{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:07:17Z","timestamp":1788653237095,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010238","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000}}],"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014054","name":"Drugs for Neglected Diseases initiative","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014054","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"\n Background<\/jats:title>\n Systemic pentavalent antimonials, mainly meglumine antimoniate, continue to be the first-choice drugs for treatment of cutaneous leishmaniasis (CL) despite their toxicity, difficulty of administration and high cost. In the search for therapeutic alternatives, combining two treatment interventions has emerged as a potential alternative to either reduce the use of antimonials with the associated toxicities, or to increase efficacy. Here, we report the results of a recently completed trial assessing the efficacy and safety of a combination of thermotherapy (TT) plus a short course of miltefosine (MLT) for the treatment of uncomplicated CL in Colombia and Peru.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A multicenter, randomized, evaluator-blinded, phase II, controled clinical trial was conducted. Adult volunteers with a parasitologically confirmed diagnosis of uncomplicated CL were randomly allocated to receive either a single session of TT or a combination of TT plus a short course of MLT (3 weeks). Therapeutic response outcomes and safety were assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 130 subjects were included in the study, of whom 64 were randomly assigned to the TT arm and 66 to the TT + MLT arm. Cure at 3 months\u2019 follow-up was achieved in 57.8% (n = 37) and 80.3% (n = 53) in the TT and TT + MLT groups, respectively, in the intention to treat analysis. The TT + MLT regimen was better that TT alone (p = 0.0055). The presence of vesicles at the site of heat application was the most common adverse event reported associated with the use of TT; while vomiting (31.8%) and elevation of liver enzymes (28.8%) were the most frequent adverse events reported associated with the use of MLT.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The combination of TT plus a short course of MLT was shown to be significantly better than TT alone for the treatment of uncomplicated CL in the New World.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n \n Registered in clinicaltrials.gov\n NCT02687971<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pntd.0010238","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T13:42:48Z","timestamp":1646660568000},"page":"e0010238","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["A phase II multicenter randomized study to evaluate the safety and efficacy of combining thermotherapy and a short course of miltefosine for the treatment of uncomplicated cutaneous leishmaniasis in the New World"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-0996","authenticated-orcid":true,"given":"Liliana","family":"L\u00f3pez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braulio","family":"Valencia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorela","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-7024","authenticated-orcid":true,"given":"Ana Pilar","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7567-5534","authenticated-orcid":true,"given":"Alejandro","family":"Llanos-Cuentas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Echevarria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"V\u00e9lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Boni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-5136","authenticated-orcid":true,"given":"Joelle","family":"Rode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-290X","authenticated-orcid":true,"given":"Juliana","family":"Quintero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulied","family":"Tabares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"M\u00e9ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8407-7093","authenticated-orcid":true,"given":"Byron","family":"Arana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"issue":"5","key":"pntd.0010238.ref001","doi-asserted-by":"crossref","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence.","volume":"7","author":"J Alvar","year":"2012","journal-title":"PLoS One"},{"issue":"10151","key":"pntd.0010238.ref002","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","volume":"392","author":"S Burza","year":"2018","journal-title":"Leishmaniasis. Lancet"},{"issue":"6","key":"pntd.0010238.ref003","first-page":"1325","article-title":"[Epidemiology of American tegumentary leishmaniasis in the State of Acre, Brazilian Amazon].","volume":"25","author":"NS Silva","year":"2009","journal-title":"Cad Saude Publica"},{"issue":"2","key":"pntd.0010238.ref004","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4269\/ajtmh.2010.10-0060","article-title":"Efficacy of miltefosine for the treatment of American cutaneous leishmaniasis","volume":"83","author":"I V\u00e9lez","year":"2010","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0010238.ref005","unstructured":"World Health Organization (WHO). Control of the leishmaniasis. 2010."},{"key":"pntd.0010238.ref006","first-page":"1","author":"Pan American Health Organization P","year":"2020","journal-title":"LEISHMANIASIS Epidemiological Report of the Americas"},{"issue":"9","key":"pntd.0010238.ref007","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":"Lancet Infect Dis"},{"issue":"3","key":"pntd.0010238.ref008","first-page":"497","article-title":"Advances in the treatment of cutaneous leishmaniasis in the new world in the last ten years: a systematic literature review","volume":"86","author":"OL Almeida","year":"2011","journal-title":"An Bras Dermatol."},{"issue":"5","key":"pntd.0010238.ref009","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1179\/000349803225001373","article-title":"The efficacy of treatment with intralesional meglumine antimoniate alone, compared with that of cryotherapy combined with the meglumine antimoniate or intralesional sodium stibogluconate, in the treatment of cutaneous leishmaniasis","volume":"97","author":"A Asilian","year":"2003","journal-title":"Ann Trop Med Parasitol"},{"issue":"4","key":"pntd.0010238.ref010","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1365-4632.2004.02002.x","article-title":"Comparative study of the efficacy of combined cryotherapy and intralesional meglumine antimoniate (Glucantime) vs. cryotherapy and intralesional meglumine antimoniate (Glucantime) alone for the treatment of cutaneous leishmaniasis","volume":"43","author":"A Asilian","year":"2004","journal-title":"Int J Dermatol"},{"issue":"9","key":"pntd.0010238.ref011","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1111\/j.1365-4632.2006.02822.x","article-title":"Comparison of intralesional meglumine antimoniate, cryotherapy and their combination in the treatment of cutaneous leishmaniasis","volume":"45","author":"R Salmanpour","year":"2006","journal-title":"Int J Dermatol"},{"issue":"5","key":"pntd.0010238.ref012","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.4269\/ajtmh.16-0435","article-title":"Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for Cutaneous Leishmaniasis","volume":"96","author":"G Brito","year":"2017","journal-title":"Am J Trop Med Hyg"},{"issue":"9","key":"pntd.0010238.ref013","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1111\/tmi.13119","article-title":"Tamoxifen and meglumine antimoniate combined therapy in cutaneous leishmaniasis patients: a randomised trial","volume":"23","author":"PRL Machado","year":"2018","journal-title":"Trop Med Int Health"},{"issue":"10","key":"pntd.0010238.ref014","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1086\/429238","article-title":"Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru","volume":"40","author":"C Miranda-Ver\u00e1stegui","year":"2005","journal-title":"Clin Infect Dis"},{"issue":"7","key":"pntd.0010238.ref015","doi-asserted-by":"crossref","first-page":"e491","DOI":"10.1371\/journal.pntd.0000491","article-title":"First-line therapy for human cutaneous leishmaniasis in Peru using the TLR7 agonist imiquimod in combination with pentavalent antimony","volume":"3","author":"C Miranda-Verastegui","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010238.ref016","unstructured":"salud O-OPdl, Organization W-WH. Leishmaniasis en las Am\u00e9ricas: recomendaciones de tratamiento. (Washington, D.C., 31 August\u20141 September 2016). Washington, D.C.: PAHO2013."},{"key":"pntd.0010238.ref017","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1745-6215-13-58","article-title":"Thermotherapy. An alternative for the treatment of American cutaneous leishmaniasis","volume":"13","author":"L L\u00f3pez","year":"2012","journal-title":"Trials"},{"issue":"1","key":"pntd.0010238.ref018","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1186\/s13063-017-2092-3","article-title":"Erratum to: Thermotherapy. 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