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索马里恶性疟原虫体外对氯喹、甲氟喹、奎宁和磺胺多辛/乙胺嘧啶的敏感性:不同药物反应之间的关系

Susceptibility of Plasmodium falciparum in vitro to chloroquine, mefloquine, quinine and sulfadoxine/pyrimethamine in Somalia: relationships between the responses to the different drugs.

作者信息

Warsame M, Wernsdorfer W H, Payne D, Björkman A

机构信息

Department of Morphology and Pathology, Faculty of Medicine, Somali National University, Mogadishu.

出版信息

Trans R Soc Trop Med Hyg. 1991 Sep-Oct;85(5):565-9. doi: 10.1016/0035-9203(91)90343-w.

Abstract

The susceptibilities of Plasmodium falciparum to chloroquine, mefloquine, quinine and sulfadoxine/pyrimethamine were investigated in Mogadishu in 1988, after chloroquine resistance had spread widely in Somalia. Possible correlations of the responses to these drugs were also investigated. Standard World Health Organization in vitro micro-tests were performed. Of 76 isolates tested for chloroquine susceptibility, 58 (76%) were resistant to the drug with mean EC50 and EC99 values of 1.06 x 10(-6) mol/litre and 10.44 x 10(-6) mol/litre of blood, respectively, indicating a high prevalence and degree of resistance. In contrast, all isolates tested were inhibited by mefloquine 3.2 x 10(-6) mol/litre of blood, quinine at 2.56 x (-6) mol/litre of blood-medium mixture, and sulfadoxine/pyrimethamine at 6.0/0.075 x 10(-6) mol/litre of blood-medium mixture, indicating full sensitivity to these 3 drugs. However, a significant positive correlation was found between responses to quinine and chloroquine and between those to quinine and mefloquine; the responses to chloroquine and mefloquine were not correlated. The results may suggest that sites responsible for the correlation are shared between quinine and chloroquine but not essentially between chloroquine and mefloquine. Thus the evolution of chloroquine resistance together with increased use of quinine treatment of P. falciparum may increase the risks of development of quinine resistance, whereas the development of mefloquine resistance would not be triggered by chloroquine resistance.

摘要

1988年,在氯喹耐药性已在索马里广泛传播之后,对摩加迪沙的恶性疟原虫对氯喹、甲氟喹、奎宁和周效磺胺/乙胺嘧啶的敏感性进行了研究。还对这些药物反应之间可能存在的相关性进行了研究。采用了世界卫生组织标准的体外微量试验。在76株接受氯喹敏感性检测的分离株中,58株(76%)对该药耐药,血液中平均半数有效浓度(EC50)和99%有效浓度(EC99)分别为1.06×10⁻⁶摩尔/升和10.44×10⁻⁶摩尔/升,表明耐药率高且耐药程度高。相比之下,所有检测的分离株都被血液中浓度为3.2×10⁻⁶摩尔/升的甲氟喹、血液-培养基混合物中浓度为2.56×10⁻⁶摩尔/升的奎宁以及血液-培养基混合物中浓度为6.0/0.075×10⁻⁶摩尔/升的周效磺胺/乙胺嘧啶所抑制,表明对这三种药物完全敏感。然而,发现对奎宁和氯喹的反应之间以及对奎宁和甲氟喹的反应之间存在显著正相关;对氯喹和甲氟喹的反应不相关。结果可能表明,负责相关性的位点在奎宁和氯喹之间共享,但在氯喹和甲氟喹之间并非本质上共享。因此,氯喹耐药性的演变以及对恶性疟原虫增加使用奎宁治疗可能会增加奎宁耐药性产生的风险,而甲氟喹耐药性的产生不会由氯喹耐药性引发。

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