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老挝新发恶性疟原虫分离株的体外抗疟药物敏感性及pfcrt基因突变情况

In vitro antimalarial drug susceptibility and pfcrt mutation among fresh Plasmodium falciparum isolates from the Lao PDR (Laos).

作者信息

Mayxay Mayfong, Barends Marion, Brockman Alan, Jaidee Anchalee, Nair Shalini, Sudimack Dan, Pongvongsa Tiengkham, Phompida Samlane, Phetsouvanh Rattanaxay, Anderson Tim, White Nicholas J, Newton Paul N

机构信息

Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR.

出版信息

Am J Trop Med Hyg. 2007 Feb;76(2):245-50.

Abstract

Recent drug trials in Laos have shown high levels of Plasmodium falciparum resistance to chloroquine, but there are no published data on in vitro antimalarial drug susceptibility. We used the double-site enzyme-linked pLDH immunodetection (DELI) assay to estimate the in vitro antimalarial drug susceptibility of 108 fresh P. falciparum isolates from southern Laos. The geometric mean (95% confidence interval) 50% inhibitory concentration values (nmol/L) were 152.4 (123.8-187.6) for chloroquine, 679.8 (533.8-863.0) for quinine, 45.9 (37.9-55.7) for mefloquine, 5.0 (4.4-6.4) for artesunate, 6.3 (4.5-8.9) for dihydroartemisinin, and 59.1 (46.4-75.3) for lumefantrine. The proportion of isolates defined as resistant were 65%, 40%, and 8% for chloroquine, quinine, and mefloquine, respectively. Of 53 isolates genotyped for the pfcrt T76K chloroquine-resistance mutation, 48 (91%) were mutants. P. falciparum in Laos is multi-drug resistant; antimalarial immunity resulting from the use of ineffective chloroquine before 2005 probably contributes significantly to the therapeutic responses in clinical trials.

摘要

老挝最近的药物试验表明,恶性疟原虫对氯喹的耐药性水平很高,但尚无关于体外抗疟药物敏感性的公开数据。我们使用双位点酶联pLDH免疫检测(DELI)分析法,对来自老挝南部的108株新鲜恶性疟原虫分离株的体外抗疟药物敏感性进行了评估。氯喹的几何平均(95%置信区间)50%抑制浓度值(nmol/L)为152.4(123.8 - 187.6),奎宁为679.8(533.8 - 863.0),甲氟喹为45.9(37.9 - 55.7),青蒿琥酯为5.0(4.4 - 6.4),双氢青蒿素为6.3(4.5 - 8.9),本芴醇为59.1(46.4 - 75.3)。被定义为耐药的分离株比例,氯喹为65%,奎宁为40%,甲氟喹为8%。在对pfcrt T76K氯喹耐药突变进行基因分型的53株分离株中,48株(91%)为突变体。老挝的恶性疟原虫对多种药物耐药;2005年前使用无效氯喹产生的抗疟免疫力可能对临床试验中的治疗反应有显著影响。

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