Curtis J, Duraisingh M T, Warhurst D C
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
J Infect Dis. 1998 May;177(5):1429-33. doi: 10.1086/517831.
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 Ile51, Arg59, and Asn108 of DHFR, which have been associated with in vitro resistance to pyrimethamine and cycloguanil. The genotype Ser436, Gly437, and Glu540 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.
对在用乙胺嘧啶 - 磺胺多辛或氯胍 - 氨苯砜治疗前及治疗3周后采集的血样中的恶性疟原虫，分析编码抗叶酸药物靶标酶二氢叶酸还原酶（DHFR）和二氢蝶酸合酶（DHPS）的基因变体。通过聚合酶链反应扩增基因片段，并通过特异性限制性内切酶消化鉴定变体。两种药物组合治疗均选择了与体外对乙胺嘧啶和环氯胍耐药相关的DHFR的Ile51、Arg59和Asn108变体。乙胺嘧啶 - 磺胺多辛治疗选择了DHPS的Ser436、Gly437和Glu540基因型，但氯胍 - 氨苯砜治疗未选择，这表明这三种变体的组合对所研究地区体内对磺胺多辛的耐药性很重要。
