2026-08-29T14:55:12Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/142302025-05-08T12:45:31Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19613

00925njm 22002777a 4500 dc Verrest, Luka author Kip, Anke E author Musa, Ahmed M author Schoone, Gerard J author Schallig, Henk DFH author Mbui, Jane author Khalil, Eltahir A G author Younis, Brima M author Olobo, Joseph author Were, Lilian author Kimutai, Robert author Monnerat, Séverine author Cruz, Israel author Wasunna, Monique author Alves, Fabiana author Dorlo, Thomas P C author 2021-09 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. Clin Infect Dis. 2021 Sep 7;73(5):775-782. 10.1093/cid/ciab124 1537-6591 Clinical Infectious Diseases: An official publication of the Infectious Diseases Society of America 33580234 http://hdl.handle.net/20.500.12105/14230 Pharmacodynamics Visceral leishmaniasis Parasitemia Biomarker qPCR Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa