Directional Selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu Loci of Plasmodium falciparum in Kenyan Children Treated With ACT

Background. The efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment w...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of infectious diseases 2014-12, Vol.210 (12), p.2001-2008
Main Authors: Henriques, Gisela, Hallett, Rachel L., Beshir, Khalid B., Gadalla, Nahla B., Johnson, Rachel E., Burrow, Rebekah, van Schalkwyk, Donelly A., Sawa, Patrick, Omar, Sabah A., Clark, Taane G., Bousema, Teun, Sutherland, Colin J.
Format: Article
Language:English
Subjects:
Alleles
Antimalarials - therapeutic use
Artemisinins
Artemisinins - therapeutic use
Biological and medical sciences
Cambodia
Child
Child, Preschool
Codons
Drug Resistance
Drug Therapy, Combination
Female
Fundamental and applied biological sciences. Psychology
Genetic loci
Genotype
Genotypes
Haplotypes
Humans
Infant
Infections
Infectious diseases
Kenya
Life cycle. Host-agent relationship. Pathogenesis
Major and Brief Reports
Malaria
Malaria, Falciparum - drug therapy
Male
Medical sciences
Membrane Transport Proteins - genetics
Microbiology
Multidrug Resistance-Associated Proteins - genetics
Parasites
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - isolation & purification
Protozoa
Protozoan Proteins - genetics
Selection, Genetic
Standardized tests
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background. The efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment was associated with subsequent microscopically detected parasitemia at days 28 or 42. Methods. DNA sequences of resistance-associated parasite loci pfcrt, pfmdr1, pfubp1, and pfap2mu were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment, and on the day of treatment failure. Results. Parasites surviving ACT on day 2 or day 3 posttreatment were significantly more likely than the baseline population to carry the wild-type haplotypes of pfcrt (CVMNK at codons 72-76; P
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiu358