K13 Propeller Alleles, mdr1 Polymorphism, and Drug Effectiveness at Day 3 after Artemether-Lumefantrine Treatment for Plasmodium falciparum Malaria in Colombia, 2014-2015

被引:0
作者
Montenegro, Madeline [1 ]
Neal, Aaron T. [2 ]
Posada, Maritza [1 ]
De las Salas, Briegel [1 ]
Lopera-Mesa, Tatiana M. [1 ]
Fairhurst, Rick M. [2 ]
Tobon-Castano, Alberto [1 ]
机构
[1] Univ Antioquia, Grp Malaria, Medellin, Colombia
[2] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA
关键词
Colombia; K13; Mdr1; antimalarial agents; artemether; artemisinin; drug resistance; lumefantrine; malaria; IN-VITRO SUSCEPTIBILITY; ARTEMISININ RESISTANCE; EX-VIVO; CHLOROQUINE RESISTANCE; THERAPEUTIC RESPONSE; ARTESUNATE-AMODIAQUINE; UNCOMPLICATED MALARIA; COMBINATION THERAPY; ANTIMALARIAL-DRUGS; WESTERN CAMBODIA;
D O I
10.1128/AAC.01036-17
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
High treatment failure rates for Plasmodium falciparum malaria have been reported in Colombia for chloroquine, amodiaquine, and sulfadoxine-pyrimethamine. Artemisinin combination therapies were introduced in 2006 in Colombia, where artemether-lumefantrine (AL) is currently used to treat uncomplicated P. falciparum malaria. Artemisinin (ART) resistance was initially observed in Southeast Asia as an increased parasite clearance time, manifesting as a positive thick-blood smear on day 3 after treatment (D3 positivity). Recently, mutations in the propeller domain of the P. falciparum kelch13 gene (K13 propeller) have been associated with ART resistance. In this study, we surveyed AL effectiveness at D3 and molecular markers of drug resistance among 187 uncomplicated P. falciparum cases in 4 regions of Colombia from June 2014 to July 2015. We found that 3.2% (4/125) of patients showed D3 positivity, 100% (163/163) of isolates carried wild-type K13 propeller alleles, 12.9% (23/178) of isolates had multiple copies of the multidrug resistance 1 gene (mdr1), and 75.8% (113/149) of isolates harbored the double mutant N (F) under barS (D) under barD mdr1 haplotype (the underlining indicates mutant alleles). These data suggest that ART resistance is not currently suspected in Colombia but that monitoring for lumefantrine resistance and AL failures should continue.
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