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印度尼西亚中爪哇省普禾加多县恶性疟原虫分离株中抗疟药物耐药等位基因的频率分布。

Frequency distribution of antimalarial drug-resistant alleles among isolates of Plasmodium falciparum in Purworejo district, Central Java Province, Indonesia.

作者信息

Syafruddin D, Asih Puji B S, Aggarwal Sona L, Shankar Anuraj H

机构信息

Eijkman Institute for Molecular Biology, Jakarta, Indonesia.

出版信息

Am J Trop Med Hyg. 2003 Dec;69(6):614-20.

Abstract

Treatment failures to the first- and second-lines antimalarial drugs chloroquine and sulfadoxine-pyrimethamine have increased in the Purworejo district on the island of Java, Indonesia. A molecular epidemiologic study was conducted to determine the frequency distribution of mutant alleles of the genes associated with the resistance among the isolates of Plasmodium falciparum from the area. Analyses using a polymerase chain reaction and restriction fragment length polymorphism showed that nearly all of the 111 samples carried mutant alleles in genes associated with chloroquine resistance: P. falciparum multi-drug resistance 1 (pfmdrl) 86Y (92%), 1042D (4.5%), and P. falciparum chloroquine resistance transporter (pfcrt) 76T (99.1%). Mutant alleles of the in the dihydrofolate reductase (dhfr) gene were also high (84.7%), either as 108N and 108T or paired with 59R, and 16V, respectively. Mutant alleles in the dihydropteroate synthase gene were the least common, either as a single 437G mutation (35.3%) or paired with 540E (26.5%). These results are consistent with the antimalarial drug resistance situation in the area and emphasize the need for a proper treatment strategy.

摘要

在印度尼西亚爪哇岛的普禾加多地区,一线和二线抗疟药物氯喹及磺胺多辛-乙胺嘧啶的治疗失败情况有所增加。开展了一项分子流行病学研究,以确定该地区恶性疟原虫分离株中与耐药性相关基因的突变等位基因频率分布。采用聚合酶链反应和限制性片段长度多态性进行分析显示,111份样本中几乎所有样本在与氯喹耐药性相关的基因中都携带突变等位基因:恶性疟原虫多药耐药1(pfmdrl)86Y(92%)、1042D(4.5%),以及恶性疟原虫氯喹耐药转运蛋白(pfcrt)76T(99.1%)。二氢叶酸还原酶(dhfr)基因中的突变等位基因也很高(84.7%),分别为108N和108T,或分别与59R和16V配对。二氢蝶酸合酶基因中的突变等位基因最不常见,要么是单个437G突变(35.3%),要么与540E配对(26.5%)。这些结果与该地区的抗疟药物耐药情况相符,并强调了制定适当治疗策略的必要性。

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