IntroductionTreatment of cutaneous and mucosal leishmaniasis (CL and ML, respectively) must be individualised as there is no universal therapeutic approach. Intravenous liposomal amphotericin B (L-AmB) is an accessible and relatively safe treatment that has been increasingly used for the treatment of CL and ML. While several descriptive studies have been published on the efficacy and safety of L-AmB, there are no interventional studies. Moreover, the findings from published studies have not yet been integrated and synthesised. Therefore, we aim to evaluate and consolidate the descriptive evidence on the efficacy and the safety of Intravenous L-AmB treatment for CL and ML in both the New and Old World.Methods and analysesA systematic review of all relevant study types with no restriction on date or language of publication will be conducted. Online databases including MEDLINE, The Cochrane Library, EMBASE, EBSCO, Scopus, Ovid and WHO databases were searched on 3 April 2020. The search included all study types that assess Intravenous L-AmB treatment for CL and ML in humans. The Population, Intervention, Comparison, Outcome and Study Design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be used to determine which studies will be selected for final inclusion. The quality of included case series and case reports will be assessed using modified quality assessment tools. A narrative synthesis of the findings will be provided and the primary outcome and secondary outcome of interest, response rate and adverse events rate, respectively, and the 95% CI will be ascertained. Estimates from individual studies will be pooled using random-effects model.Ethics and disseminationThis systematic review does not require formal ethical approval since no primary data will be collected. Findings will be disseminated through a peer-reviewed publication and relevant conferences.PROSPERO registration numberCRD42020173440.

Background Tegumentary leishmaniasis is often subject to limited funding, underpowered studies and a paucity of high-quality interventional studies. Intravenous liposomal amphotericin B (L-AmB) has been increasingly used to treat cutaneous and mucosal leishmaniasis (CL and ML respectively) despite the lack of well-conducted interventional studies. We conducted a systematic review to consolidate the descriptive evidence on the efficacy and safety of L-AmB in treating CL and ML. Methods Several online databases and the reference lists of included studies were searched to extract data from 132 studies comprising of both case reports and case series. The population, intervention, comparison, outcome and study design strategy and the preferred reporting items for systematic reviews and meta-analyses guidelines were used. Results Of 132 studies included, 92 were case reports and 40 were case series. Of the 92 cases, 65 (82.3%) were considered cured after receiving L-AmB as part of their treatment regimen. 21 of the 92 (22.8%) cases reported adverse reactions to L-AmB. A pooled cure rate of 87.0% (CI95%:79.0%-92.0%) was reported for the 38 case series that reported on treatment efficacy. 40.7% of the cases were associated with an adverse reaction. Conclusions Observational data on cure rates using L-AmB suggests efficacy between 80 and 90%, similar to rates reported for other anti-leishmanial drugs. The highest efficacy rates were observed when a single cycle of L-AmB was administered to patients with mild-moderate CL and ML. The limitations of this study include the heterogeneity observed among the included studies and the increased likelihood of publication bias associated with the inclusion of case reports and case series.This systematic review further illustrates the need for high-quality comparative trials of IV L-AmB for the treatment of tegumentary leishmaniasis.

A12-year-old girl, who had immigrated from Syria 7 months prior, presented to her general practitioner with a 6-month history of nonpainful papules over her right hand that had increased in size and eventually ulcerated. Over a follow-up period of 2 months, she did not improve despite receiving topical corticosteroids, mupirocin, and oral trimethoprim-sulfamethoxazole for suspected superinfected atopic dermatitis. When we saw her in our tropical diseases clinic, she was afebrile and systemically well, but had erythematous plaques, edema, ulcerations and restricted mobility on her right hand (Figure 1A).Giemsa staining from an ulcer scraping specimen showed numerous amastigotes. The culture was positive for Leishmania species, and polymerase chain reaction (PCR) identified Leishmania tropica. Because we were concerned about the functional mobility of the patient's hand, we prescribed systemic therapy with liposomal amphotericin B, based on local guidelines, which she tolerated well. At followup 4 months later, her lesions had resolved (Figure 1B) and joint mobility was restored.Cutaneous leishmaniasis is a protozoan infection transmitted by the female sandfly. This tropical disease affects 700 000 to 1 million new people annually. 1 Nonhealing ulcers in travellers and migrants from endemic regions, such as Central and South America, the Mediterranean basin, the Middle East and Central Asia, should raise suspicion of cutaneous leishmaniasis. Lack of physician knowledge about the acquisition of cutaneous leishmaniasis, even during short stays abroad, has historically led to delayed diagnosis. 2,3 Differential diagnoses include Nocardia species, mycobacteria, endemic fungi, vasculitis, neoplasia, sarcoidosis and pyoderma gangrenosum. Identification of parasites on smear, histopathology, culture or PCR confirm the diagnosis. 4 The type of Leishmania species, concomitant mucosal involvement, the size, number and location of the lesions, and host immune status are important guides to individualized management. 5 Treatment may be local (e.g., paromomycin preparations, cryotherapy, heat therapy) or systemic (e.g., pentavalent antimonials, miltefosine, azoles and amphotericin B).

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