1. Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa.
- Author
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Verrest, Luka, Kip, Anke E, Musa, Ahmed M, Schoone, Gerard J, Schallig, Henk D F H, Mbui, Jane, Khalil, Eltahir A G, Younis, Brima M, Olobo, Joseph, Were, Lilian, Kimutai, Robert, Monnerat, Séverine, Cruz, Isra, Wasunna, Monique, Alves, Fabiana, and Dorlo, Thomas P C
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ANTIPARASITIC agents , *BIOMARKERS , *REVERSE transcriptase polymerase chain reaction , *LEISHMANIASIS , *PREDICTIVE tests , *DNA , *VIRAL load , *TREATMENT effectiveness , *DISEASE relapse , *DESCRIPTIVE statistics , *POLYMERASE chain reaction , *RECEIVER operating characteristic curves , *PHARMACODYNAMICS , *EVALUATION - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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