AUTHOR=Walz Annabelle , Sax Sibylle , Scheurer Christian , Tamasi Balint , Mäser Pascal , Wittlin Sergio 

TITLE=Incomplete Plasmodium falciparum growth inhibition following piperaquine treatment translates into increased parasite viability in the in vitro parasite reduction ratio assay

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1396786

DOI=10.3389/fcimb.2024.1396786

ISSN=2235-2988

ABSTRACT=<p>Antimalarial resistance to the first-line partner drug piperaquine (PPQ) threatens the effectiveness of artemisinin-based combination therapy. <italic>In vitro</italic> piperaquine resistance is characterized by incomplete growth inhibition, i.e. increased parasite growth at higher drug concentrations. However, the 50% inhibitory concentrations (IC<sub>50</sub>) remain relatively stable across parasite lines. Measuring parasite viability of a drug-resistant Cambodian <italic>Plasmodium falciparum</italic> isolate in a parasite reduction ratio (PRR) assay helped to better understand the resistance phenotype towards PPQ. In this parasite isolate, incomplete growth inhibition translated to only a 2.5-fold increase in IC<sub>50</sub> but a dramatic decrease of parasite killing in the PRR assay. Hence, this pilot study reveals the potential of <italic>in vitro</italic> parasite viability assays as an important, additional tool when it comes to guiding decision-making in preclinical drug development and post approval. To the best of our knowledge, this is the first time that a compound was tested against a drug-resistant parasite in the <italic>in vitro</italic> PRR assay.</p>