Improving diagnosis and treatment of TB meningitis (360G-Wellcome-210772_Z_18_Z)

Tuberculous meningitis (TBM), the most severe form of TB, affects the brain and spine. Over 100,000 children and adults suffer from TBM yearly, of which up to a half die and a quarter are left disabled. These appalling outcomes are driven by: Delay in diagnosis - there is no reliable test; Suboptimal antibiotic treatment – rifampicin, the key antibiotic, doesn’t reach therapeutic levels in spinal fluid. I will address these challenges through TBM research based in Uganda. We will perform lumbar puncture (spinal tap) on ~240 people presenting to hospital with symptoms of meningitis. We will evaluate an exciting new test ‘Xpert MTB/Rif Ultra’ on spinal fluid, potentially a fast and reliable fully-automated way of diagnosing TBM. Persons with TBM will be invited to join a clinical trial (RIFT trial). Participants will be randomly allocated to one of three groups receiving different rifampicin doses. We will then measure levels of rifampicin in blood, spinal fluid, and brain tissue (among deaths) to determine whether target levels are reached. We will also study other important clinical factors.