Tuberculous meningitis
Tuberculous meningitis (TBM) is the most severe form of tuberculosis affecting >100,000 people/year with mortality approaching 50% in those co-infected with HIV. In those who survive, half are left with severe disability due to neurological sequalae, which in most cases relate to inflammation initiating neuronal injury regardless of treatment. Despite the impact of this disability on the individual and society, little understanding exists around the precise mechanisms and predictive factors underlying these neurological sequelae, most notably stroke (occurring in up to 60% of patients with TBM), cognitive impairment (present in 50% of patients at 6 months post-diagnosis) and paradoxical enlargement or development of new intracranial mass lesions (typically occurring within the first six months of treatment, but also described at a year or more).
On-going research in this area uses multi-omics approaches to understand pathogenesis of long-term morbidity in TBM. This will uncover potential therapeutic targets and inform the development of host-directed therapies and other interventions to prevent and treat neurological complications that lead to long-term morbidity and mortality in TBM. There is also a programme of research on evaluating novel diagnostics for TBM in children nested within the SURE randomized controlled trial of short intensive treatment for paediatric TB meningitis.
Outputs
- Davis AG, Rohlwink UK, Proust A, Figaji AA, Wilkinson RJ. The pathogenesis of tuberculous meningitis. J Leukoc Biol. 2019;105(2):267-80.
- Davis AG, Dreyer AJ, Albertyn C, Maxebengula M, Stek C, Wasserman S, Marais S, Bateman K, Solms M, Joska J, Wilkinson RJ, Nightingale S. Cognitive Impairment in Tuberculous Meningitis. Clin Infect Dis. 2023;76(5):842-9.
- Davis AG, Wasserman S, Stek C, Maxebengula M, Jason Liang C, Stegmann S, Koekemoer S, Jackson A, Kadernani Y, Bremer M, Daroowala R, Aziz S, Goliath R, Lai Sai L, Sihoyiya T, Denti P, Lai RPJ, Crede T, Naude J, Szymanski P, Vallie Y, Banderker IA, Moosa MS, Raubenheimer P, Candy S, Offiah C, Wahl G, Vorster I, Maartens G, Black J, Meintjes G, Wilkinson RJ. A Phase 2A Trial of the Safety and Tolerability of Increased Dose Rifampicin and Adjunctive Linezolid, With or Without Aspirin, for Human Immunodeficiency Virus-Associated Tuberculous Meningitis: The LASER-TBM Trial. Clin Infect Dis. 2023;76(8):1412-22.
Projects
High dose oral rifampicin to improve survival from adult tuberculous meningitis (HARVEST trial)
SURE randomized controlled trial of short intensive treatment for paediatric TB meningitis