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<jats:title>ABSTRACT</jats:title> <jats:p> High-grade chloroquine (CQ) resistance has emerged in both <jats:named-content content-type="genus-species">Plasmodium falciparum</jats:named-content> and <jats:named-content content-type="genus-species">P. vivax</jats:named-content> . The aim of the present study was to investigate the phenotypic differences of CQ resistance in both of these species and the ability of known CQ resistance reversal agents (CQRRAs) to alter CQ susceptibility. Between April 2015 and April 2016, the potential of verapamil (VP), mibefradil (MF), L703,606 (L7), and primaquine (PQ) to reverse CQ resistance was assessed in 46 <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> and 34 <jats:named-content content-type="genus-species">P. vivax</jats:named-content> clinical isolates in Papua, Indonesia, where CQ resistance is present in both species, using a modified schizont maturation assay. In <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> , CQ 50% inhibitory concentrations (IC <jats:sub>50</jats:sub> s) were reduced when CQ was combined with VP (1.4-fold), MF (1.2-fold), L7 (4.2-fold), or PQ (1.8-fold). The degree of CQ resistance reversal in <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> was highly correlated with CQ susceptibility for all CQRRAs ( <jats:italic>R</jats:italic> <jats:sup>2</jats:sup> = 0.951, 0.852, 0.962, and 0.901 for VP, MF, L7, and PQ, respectively), in line with observations in <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> laboratory strains. In contrast, no reduction in the CQ IC <jats:sub>50</jats:sub> s was observed with any of the CQRRAs in <jats:named-content content-type="genus-species">P. vivax</jats:named-content> , even in those isolates with high chloroquine IC <jats:sub>50</jats:sub> s. The differential effect of CQRRAs in <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> and <jats:named-content content-type="genus-species">P. vivax</jats:named-content> suggests significant differences in CQ kinetics and, potentially, the likely mechanism of CQ resistance between these two species. </jats:p>

Original publication

DOI

10.1128/aac.00355-17

Type

Journal article

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

08/2017

Volume

61