Leptospirosis-associated meningitis in an urban tropical endemic setting in northeastern Brazil: Three New cases and a meta-summary of 176 reported cases

BACKGROUND: Leptospirosis is a globally distributed zoonotic disease with a broad clinical spectrum. Central nervous system (CNS) involvement is uncommon and under-recognized, and leptospiral-associated meningitis (LAM) is primarily described in isolated case reports and small series. No study to date has integrated institutional cases with published reports to characterize cerebrospinal fluid (CSF) profiles in LAM. METHODS: We conducted a retrospective cohort study of patients with meningitis, encephalitis, or meningoencephalitis admitted to a tertiary infectious diseases center in northeastern Brazil. Cases of LAM were identified among patients with aseptic meningitis. In parallel, a narrative literature review was performed, and a meta-summary of published cases was constructed. CSF parameters from both datasets were extracted and analyzed using descriptive statistics and graphical (boxplot) methods. RESULTS: Among 809 patients with meningitis or encephalitis, 447 presented with aseptic meningitis. Three cases (0.67%) of LAM were identified, presenting as isolated meningitis or meningoencephalitis. Among 179 patients, including 176 identified in the medical literature, mean CSF values were: cellularity 68 cells/mm3 (range, 30-7800), lymphocytes 73% (0-100), neutrophils 18% (0-96), glucose 60 mg/dL (0-140), and protein 67-90 mg/dL (31-2590). CSF findings in the institutional cohort showed mild to moderate pleocytosis with lymphocytic predominance, normal to elevated glucose levels, and increased protein concentrations. The integrated analysis of cohort and published cases-the first combined CSF profile synthesis of LAM-demonstrated a consistent pattern of lymphocytic pleocytosis, mildly elevated cellularity, preserved glucose levels, and increased protein, with substantial inter-case variability. CONCLUSION: LAM is an uncommon but clinically relevant cause of CNS infection in endemic settings. This study provides the first integrated synthesis of CSF profiles from both institutional cases and published literature, supporting a characteristic but variable CSF pattern in leptospiral CNS disease. Clinicians should consider leptospirosis in patients with aseptic meningitis in endemic areas, particularly when epidemiological risk factors are present. Improved diagnostic capacity and prospective studies using standardized criteria are needed to better define disease burden and refine diagnostic and therapeutic approaches.