Tuberculous meningitis

Key Points Tuberculous meningitis (TBM) causes death and disability, with especially high rates of poor outcomes in children and individuals with an HIV-1 co-infection Important risk factors for poor outcome are delayed diagnosis, delayed treatment, advanced disease, and antitubercular drug resistance Intracerebral and spinal pathology in TBM is mediated by a dysregulated inflammatory response that contributes to meningitis, tuberculoma formation, arteritis, obstruction of cerebrospinal fluid (CSF) flow, and vascular complications including stroke Diagnosis of TBM is insensitive and laborious; clinical scoring algorithms are imperfect and few rigorous evaluations of diagnostics have been performed Multidrug antitubercular antibiotic therapy is the mainstay of treatment; however, CSF penetration is probably a major limitation of these therapies, and evidence supporting dosage and treatment combinations is weak The supportive management of TBM complications, which include hyponatraemia, hydrocephalus, hypoxic brain damage and infarction, is poorly understood and researched, but is vital to outcome Tuberculous menigitis (TBM) presents a major health burden around the world, especially in individuals with concomitant HIV infection, in whom mortality is nearly 50%. Here, members of the TBM International Research Consortium summarize our current understanding of TBM pathogenesis, diagnosis and management, and discuss key avenues for future research. Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood–brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies — including corticosteroids, aspirin and thalidomide — has not been extensively explored. To address this deficit, two expert meetings