Blood Parasite Load as an Early Marker to Predict Treatment Response in Visceral Leishmaniasis in Eastern Africa. (13th February 2021)

• Record Type: Journal Article
• Authors: 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; Dorlo, Thomas P C
• Is Part Of: Clinical infectious diseases. Volume 73:Number 5(2021)
• Page Start: 775
• Page End: 782
• Publication Date: 2021-02-13
• Subjects: visceral leishmaniasis -- parasitemia -- biomarker -- pharmacodynamics -- qPCR; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciab124
• Languages: English
• ISSNs: 1058-4838

Abstract

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 : Blood Leishmania parasite load, determined by qPCR, is a promising early biomarker to predict relapse in visceral leishmaniasis patients and might particularly be useful in the context of dose finding studies of new chemical entities.