Plasmodium falciparum:: Selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children
Plasmodium falciparum:: Selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children
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DOI：
10.4269/ajtmh.1999.61.125
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发表时间：
1999-07-01
影响因子：
3.3
通讯作者：
Warhurst, DC
中科院分区：
文献类型：
--
作者：
Jelinek, T;Kilian, AHD;Warhurst, DC
在乌干达，对 41 名无并发症疟疾儿童进行了恶性疟原虫对复方新诺明（甲氧苄啶/磺胺甲恶唑）耐药性的体内测试，并在治疗前后的血液样本中筛查了二氢叶酸还原酶 (DHFR) 和二氢叶酸合成酶 (DHPS) 抗叶酸靶基因的多态性。在暴露于复方新诺明药物压力后收集的样品中观察到 DHFR 和 DHPS 基因的一些密码子针对特定基因型的选择。 DHFR 的等位基因 51-异亮氨酸、59-精氨酸和 108-丝氨酸与临床耐药性显着相关，DHPS 的等位基因 581-丙氨酸也是如此。对抗叶酸组合物的耐药性可能需要 DHFR 和 DHPS 基因中与耐药性相关的多态性。此外，甲氧苄啶抗性 DHFR 基因型与乙胺嘧啶的基因型在残基 108 处有所不同。
In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108.