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恶性疟原虫对五种药物的敏感性:一项主要针对泰国分离株的体外研究

Susceptibility of Plasmodium falciparum to five drugs: an in vitro study of isolates mainly from Thailand.

作者信息

Thaithong S, Beale G H, Chutmongkonkul M

出版信息

Trans R Soc Trop Med Hyg. 1983;77(2):228-31. doi: 10.1016/0035-9203(83)90080-9.

DOI:10.1016/0035-9203(83)90080-9
PMID:6346591
Abstract

This paper describes the results of testing the susceptibility of 60 isolates of the human malaria parasite Plasmodium falciparum from Thailand, and single isolates from five other countries, to five drugs: chloroquine, pyrimethamine, quinine, mefloquine and amodiaquine. The Thai isolates were obtained from patients in three different regions of the country (Chantaburi, Songkhla and Mae Sod), and were first grown in culture by the Trager-Jensen candle-jar technique. Samples were then exposed to a range of concentrations of the five drugs, in Falcon microtest culture wells, for 72 hours, with daily changes of medium (with or without added drug solutions). Presence or absence of parasites was then determined by microscope observations on thin-film Giemsa-stained preparations. Most Thai isolates showed a minimum inhibitory concentration (MIC) for chloroquine of 10(-6) M or higher, and were classified as highly resistant, though one cloned isolate was as sensitive to this drug as a chloroquine-sensitive isolate from West Africa. Similarly most Thai isolates showed a very high resistance to pyrimethamine (MIC 10(-4) M to 10(-6) M), but a few clones were sensitive (MIC 10(-9)) to it. Susceptibility to quinine showed some variation (MIC varied between 10(-6) M and 10(-8) M), and some isolates were thought to be incapable of responding to a therapeutically permissible dose of this drug. Little variation was found in the reaction of any of the isolates to mefloquine or amodiaquine, and by the in vitro technique used in this study, it was found that chloroquine-resistant and chloroquine-sensitive isolates were equally susceptible to amodiaquine. In general the survey showed the existence of a marked correlation between development of drug resistance of Plasmodium falciparum and the extent to which a given drug had been used in Thailand.

摘要

本文描述了对来自泰国的60株人类疟原虫恶性疟原虫分离株以及来自其他五个国家的单株分离株,进行五种药物敏感性测试的结果。这五种药物分别是:氯喹、乙胺嘧啶、奎宁、甲氟喹和阿莫地喹。泰国的分离株取自该国三个不同地区(尖竹汶府、宋卡府和夜丰颂府)的患者,并首先通过特拉格 - 詹森烛缸技术在培养基中培养。然后将样本置于Falcon微量测试培养孔中,暴露于一系列浓度的这五种药物中72小时,每天更换培养基(添加或不添加药物溶液)。随后通过对薄血膜吉姆萨染色制剂进行显微镜观察来确定是否存在疟原虫。大多数泰国分离株对氯喹的最低抑菌浓度(MIC)为10^(-6) M或更高,被归类为高度耐药,不过有一个克隆分离株对该药物的敏感性与来自西非的氯喹敏感分离株相同。同样,大多数泰国分离株对乙胺嘧啶表现出极高的耐药性(MIC为10^(-4) M至10^(-6) M),但有少数克隆株对其敏感(MIC为10^(-9))。对奎宁的敏感性存在一些差异(MIC在10^(-6) M至10^(-8) M之间变化),一些分离株被认为无法对该药物的治疗许可剂量产生反应。在任何分离株对甲氟喹或阿莫地喹的反应中几乎没有发现差异,并且通过本研究中使用的体外技术发现,氯喹耐药和氯喹敏感的分离株对阿莫地喹的敏感性相同。总体而言,该调查表明恶性疟原虫耐药性的发展与泰国特定药物的使用程度之间存在显著相关性。

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