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泰国恶性疟原虫对青蒿琥酯的体外敏感性

In vitro sensitivity of Plasmodium falciparum to artesunate in Thailand.

作者信息

Wongsrichanalai C, Wimonwattrawatee T, Sookto P, Laoboonchai A, Heppner D G, Kyle D E, Wernsdorfer W H

机构信息

Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.

出版信息

Bull World Health Organ. 1999;77(5):392-8.

Abstract

Reported are the in vitro susceptibilities of Plasmodium falciparum to artesunate, mefloquine, quinine and chloroquine of 86 isolates and to dihydroartemisinin of 45 isolates collected from areas of high resistance to mefloquine within Thailand near the borders with Myanmar and Cambodia, and from southern Thailand where P. falciparum is generally still sensitive to mefloquine. All the isolates were highly sensitive to artesunate, but the geometric mean IC50S were higher in isolates from the Thai-Myanmar and Thai-Cambodian borders than in those from southern Thailand. The IC50S for mefloquine and artesunate were strongly correlated (Pearson r = 0.605; n = 86; P < 0.00001). As expected, the in vitro sensitivities to dihydroartemisinin and artesunate were similar and strongly correlated (at IC50, Pearson r = 0.695; n = 45; P < 0.00002). The correlation between the activity of mefloquine and artesunate requires further investigation in order to determine the potential for development of cross-resistance in nature. Our results suggest that combination with mefloquine is not the ideal way of protecting the usefulness of artemisinin and its derivatives. A search for more suitable partner drugs to these compounds and careful regulation of their use are necessary in the interest of ensuring their long therapeutic life span.

摘要

报告了从泰国与缅甸和柬埔寨接壤边境附近对甲氟喹高度耐药地区以及泰国南部(那里恶性疟原虫通常仍对甲氟喹敏感)收集的86株恶性疟原虫对青蒿琥酯、甲氟喹、奎宁和氯喹的体外敏感性,以及45株对双氢青蒿素的体外敏感性。所有分离株对青蒿琥酯均高度敏感,但来自泰国-缅甸和泰国-柬埔寨边境的分离株的几何平均半数抑制浓度(IC50)高于来自泰国南部的分离株。甲氟喹和青蒿琥酯的IC50高度相关(Pearson相关系数r = 0.605;n = 86;P < 0.00001)。正如预期的那样,双氢青蒿素和青蒿琥酯的体外敏感性相似且高度相关(在IC50时,Pearson相关系数r = 0.695;n = 45;P < 0.00002)。甲氟喹和青蒿琥酯活性之间的相关性需要进一步研究,以确定自然界中交叉耐药性产生的可能性。我们的结果表明,与甲氟喹联合使用并非保护青蒿素及其衍生物有效性的理想方式。为确保这些化合物的长效治疗寿命,有必要寻找更合适的联合用药伙伴并仔细规范其使用。

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