Anicteric Leptospirosis-Associated Meningitis in a Tropical Urban Environment, Brazil

Abstract

T he clinical signs of leptospirosis can vary widely, which complicates timely diagnosis and targeted therapy. Aseptic meningitis associated with Leptospira infection, hereafter termed leptospirosis-associated meningitis (LAM), has been well described (1-3). However, clinicians diagnose atypical forms of leptospirosis less frequently, particularly in the absence of classic signs (i.e., renal insufficiency or hepatitis). Detection requires a high level of clinical suspicion, and even then imperfect diagnostics for leptospirosis limit timely confirmation. Leptospirosis causes ≈1 million illnesses annually; this figure does not include LAM (4). Despite the high global burden of leptospirosis and early knowledge that anicteric LAM is underappreciated (1), few existing studies delineate the proportion of aseptic meningitis caused by Leptospira sp. infection in settings in which it is endemic. We performed surveillance for aseptic meningitis in an area of high transmission of urban leptospirosis. Hospital Couto Maia, the Oswaldo Cruz Foundation, and Yale University provided ethics approval for this study. The Study We conducted the study at a public referral hospital for infectious diseases in Salvador, Brazil, April 18-October 18, 2012, during a period of seasonal increased risk for severe leptospirosis such as Weil's disease (5) and severe pulmonary hemorrhagic syndrome (6). We enrolled consecutive patients >5 years of age who had a diagnosis of aseptic meningitis, defined by clinical meningitis (fever with severe headache or meningismus); nonturbid, nonpurulent cerebrospinal fluid (CSF) containing 10-2,000 cells/m 3 , protein <150 mg/dL, glucose >40 mg/dL; and negative results for bacterial meningitis on Gram stain, culture isolation, and latex agglutination tests. From the patients with aseptic meningitis, we aimed to select those most likely to elicit clinical suspicion for leptospirosis; a selection requirement was >1 epidemiologic risk factor for classic leptospirosis in the 30 days before symptom onset for leptospirosis testing. Risk factors were contact with floodwater, sewer water, or mud; rats at home or work; and residence or employment in a high-risk environment (i.e., slum community or animal farm) (7). We confirmed LAM by either Leptospira blood culture on EMJH media using 150 µL inoculum, or by reactive microagglutination test (MAT) by >1 of the following criteria: >4-fold acute-convalescent titer rise; seroconversion (undetectable acute-phase titer and convalescent-phase titer >1:200); or sample titer >1:800. The public hospital received regional referrals for lumbar puncture and CSF analysis for suspected meningitis as standard practice; CSF showing >10 cells/ mm 3 required inpatient observation. At enrollment, we obtained demographic, epidemiologic, and clinical data from patients. We followed the patients during hospitalization to ascertain outcomes. We compared clinical characteristics between leptospirosis-confirmed and unconfirmed patients >15 years of age to avoid age confounding. Comparisons we...

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