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dc.contributor.author | Verrest, Luka | |
dc.contributor.author | Kip, Anke E | |
dc.contributor.author | Musa, Ahmed M | |
dc.contributor.author | Schoone, Gerard J | |
dc.contributor.author | Schallig, Henk D F H | |
dc.contributor.author | Mbui, Jane | |
dc.contributor.author | Khalil, Eltahir A G | |
dc.contributor.author | Younis, Brima M | |
dc.contributor.author | Olobo, Joseph | |
dc.contributor.author | Were, Lilian | |
dc.contributor.author | Kimutai, Robert | |
dc.contributor.author | Monnerat, Séverine | |
dc.contributor.author | Cruz, Israel | |
dc.contributor.author | Wasunna, Monique | |
dc.contributor.author | Alves, Fabiana | |
dc.contributor.author | Dorlo, Thomas P C | |
dc.date.accessioned | 2022-05-03T09:04:44Z | |
dc.date.available | 2022-05-03T09:04:44Z | |
dc.date.issued | 2021-09 | |
dc.identifier.citation | Clin Infect Dis. 2021 Sep 7;73(5):775-782. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/14230 | |
dc.description.abstract | Background: 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. Methods: 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. Results: 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 (ρ = 0.80) and with microscopy gradings of bone marrow and spleen aspirate smears. Clinical trial simulations indicated a > 80% power to detect a difference in cure rate between treatment regimens if this difference was high (> 50%) and when minimally 30 patients were included per regimen. Conclusions: 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. | es_ES |
dc.description.sponsorship | This work was supported by the European Union Seventh Framework Programme Africoleish (grant number 305178); the World Health Organization—Special Programme for Research and Training in Tropical Diseases (WHO-TDR); the French Development Agency, France (grant number CZZ2062); UK aid, UK; the Federal Ministry of Education and Research through KfW, Germany; the Medicor Foundation, Liechtenstein; Médecins Sans Frontières, International; the Swiss Agency for Development and Cooperation (SDC), Switzerland (grant number 81017718); the Dutch Ministry of Foreign Affairs (DGIS), the Netherlands (grant number PDP15CH21); the French Ministry for Europe and Foreign Affairs (MEAE), France; The Rockefeller Foundation, USA; BBVA Foundation, Spain; the European Union—AfriKADIA project of the Second European and Developing Countries Clinical Trials Partnership Programme (EDCTP2) (grant number RIA2016S1635); and ZonMw/Dutch Research Council (NWO) Veni grant (project number 91617140 to T. P. C. D.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Pharmacodynamics | es_ES |
dc.subject | Visceral leishmaniasis | es_ES |
dc.subject | Parasitemia | es_ES |
dc.subject | Biomarker | es_ES |
dc.subject | qPCR | es_ES |
dc.subject.mesh | Leishmaniasis, Visceral | es_ES |
dc.subject.mesh | Parasites | es_ES |
dc.subject.mesh | Africa, Eastern | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Biomarkers | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Parasite Load | es_ES |
dc.title | Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 33580234 | es_ES |
dc.format.volume | 73 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | 775-782 | es_ES |
dc.identifier.doi | 10.1093/cid/ciab124 | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. 7 Programa Marco | es_ES |
dc.contributor.funder | World Health Organization (WHO/OMS) | es_ES |
dc.contributor.funder | French Development Agency | es_ES |
dc.contributor.funder | Government of the United Kingdom | es_ES |
dc.contributor.funder | Federal Ministry of Education & Research (Alemania) | es_ES |
dc.contributor.funder | Medicor Foundation | es_ES |
dc.contributor.funder | Médecins Sans Frontières | es_ES |
dc.contributor.funder | Swiss Agency for Development and Cooperation | es_ES |
dc.contributor.funder | Ministry of Foreign Affairs (Holanda) | es_ES |
dc.contributor.funder | Ministry of Foreign Affairs and International Development (Francia) | es_ES |
dc.contributor.funder | Rockefeller Foundation | es_ES |
dc.contributor.funder | Fundación BBVA | es_ES |
dc.contributor.funder | Unión Europea | es_ES |
dc.contributor.funder | Dutch Research Council (Holanda) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1537-6591 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1093/cid/ciab124 | es_ES |
dc.identifier.journal | Clinical Infectious Diseases: An official publication of the Infectious Diseases Society of America | es_ES |
dc.repisalud.centro | ISCIII::Escuela Nacional de Sanidad | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/305178/EU | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/RIA2016S1635 | es_ES |
dc.rights.accessRights | open access | es_ES |