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<jats:title>ABSTRACT</jats:title><jats:p>In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium falciparum</jats:named-content>malaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is now adversely affecting treatment. While artemisinin (ART) resistance is established in western Cambodia, there is no evidence of PPQ resistance. To monitor for resistance to PPQ and other antimalarials, we measured drug susceptibilities for parasites collected in 2011 and 2012 from Pursat, Preah Vihear, and Ratanakiri, in western, northern, and eastern Cambodia, respectively. Using a SYBR green I fluorescence assay, we calculated the<jats:italic>ex vivo</jats:italic>50% inhibitory concentrations (IC<jats:sub>50</jats:sub>s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC<jats:sub>50</jats:sub>s (GMIC<jats:sub>50</jats:sub>s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (<jats:italic>P</jats:italic>≤ 0.001). An increased copy number of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content><jats:italic>mdr1</jats:italic>(<jats:italic>pfmdr1</jats:italic>), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC<jats:sub>50</jats:sub>s for MQ, QN, ATS, and DHA. An increased copy number of a chromosome 5 region (X5r), a candidate PPQ resistance marker, was detected in Pursat but was not associated with reduced susceptibility to PPQ. The<jats:italic>ex vivo</jats:italic>IC<jats:sub>50</jats:sub>and<jats:italic>pfmdr1</jats:italic>copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDR<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>is prevalent in western and northern Cambodia, there is no evidence for PPQ resistance, suggesting that DHA-PPQ treatment failures result mainly from ART resistance.</jats:p>

Original publication

DOI

10.1128/aac.00687-13

Type

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

11/2013

Volume

57

Pages

5277 - 5283