Global burden of tuberculous meningitis in children aged 0-14 years in 2019: a mathematical modelling study

Background Tuberculous meningitis is fatal if untreated and can lead to lifelong neurological sequelae. However, to our knowledge, there are no data on the number of children affected by this disease. We aimed to estimate the global disease burden and attributable mortality of childhood tuberculous meningitis by WHO regions, age groups, treatment status, and HIV status in 2019. Methods We developed a Bayesian mathematical model to estimate the number of children aged 0-14 years who developed tuberculous meningitis, died from tuberculous meningitis, and did not die from tuberculous meningitis but had neurological sequelae in 2019. We reviewed the literature and used meta-analyses to quantify key parameters used as model inputs: risk of tuberculous meningitis after Mycobacterium tuberculosis infection, tuberculous meningitis as a proportion of tuberculosis notification data (ie, routine surveillance data that countries report to WHO), and risk ratios for tuberculous-meningitis mortality by age group. We identified routine tuberculosis surveillance data from countries and literature that reported the proportion of notified childhood tuberculosis that was due to tuberculous meningitis. Country-level data were from Brazil; the USA; Ukraine; South Africa; and the European Centre for Disease Prevention and Control, which included 29 countries but was aggregated and considered as one site. We assumed tuberculosis notification was synonymous with detection and treatment, combined age-disaggregated risk ratios and published meta-analytic estimates of the case-fatality rate in children who received treatment to produce estimates of tuberculous-meningitis mortality by age group and HIV status, and assumed that untreated tuberculous meningitis was always fatal. We assumed similar age-disaggregated risk ratios for neurological sequelae among children who had treatment for tuberculous meningitis and lived as for children who died. Findings An estimated 24 000 (95% credible interval 22 300-25 700) children younger than 15 years developed tuberculous meningitis in 2019. Of these children, 13 000 (12 100-13 900) were estimated to have been diagnosed and treated for tuberculous meningitis. Most untreated children were younger than 5 years. Among the 24 000 children with tuberculous meningitis, 16 100 (14 900-17 300) were estimated to have died in 2019, of whom 1101 (6<middle dot>8%) had HIV. 13 380 (83<middle dot>1%) of 16 100 deaths were estimated to be in children younger than 5 years and 11 000 (68<middle dot>3%) were estimated to be in children who did not receive tuberculous-meningitis treatment. Of the 7900 (5800-10 000) children who did not die, 5550 (5110-5980) were estimated to have neurological sequelae. Interpretation Our estimates of tuberculous meningitis in children younger than 15 years showed substantial mortality and morbidity. Improved diagnostics and strong health-care systems to facilitate early diagnosis are crucial to improve outcomes, and tuberculosis prevention should be a public health priority.