Neuroleptospirosis in patients presenting with primary central nervous system infection: A multicentre study

BACKGROUND: Leptospirosis is well-known to cause neurological involvement. However, data on the frequency of neuroleptospirosis as a cause of primary central nervous system (CNS) infections is sparse. METHODOLOGY/PRINCIPAL FINDINGS: An observational study was conducted in three regions in Sri Lanka between October 2021-March 2024. Patients with a primary diagnosis of meningitis, meningoencephalitis or encephalitis were recruited. Blood and cerebrospinal fluid (CSF) were analysed for pathogenic Leptospira DNA by real-time PCR, and serology by microscopic agglutination test (MAT) on admission and after 10-14 days. A confirmed case was a patient with evidence of CNS infection with positive CSF or blood PCR and/or 4-fold rise/single titre ≥1:320 in MAT. A total of 100 patients were studied with a median age of 55 (IQR 39.7 - 69.7) years and 52 (52%) males. Suspected clinical diagnoses were meningitis (n = 66,66%), meningoencephalitis (n = 22,22%) and encephalitis (n = 12,12%). Eleven (11%) patients were laboratory-confirmed as neuroleptospirosis; meningitis (n = 3), meningoencephalitis (n = 3), encephalitis (n = 5). Three patients had positive blood Leptospira PCR, one had positive blood and CSF Leptospira PCR, three had high initial MAT and four had a 4-fold rise in MAT. Neurological manifestations included headache (n = 8), seizures (n = 2), confusion (n = 7), photophobia (n = 4), neck stiffness (n = 6) and limb weakness (n = 5). Majority of patients with positive blood or CSF PCR for Leptospira (n = 3, 75%) did not have a CSF cellular reaction. The neuroleptospirosis group had a lower requirement for intensive care compared to other CNS infections (9% vs 13.5%) and recovered without residual neurological disability. There were no deaths in the neuroleptospirosis group compared to 11 (12.4%) deaths in other CNS infections. CONCLUSIONS: Leptospirosis is an important cause of primary CNS infections, and may lead to more favourable outcomes. It is important to consider leptospirosis as an aetiological agent in the laboratory workup of primary CNS infections in leptospirosis-prevalent settings.