1. Baseline in vivo, ex vivo and molecular responses of Plasmodium falciparum to artemether and lumefantrine in three endemic zones for malaria in Colombia.
- Author
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Aponte S, Guerra ÁP, Álvarez-Larrotta C, Bernal SD, Restrepo C, González C, Yasnot MF, and Knudson-Ospina A
- Subjects
- Adolescent, Adult, Aged, Antimalarials pharmacology, Artemether, Artemether, Lumefantrine Drug Combination, Artemisinins pharmacology, Child, Colombia, DNA Copy Number Variations, Drug Combinations, Drug Resistance drug effects, Drug Resistance genetics, Drug Therapy, Combination, Ethanolamines pharmacology, Female, Fluorenes pharmacology, Humans, Lumefantrine, Malaria parasitology, Male, Middle Aged, Parasitemia drug therapy, Plasmodium falciparum isolation & purification, Polymorphism, Genetic, Protozoan Proteins genetics, Young Adult, Antimalarials therapeutic use, Artemisinins therapeutic use, Ethanolamines therapeutic use, Fluorenes therapeutic use, Malaria drug therapy, Plasmodium falciparum drug effects
- Abstract
Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools., Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days. Ex vivo test was performed using the microtest technique for chloroquine, arthemeter, dihydroartemisinin and lumefantrine. Pfmdr1 copy number and polymorphisms in Pfk13, Pfatp6, Pfcrt and Pfmdr1 genes were analyzed., Results: From a total of 150 screened patients, 49 completed follow-up for 28 days. All treated patients had adequate clinical and parasitological responses. Parasitic clearance showed a drastic reduction of parasite biomass at 24 hours and complete elimination at 48 hours. One hundred eleven isolates were processed, all exhibited high susceptibility to artemisinins and a slight decrease in susceptibility to lumefantrine. No genetic polymorphisms associated with resistance to artemisinin were found., Conclusion: This study generated a susceptibility baseline in response to therapy with Coartem (artemether-lumefantrine) with numerical reference values, which will allow data comparison with future studies to systematically monitor changes in the parasite and to provide an early alert to the health authorities., (© The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
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