{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:01:20Z","timestamp":1789718480673,"version":"4.0.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T00:00:00Z","timestamp":1613174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011061","name":"French Development Agency","doi-asserted-by":"publisher","award":["CZZ2062"],"award-info":[{"award-number":["CZZ2062"]}],"id":[{"id":"10.13039\/501100011061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009131","name":"Swiss Agency for Development and Cooperation","doi-asserted-by":"publisher","award":["81017718"],"award-info":[{"award-number":["81017718"]}],"id":[{"id":"10.13039\/100009131","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007729","name":"Dutch Ministry of Foreign Affairs","doi-asserted-by":"publisher","award":["PDP15CH21"],"award-info":[{"award-number":["PDP15CH21"]}],"id":[{"id":"10.13039\/501100007729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","award":["91617140"],"award-info":[{"award-number":["91617140"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>To expedite the development of new oral treatment regimens for visceral leishmaniasis (VL), there is a need for early markers to evaluate treatment response and predict long-term outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data from 3 clinical trials were combined in this study, in which Eastern African VL patients received various antileishmanial therapies. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative polymerase chain reaction (qPCR) before, during, and up to 6 months after treatment. The predictive performance of pharmacodynamic parameters for clinical relapse was evaluated using receiver-operating characteristic curves. Clinical trial simulations were performed to determine the power associated with the use of blood parasite load as a surrogate endpoint to predict clinical outcome at 6 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The absolute parasite density on day 56 after start of treatment was found to be a highly sensitive predictor of relapse within 6 months of follow-up at a cutoff of 20 parasites\/mL (area under the curve 0.92, specificity 0.91, sensitivity 0.89). Blood parasite loads correlated well with tissue parasite loads (\u03c1\u2005=\u20050.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a &amp;gt; 80% power to detect a difference in cure rate between treatment regimens if this difference was high (&amp;gt; 50%) and when minimally 30 patients were included per regimen.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Blood Leishmania parasite load determined by qPCR is a promising early biomarker to predict relapse in VL patients. Once optimized, it might be useful in dose finding studies of new chemical entities.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab124","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T20:14:23Z","timestamp":1612815263000},"page":"775-782","source":"Crossref","is-referenced-by-count":32,"title":["Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa"],"prefix":"10.1093","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-5902","authenticated-orcid":false,"given":"Luka","family":"Verrest","sequence":"first","affiliation":[{"name":"Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital\/the Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke E","family":"Kip","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital\/the Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M","family":"Musa","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard J","family":"Schoone","sequence":"additional","affiliation":[{"name":"Academic Medical Centre, Department of Medical Microbiology, Parasitology Unit, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk D F H","family":"Schallig","sequence":"additional","affiliation":[{"name":"Academic Medical Centre, Department of Medical Microbiology, Parasitology Unit, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Mbui","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eltahir A G","family":"Khalil","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brima M","family":"Younis","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Olobo","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Were","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi) Africa, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kimutai","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya"},{"name":"Drugs for Neglected Diseases initiative (DNDi) Africa, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Monnerat","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isra","family":"Cruz","sequence":"additional","affiliation":[{"name":"Foundation for Innovative New Diagnostics, Geneva, Switzerland"},{"name":"National School of Public Health, Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Wasunna","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi) Africa, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Alves","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P C","family":"Dorlo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital\/the Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,13]]},"reference":[{"key":"2021090721020321300_CIT0001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.00048-18","article-title":"Recent development of visceral leishmaniasis treatments: successes, pitfalls, and perspectives","volume":"31","author":"Alves","year":"2018","journal-title":"Clin Microbiol Rev"},{"key":"2021090721020321300_CIT0002","first-page":"1","author":"World Health Organization. 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