Verrest, LukaKip, Anke EMusa, Ahmed MSchoone, Gerard JSchallig, Henk DFHMbui, JaneKhalil, Eltahir A GYounis, Brima MOlobo, JosephWere, LilianKimutai, RobertMonnerat, SéverineCruz, IsraelWasunna, MoniqueAlves, FabianaDorlo, Thomas P C2022-05-032022-05-032021-09Clin Infect Dis. 2021 Sep 7;73(5):775-782.http://hdl.handle.net/20.500.12105/14230Background: 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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/PharmacodynamicsVisceral leishmaniasisParasitemiaBiomarkerqPCRLeishmaniasis, VisceralParasitesAfrica, EasternAnimalsBiomarkersHumansParasite LoadAttribution-NonCommercial-NoDerivatives 4.0 Internacional33580234735775-78210.1093/cid/ciab1241537-6591Clinical Infectious Diseases: An official publication of the Infectious Diseases Society of Americaopen access