K13-propeller Alleles, Mdr1 Polymorphism, and Drug Effectiveness at Day 3 after Artemether-lumefantrine Treatment for Plasmodium falciparum Malaria in Colombia, 2014-2015 [PublishAheadOfPrint]

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 a delayed 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 parasite isolates 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 NFSDD mdr1 haplotype. 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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