{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:53:34Z","timestamp":1788054814651,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009460","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000}}],"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007920","name":"Directorate-General for International Cooperation and Development","doi-asserted-by":"publisher","award":["FA4 framework collaboration"],"award-info":[{"award-number":["FA4 framework collaboration"]}],"id":[{"id":"10.13039\/501100007920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007920","name":"Directorate-General for International Cooperation and Development","doi-asserted-by":"publisher","award":["FA4 framework collaboration"],"award-info":[{"award-number":["FA4 framework collaboration"]}],"id":[{"id":"10.13039\/501100007920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Cutaneous leishmaniasis (CL) in Ethiopia, caused by <jats:italic>Leishmania aethiopica<\/jats:italic>, 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 <jats:italic>L<\/jats:italic>. <jats:italic>aethiopica<\/jats:italic> is lacking.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology and principal findings<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/Significance<\/jats:title>\n<jats:p>Based on miltefosine\u2019s 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>ClinicalTrials.gov <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04004754\" xlink:type=\"simple\">NCT04004754<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0009460","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T19:54:23Z","timestamp":1622231663000},"page":"e0009460","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["Miltefosine for the treatment of cutaneous leishmaniasis\u2014A pilot study from Ethiopia"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6627-0474","authenticated-orcid":true,"given":"Saskia","family":"van Henten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annisa Befekadu","family":"Tesfaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seid 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aethiopica","volume":"6","author":"S van Henten","year":"2018","journal-title":"EClinicalMedicine."},{"key":"pntd.0009460.ref007","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1111\/tmi.12928","article-title":"Clinical features and treatment response of cutaneous leishmaniasis in North-West Ethiopia","volume":"22","author":"H Fikre","year":"2017","journal-title":"Trop Med Int Heal"},{"key":"pntd.0009460.ref008","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.exppara.2006.09.014","article-title":"Leishmania (Kinetoplastida): Species typing with isoenzyme and PCR\u2013RFLP from cutaneous leishmaniasis patients in Ethiopia","volume":"115","author":"E Gadisa","year":"2007","journal-title":"Exp Parasitol"},{"key":"pntd.0009460.ref009","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/0035-9203(73)90088-6","article-title":"The epidemiology of cutaneous leishmaniasis in Ethiopia","volume":"67","author":"RW 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