Atypical presentation of leptospirosis as aseptic meningitis in an immunocompromised patient: Impact of rituximab on recovery and prolonged inflammatory response

Leptospirosis is a zoonotic spirochaetal infection with a broad clinical spectrum, ranging from mild anicteric illness to severe systemic disease. Central nervous system (CNS) involvement, particularly aseptic meningitis, is an underrecognized and diagnostically challenging manifestation, especially when isolated from systemic signs. We report a case of a 43-year-old male with a history of CNS demyelinating disease, treated with rituximab, who presented with a one-month history of recurrent fever, headache, and painful lower extremity nodules. He also experienced unintentional weight loss. After a thorough infectious workup, cerebrospinal fluid (CSF) analysis, including broad-range PCR and the Karius test, confirmed the diagnosis of leptospirosis caused by <i>Leptospira noguchii</i>. He was initially treated with intravenous ceftriaxone and oral doxycycline for 7 days, resulting in symptomatic improvement. However, symptoms recurred two weeks later, with repeat CSF analysis revealing persistent pleocytosis, necessitating a prolonged course of treatment. This case underscores the limitations of conventional testing in immunocompromised hosts and highlights the critical role of advanced molecular diagnostics for early and accurate detection of neuroleptospirosis. Clinicians should maintain high suspicion for leptospiral meningitis in appropriate clinical contexts to improve outcomes through timely intervention.