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Background Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). Methods Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10–20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. Results We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5–91.4) and 67.8% (53.3–78.3) per protocol (PP) and 70.6% (58.3–81.0) and 59.7% (47.0–71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6–88 + 8) and 71.2% (57.9–82.2) PP and 69.1% (55.2–78.5) and 64.2% (50.0–74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. Conclusions IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. Clinical Trials Registration REBEC: RBR-6mk5n4. [ABSTRACT FROM AUTHOR]

Background: Treatment guidance for children and older adult patients affected by cutaneous leishmaniasis (CL) is unclear due to limited representation of these groups in clinical trials. Methods: We conducted a collaborative retrospective study to describe the effectiveness and safety of antileishmanial treatments in children ≤ 10 and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in Latin America. Results: 2,037 clinical records were assessed for eligibility. Of them, the main reason for non-inclusion was lack of data on treatment follow-up and therapeutic response (182/242, 75% of children and 179/468, 38% of adults). Data on 1,325 eligible CL patients (736 children and 589 older adults) were analyzed. In both age groups, disease presentation was mild, with a median number of lesions of one (IQR: 1–2) and median lesion diameter of less than 3 cm. Less than 50% of the patients had data for two or more follow-up visits post-treatment (being only 28% in pediatric patients). Systemic antimonials were the most common monotherapy regimen in both age groups (590/736, 80.2% of children and 308/589, 52.3% of older adults) with overall cure rates of 54.6% (95% CI: 50.5–58.6%) and 68.2% (95% CI: 62.6–73.4%), respectively. Other treatments used include miltefosine, amphotericin B, intralesional antimonials, and pentamidine. Adverse reactions related to the main treatment were experienced in 11.9% (86/722) of children versus 38.4% (206/537) of older adults. Most adverse reactions were of mild intensity. Conclusion: Our findings support the need for greater availability and use of alternatives to systemic antimonials, particularly local therapies, and development of strategies to improve patient follow-up across the region, with special attention to pediatric populations. Author summary: Cutaneous leishmaniasis (CL) is a vector-borne disease caused by a parasite called Leishmania that affects more than 1 million people worldwide each year and mostly causes chronic skin ulcers. The first line treatment continues to be systemic antimonials, despite drawbacks such as numerous daily injections and toxic side effects. Some groups, including children and older adults, are usually not included in clinical trials and, therefore, specific treatment guidance for them is uncertain due to the scarcity of robust evidence. RedeLEISH, a Latin American network of leishmaniasis researchers, conducted a retrospective study of the medical records of children ≤ 10 years of age and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in the region, with the aim of learning about and documenting the effectiveness and tolerability of routine antileishmanial treatments, and ultimately contributing to improving the management of these patient groups. Our findings, based on 1,325 eligible patients' records (589 adults ≥ 60 years of age and 736 children ≤ 10 years of age), showed that in both age groups the disease presents predominantly in a mild form, but that the most commonly used treatment, systemic antimonials, has limited effectiveness. This supports and encourages greater use of local therapies, and other treatment alternatives in these special populations. The results of this study also highlight the need to develop strategies for better follow-up of routine CL treatment and determination of effectiveness, as lack of such information was the principal criterion for exclusion of patients screened for eligibility, and less than 50% of eligible patients had information on two or more follow-up visits. [ABSTRACT FROM AUTHOR]