{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:41:11Z","timestamp":1784641271369,"version":"3.55.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Skin Health Africa Research Program","award":["student stipend"],"award-info":[{"award-number":["student stipend"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic>Leishmania aethiopica<\/jats:italic> is a unique species that causes cutaneous leishmaniasis (CL), and studies evaluating treatment outcomes for this condition reported inconsistent findings. This study aimed to summarize the evidence on treatment outcomes of CL caused by <jats:italic>L<\/jats:italic>. <jats:italic>aethiopica<\/jats:italic> to support decisions or propose further study.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We searched PubMed, Scopus, and ScienceDirect. In addition, we searched grey literature on Google Scholar and performed manual searching on the reference list of articles. Two authors did the screening, selection, critical appraisal, and data extraction. With the narrative synthesis of evidence, we performed a random effects model meta-analysis using the <jats:italic>metaprop<\/jats:italic> package in Stata 17. We did sensitivity and subgroup analyses after assessing heterogeneity using the I-squared test and forest plots. The funnel plot and Egger\u2019s test were used to assess publication bias.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The review included 22 studies with 808 participants, and the meta-analysis included seven studies with 677 participants. Most studies documented treatment outcomes with antimonial monotherapy, and only one study reported outcomes with combination therapy. The overall pooled proportion of cure was 63% (95% CI: 38\u201386%). In the subgroup analysis, systemic antimonial monotherapy showed a cure rate of 61%, and the proportion of cure was 87% with topical therapy. Topical therapy showed a better cure for the localized clinical phenotype. A cohort study documented a cure rate of 94.8% with combination therapy for the localized, mucocutaneous, and diffuse clinical phenotypes. The pooled proportion of unfavourable outcomes was partial response (19%), relapse (17%), discontinuation (19%), and unresponsiveness (6%).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The pooled proportion of cure is low with antimonial monotherapy. Despite limited evidence, combination therapies are a promising treatment option for all clinical phenotypes of CL caused by <jats:italic>L<\/jats:italic>. <jats:italic>aethiopica<\/jats:italic>. Future high-quality randomized control trials are needed to identify effective monotherapies and evaluate the effectiveness of combination therapies.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0293529","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T17:38:23Z","timestamp":1698946703000},"page":"e0293529","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Treatment outcomes of cutaneous leishmaniasis due to Leishmania aethiopica: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5722-250X","authenticated-orcid":true,"given":"Abebaw Yeshambel","family":"Alemu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lemma","family":"Derseh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirgissa","family":"Kaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endalamaw","family":"Gadisa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassahun","family":"Alemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"issue":"6","key":"pone.0293529.ref001","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s40257-022-00726-8","article-title":"Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments","volume":"23","author":"HJC de Vries","year":"2022","journal-title":"Am J Clin Dermatol"},{"issue":"2","key":"pone.0293529.ref002","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1365-4632.2007.03154.x","article-title":"Clinical manifestations and classification of Old World cutaneous leishmaniasis","volume":"46","author":"OE Akilov","year":"2007","journal-title":"International journal of dermatology"},{"key":"pone.0293529.ref003","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.eclinm.2018.12.009","article-title":"Cutaneous leishmaniasis due to Leishmania aethiopica","volume":"6","author":"S van Henten","year":"2018","journal-title":"EClinicalMedicine"},{"issue":"1","key":"pone.0293529.ref004","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1756-3305-2-60","article-title":"A zoonotic focus of cutaneous leishmaniasis in Addis Ababa, Ethiopia","volume":"2","author":"W Lemma","year":"2009","journal-title":"Parasites & vectors"},{"issue":"1","key":"pone.0293529.ref005","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/qjmed\/hct116","article-title":"Leishmaniasis: clinical syndromes and treatment","volume":"107","author":"BS McGwire","year":"2013","journal-title":"QJM: An International Journal of Medicine"},{"issue":"4","key":"pone.0293529.ref006","article-title":"Interventions for Old World cutaneous leishmaniasis","volume":"2008","author":"U Gonzalez","journal-title":"Cochrane database of systematic reviews"},{"key":"pone.0293529.ref007","first-page":"1","article-title":"Treatment of cutaneous leishmaniasis and insights into species-specific responses: a narrative review","author":"RK Madusanka","year":"2022","journal-title":"Infectious Diseases and Therapy"},{"issue":"5","key":"pone.0293529.ref008","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/0035-9203(83)90213-4","article-title":"High-dose sodium stibogluconate treatment of cutaneous leishmaniasis in Kenya","volume":"77","author":"J Chulay","year":"1983","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"6","key":"pone.0293529.ref009","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/S0190-9622(87)80033-6","article-title":"Leishmania aethiopica: topical treatment with paromomycin and methylbenzethonium chloride ointment","volume":"16","author":"L Weinrauch","year":"1987","journal-title":"Journal of the American Academy of Dermatology"},{"issue":"5","key":"pone.0293529.ref010","doi-asserted-by":"crossref","first-page":"692","DOI":"10.4269\/ajtmh.2011.10-0712","article-title":"Case report: Successful treatment of cutaneous leishmaniasis caused by Leishmania aethiopica with liposomal amphothericin B in an immunocompromised traveler returning from Eritrea","volume":"84","author":"P Zanger","year":"2011","journal-title":"The American journal of tropical medicine and hygiene"},{"key":"pone.0293529.ref011","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jdcr.2021.12.028","article-title":"Cutaneous leishmaniasis due to Leishmania aethiopica: A therapeutic challenge","volume":"20","author":"L Mengeot","year":"2022","journal-title":"JAAD Case Reports"},{"key":"pone.0293529.ref012","unstructured":"Ministry of Health Ethiopia. Guideline for Diagnosis, Treatment and Prevention of Leishmaniasis in Ethiopia. In: Directorate AHPaDP, editor. 2nd Edition ed. Addis Ababa: FMoH; 2013."},{"key":"pone.0293529.ref013","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/5984709","article-title":"Exploratory, phase II controlled trial of Shiunko ointment local application twice a day for 4 weeks in Ethiopian patients with localized cutaneous leishmaniasis","volume":"2016","author":"K Na-Bangchang","year":"2016","journal-title":"Evidence-Based Complementary and Alternative Medicine"},{"issue":"7","key":"pone.0293529.ref014","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.trstmh.2009.02.023","article-title":"Cutaneous and mucocutaneous leishmaniasis in Tigray, northern Ethiopia: clinical aspects and therapeutic concerns","volume":"103","author":"V Padovese","year":"2009","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"8","key":"pone.0293529.ref015","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.trstmh.2012.02.006","article-title":"Treatment response of cutaneous leishmaniasis due to Leishmania aethiopica to cryotherapy and generic sodium stibogluconate from patients in Silti, Ethiopia","volume":"106","author":"E Negera","year":"2012","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"10","key":"pone.0293529.ref016","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1111\/tmi.12928","article-title":"Clinical features and treatment response of cutaneous leishmaniasis in North\u2010West Ethiopia","volume":"22","author":"H Fikre","year":"2017","journal-title":"Tropical Medicine & International Health"},{"issue":"5","key":"pone.0293529.ref017","doi-asserted-by":"crossref","first-page":"e0009460","DOI":"10.1371\/journal.pntd.0009460","article-title":"Miltefosine for the treatment of cutaneous leishmaniasis\u2014A pilot study from Ethiopia","volume":"15","author":"S van Henten","year":"2021","journal-title":"PLoS neglected tropical diseases"},{"issue":"9","key":"pone.0293529.ref018","doi-asserted-by":"crossref","first-page":"e0010578","DOI":"10.1371\/journal.pntd.0010578","article-title":"Effectiveness of intralesional sodium stibogluconate for the treatment of localized cutaneous leishmaniasis at Boru Meda general hospital, Amhara, Ethiopia: Pragmatic trial","volume":"16","author":"F Tilahun Zewdu","year":"2022","journal-title":"PLoS neglected tropical diseases"},{"issue":"3","key":"pone.0293529.ref019","doi-asserted-by":"crossref","first-page":"e0004495","DOI":"10.1371\/journal.pntd.0004495","article-title":"Treatment of cutaneous leishmaniasis caused by Leishmania aethiopica: a systematic review","volume":"10","author":"J van Griensven","year":"2016","journal-title":"PLoS neglected tropical diseases"},{"key":"pone.0293529.ref020","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"MJ Page","year":"2021","journal-title":"BMJ"},{"issue":"1","key":"pone.0293529.ref021","first-page":"1","article-title":"The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses","volume":"2","author":"J Peterson","year":"2011","journal-title":"Ottawa: Ottawa Hospital Research Institute"},{"key":"pone.0293529.ref022","unstructured":"Cochrane Group. Cochrane Handbook for Systematic Reviews of Interventions. Current version of RoB 2. 2019 [https:\/\/www.riskofbias.info\/welcome\/rob-2-0-tool\/current-version-of-rob-2."},{"issue":"1","key":"pone.0293529.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2049-3258-72-39","article-title":"Metaprop: a Stata command to perform meta-analysis of binomial data","volume":"72","author":"VN Nyaga","year":"2014","journal-title":"Archives of Public Health"},{"key":"pone.0293529.ref024","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-3-030-71921-0_9","volume-title":"Principles and Practice of Systematic Reviews and Meta-Analysis","author":"M Deshmukh","year":"2021"},{"issue":"3","key":"pone.0293529.ref025","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/0035-9203(70)90173-2","article-title":"Diffuse cutaneous leishmaniasis in Ethiopia: II Treatment","volume":"64","author":"A. Bryceson","year":"1970","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"2","key":"pone.0293529.ref026","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/0035-9203(78)90052-4","article-title":"Cutaneous leishmaniasis and leprosy","volume":"72","author":"RS Barnetson","year":"1978","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"4","key":"pone.0293529.ref027","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1365-2133.1978.tb06181.x","article-title":"Failure of metronidazole treatment in Ethiopian mucocutaneous leishmaniasis","volume":"99","author":"A Belehu","year":"1978","journal-title":"Brit J Derm"},{"key":"pone.0293529.ref028","first-page":"197","article-title":"Limited therapeutic action of rifampicin\/isoniazid against Leishmania aethiopica","volume":"2","author":"J Van der Meulen","year":"1981","journal-title":"Limited therapeutic action of rifampicin\/isoniazid against Leishmania aethiopica"},{"issue":"6","key":"pone.0293529.ref029","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1080\/00034983.1982.11687589","article-title":"Electron microscopical studies on cutaneous leishmaniasis in Ethiopia: I. The diffuse form and its treatment with pentamidine","volume":"76","author":"K Zaar","year":"1982","journal-title":"Annals of Tropical Medicine & Parasitology"},{"issue":"8316","key":"pone.0293529.ref030","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S0140-6736(83)91769-5","article-title":"Treatment of diffuse cutaneous leishmaniasis with chlorpromazine ointment","volume":"321","author":"T-H Henriksen","year":"1983","journal-title":"The Lancet"},{"issue":"4","key":"pone.0293529.ref031","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/0035-9203(90)90028-D","article-title":"The use of itraconazole in the treatment of leishmaniasis caused by Leishmania aethiopica","volume":"84","author":"H Akuffo","year":"1990","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"3","key":"pone.0293529.ref032","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/0035-9203(94)90106-6","article-title":"Aminosidine and its combination with sodium stibogluconate in the treatment of diffuse cutaneous leishmaniasis caused by Leishmania aethiopica","volume":"88","author":"S Teklemariam","year":"1994","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"4","key":"pone.0293529.ref033","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/0035-9203(95)90027-6","article-title":"Human immunodeficiency virus and recurrence of cutaneous leishmaniasis long after healed localized cutaneous leishmaniasis due to Leishmania aethiopica","volume":"89","author":"N Berhe","year":"1995","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"03","key":"pone.0293529.ref034","doi-asserted-by":"crossref","DOI":"10.4172\/2155-9554.1000450","article-title":"Treatment patterns and effectivness of anti-leishmaniasis agents for patients with cutaneous leishmaniasis at Boru Meda Hospital, South Wollo, North East Ethiopia, 2017\/18","volume":"9","author":"T Seife","year":"2018","journal-title":"J Clin Exp Dermatol Res"},{"key":"pone.0293529.ref035","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2147\/IMCRJ.S275133","article-title":"Progress of mucocutaneous leishmaniasis to drug nonresponsive diffuse cutaneous leishmaniasis in Ethiopia. A case report","volume":"13","author":"B Tegegne","year":"2020","journal-title":"International medical case reports journal"},{"issue":"08.1","key":"pone.0293529.ref036","doi-asserted-by":"crossref","first-page":"26S","DOI":"10.3855\/jidc.15979","article-title":"Clinical pattern and treatment outcome of Cutaneous Leishmaniasis in two hospitals in Bahir Dar, Ethiopia (2017\u20132021)","volume":"16","author":"D Tesfa","year":"2022","journal-title":"The Journal of Infection in Developing Countries"},{"issue":"8","key":"pone.0293529.ref037","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1017\/S0031182017000385","article-title":"Safety and efficacy of current alternatives in the topical treatment of cutaneous leishmaniasis: a systematic review","volume":"144","author":"PW Nassif","year":"2017","journal-title":"Parasitology"},{"key":"pone.0293529.ref038","article-title":"Pentavalent antimonials combined with other therapeutic alternatives for the treatment of cutaneous and mucocutaneous leishmaniasis: A systematic review","volume":"2018","author":"TRN Berbert","year":"2018","journal-title":"Dermatology research and practice"},{"issue":"9","key":"pone.0293529.ref039","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1473-3099(07)70209-8","article-title":"Cutaneous leishmaniasis","volume":"7","author":"R Reithinger","year":"2007","journal-title":"The Lancet Infectious Diseases"},{"issue":"Suppl 1","key":"pone.0293529.ref040","first-page":"29","article-title":"Meta-analysis in medical research","volume":"14","author":"A-B Haidich","year":"2010","journal-title":"Hippokratia"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0293529","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T17:39:09Z","timestamp":1698946749000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0293529"}},"subtitle":[],"editor":[{"given":"Balew","family":"Arega Negatie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,2]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0293529","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,2]]}}}