{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:34:24Z","timestamp":1792640064239,"version":"4.5.0"},"reference-count":18,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,2]]},"abstract":"<jats:p>\n                    In India, visceral leishmaniasis (VL) caused by\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    has been successfully treated with miltefosine with a cure rate of &gt; 90%. To assess the efficacy and safety of oral miltefosine against Brazilian VL, which is caused by\n                    <jats:italic>Leishmania infantum<\/jats:italic>\n                    , a phase II, open-label, dose-escalation study of oral miltefosine was conducted in children (aged 2\u201312 years) and adolescent-adults (aged 13\u201360 years). Definitive cure was assessed at a 6-month follow-up visit. The cure rate was only 42% (6 of 14 patients) with a recommended treatment of 28 days and 68% (19 of 28 patients) with an extended treatment of 42 days. The in vitro miltefosine susceptibility profile of intracellular amastigote stages of the pretreatment isolates, from cured and relapsed patients, showed a positive correlation with the clinical outcome. The IC\n                    <jats:sub>50<\/jats:sub>\n                    mean (SEM) of eventual cures was 5.1 (0.4) \u00b5M, whereas that of eventual failures was 12.8 (1.9) \u00b5M (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0002). An IC\n                    <jats:sub>50<\/jats:sub>\n                    above 8.0 \u00b5M predicts failure with 82% sensitivity and 100% specificity. The finding of\n                    <jats:italic>L. infantum<\/jats:italic>\n                    amastigotes resistant to miltefosine in isolates from patients who eventually failed treatment strongly suggests natural resistance to this drug, as miltefosine had never been used in Brazil before this trial was carried out.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.18-0949","type":"journal-article","created":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T03:00:27Z","timestamp":1566270027000},"page":"789-794","source":"Crossref","is-referenced-by-count":54,"title":["Natural Resistance of Leishmania infantum to Miltefosine Contributes to the Low Efficacy in the Treatment of Visceral Leishmaniasis in Brazil"],"prefix":"10.4269","volume":"101","author":[{"given":"Juliana B. T.","family":"Carnielli","sequence":"first","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo, Vit\u00f3ria, Brazil;"},{"name":"York Biomedical Research Institute, Department of Biology, University of York, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Monti-Rocha","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo, Vit\u00f3ria, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorcas Lamounier","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto Natan Portella para Doen\u00e7as Tropicais, Universidade Federal do Piau\u00ed, Teresina, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aretha","family":"Molina Sesana","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo, Vit\u00f3ria, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura N. N.","family":"Pansini","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo, Vit\u00f3ria, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Segatto","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo, Vit\u00f3ria, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy C.","family":"Mottram","sequence":"additional","affiliation":[{"name":"York Biomedical Research Institute, Department of Biology, University of York, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique Nery","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto Natan Portella para Doen\u00e7as Tropicais, Universidade Federal do Piau\u00ed, Teresina, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvio F. G.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade, Universidade Estadual de Montes Claros, Montes Claros, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reynaldo","family":"Dietze","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas, Universidade Federal do Esp\u00edrito Santo, Vit\u00f3ria, Brazil;"},{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Infection","first-page":"174","article-title":"Prognostic factors for death from visceral leishmaniasis in Teresina, Brazil","volume":"31","author":"Werneck","year":"2003"},{"key":"b2","series-title":"Leishmaniose Visceral: Recomenda\u00e7\u00f5es Cl\u00ednicas para Redu\u00e7\u00e3o da Letalidade","first-page":"78","author":"Minist\u00e9rio da Sa\u00fade","year":"2011"},{"key":"b3","series-title":"N Engl J Med","first-page":"1795","article-title":"Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis","volume":"341","author":"Jha","year":"1999"},{"key":"b4","series-title":"N Engl J Med","first-page":"1739","article-title":"Oral miltefosine for Indian visceral leishmaniasis","volume":"347","author":"Sundar","year":"2002"},{"key":"b5","series-title":"Clin Infect Dis","first-page":"543","article-title":"Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use","volume":"55","author":"Sundar","year":"2012"},{"key":"b6","series-title":"Clin Infect Dis","first-page":"1530","article-title":"Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance","volume":"56","author":"Rijal","year":"2013"},{"key":"b7","series-title":"Am J Trop Med Hyg","first-page":"66","article-title":"Phase IV trial of miltefosine in adults and children for treatment of visceral leishmaniasis (kala-azar) in Bangladesh","volume":"85","author":"Rahman","year":"2011"},{"key":"b8","series-title":"Mem Inst Oswaldo Cruz","first-page":"39","article-title":"Genetic diversity of Leishmania infantum field populations from Brazil","volume":"107","author":"Segatto","year":"2012"},{"key":"b9","series-title":"EBioMedicine","first-page":"83","article-title":"A Leishmania infantum genetic marker associated with miltefosine treatment failure for visceral leishmaniasis","volume":"36","author":"Carnielli","year":"2018"},{"key":"b10","series-title":"J Antimicrob Chemother","first-page":"3131","article-title":"Visceral leishmaniasis relapse hazard is linked to reduced miltefosine exposure in patients from Eastern Africa: a population pharmacokinetic\/pharmacodynamic study","volume":"72","author":"Dorlo","year":"2017"},{"key":"b11","series-title":"J Infect Dis","first-page":"146","article-title":"Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure","volume":"210","author":"Dorlo","year":"2014"},{"key":"b12","series-title":"Clin Infect Dis","first-page":"1530","article-title":"Pharmacokinetics, safety and efficacy of an allometric miltefosine regimen for the treatment of visceral leishmaniasis in Eastern African children: an open-label, phase-II clinical trial","volume":"68","author":"Mbui","year":"2019"},{"key":"b13","series-title":"J Infect Dis","first-page":"591","article-title":"Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis","volume":"196","author":"Bhattacharya","year":"2007"},{"key":"b14","series-title":"PLoS One","first-page":"e100220","article-title":"Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia","volume":"9","author":"Ostyn","year":"2014"},{"key":"b15","series-title":"Antimicrob Agents Chemother","first-page":"3864","article-title":"Optimal dosing of miltefosine in children and adults with visceral leishmaniasis","volume":"56","author":"Dorlo","year":"2012"},{"key":"b16","series-title":"Am J Trop Med Hyg","first-page":"750","article-title":"In vitro susceptibility of Leishmania donovani to miltefosine in Indian visceral leishmaniasis","volume":"89","author":"Prajapati","year":"2013"},{"key":"b17","series-title":"PLoS Negl Trop Dis","first-page":"e1657","article-title":"Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis","volume":"6","author":"Bhandari","year":"2012"},{"key":"b18","series-title":"PLoS Negl Trop Dis","first-page":"e0005641","article-title":"Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress","volume":"11","author":"Deep","year":"2017"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/101\/4\/article-p789.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/101\/4\/article-p789.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/101\/4\/article-p789.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T17:34:06Z","timestamp":1722447246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/101\/4\/article-p789.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,2]]},"references-count":18,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.18-0949","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,2]]}}}