Leishmania braziliensis infection frequently results in cutaneous leishmaniasis (CL). An increase in incidence of drug-resistant CL leading to treatment failure has been reported. Identification of reliable predictors of treatment outcomes is necessary to optimize patient care. Here, we performed a prospective case-control study in which plasma levels of cytokines and lipid mediators were assessed at different time points during antileishmanial therapy in patients with CL from Brazil. Multidimensional analyses were employed to describe a combination of biomarkers able to predict and characterize treatment failure. We found a biosignature influenced mainly by plasma levels of lipid mediators that accurately predicted treatment failure. Furthermore, transcriptomic analysis of a publicly available data set revealed that expression levels of genes related to lipid metabolism measured in skin lesions could distinguish treatment outcomes in CL. Thus, activation of pathways linked to lipid biosynthesis predicts treatment failure in CL. The biomarkers identified may be further explored as therapeutic targets.

巴西利什曼原虫感染经常导致皮肤利什曼病（CL）。据报道，导致治疗失败的耐药性CL的发生率增加。确定治疗结果的可靠预测指标对于优化患者护理至关重要。在这里，我们进行了一项前瞻性病例对照研究，在该研究中，对巴西CL患者进行抗盲肠治疗期间在不同时间点评估了细胞因子和脂质介质的血浆水平。多维分析用于描述能够预测和表征治疗失败的生物标志物的组合。我们发现生物签名主要受血浆脂质介质的水平影响，该水平可以准确预测治疗失败。此外，公开数据集的转录组分析显示，皮肤病变中与脂质代谢相关的基因的表达水平可以区分CL的治疗结果。因此，与脂质生物合成相关的途径的激活预示着CL的治疗失败。鉴定出的生物标志物可以进一步探索作为治疗靶标。