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Background The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their recognized toxicity, which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure. As result of these drawbacks, the WHO Expert Committee on leishmaniasis has expanded the recommendations for the use of local therapies, including Sbv intralesional infiltration (IL-Sbv), as CL therapy alternatives even in the New World. However, the efficacy of these approaches has never been compiled. The aim of this study was to critically and systematically assess the efficacy of IL-Sbv for CL treatment. Methodology The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the MEDLINE and LILACS databases and the International Clinical Trials Registry Platform of the World Health Organization. The outcome of interest was a clinical cure, defined as complete re-epithelialization of all lesions. The IL-Sbv pooled cure rate was estimated for several subgroups and direct comparisons were performed when possible. Results Thirty nine articles (40 studies) involving 5679 patients treated with IL-Sbv infiltration were included. In direct comparison, only three studies involving 229 patients compared IL-Sbv infiltration versus placebo and no difference was observed (OR: 1,9; 95%IC 0,93 to 3,82) based on cure rate 69.6% (95%CI 17.6–96.1%) and 83,2% (95%CI 66–92.7%) for placebo and IL-Sbv, respectively. In an alternative and non-comparative analysis, gathering all study arms using the intervention, the pooled IL-Sbv efficacy rate was 75% (95%CI 68–81%). In the Old World, the observed overall IL-Sbv efficacy rate was 75% (95%CI 66–82%), and the cure rates were significantly higher with sodium stibogluconate (SSG) than with meglumine antimoniate (MA): 83% (95%CI 75–90%) versus 68% (95%CI 54–79%), p = 0.03. Studies directly comparing IL-Sbv with topical 15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4–92.4%) when compared with IL-Sbv alone (53.3%, 95%IC 46.1–66%), OR: 3.14 (95%CI 1.1–8.9), p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66–85%). In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49–73%) versus 82% (95%CI 70–89%).By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates. Conclusions Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications.

Cutaneous leishmaniasis (LC) is a complex and variable disease in terms of epidemiology, aetiology, pathology and clinical characteristics. The mainstay of treatment is still pentavalent antimony (Sbv) compounds administered systemically, despite their recognized toxicity. The advantages of antimony intralesional (IL) infiltration are the use of lower doses of Sbv and, therefore, less toxic effects. The objective of this study was to estimate the cost-effectiveness ratio of intralesional meglumine antimoniate therapy (IL-MA) compared with endovenous meglumine antimoniate therapy (EV-MA) for the treatment of CL in the context of the Brazilian National Health System (SUS). An analytical decision model (decision tree) was developed using TreeAge Pro 2018 software. Data from the open-label, uncontrolled phase II clinical trial evaluating IL-MA were used as a reference for posology, efficacy, and adverse event rates (AE). The same premises for the intravenous approach (EV-MA) were extracted from systematic literature reviews. Macro and micro calculations of spending were included in the analysis. The IL-MA and EV-MA strategies had a total cost per patient cured of US$330.81 and US$494.16, respectively. The intralesional approach was dominant, meaning it was more economic and effective than was endovenous therapy. The incremental cost-effectiveness ratio showed that IL-MA could result in savings of US$864.37 for each additional patient cured, confirming that the IL-MA strategy is cost effective in the context of the Brazilian public health scenario., Author summary Cutaneous leishmaniasis (LC) is a parasitic disease characterized by a non-fatal evolution but marked by significant morbidity resulting from lesions that are usually ulcerated, sometimes disfiguring, and distributed in exposed areas of the body. Pentavalent antimony compounds administered systemically (EV) are still considered the pillars of cutaneous leishmaniasis (CL) treatment despite its high toxicity. Other therapeutic approaches, including the intralesional infiltration of antimony derivatives have been proposed as an alternative as effective as the systemic route. In this study we performed a cost-effectiveness analysis of the meglumine antimoniate intralesional treatment (IL-MA) compared to systemic therapy with the same drug, from the perspective of the main source of pay in Brazil, Brazilian Public Health System (SUS). This is the first cost-effectiveness study evaluating the IL-MA approach compared to MA endovenously for the treatment of CL. Cost-effectiveness was expressed as the incremental costs per patient cured. In our model, IL-MA was more effective and led to substantially lower costs for the public health system. Analytical decision model showed that the IL-MA therapy could represent a cost saving of approximately US$ 877.64 per additional patient cured compared with the endovenous route, representing the more cost-effectiveness approach for treatment of selected CL cases in Brazil.