Abstract
Control of cutaneous leishmaniasis (CL) in the Americas is dependent on chemotherapy with parenteral pentavalent antimonials. High rates of treatment failure urge the search for predictive and prognostic markers of therapeutic responsiveness. In this study, we aimed to identify biomarkers of therapeutic response during treatment with meglumine antimoniate (MA). We conducted untargeted metabolomic profiling of plasma samples from CL patients (n = 39; 25 who cured and 14 who did not cure), obtained before and at the end of treatment. Exposure to MA induced metabolic perturbations primarily reflecting alteration in long-chain fatty acid β-oxidation and energy production. Allantoin, N-acetylglutamine, taurine, and pyruvate were significantly more abundant in samples from patients who responded to treatment, and were predictive and prognostic of treatment outcome in this patient cohort (AUC > 0.7). In an ex vivo model of infection, allantoin but not taurine enhanced the MA-dependent killing of intracellular Leishmania (Viannia) panamensis. Our results support the participation of metabolites mediating antioxidant and wound healing responses in clinical cure of CL, revealing relationships between metabolism and immune responses in the outcome of antileishmanial treatment.
Highlights
Cutaneous leishmaniasis (CL) is endemic in more than 90 countries and 1 million new cases are estimated to be globally reported each year
A total of 39 participants were included in this study, 25 who responded to meglumine antimoniate (MA) treatment and 14 who did not respond (Table 1, Figure 1)
No significant differences were found in demographic or clinical characteristics between groups, with the exception of gender where the only three female participants were recruited to the treatment failure group (p = 0.04)
Summary
Cutaneous leishmaniasis (CL) is endemic in more than 90 countries and 1 million new cases are estimated to be globally reported each year. Control of CL in the Americas is contingent upon active case detection and treatment. Pentavalent antimonials (SbV) remain the first-line treatment option, therapeutic failure rates of 19% to 75% challenge its usefulness (Palacios et al, 2001; Vélez et al, 2010). Adverse drug reactions (ADRs) have been reported to occur in up to 64% of individuals treated with these drugs (Oliveira et al, 2011), and can result in acute pancreatitis, hepatotoxicity, and death in most severe cases (Oliveira et al, 2011). The high rates of treatment failure and of ADR urge the identification of readily accessible and objectively measured biomarkers of therapeutic response and toxicity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
