Hapuarachchi Hapuarachchige C, Dayanath Meegoda Y D, Bandara Kandeyaye Bandaralage A T, Abeysundara Sudusinghe, Abeyewickreme Wimaladharma, de Silva Nilanthi R, Hunt Sonia Y, Sibley Carol Hopkins
Department of Parasitology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
Am J Trop Med Hyg. 2006 Feb;74(2):198-204.
Sulfadoxine-pyrimethamine (SP) is the second-line treatment for Plasmodium falciparum malaria in Sri Lanka. Resistance to SP is caused by point mutations in the dihydrofolate reductase (Pf-dhfr) and dihydropteroate synthase (Pf-dhps) genes of P. falciparum. We determined the genotype of Pf-dhfr and Pf-dhps and the clinical response to SP in 30 field isolates of P. falciparum from Sri Lanka. All patients treated with SP had an adequate clinical response. Eighty-five percent (23 of 27) of pure field isolates carried parasites with double mutant alleles of Pf-dhfr (C59R + S108N) and showed about 200-fold higher levels of resistance to pyrimethamine than the wild type in a yeast system. None of the isolates had either known or novel mutations at other positions in the dhfr domain. In contrast, 67% (20 of 30) of the isolates carried parasites that were wild type for Pf-dhps. In Sri Lanka, detection of the triple mutant allele of Pf-dhfr will require tracking mutations at codon 51.
磺胺多辛-乙胺嘧啶（SP）是斯里兰卡治疗恶性疟原虫疟疾的二线药物。对SP的耐药性是由恶性疟原虫的二氢叶酸还原酶（Pf-dhfr）和二氢蝶酸合酶（Pf-dhps）基因中的点突变引起的。我们测定了来自斯里兰卡的30株恶性疟原虫野外分离株的Pf-dhfr和Pf-dhps基因型以及对SP的临床反应。所有接受SP治疗的患者都有良好的临床反应。85%（27株中的23株）的纯野外分离株携带具有Pf-dhfr双突变等位基因（C59R + S108N）的寄生虫，在酵母系统中对乙胺嘧啶的耐药水平比野生型高约200倍。所有分离株在dhfr结构域的其他位置均未出现已知或新的突变。相比之下，67%（30株中的20株）的分离株携带Pf-dhps野生型寄生虫。在斯里兰卡，检测Pf-dhfr的三重突变等位基因需要追踪第51位密码子的突变情况。
