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

While studying aseptic meningitis in Salvador, Brazil, we diagnosed anicteric leptospirosis in 1.7% (5/295) of patients hospitalized for aseptic meningitis. Leptospirosis-associated meningitis patients had lower mean cerebrospinal fluid cell counts and protein than other-cause aseptic meningitis (p<0.05). Clinicians must consider leptospirosis-associated meningitis in appropriate clinical-epidemiologic contexts.

Correction: Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

[This corrects the article DOI: 10.1371/journal.ppat.1005943.].

Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.

Oxidative stress markers correlate with renal dysfunction and thrombocytopenia in severe leptospirosis.

Leptospirosis is a zoonotic disease that causes severe manifestations such as Weil's disease and pulmonary hemorrhage syndrome. The aim of this study was to evaluate whether reactive oxygen species (ROS) production and antioxidant reduced glutathione (GSH) levels are related to complications in patients hospitalized with leptospirosis. The ROS production and GSH levels were measured in blood samples of 12 patients and nine healthy controls using chemiluminescence and absorbance assays. We found that ROS production was higher and GSH levels were lower in leptospirosis patients compared with healthy individuals. Among patients, GSH depletion was correlated with thrombocytopenia and elevated serum creatinine, whereas a strong positive correlation was observed between ROS production and elevated serum potassium. Additional investigation of the biological significance of ROS production and GSH levels is warranted as they may guide the development of novel adjuvant therapies for leptospirosis targeting oxidative stress.