The Parasite Reduction Ratio (PRR) assay version 2: standardized assessment of Plasmodium falciparum viability after antimalarial treatment in vitro
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
4665602
Author(s)
Walz, A.; Duffey, M.; Aljayyoussi, G.; Sax, S.; Leroy, D.; Besson, A.; Burrows, J. N.; Cherkaoui-Rbati, M. H.; Gobeau, N.; Westwood, M.-A.; Siethoff, C.; Gamo, S.; Mäser, P.; Wittlin, S.
Author(s) at UniBasel
Walz, Annabelle Sax, Sibylle Mäser, Pascal Wittlin, Sergio
Year
2023
Title
The Parasite Reduction Ratio (PRR) assay version 2: standardized assessment of Plasmodium falciparum viability after antimalarial treatment in vitro
Journal
Pharmaceuticals (Basel)
Volume
16
Number
2
Pages / Article-Number
163
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.
ISSN/ISBN
14248247
URL
https://doi.org/10.3390/ph16020163
edoc-URL
https://edoc.unibas.ch/94582/
Full Text on edoc
Available
Digital Object Identifier DOI
10.3390/ph16020163
PubMed ID
http://www.ncbi.nlm.nih.gov/pubmed/37009844
ISI-Number
WOS:000941639500001
Document type (ISI)
Journal Article
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