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.

Effectiveness of intralesional sodium stibogluconate for the treatment of localized cutaneous leishmaniasis at Boru Meda general hospital, Amhara, Ethiopia: Pragmatic trial

“…The results from this study showed that increasing age and being male were associated with a higher chance of cure after IL SSG treatment of LCL caused by L. aethiopica. Increasing age being related to better cure rates was also observed in several other studies [15], of which one investigated systemic miltefosine treatment in Ethiopia [19], and two studies were done in Latin America and studied antimony treatment [20]. The association between increasing lesion size and lower cure rates was also seen in the Ethiopian paper, while a study from Brazil similarly showed that lesions <1 cm in size were associated with cure [25,26].…”

“…In contrast, our results are much lower than those from Sri Lanka, where a 96.3% cure rate was observed, although they also graded 80–90% improvement as cure [ 12 ]. In Iraq, 97.2% of patients were cured six months after receiving a total of ten IL SSG injections in five weeks [ 20 ].…”

“…In general, it is recommened to use clinical outcomes to assess cure [ 19 ], but in practice, skin slit is often still done to monitor outcomes and to decide whether to extend treatment in Ethiopia [ 24 ]. Two studies using molecular techniques have shown that measurable parasite load weeks after treatment was related with treatment outcomes [ 20 , 23 ], and therefore it would be worthwhile to further explore the clinical value of a persistingly positive SSS after treatment.…”

Cutaneous leishmaniasis due to Leishmania aethiopica: A therapeutic challenge

“…5 Despite its growing use as a first-line CL treatment in some countries, we did not consider miltefosine due to safety concerns, inaccessibility in Belgium, and the unsatisfactory results of a recent pilot study using this molecule for the treatment of CL in Ethiopia. 6 Therefore, amphotericin B liposomal was used as first-line therapy.…”

Clinical pattern and treatment outcome of Cutaneous Leishmaniasis in two hospitals in Bahir Dar, Ethiopia (2017-2021)

“…However, no follow-up was done after discharge, and the effectiveness of local pentavalent antimonial therapy was not evaluated in this study [4]. Only one study reported six-month treatment outcomes; however, this study used miltefosine, a drug that is hardly available in the country [13]. Furthermore, no CL clinical studies have been conducted in Ethiopia.…”