{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:45:18Z","timestamp":1791089118943,"version":"4.1.0"},"reference-count":14,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T00:00:00Z","timestamp":1381190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Leishmania donovani<\/jats:named-content>\n                    is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. Miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the Indian subcontinent. This relapse rate of up to 20% within 12\u00a0months after treatment was shown not to be related to reinfection, drug quality, drug exposure, or drug-resistant parasites. We therefore aimed to assess other phenotypes of the parasite that may affect treatment outcome and found a significant association between the number of metacyclic parasites, parasite infectivity, and patient treatment outcome in the Indian subcontinent. Together with previous studies on resistance of\n                    <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n                    against pentavalent antimonials, these data suggest that the infectivity of the parasite, or related phenotypes, might be a more determinant factor for treatment failure in visceral leishmaniasis than drug susceptibility, warranting a reassessment of our current view on treatment failure and drug resistance in leishmaniasis and beyond.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The high miltefosine relapse rate poses a major challenge for the current Kala-Azar Elimination Program in the Indian subcontinent and other leishmaniasis control programs worldwide. This relapse rate could not be related to reinfection, drug-resistant parasites, or reduced treatment quality. Here we report that an increased infectivity of the parasite is associated with miltefosine relapse of visceral leishmaniasis (VL) patients. These results supplement those obtained with antimonial-resistant\n                    <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n                    where an increased infectivity was also observed. This challenges the current view of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    drug susceptibility being the biggest parasitic factor that contributes to treatment failure in leishmaniasis. These selected more infectious parasites may pose an additional burden to leishmaniasis control programs, highlighting the importance of multifaceted control measures to achieve leishmaniasis elimination in the Indian subcontinent and other regions where leishmaniasis is endemic.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00611-13","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T23:59:49Z","timestamp":1381276789000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting Leishmania donovani Strain"],"prefix":"10.1128","volume":"4","author":[{"given":"Keshav","family":"Rai","sequence":"first","affiliation":[{"name":"Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"},{"name":"Department of Microbiology, B. P. Koirala Institute of Health Sciences, Dharan, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Cuypers","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan Raj","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Department of Microbiology, B. P. Koirala Institute of Health Sciences, Dharan, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surendra","family":"Uranw","sequence":"additional","affiliation":[{"name":"Department of Microbiology, B. P. Koirala Institute of Health Sciences, Dharan, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Berg","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Ostyn","sequence":"additional","affiliation":[{"name":"Epidemiology and Disease Control Unit, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Dujardin","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"},{"name":"Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Rijal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Vanaerschot","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671"},{"key":"e_1_3_2_3_2","unstructured":"World Health Organization\n. 2005. Regional strategic framework for elimination of kala-azar from the South-East Asia Region (2005\u20132015). World Health Organization Regional Office for South-East Asia New Delhi India. http:\/\/apps.searo.who.int\/pds_docs\/B0211.pdf."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis474"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit102"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.01.009"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0096"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182011001120"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012211"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.11.2802-2806.1987"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-012-3212-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2005.01.004"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000907"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.123430.111"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2012.716818"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00611-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00611-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T20:50:11Z","timestamp":1646686211000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00611-13"}},"subtitle":[],"editor":[{"given":"Louis M.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,11]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1128\/mBio.00611-13"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00611-13","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11]]},"assertion":[{"value":"2013-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-10-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00611-13"}}