{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:39:47Z","timestamp":1789666787615,"version":"4.0.1"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011061","name":"Agence Fran\u00e7aise de D\u00e9veloppement","doi-asserted-by":"publisher","award":["CZZ2062"],"award-info":[{"award-number":["CZZ2062"]}],"id":[{"id":"10.13039\/501100011061","id-type":"DOI","asserted-by":"publisher"}]},{"name":"WHO-TDR"},{"DOI":"10.13039\/100009131","name":"Direktion f\u00fcr Entwicklung und Zusammenarbeit","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009131","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007729","name":"Ministerie van Buitenlandse Zaken","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007729","id-type":"DOI","asserted-by":"publisher"}]},{"name":"M\u00e9decins Sans Fronti\u00e8res"},{"DOI":"10.13039\/100008196","name":"M\u00e9decins Sans Fronti\u00e8res","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK aid"}],"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>In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal findings<\/jats:title>\n                    <jats:p>An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to \u226460 years. Patients were assigned to 20 mg\/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and &gt;80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118\/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18\/63) patients receiving LAmB and 30% (19\/63) receiving LAmB\/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved\/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB\/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/Significance<\/jats:title>\n                    <jats:p>Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/CTRI\/2017\/04\/008421\" xlink:type=\"simple\">CTRI\/2017\/04\/008421<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0012242","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T13:40:26Z","timestamp":1718890826000},"page":"e0012242","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh"],"prefix":"10.1371","volume":"18","author":[{"given":"Shyam","family":"Sundar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Mondal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Major","family":"Madhukar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Kamal Topno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Kumar Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Chakravarty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Chaubey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Utba","family":"Rashid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shomik","family":"Maruf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheeraz","family":"Raja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Rode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margriet","family":"den Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Alvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Rijal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-5224","authenticated-orcid":true,"given":"Fabiana","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"pntd.0012242.ref001","doi-asserted-by":"crossref","first-page":"e0007653","DOI":"10.1371\/journal.pntd.0007653","article-title":"Relationship between treatment regimens for visceral leishmaniasis and development of post-kala-azar dermal leishmaniasis and visceral leishmaniasis relapse: A cohort study from Bangladesh","volume":"13","author":"D Mondal","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012242.ref002","doi-asserted-by":"crossref","first-page":"e0008429","DOI":"10.1371\/journal.pntd.0008429","article-title":"Long-term incidence of relapse and post-kala-azar dermal leishmaniasis after three different visceral leishmaniasis treatment regimens in Bihar, India.","volume":"14","author":"V Goyal","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012242.ref003","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/cid\/ciy891","article-title":"Quantifying the Infectiousness of Post-Kala-Azar Dermal Leishmaniasis Toward Sand Flies","volume":"69","author":"D Mondal","year":"2019","journal-title":"Clinical Infectious Diseases"},{"key":"pntd.0012242.ref004","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1016\/S2666-5247(20)30166-X","article-title":"Xenodiagnosis to evaluate the infectiousness of humans to sandflies in an area endemic for visceral leishmaniasis in Bihar, India: a transmission-dynamics study","volume":"2","author":"OP Singh","year":"2021","journal-title":"Lancet Microbe"},{"key":"pntd.0012242.ref005","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1080\/00034983.1997.11813179","article-title":"Amphotericin B is superior to sodium antimony gluconate in the treatment of Indian post-kala-azar dermal leishmaniasis","volume":"91","author":"CP Thakur","year":"1997","journal-title":"Ann Trop Med Parasitol"},{"key":"pntd.0012242.ref006","first-page":"144","article-title":"Efficacy of prolonged therapy with stibogluconate in post kala-azar dermal leishmaniasis","volume":"91","author":"CP Thakur","year":"1990","journal-title":"Indian J Med Res"},{"key":"pntd.0012242.ref007","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/tmi.12015","article-title":"Oral miltefosine for Indian post-kala-azar dermal leishmaniasis: a randomised trial","volume":"18","author":"S Sundar","year":"2013","journal-title":"Trop Med Int Health"},{"key":"pntd.0012242.ref008","doi-asserted-by":"crossref","first-page":"767","DOI":"10.4269\/ajtmh.14-0721","article-title":"Inadequacy of 12-Week Miltefosine Treatment for Indian Post-Kala-Azar Dermal Leishmaniasis","volume":"93","author":"S Ghosh","year":"2015","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0012242.ref009","doi-asserted-by":"crossref","first-page":"e0007173","DOI":"10.1371\/journal.pntd.0007173","article-title":"The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia\u2013A review and meta-analysis.","volume":"13","author":"J Pijpers","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012242.ref010","article-title":"Safety and Effectiveness of Miltefosine in Post-Kala-Azar Dermal Leishmaniasis: An Observational Study.","author":"S Sundar","year":"2023","journal-title":"Open Forum Infect Dis."},{"key":"pntd.0012242.ref011","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/cid\/ciy172","article-title":"Safety and Effectiveness of Short-Course AmBisome in the Treatment of Post\u2013Kala-Azar Dermal Leishmaniasis: A Prospective Cohort Study in Bangladesh","volume":"67","author":"M Den Boer","year":"2018","journal-title":"Clinical Infectious Diseases"},{"key":"pntd.0012242.ref012","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0005877","article-title":"Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme.","author":"EE Zijlstra","year":"2017"},{"key":"pntd.0012242.ref013","doi-asserted-by":"crossref","first-page":"e2864","DOI":"10.1371\/journal.pntd.0002864","article-title":"Hypokalaemia-Induced Rhabdomyolysis after Treatment of Post-Kala-azar Dermal Leishmaniasis (PKDL) with High-Dose AmBisome in Bangladesh\u2014A Case Report.","volume":"8","author":"U Marking","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012242.ref014","doi-asserted-by":"crossref","first-page":"e2613","DOI":"10.1371\/journal.pntd.0002613","article-title":"Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial.","volume":"8","author":"EAG Khalil","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012242.ref015","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1186\/s12889-015-2424-8","article-title":"Clinico-epidemiological analysis of Post kala-azar dermal leishmaniasis (PKDL) cases in India over last two decades: A hospital based retrospective study Infectious Disease epidemiology.","volume":"15","author":"V Ramesh","year":"2015","journal-title":"BMC Public Health."},{"key":"pntd.0012242.ref016","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/infdis\/jiz486","article-title":"Assessing the Efficacy and Safety of Liposomal Amphotericin B and Miltefosine in Combination for Treatment of Post Kala-Azar Dermal Leishmaniasis","volume":"221","author":"V Ramesh","year":"2020","journal-title":"Journal of Infectious Diseases"},{"key":"pntd.0012242.ref017","article-title":"Clinical study protocol","author":"DNDi"},{"key":"pntd.0012242.ref018","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1128\/AAC.00292-12","article-title":"Optimal dosing of miltefosine in children and adults with visceral leishmaniasis","volume":"56","author":"TPC Dorlo","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"pntd.0012242.ref019","article-title":"Advisory Committee on Safety of Medicinal Products (ACSoMP): Measures to minimize the risk of ocular adverse events with miltefosine.","author":"World Health Organization","year":"2023"},{"key":"pntd.0012242.ref020","doi-asserted-by":"crossref","first-page":"e010050","DOI":"10.1136\/bmjopen-2015-010050","article-title":"Study on the safety and efficacy of miltefosine for the treatment of children and adolescents with post-kala-azar dermal leishmaniasis in Bangladesh, and an association of serum vitamin E and exposure to arsenic with post-kala-azar dermal leishmaniasis: an open clinical trial and case\u2013control study protocol","volume":"6","author":"D Mondal","year":"2016","journal-title":"BMJ Open"},{"key":"pntd.0012242.ref021","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41746-023-00914-8","article-title":"Systematic review of deep learning image analyses for the diagnosis and monitoring of skin disease.","volume":"6","author":"SP Choy","year":"2023","journal-title":"NPJ Digit Med"},{"key":"pntd.0012242.ref022","doi-asserted-by":"crossref","first-page":"34","DOI":"10.25259\/IJDVL_410_19","article-title":"A randomized, open-label study to evaluate the efficacy and safety of liposomal amphotericin B (AmBisome) versus miltefosine in patients with post-kala-azar dermal leishmaniasis.","volume":"87","author":"K Pandey","year":"2021","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"pntd.0012242.ref023","doi-asserted-by":"crossref","first-page":"e0004093","DOI":"10.1371\/journal.pntd.0004093","article-title":"Decline in Clinical Efficacy of Oral Miltefosine in Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) in India.","volume":"9","author":"V Ramesh","year":"2015","journal-title":"PLoS Negl Trop Dis."},{"key":"pntd.0012242.ref024","doi-asserted-by":"crossref","first-page":"656","DOI":"10.4269\/ajtmh.23-0197","article-title":"Monitoring the Long-Term Effectiveness of Miltefosine in Indian Post-Kala-Azar Dermal Leishmaniasis","volume":"110","author":"S Roy","year":"2024","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0012242.ref025","doi-asserted-by":"crossref","first-page":"e0006781","DOI":"10.1371\/journal.pntd.0006781","article-title":"Corneal complications following Post Kala-azar Dermal Leishmaniasis treatment","volume":"12","author":"S Maruf","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012242.ref026","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1177\/0049475519877317","article-title":"Adverse ocular events on miltefosine treatment for post-kala-azar dermal leishmaniasis in India.","volume":"50","author":"S Saurabh","year":"2020","journal-title":"Trop Doct"},{"key":"pntd.0012242.ref027","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1111\/j.1462-5822.2008.01146.x","article-title":"Mechanisms and consequences of persistence of intracellular pathogens: leishmaniasis as an example.","volume":"10","author":"C. Bogdan","year":"2008","journal-title":"Cell Microbiol"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T13:40:45Z","timestamp":1718890845000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012242"}},"subtitle":[],"editor":[{"given":"Mitali","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,6,20]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0012242","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,20]]}}}