Tolerance of Plasmodium falciparum mefloquine-resistant clinical isolates to mefloquine-piperaquine with implications for triple artemisinin-based combination therapies.

ABSTRACT: Triple artemisinin-based combination therapies (TACTs) have been proposed to delay the emergence of multidrug-resistant Plasmodium falciparum by combining two partner drugs with an artemisinin derivative. Among these, mefloquine-piperaquine (MQ-PPQ) is a leading candidate, based on the assumption that simultaneous resistance to both partner drugs would be difficult to develop. Here, we assess the efficacy and resistance potential of MQ-PPQ using Cambodian clinical isolates with distinct resistance profiles. We find that MQ resistance confers significant cross-tolerance to the MQ-PPQ combination, whereas PPQ-resistant and -sensitive strains remain susceptible. Under repeated MQ-PPQ pressure for four months, parasites rapidly acquire MQ-PPQ tolerance, driven by pfmdr1 amplification. Mechanis

SUBMITTER: Roesch C 

PROVIDER: S-EPMC12660809 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature