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The Parasite Reduction Ratio (PRR) assay version 2: standardized assessment of Plasmodium falciparum viability after antimalarial treatment in vitro

Walz, A. and Duffey, M. and Aljayyoussi, G. and Sax, S. and Leroy, D. and Besson, A. and Burrows, J. N. and Cherkaoui-Rbati, M. H. and Gobeau, N. and Westwood, M.-A. and Siethoff, C. and Gamo, S. and Mäser, P. and Wittlin, S.. (2023) The Parasite Reduction Ratio (PRR) assay version 2: standardized assessment of Plasmodium falciparum viability after antimalarial treatment in vitro. Pharmaceuticals (Basel), 16 (2). p. 163.

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Abstract

With artemisinin-resistant Plasmodium falciparum parasites emerging in Africa, the need for new antimalarial chemotypes is persistently high. The ideal pharmacodynamic parameters of a candidate drug are a rapid onset of action and a fast rate of parasite killing or clearance. To determine these parameters, it is essential to discriminate viable from nonviable parasites, which is complicated by the fact that viable parasites can be metabolically inactive, whilst dying parasites can still be metabolically active and morphologically unaffected. Standard growth inhibition assays, read out via microscopy or [3H] hypoxanthine incorporation, cannot reliably discriminate between viable and nonviable parasites. Conversely, the in vitro parasite reduction ratio (PRR) assay is able to measure viable parasites with high sensitivity. It provides valuable pharmacodynamic parameters, such as PRR, 99.9% parasite clearance time (PCT99.9%) and lag phase. Here we report the development of the PRR assay version 2 (V2), which comes with a shorter assay duration, optimized quality controls and an objective, automated analysis pipeline that systematically estimates PRR, PCT99.9% and lag time and returns meaningful secondary parameters such as the maximal killing rate of a drug (Emax) at the assayed concentration. These parameters can be fed directly into pharmacokinetic/pharmacodynamic models, hence aiding and standardizing lead selection, optimization, and dose prediction. © 2023 by the authors.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Walz, Annabelle and Sax, Sibylle and Mäser, Pascal and Wittlin, Sergio
Item Type:Article, refereed
Article Subtype:Research Article
ISBN:14248247
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:09 May 2023 07:40
Deposited On:09 May 2023 07:40

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