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恶性疟原虫二氢蝶酸合酶和二氢叶酸还原酶的突变是否使伊朗的疟原虫对周效磺胺-乙胺嘧啶产生耐药性?

Do mutations in Plasmodium falciparum dihydropteroate synthase and dihydrofolate reductase confer resistance to sulfadoxine-pyrimethamine in Iran?

作者信息

Eskandarian Abbas-Ali, Keshavarz Hossein, Basco Leonardo K, Mahboudi Fereidoun

机构信息

Department of Medical Parasitology and Mycology, School of Health, Institute for Health Researches, University of Medical Sciences of Tehran, Tehran, Iran.

出版信息

Trans R Soc Trop Med Hyg. 2002 Jan-Feb;96(1):96-8. doi: 10.1016/s0035-9203(02)90254-3.

Abstract

The key codons of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) genes implicated in sulfadoxine-pyrimethamine (SP) resistance were determined by allele-specific polymerase chain reaction in Plasmodium falciparum isolates collected in 1999 from 35 Iranian patients treated with SP. Seven isolates had Glu-540 dhps allele but 5 of these isolates were characterized to possess wild-type dhfr alleles. Seven additional isolates were polyclonal with mixed Lys- and Glu-540. The key dhfr mutation associated with pyrimethamine resistance, Asn-108, was found in 4 isolates. In one patient the presence of Lys- and Glu-540 in dhps and Asn-108 and Arg-59 in dhfr was associated with treatment failure. However, more studies are needed to determine whether clinical response to SP and mutations in these genes are correlated in Iran.

摘要

采用等位基因特异性聚合酶链反应,对1999年从35例接受周效磺胺-乙胺嘧啶(SP)治疗的伊朗患者中分离出的恶性疟原虫进行检测,确定了与SP耐药性相关的二氢蝶酸合酶(dhps)和二氢叶酸还原酶(dhfr)基因的关键密码子。7株分离株含有Glu-540 dhps等位基因,但其中5株分离株具有野生型dhfr等位基因特征。另外7株分离株为Lys-540和Glu-540混合的多克隆株。在4株分离株中发现了与乙胺嘧啶耐药性相关的关键dhfr突变Asn-108。在1例患者中,dhps基因的Lys-540和Glu-540以及dhfr基因的Asn-108和Arg-59与治疗失败有关。然而,在伊朗,还需要更多研究来确定对SP的临床反应与这些基因中的突变是否相关。

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