{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T20:01:07Z","timestamp":1772740867429,"version":"3.50.1"},"reference-count":70,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    Diffuse cutaneous leishmaniasis (DCL) is a rare chronic disease caused by\n                    <jats:italic>Leishmania<\/jats:italic>\n                    (\n                    <jats:italic>Leishmania<\/jats:italic>\n                    )\n                    <jats:italic>amazonensis<\/jats:italic>\n                    in Brazil, which is characterized by anergy of the host cellular immune response and refractory to available treatments. We report the case of a 41-year-old male patient with DCL in Goi\u00e2nia, Goi\u00e1s, Brazil with a history of more than 60 drug treatment regimens over 22 years who presented complete disease remission after 180 days of a miltefosine treatment regimen. Disease remission was followed by a considerable increase in proinflammatory cytokines interferon-gamma, tumor necrosis factor, and interleukin-6 in the patient\u2019s serum. Twenty-two months after the end of treatment with miltefosine, the patient remained without recurrence of DCL and did not require any additional therapeutic intervention. Long-term treatment with miltefosine, at least for 180 days, may represent an alternative to treat patients with DCL to obtain clinical cure and considerable improvement in the quality of life of patients.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.25-0208","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:45:17Z","timestamp":1766069117000},"page":"481-485","source":"Crossref","is-referenced-by-count":0,"title":["Success in the Treatment of Diffuse Cutaneous Leishmaniasis after Prolonged Use of Miltefosine"],"prefix":"10.4269","volume":"114","author":[{"given":"Ramon Vieira","family":"Nunes","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Imunidade Natural, Instituto de Patologia Tropical e Sa\u00fade P\u00fablica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Brazil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Freire","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunidade Natural, Instituto de Patologia Tropical e Sa\u00fade P\u00fablica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Brazil;"},{"name":"Hospital de Doen\u00e7as Tropicais Dr. Anuar Auad, Goi\u00e2nia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo Saar","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunidade Natural, Instituto de Patologia Tropical e Sa\u00fade P\u00fablica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Brazil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1tima","family":"Ribeiro-Dias","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunidade Natural, Instituto de Patologia Tropical e Sa\u00fade P\u00fablica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia, Brazil;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Br Med J","first-page":"1261","article-title":"Note on the bodies recently described by Leishman and Donovan","volume":"2","author":"Ross","year":"1903"},{"key":"b2","series-title":"Mem Inst Oswaldo Cruz","first-page":"471","article-title":"Taxonomy of the genus Leishmania: Present and future trends and their implications","volume":"89","author":"Shaw","year":"1994"},{"key":"b3","series-title":"PLoS Negl Trop Dis","first-page":"e0005090","article-title":"Psychological and psychosocial consequences of zoonotic cutaneous leishmaniasis among women in Tunisia: Preliminary findings from an exploratory study","volume":"10","author":"Chahed","year":"2016"},{"key":"b4","series-title":"Manual de vigil\u00e2ncia da leishmaniose tegumentar","year":"2017"},{"key":"b5","article-title":"Leishmaniasis.","year":"2023"},{"key":"b6","series-title":"Clin Microbiol Rev","first-page":"230","article-title":"Leishmaniases of the New World: Current concepts and implications for future research","volume":"6","author":"Grimaldi","year":"1993"},{"key":"b7","series-title":"Lancet Infect Dis","first-page":"581","article-title":"Cutaneous leishmaniasis","volume":"7","author":"Reithinger","year":"2007"},{"key":"b8","series-title":"An Bras Dermatol","first-page":"602","article-title":"Successful treatment of diffuse cutaneous leishmaniasis caused by Leishmania amazonensis.","volume":"96","author":"Sampaio","year":"2021"},{"key":"b9","series-title":"Cochrane Database Syst Rev","first-page":"CD004834","article-title":"Interventions for American cutaneous and mucocutaneous leishmaniasis","volume":"8","author":"Pinart","year":"2020"},{"key":"b10","series-title":"Gaz M\u00e9d Bahia","first-page":"16","article-title":"Diffuse cutaneous leishmaniasis (DCL) in Brazil after 60 years of its first description","volume":"79","author":"Costa","year":"2009"},{"key":"b11","series-title":"An Bras Dermatol","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":"Almeida","year":"2011"},{"key":"b12","series-title":"Am J Trop Med Hyg","first-page":"255","article-title":"Randomized controlled clinical trial to access efficacy and safety of miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis in Manaus, Brazil","volume":"84","author":"Chrusciak-Talhari","year":"2011"},{"key":"b13","series-title":"PLoS One","first-page":"e61843","article-title":"Interventions for American cutaneous and mucocutaneous leishmaniasis: A systematic review update","volume":"8","author":"Reveiz","year":"2013"},{"key":"b14","series-title":"PLoS Negl Trop Dis","first-page":"e912","article-title":"Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: A randomized and controlled trial","volume":"4","author":"Machado","year":"2010"},{"key":"b15","article-title":"Relat\u00f3rio de Recomenda\u00e7\u00e3o, Miltefosina para o tratamentoda Leishmaniose Tegumentar, no 365.","year":"2018"},{"key":"b16","series-title":"N Engl J Med","first-page":"350","article-title":"Current concepts in parasitology. Leishmaniasis","volume":"300","author":"Marsden","year":"1979"},{"key":"b17","series-title":"Am J Trop Med Hyg","first-page":"378","article-title":"Increase of NK cells and proinflammatory monocytes are associated with the clinical improvement of diffuse cutaneous leishmaniasis after immunochemotherapy with BCG\/Leishmania antigens","volume":"81","author":"Pereira","year":"2009"},{"key":"b18","series-title":"Am J Trop Med Hyg","first-page":"543","article-title":"Clinical observations of unresponsive mucosal leishmaniasis","volume":"59","author":"Marsden","year":"1998"},{"key":"b19","series-title":"Int J Dermatol","first-page":"751","article-title":"Treatment of diffuse cutaneous leishmaniasis with miltefosine: A case report","volume":"45","author":"Zerpa","year":"2006"},{"key":"b20","series-title":"Am J Trop Med Hyg","first-page":"153","article-title":"Case report: Transient success using prolonged treatment with miltefosine for a patient with diffuse cutaneous leishmaniasis infected with Leishmania mexicana mexicana.","volume":"88","author":"Ordaz-Farias","year":"2013"},{"key":"b21","series-title":"Acta Trop","first-page":"87","article-title":"Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World","volume":"118","author":"Oliveira","year":"2011"},{"key":"b22","series-title":"Expert Rev Anti Infect Ther","first-page":"177","article-title":"Miltefosine: Oral treatment of leishmaniasis","volume":"4","author":"Soto","year":"2006"},{"key":"b23","series-title":"Pharmacotherapy","first-page":"536","article-title":"Pharmacotherapy for leishmaniasis in the United States: Focus on miltefosine","volume":"35","author":"Vakil","year":"2015"},{"key":"b24","series-title":"N Engl J Med","first-page":"1739","article-title":"Oral miltefosine for Indian visceral leishmaniasis","volume":"347","author":"Sundar","year":"2002"},{"key":"b25","series-title":"Trop Doct","first-page":"37","article-title":"Adverse ocular events on miltefosine treatment for post-kala-azar dermal leishmaniasis in India","volume":"50","author":"Saurabh","year":"2020"},{"key":"b26","series-title":"Med J Mashhad Univ Med Sci","first-page":"371","article-title":"A study of hematologic, hepatic and renal side effects of intramuscular injection of meglumine antimoniate (glucantime) on patients with cutaneous leishmaniasis","volume":"50","author":"Maleki","year":"2007"},{"key":"b27","series-title":"J Basic Microbiol","first-page":"e2300490","article-title":"Comparison of biosynthetic zinc oxide nanoparticle and glucantime cytotoxic effects on Leishmania major (MRHO\/IR\/75\/ER)","volume":"64","author":"Saleh","year":"2024"},{"key":"b28","series-title":"Shiraz E-Med J","first-page":"155","article-title":"Therapeutic and adverse effects of glucantime used for treatment of cutaneous leishmaniasis","volume":"8","author":"Beheshti","year":"2007"},{"key":"b29","series-title":"J Infect Dis","first-page":"570","article-title":"Immunologic markers of protection in Leishmania (Viannia) braziliensis infection: A 5-year cohort study","volume":"214","author":"Muniz","year":"2016"},{"key":"b30","series-title":"Front Cell Infect Microbiol","first-page":"222","article-title":"Biomarkers of cutaneous leishmaniasis","volume":"8","author":"Bahrami","year":"2018"},{"key":"b31","series-title":"Cytokine","first-page":"155297","article-title":"A historical review of the role of cytokines involved in leishmaniasis","volume":"145","author":"Mirzaei","year":"2021"},{"key":"b32","series-title":"PLoS One","first-page":"e112410","article-title":"NK cell activity differs between patients with localized and diffuse cutaneous leishmaniasis infected with Leishmania mexicana: A comparative study of TLRs and cytokines","volume":"9","author":"Ca\u00f1eda-Guzm\u00e1n","year":"2014"},{"key":"b33","series-title":"Antimicrob Agents Chemother","first-page":"e02507","article-title":"Systematic review of host-mediated activity of miltefosine in leishmaniasis through immunomodulation","volume":"63","author":"Pali\u0107","year":"2019"},{"key":"b34","series-title":"PLoS Negl Trop Dis","first-page":"e0003820","article-title":"Ex vivo host and parasite response to antileishmanial drugs and immunomodulators","volume":"9","author":"Gonzalez-Fajardo","year":"2015"},{"key":"b35","series-title":"J Immunol","first-page":"3682","article-title":"IL-6 down-modulates the cytokine-enhanced antileishmanial activity in human macrophages","volume":"151","author":"Hatzigeorgiou","year":"1993"},{"key":"b1","series-title":"Br Med J","first-page":"1261","article-title":"Note on the bodies recently described by Leishman and Donovan","volume":"2","author":"Ross","year":"1903"},{"key":"b2","series-title":"Mem Inst Oswaldo Cruz","first-page":"471","article-title":"Taxonomy of the genus Leishmania: Present and future trends and their implications","volume":"89","author":"Shaw","year":"1994"},{"key":"b3","series-title":"PLoS Negl Trop Dis","first-page":"e0005090","article-title":"Psychological and psychosocial consequences of zoonotic cutaneous leishmaniasis among women in Tunisia: Preliminary findings from an exploratory study","volume":"10","author":"Chahed","year":"2016"},{"key":"b4","series-title":"Manual de vigil\u00e2ncia da leishmaniose tegumentar","year":"2017"},{"key":"b5","article-title":"Leishmaniasis.","year":"2023"},{"key":"b6","series-title":"Clin Microbiol Rev","first-page":"230","article-title":"Leishmaniases of the New World: Current concepts and implications for future research","volume":"6","author":"Grimaldi","year":"1993"},{"key":"b7","series-title":"Lancet Infect Dis","first-page":"581","article-title":"Cutaneous leishmaniasis","volume":"7","author":"Reithinger","year":"2007"},{"key":"b8","series-title":"An Bras Dermatol","first-page":"602","article-title":"Successful treatment of diffuse cutaneous leishmaniasis caused by Leishmania amazonensis.","volume":"96","author":"Sampaio","year":"2021"},{"key":"b9","series-title":"Cochrane Database Syst Rev","first-page":"CD004834","article-title":"Interventions for American cutaneous and mucocutaneous leishmaniasis","volume":"8","author":"Pinart","year":"2020"},{"key":"b10","series-title":"Gaz M\u00e9d Bahia","first-page":"16","article-title":"Diffuse cutaneous leishmaniasis (DCL) in Brazil after 60 years of its first description","volume":"79","author":"Costa","year":"2009"},{"key":"b11","series-title":"An Bras Dermatol","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":"Almeida","year":"2011"},{"key":"b12","series-title":"Am J Trop Med Hyg","first-page":"255","article-title":"Randomized controlled clinical trial to access efficacy and safety of miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis in Manaus, Brazil","volume":"84","author":"Chrusciak-Talhari","year":"2011"},{"key":"b13","series-title":"PLoS One","first-page":"e61843","article-title":"Interventions for American cutaneous and mucocutaneous leishmaniasis: A systematic review update","volume":"8","author":"Reveiz","year":"2013"},{"key":"b14","series-title":"PLoS Negl Trop Dis","first-page":"e912","article-title":"Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: A randomized and controlled trial","volume":"4","author":"Machado","year":"2010"},{"key":"b15","article-title":"Relat\u00f3rio de Recomenda\u00e7\u00e3o, Miltefosina para o tratamentoda Leishmaniose Tegumentar, no 365.","year":"2018"},{"key":"b16","series-title":"N Engl J Med","first-page":"350","article-title":"Current concepts in parasitology. Leishmaniasis","volume":"300","author":"Marsden","year":"1979"},{"key":"b17","series-title":"Am J Trop Med Hyg","first-page":"378","article-title":"Increase of NK cells and proinflammatory monocytes are associated with the clinical improvement of diffuse cutaneous leishmaniasis after immunochemotherapy with BCG\/Leishmania antigens","volume":"81","author":"Pereira","year":"2009"},{"key":"b18","series-title":"Am J Trop Med Hyg","first-page":"543","article-title":"Clinical observations of unresponsive mucosal leishmaniasis","volume":"59","author":"Marsden","year":"1998"},{"key":"b19","series-title":"Int J Dermatol","first-page":"751","article-title":"Treatment of diffuse cutaneous leishmaniasis with miltefosine: A case report","volume":"45","author":"Zerpa","year":"2006"},{"key":"b20","series-title":"Am J Trop Med Hyg","first-page":"153","article-title":"Case report: Transient success using prolonged treatment with miltefosine for a patient with diffuse cutaneous leishmaniasis infected with Leishmania mexicana mexicana.","volume":"88","author":"Ordaz-Farias","year":"2013"},{"key":"b21","series-title":"Acta Trop","first-page":"87","article-title":"Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World","volume":"118","author":"Oliveira","year":"2011"},{"key":"b22","series-title":"Expert Rev Anti Infect Ther","first-page":"177","article-title":"Miltefosine: Oral treatment of leishmaniasis","volume":"4","author":"Soto","year":"2006"},{"key":"b23","series-title":"Pharmacotherapy","first-page":"536","article-title":"Pharmacotherapy for leishmaniasis in the United States: Focus on miltefosine","volume":"35","author":"Vakil","year":"2015"},{"key":"b24","series-title":"N Engl J Med","first-page":"1739","article-title":"Oral miltefosine for Indian visceral leishmaniasis","volume":"347","author":"Sundar","year":"2002"},{"key":"b25","series-title":"Trop Doct","first-page":"37","article-title":"Adverse ocular events on miltefosine treatment for post-kala-azar dermal leishmaniasis in India","volume":"50","author":"Saurabh","year":"2020"},{"key":"b26","series-title":"Med J Mashhad Univ Med Sci","first-page":"371","article-title":"A study of hematologic, hepatic and renal side effects of intramuscular injection of meglumine antimoniate (glucantime) on patients with cutaneous leishmaniasis","volume":"50","author":"Maleki","year":"2007"},{"key":"b27","series-title":"J Basic Microbiol","first-page":"e2300490","article-title":"Comparison of biosynthetic zinc oxide nanoparticle and glucantime cytotoxic effects on Leishmania major (MRHO\/IR\/75\/ER)","volume":"64","author":"Saleh","year":"2024"},{"key":"b28","series-title":"Shiraz E-Med J","first-page":"155","article-title":"Therapeutic and adverse effects of glucantime used for treatment of cutaneous leishmaniasis","volume":"8","author":"Beheshti","year":"2007"},{"key":"b29","series-title":"J Infect Dis","first-page":"570","article-title":"Immunologic markers of protection in Leishmania (Viannia) braziliensis infection: A 5-year cohort study","volume":"214","author":"Muniz","year":"2016"},{"key":"b30","series-title":"Front Cell Infect Microbiol","first-page":"222","article-title":"Biomarkers of cutaneous leishmaniasis","volume":"8","author":"Bahrami","year":"2018"},{"key":"b31","series-title":"Cytokine","first-page":"155297","article-title":"A historical review of the role of cytokines involved in leishmaniasis","volume":"145","author":"Mirzaei","year":"2021"},{"key":"b32","series-title":"PLoS One","first-page":"e112410","article-title":"NK cell activity differs between patients with localized and diffuse cutaneous leishmaniasis infected with Leishmania mexicana: A comparative study of TLRs and cytokines","volume":"9","author":"Ca\u00f1eda-Guzm\u00e1n","year":"2014"},{"key":"b33","series-title":"Antimicrob Agents Chemother","first-page":"e02507","article-title":"Systematic review of host-mediated activity of miltefosine in leishmaniasis 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