The global burden of tuberculous meningitis in adults: A modelling study

Abstract

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. The incidence and mortality of TBM is unknown due to diagnostic challenges and limited disaggregated reporting of treated TBM by existing surveillance systems. We aimed to estimate the incidence and mortality of TBM in adults (15+ years) globally. Using national surveillance data from Brazil, South Africa, the United Kingdom, the United States of America, and Vietnam, we estimated the fraction of reported tuberculosis that is TBM, and the case fatality ratios for treated TBM in each of these countries. We adjusted these estimates according to findings from a systematic review and meta-analysis and applied them to World Health Organization tuberculosis notifications and estimates to model the global TBM incidence and mortality. Assuming the case detection ratio (CDR) for TBM was the same as all TB, we estimated that in 2019, 164,000 (95% UI; 129,000-199,000) adults developed TBM globally; 23% were among people living with HIV. Almost 60% of incident TBM occurred in males and 20% were in adults 25-34 years old. 70% of global TBM incidence occurred in Southeast Asia and Africa. We estimated that 78,200 (95% UI; 52,300-104,000) adults died of TBM in 2019, representing 48% of incident TBM. TBM case fatality in those treated was on average 27%. Sensitivity analysis assuming improved detection of TBM compared to other forms of TB (CDR odds ratio of 2) reduced estimated global mortality to 54,900 (95% UI; 32,200-77,700); assuming instead worse detection for TBM (CDR odds ratio of 0.5) increased estimated mortality to 125,000 (95% UI; 88,800-161,000). Our results highlight the need for improved routine TBM monitoring, especially in high burden countries. Reducing TBM incidence and mortality will be necessary to achieve the End TB Strategy targets.

Fig 1. Flow chart of overall methods.

TB: tuberculosis; TBM: tuberculous meningitis; CRF: Case fatality Rate; WHO: World Health Organization.

Fig 2

Age, sex, and HIV-stratified fraction of notified tuberculosis that is TB meningitis (top row, A & B), and case fatality ratio among treated TB meningitis (bottom row, C & D). HIV-negative (first column, A & C); HIV-positive (second column, B & D). Meta-analytic results for each country are shown by solid points and lines (central estimate) and shaded ribbons (95% confidence intervals). Open points show data for individual years in each country, with size proportional to denominator count. Pooled meta-analytic estimates are shown as red points, lines and 95% confidence interval error bars. (ISO3 country codes: ZAF = South Africa, GBR = United Kingdom, USA = United States of America, BRA = Brazil). Brazil has different age categories and no sex disaggregation. Map data from https://datacatalog.worldbank.org/search/dataset/0038272.

Fig 3. TBM incidence and deaths sex, age, WHO region, HIV-infection and anti-tuberculosis treatment status.

TBM: tuberculous meningitis; AFR: African Region; AMR: Americas Region; EMR: Eastern Mediterranean Region; EUR: European Region: SEA: South East Asian Region: WPR: Western Pacific Region; WHO: World Health Organization; F: female; M: male.

Fig 4. Absolute (dot size) and per capita incidence (colour) of TBM by country.