Miltefosine for the treatment of cutaneous leishmaniasis-A pilot study from Ethiopia

Abstract

Background: Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.

Methodology and principal findings: In an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.

Conclusions/significance: Based on miltefosine's good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.

Trial registration: ClinicalTrials.gov NCT04004754.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flow chart of patients.

aWe initially only planned to include microscopy confirmed patients, but due to the high proportion of patients treated empirically, we amended the inclusion criteria. One patient treated empirically was excluded because at the time of starting miltefosine, the amendment was not yet approved.

Fig 2. Patient with large lesion of 12 months duration classified as DCL on the nose and cheeks with features of erythema, swelling, and crusted plaques on the nose.

(A) Lesion before treatment. (B) The lesion healed without residual scar at day 180.

Fig 3. Patient with two large symmetric lesions classified as LCL on both wrists of nine months duration.

Lesions show nodular erythema with central ulceration and superinfection at day 0 (A). The lesion showed progressive improvement at day 28 (B) and day 90 (C) with almost complete flattening and reepithelization. At day 180, new nodules appeared on the site of the previous lesion, indicating relapse (D).