Limited geographical origin and global spread of sulfadoxine-resistant dhps alleles in Plasmodium falciparum populations.
BACKGROUND
Plasmodium falciparum malaria resistant to chloroquine and pyrimethamine originated in limited foci and migrated to Africa. It remains unresolved whether P. falciparum resistance to sulfadoxine, which is conferred by mutations in dihydropteroate synthase (DHPS), evolved following a similar pattern.


METHODS
The dhps locus of 893 P. falciparum isolates from 12 countries in Asia, the Pacific Islands, Africa, and South America was sequenced. Haplotypes of 6 microsatellite loci flanking the dhps locus were determined to define the genetic relationships among sulfadoxine-resistant lineages.


RESULTS
Six distinct sulfadoxine-resistant lineages were identified. Highly resistant lineages appear to have originated only in Southeast Asia and South America. Two resistant lineages found throughout Southeast Asia have been introduced to East Africa, where they appear to have spread.


CONCLUSIONS
The infrequent selection of parasites highly resistant to sulfadoxine and the subsequent migration of resistant lineages from Asia to Africa are similar to the patterns observed in chloroquine and pyrimethamine resistance. These findings strongly suggest that the global migration of resistant parasites has played a decisive role in the establishment of drug-resistant P. falciparum parasites, and that similar patterns may be anticipated for the spread of artemisinin resistance.
Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Japan. hiro-tm@research.twmu.ac.jp
Toshihiro
T
Mita
Meera
M
Venkatesan
Jun
J
Ohashi
Richard
R
Culleton
Nobuyuki
N
Takahashi
Takahiro
T
Tsukahara
Mathieu
M
Ndounga
Lek
L
Dysoley
Hiroyoshi
H
Endo
Francis
F
Hombhanje
Marcelo U
MU
Ferreira
Christopher V
CV
Plowe
Kazuyuki
K
Tanabe
D000351:Africa, Eastern; D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001210:Asia, Southeastern; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D017125:Genes, Protozoan; D006239:Haplotypes; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013020:South America; D013413:Sulfadoxine / Q000494:pharmacology*
D000962:Antimalarials; D013413:Sulfadoxine; D004094:Dihydropteroate Synthase