Invasion of Africa by a single pfcrt allele of South East Asian type.
BACKGROUND
Because of its dramatic public health impact, Plasmodium falciparum resistance to chloroquine (CQ) has been documented early on. Chloroquine-resistance (CQR) emerged in the late 1950's independently in South East Asia and South America and progressively spread over all malaria areas. CQR was reported in East Africa in the 1970's, and has since invaded the African continent. Many questions remain about the actual selection and spreading process of CQR parasites, and about the evolution of the ancestral mutant gene(s) during spreading.


METHODS
Eleven clinical isolates of P. falciparum from Cambodia and 238 from Africa (Senegal, Ivory Coast, Bukina Faso, Mali, Guinea, Togo, Benin, Niger, Congo, Madagascar, Comoros Islands, Tanzania, Kenya, Mozambique, Cameroun, Gabon) were collected during active case detection surveys carried out between 1996 and 2001. Parasite DNA was extracted from frozen blood aliquots and amplification of the gene pfcrt exon 2 (codon 72-76), exon 4 and intron 4 (codon 220 and microsatellite marker) were performed. All fragments were sequenced.


RESULTS
124 isolates with a sensitive (c76/c220:CVMNK/A) haplotype and 125 isolates with a resistant c76/c220:CVIET/S haplotype were found. The microsatellite showed 17 different types in the isolates carrying the c76/c220:CVMNK/A haplotype while all 125 isolates with a CVIET/S haplotype but two had a single microsatellite type, namely (TAAA)3(TA)15, whatever the location or time of collection.


CONCLUSIONS
Those results are consistent with the migration of a single ancestral pfcrt CQR allele from Asia to Africa. This is related to the importance of PFCRT in the fitness of P. falciparum point out this protein as a potential target for developments of new antimalarial drugs.
Ariey
Frédéric
F
Institut Pasteur du Cambodge, Phnom-Penh, Cambodia. fariey@pasteur-kh.org
Fandeur
Thierry
T
Durand
Remy
R
Randrianarivelojosia
Milijaona
M
Jambou
Ronan
R
Legrand
Eric
E
Ekala
Marie Thérèse
MT
Bouchier
Christiane
C
Cojean
Sandrine
S
Duchemin
Jean Bernard
JB
Robert
Vincent
V
Le Bras
Jacques
J
Mercereau-Puijalon
Odile
O
D000349:Africa / Q000453:epidemiology; D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001483:Base Sequence; D002160:Cambodia / Q000453:epidemiology; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology / Q000635:transmission*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D026901:Membrane Transport Proteins; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D015800:Protozoan Proteins
D000962:Antimalarials; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine