculous meningitis: progress and remaining questions