Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions

Abstract

Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p < 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis.

Keywords: Leishmania braziliensis; meglumine antimoniate; skin lesion; topical therapy; wound dressing.

Figure 1

Kaplan–Meier curve comparing time-to-cure in the study group (BNC+MA), placebo group (PL+MA), and control group (MA alone). Time-to-cure is the number of days required for the complete resolution of ulcers, when signs of clinical activity such as inflammation or raised borders are no longer observed.

Figure 2

Use of wound dressings on CL lesions modulates the systemic immune response. (A) Data (mean PBMC supernatant concentration of each indicated mediator per patient group and time point) were log-transformed, and a heatmap was used to illustrate trends in data variation. (B) Fold differences for each mediator (D30–D0) were calculated, and log10 values (Supplementary Table S1) were plotted.

Figure 3

Cytokine production in CL patients. PBMCs were obtained from CL patients before (D0) and after therapy (D30). Cells were cultured with SLA for 72 h. Levels of IL-1a and IL-6 were determined by Luminex. Each symbol represents one CL patient. Blue (study group) (n = 25), orange (Placebo group, n = 21), and red (control group, n = 23). (A) IL-1a, (B) IL-6. * p < 0.05. Abbreviations: ns, not significant.