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氯喹抗性疟原虫分离株中恶性疟原虫氯喹抗性转运蛋白(pfcrt)基因的新单倍型

New haplotypes of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene among chloroquine-resistant parasite isolates.

作者信息

Nagesha Hadya S, Casey Gerard J, Rieckmann Karl H, Fryauff David J, Laksana Budi S, Reeder John C, Maguire Jason D, Baird J Kevin

机构信息

The Walter and Eliza Hall Institute for Medical Research, Melbourne, Australia.

出版信息

Am J Trop Med Hyg. 2003 Apr;68(4):398-402.

Abstract

Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P < 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16-64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2-8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures.

摘要

对恶性疟原虫氯喹抗性转运蛋白(pfcrt)基因的突变进行了检测,以评估其与来自阿尔莫帕(巴布亚)和巴布亚新几内亚临床样本中氯喹抗性的关联。在巴布亚,发现的5种pfcrt单倍型中有两种是新的:来自阿尔莫帕的SVIET和来自蒂米卡一个分离株的CVIKT。在50个样本中,pfcrt 76T等位基因与氯喹抗性之间也存在很强的关联(P < 0.0001)。在巴布亚新几内亚,在15个氯喹最低抑菌浓度(MIC)为16 - 64 pmol的分离株中观察到pfcrt基因的突变,而其余6个在密码子76处具有野生型pfcrt基因的分离株,其MIC为2 - 8 pmol。这些观察结果证实,pfcrt基因密码子76处的突变在氯喹抗性的体内和体外病例中均存在,并且检测到pfcrt 76T等位基因可以预测潜在的氯喹治疗失败。

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