Molecular epidemiology of malaria in Yaounde, Cameroon II. Baseline frequency of point mutations in the dihydropteroate synthase gene of Plasmodium falciparum.
Sulfadoxine-pyrimethamine is one of the alternative antimalarial drugs used to treat chloroquine-resistant Plasmodium falciparum malaria. The molecular target of sulfadoxine, an analog of p-aminobenzoic acid that inhibits the folate biosynthetic pathway, is dihydropteroate synthase (DHPS). The nucleotide sequence of the DHPS gene was determined in 32 clinical isolates obtained in Yaounde, Cameroon, and compared with the sequence of reference clones and Cambodian strains of P. falciparum. Of the 32 Cameroonian isolates, 31 displayed one of the sulfadoxine-sensitive mutation patterns: Ala-436/Ala-437/Ala-581/Ala-613 (n = 20), Ser-436/Gly-437/Ala-581/Ala-613 (n = 6), Ser-436/Ala-437/Ala-581/Ala-613 (n = 4), and Ala-436/Gly-437/Ala-581/Ala-613 (n = 1). One isolate had a sulfadoxine-resistant profile characterized by a double mutation: Phe-436/Ala-437/Ala-581/Ser-613. Although the majority of the isolates had a sulfadoxine-sensitive genetic profile, further studies are needed to correlate the mutation patterns and in vitro and in vivo sulfadoxine sensitivity.
Basco
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LK
Institut Francais de Recherche Scientifique pour le Developpement en Cooperation (ORSTOM), Organisation de Coordination pour la lutte contre les Endemies en Afrique Centrale, Yaounde, Cameroon.
Ringwald
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P
D000818:Animals; D002163:Cameroon / Q000453:epidemiology; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D016054:DNA, Protozoan / Q000032:analysis / Q000737:chemistry; D004094:Dihydropteroate Synthase / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology; D017720:Molecular Epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D003062:Codon; D016054:DNA, Protozoan; D004094:Dihydropteroate Synthase