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

Madeline Montenegro | Zendy; Aaron Neal | Zendy; Maritza Posada | Zendy; Briegel De Las Salas | Zendy; Tatiana M. Lopera-Mesa | Zendy; Rick M. Fairhurst | Zendy; Alberto Tobón-Castaño | Zendy

Open Access

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

Author(s) -

Madeline Montenegro,

Aaron Neal,

Maritza Posada,

Briegel De Las Salas,

Tatiana M. Lopera-Mesa,

Rick M. Fairhurst,

Alberto Tobón-Castaño

Publication year - 2017

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.01036-17

Subject(s) - artemether/lumefantrine , plasmodium falciparum , lumefantrine , malaria , artemether , biology , artemisinin , allele , polymorphism (computer science) , drug , virology , drug resistance , genetics , medicine , pharmacology , immunology , gene

High treatment failure rates forPlasmodium 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 uncomplicatedP. 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 theP. 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 uncomplicatedP. 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-typeK13 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 NF SD Dmdr1 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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