In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment

被引：70
作者：
Curtis, J [1 ]
Duraisingh, MT [1 ]
Warhurst, DC [1 ]
机构：
[1] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
来源：
JOURNAL OF INFECTIOUS DISEASES | 1998年 / 177卷 / 05期
基金：
英国惠康基金;
关键词：
D O I：
10.1086/517831
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Plasmodium falciparum present in blood samples collected before and 3 weeks after treatment with either pyrimethamine-sulfadoxine or chlorproguanil-dapsone was analyzed for variants of the genes coding for the target enzymes of antifolate drugs, dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS), Fragments of the genes were amplified by polymerase chain reactions, and variants were identified by specific restriction endonuclease digestion. Treatment with either drug combination selected for the variants Ile(51), Arg(59), and Asn(108) of DHFR, which have been associated with in vitro resistance to pyrimethamine and cycloguanil. The genotype Ser(436), Gly(437), and Glu(540) of DHPS was selected by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment, showing that a combination of these three variants is important for in vivo resistance to sulfadoxine in the area studied.
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页码：1429 / 1433
页数：5
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