Plowe C V, Kublin J G, Doumbo O K
Molecular Parasitology and Malaria Field Studies Unit, Center for Vaccine Development/Division of Geographic Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Drug Resist Updat. 1998;1(6):389-96. doi: 10.1016/s1368-7646(98)80014-9.
Plasmodium falciparum resistance to the antifolates has arisen rapidly in Asia and South America, and threatens the usefulness of these drugs in Africa. In vitro resistance to the antifolates is determined by mutations in parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS). The role of DHFR and DHPS mutations in therapeutic failure of antifolate antimalarials is less clear. This review summarizes molecular epidemiological surveys, studies of in vivo selection of mutant alleles by drug treatment, and prospective studies of the ability of mutation-specific assays to predict clinical outcomes, and discusses the potential use of these assays for surveillance of resistance.
恶性疟原虫对抗叶酸药物的耐药性在亚洲和南美洲迅速出现，并威胁到这些药物在非洲的有效性。寄生虫二氢叶酸还原酶（DHFR）和二氢蝶酸合酶（DHPS）的突变决定了对这些抗叶酸药物的体外耐药性。DHFR和DHPS突变在抗叶酸抗疟药治疗失败中的作用尚不清楚。本综述总结了分子流行病学调查、药物治疗对突变等位基因的体内选择研究，以及突变特异性检测预测临床结果能力的前瞻性研究，并讨论了这些检测在耐药性监测中的潜在用途。
