Efficacy of pentavalent antimoniate intralesional infiltration therapy for cutaneous leishmaniasis: A systematic review

Abstract

BackgroundThe 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.MethodologyThe 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.ResultsThirty 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.ConclusionsDespite 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 the...

Treatment Patterns and Effectivness of Anti-Leishmaniasis Agents for Patients with Cutaneous Leishmaniasis at Boru Meda Hospital, South Wollo, North East Ethiopia, 2017/18

“…Such a difference might be due to duration and numbers of applications i.e 12 weeks of application vs. 6 weeks and 6-8 times, application technique (using cotton tipped vs. cryo gun) and size of lesions. But to the contrary our result is relatively low when compared to trials in Egypt (100%) [16], This might be due to application of cryotherapy for undetermined times, till all lesions are cleared. In addition, other groups containing 26 patients had a combined cryotherapy and IL SSG therapy with a cure rate of 96.1%.…”

Plasma antimony determination during cutaneous leishmaniasis treatment with intralesional infiltration of meglumine antimoniate

“…In 2013, the Pan American Health Organization Expert Committee on leishmaniasis also included this approach in regional guidelines restricted to reference centres and to single lesions not involving the face or joints . Recently, a systematic review confirmed a global efficacy of 75% for pentavalent antimony intralesional therapy, a similar cure rate to that described in the New World for parenteral antimony treatment . It is important to note that this is an off‐label route of a drug that has been used for decades, but was only just incorporated into the Brazil's public health system officially, with expanding large‐scale use.…”

“…The patients were treated with MA – Glucantime ® – ampoules of 81 mg/ml, using the same lot control number (528240), produced by Sanofi‐Aventis Pharma and assigned by the Brazilian Ministry of Health. Patients were submitted to weekly intralesional infiltration using a standardised and previously validated technique . According to the study protocol, a maximum of eight infiltrations was performed deeply in the dermis and in the adjunctive subcutaneous tissue aiming to achieve saturation of the lesion, defined as swelling of the entire lesion accompanied or not by pallor.…”

Eligibility for Local Therapies in Adolescents and Adults with Cutaneous Leishmaniasis from Southwestern Colombia: A Cross-Sectional Study

“…8 Available data on the feasibility of local therapies in the Americas is limited. 9,11,13 A previous study in our center showed modest applicability of local therapies to pediatric populations (26% and 53% were eligible, based on PAHO and WHO criteria, respectively). 14 Children constitute a population with special needs for therapy but represent only around 11% of Colombian cases.…”

“…3,6 To address these issues, in 2010 the World Health Organization (WHO) issued recommendations for the use of local therapies as alternatives for treating CL. 8 These therapies include intralesional antileishmanials (antimony and pentamidine), 9,10 physical therapies (cryotherapy and thermotherapy), 11 and topical drugs (e.g., paramomycin). 5 The WHO recommendations aim to reduce toxicity and increase adherence, given the better risk-benefit ratio of local therapies compared with systemic drugs for CL, especially for mild clinical presentations.…”