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Title: Reduced artemisinin susceptibility of plasmodium falciparum ring stages in western cambodia
Authors: Benoit Witkowski
Nimol Khim
Pheaktra Chim
Saorin Kim
Sopheakvatey Ke
Nimol Kloeung
Sophy Chy
Socheat Duong
Rithea Leang
Pascal Ringwald
Arjen M. Dondorp
Rupam Tripura
Francoise Benoit-Vical
Antoine Berry
Olivier Gorgette
Frédéric Ariey
Jean Christophe Barale
Odile Mercereau-Puijalon
Didier Menard
Institut Pasteur du Cambodge
Ministry of Health Cambodia
Organisation Mondiale de la Sante
Mahidol University
CHU de Toulouse
CNRS Centre National de la Recherche Scientifique
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Feb-2013
Citation: Antimicrobial Agents and Chemotherapy. Vol.57, No.2 (2013), 914-923
Abstract: The declining efficacy of artemisinin derivatives against Plasmodium falciparum in western Cambodia is a major concern. The knowledge gap in the understanding of the mechanisms involved hampers designing monitoring tools. Here, we culture-adapted 20 isolates from Pailin and Ratanakiri (areas of artemisinin resistance and susceptibility in western and eastern Cambodia, respectively) and studied their in vitro response to dihydroartemisinin. No significant difference between the two sets of isolates was observed in the classical isotopic test. However, a 6-h pulse exposure to 700 nM dihydroartemisinin (ring-stage survival assay -RSA]) revealed a clear-cut geographic dichotomy. The survival rate of exposed ring-stage parasites (ring stages) was 17-fold higher in isolates from Pailin (median, 13.5%) than in those from Ratanakiri (median, 0.8%), while exposed mature stages were equally and highly susceptible (0.6% and 0.7%, respectively). Ring stages survived drug exposure by cell cycle arrest and resumed growth upon drug withdrawal. The reduced susceptibility to artemisinin in Pailin appears to be associated with an altered in vitro phenotype of ring stages from Pailin in the RSA. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
ISSN: 10986596
Appears in Collections:Scopus 2011-2015

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