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Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in western, northern, and eastern Cambodia, 2011-2012: association with molecular markers.

Authors :
Lim P
Dek D
Try V
Eastman RT
Chy S
Sreng S
Suon S
Mao S
Sopha C
Sam B
Ashley EA
Miotto O
Dondorp AM
White NJ
Su XZ
Char MC
Anderson JM
Amaratunga C
Menard D
Fairhurst RM
Source :
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2013 Nov; Vol. 57 (11), pp. 5277-83. Date of Electronic Publication: 2013 Aug 12.
Publication Year :
2013

Abstract

In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated Plasmodium falciparum 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 ex vivo 50% inhibitory concentrations (IC50s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC50s (GMIC50s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (P ≤ 0.001). An increased copy number of P. falciparum mdr1 (pfmdr1), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC50s 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 ex vivo IC50 and pfmdr1 copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDR P. falciparum 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.

Details

Language :
English
ISSN :
1098-6596
Volume :
57
Issue :
11
Database :
MEDLINE
Journal :
Antimicrobial agents and chemotherapy
Publication Type :
Academic Journal
Accession number :
23939897
Full Text :
https://doi.org/10.1128/AAC.00687-13