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

Autor: Montenegro M; Grupo Malaria, Universidad de Antioquia, Medellín, Colombia., Neal AT; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA., Posada M; Grupo Malaria, Universidad de Antioquia, Medellín, Colombia., De Las Salas B; Grupo Malaria, Universidad de Antioquia, Medellín, Colombia., Lopera-Mesa TM; Grupo Malaria, Universidad de Antioquia, Medellín, Colombia., Fairhurst RM; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA rfairhurst@niaid.nih.gov alberto.tobon1@udea.edu.co., Tobon-Castaño A; Grupo Malaria, Universidad de Antioquia, Medellín, Colombia rfairhurst@niaid.nih.gov alberto.tobon1@udea.edu.co.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2017 Nov 22; Vol. 61 (12). Date of Electronic Publication: 2017 Nov 22 (Print Publication: 2017).
DOI: 10.1128/AAC.01036-17
Abstrakt: 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 S D D 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.
(Copyright © 2017 American Society for Microbiology.)
Databáze: MEDLINE