Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia.
Western Cambodia is recognized as the epicentre of emergence of Plasmodium falciparum multi-drug resistance. The emergence of artemisinin resistance has been observed in this area since 2008-2009 and molecular signatures associated to artemisinin resistance have been characterized in k13 gene. At present, one of the major threats faced, is the possible spread of Asian artemisinin resistant parasites over the world threatening millions of people and jeopardizing malaria elimination programme efforts. To anticipate the diffusion of artemisinin resistance, the identification of the P. falciparum population structure and the gene flow among the parasite population in Cambodia are essential.



To this end, a mid-throughput PCR-LDR-FMA approach based on LUMINEX technology was developed to screen for genetic barcode in 533 blood samples collected in 2010-2011 from 16 health centres in malaria endemics areas in Cambodia.



Based on successful typing of 282 samples, subpopulations were characterized along the borders of the country. Each 11-loci barcode provides evidence supporting allele distribution gradient related to subpopulations and gene flow. The 11-loci barcode successfully identifies recently emerging parasite subpopulations in western Cambodia that are associated with the C580Y dominant allele for artemisinin resistance in k13 gene. A subpopulation was identified in northern Cambodia that was associated to artemisinin (R539T resistant allele of k13 gene) and mefloquine resistance.



The gene flow between these subpopulations might have driven the spread of artemisinin resistance over Cambodia.
Institut de Biologie Computationnelle (IBC), Montpellier, France.|IRCM-INSERM U1194, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France.|Université de Montpellier, Montpellier, France.|ICM, Institut régional du Cancer Montpellier, Montpellier, France.
Ankit
A
Dwivedi
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Nimol
N
Khim
Laboratoire de Biostatistiques, Informatique et Physique Pharmaceutique, UFR Pharmacie, Université de Montpellier, Montpellier, France.|Institut de Génomique Fonctionnelle, Montpellier, France.
Christelle
C
Reynes
IRCM-INSERM U1194, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France.|Université de Montpellier, Montpellier, France.|ICM, Institut régional du Cancer Montpellier, Montpellier, France.
Patrice
P
Ravel
Genopole Sequencing Platform, Institut Pasteur, Paris, France.
Laurence
L
Ma
Genopole Sequencing Platform, Institut Pasteur, Paris, France.
Magali
M
Tichit
Genopole Sequencing Platform, Institut Pasteur, Paris, France.
Christiane
C
Bourchier
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Saorin
S
Kim
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Dany
D
Dourng
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Chanra
C
Khean
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Pheaktra
P
Chim
National Centre for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
Sovannaroth
S
Siv
UMR 17, Intertryp, Cirad-IRD, Campus International de Baillarguet, Montpellier, France.|IES-UMR 5214, Institut d'Electronique et des Systèmes, Université de Montpellier-CNRS, Montpellier, France.
Roger
R
Frutos
National Centre for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
Dysoley
D
Lek
Parasite Molecular Immunology Unit, Institut Pasteur, Paris, France.
Odile
O
Mercereau-Puijalon
Parasite Molecular Immunology Unit, Institut Pasteur, Paris, France.
Frédéric
F
Ariey
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia. dmenard@pasteur-kh.org.
Didier
D
Menard
Institut de Biologie Computationnelle (IBC), Montpellier, France. emmanuel.cornillot@umontpellier.fr.|IRCM-INSERM U1194, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France. emmanuel.cornillot@umontpellier.fr.|Université de Montpellier, Montpellier, France. emmanuel.cornillot@umontpellier.fr.|ICM, Institut régional du Cancer Montpellier, Montpellier, France. emmanuel.cornillot@umontpellier.fr.
Emmanuel
E
Cornillot
D000962:Antimalarials / Q000494:pharmacology*; D002160:Cambodia; D058893:DNA Barcoding, Taxonomic; D004351:Drug Resistance; D051456:Gene Flow; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification
D000962:Antimalarials