Background
Cryptococcal meningitis (CM) remains a frequent opportunistic infection among individuals with advanced HIV disease, causing significant morbidity and mortality. CM incidence has fallen in high HIV-prevalence settings with expansion of ART. Few countries other than South Africa collect reliable data on CM; robust longitudinal data describing the impact of HIV programme interventions and changes in management of CM on mortality in the rest of Africa are lacking.
Methods
National mortality estimates from CM in Botswana were described using 8 years of national meningitis surveillance data (2015-2022) from electronic health records. All laboratory records from CSF samples analysed in government healthcare facilities in Botswana were extracted from a central online repository. CM case frequency was enumerated using a case definition. Mortality data were manually extracted from the national registry in duplicate using national identification numbers with arbitration by a third reviewer in discrepant cases. Outcomes were stratified as short-term (2 weeks), medium-term (10 weeks), long-term (1 year) from lumbar puncture date, and analysed by calendar year. Repeat presentation and cases without a national identification number were excluded.
Results
Outcome data from 1259 first presentations of CM between 2015-2022 were analysed. Mortality at 2 weeks was 19% (95% CI 0.14-0.25, 37/193) in 2015 and 23% (95% CI 0.16-0.33, 24/103) in 2022, at 10 weeks 27% (95% CI 0.21-0.34, 52/193) and 32% (95% CI 0.23-0.42, 33/103) and at 1 year 32% (95% CI 0.25-0.38, 60/193) and 38% (95% CI 0.28-0.48, 39/103), respectively, with no clear temporal trend (fig 1). Early mortality was significantly higher in older patients and those with positive CSF India ink, or lower CSF protein, glucose, or white cell count. Early mortality was higher in district or primary hospitals (21.5%, 165/767) compared to referral hospitals (19.8%, 111/561), OR 1.6 (CI 1.3-1.9, p<0.01).
Conclusions
Mortality from CM in Botswana remains high with no evidence of decline in 8 years of observation despite excellent ART coverage and improved diagnosis and management strategies. Increased mortality was observed in 2020, likely either directly attributable to COVID-19 or indirectly from disruptions to healthcare services. Treatment for CM has been simplified in updated WHO guidelines but access to effective antifungals including flucytosine in resource-limited settings remains restricted and must be addressed to reduce mortality.