Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2021 Sep 07

filter terms:

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. 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. 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. 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. © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Citation

Luka Verrest, Anke E Kip, Ahmed M Musa, Gerard J Schoone, Henk D F H Schallig, Jane Mbui, Eltahir A G Khalil, Brima M Younis, Joseph Olobo, Lilian Were, Robert Kimutai, Séverine Monnerat, Isra Cruz, Monique Wasunna, Fabiana Alves, Thomas P C Dorlo. Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021 Sep 07;73(5):775-782