Etiology and Outcomes of Meningitis among Adults in Three Ugandan Referral Hospitals, 2018–2023: A Prospective Cohort Study in a High-HIV Endemic Setting

Studies describing the global burden of meningitis often exclude HIV- or tuberculosis (TB)-related etiologies, thereby presenting a limited view of meningitis etiology in low- and middle-income countries. This study provides an updated evaluation of the etiology of meningitis and treatment outcomes in Uganda given advancements in molecular and TB diagnostics. We conducted a prospective observational cohort study from December 2018 to October 2023, for which adults with suspected meningitis were recruited from three referral hospitals in Uganda. We used a comprehensive diagnostic algorithm to determine microbiological etiologies of cases. Participants were followed through hospital discharge, and mortality was summarized by meningitis etiology. We enrolled 1,577 participants with suspected meningitis, of whom 96% (n = 1,511/1,577) had HIV infection and 51% (n = 772/1,577) were antiretroviral therapy naive. The median CD4 cell count was 39 cells/µL (interquartile range: 14–97 cells/µL). Cryptococcal meningitis was the most frequently diagnosed etiology of meningitis (62%) followed by TB meningitis (21%). Inpatient mortality was highest among participants diagnosed with possible TB meningitis (32%) followed by probable TB meningitis (29%) and bacterial meningitis (24%). Among the 4% (n = 66/1,577) of HIV-seronegative participants, TB meningitis was the most frequently (38%) diagnosed cause of meningitis. Despite improvements in access to HIV therapy, cryptococcal meningitis and tuberculous meningitis persist as the most common etiologies of meningitis in Uganda. Improved access to meningitis diagnostics and treatments is critically needed to mitigate the morbidity and mortality, particularly in the resource-limited settings of HIV and TB endemic regions.