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抗疟药物:现状与新进展

Antimalarial drugs: current status and new developments.

作者信息

Rathore Dharmendar, McCutchan Thomas F, Sullivan Margery, Kumar Sanjai

机构信息

Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Washington Street, Blacksburg, VA 24061, USA.

出版信息

Expert Opin Investig Drugs. 2005 Jul;14(7):871-83. doi: 10.1517/13543784.14.7.871.

Abstract

Malaria continues to be a major threat in the developing world, with > 1 million clinical episodes and 3000 deaths every day. In the last century, malaria claimed between 150 and 300 million lives, accounting for 2 - 5% of all deaths. Currently approximately 40% of the world population resides in areas of active malaria transmission. The disease symptoms are most severe in young children and pregnant women. A total of 90% of the disease-associated mortality occurs in Subsaharan Africa, despite the fact that malaria is indigenous to most tropical regions. A licensed vaccine for malaria has not become a reality and antimalarial drugs are the only available method of treatment. Although chloroquine, the first synthetically developed antimalarial, proved to be an almost magical cure for > 30 years, the emergence and spread of chloroquine-resistant parasites has made it virtually ineffective in most parts of the world. Currently, artemisinin, a plant-derived antimalarial, is the only available drug that is globally effective against the parasite. Although several new drugs have been introduced in the past 30 years, widespread or isolated cases of resistance indicate that their window of effectiveness will be limited. Thus, there is an urgent need to develop new therapeutics and regimens for malaria control. This article presents an overview of the currently available antimalarial chemotherapy options and the efforts being undertaken to develop new drugs based on both the recent technological advances and modifications to the old remedies, and on combination therapies.

摘要

疟疾仍然是发展中世界的一大威胁,每天有超过100万例临床发病和3000人死亡。在上个世纪,疟疾夺去了1.5亿至3亿人的生命,占所有死亡人数的2%至5%。目前,世界上约40%的人口居住在疟疾活跃传播地区。该疾病症状在幼儿和孕妇中最为严重。尽管疟疾在大多数热带地区都有本土病例,但90%与该疾病相关的死亡发生在撒哈拉以南非洲。疟疾的许可疫苗尚未成为现实,抗疟药物是唯一可用的治疗方法。虽然第一种合成开发的抗疟药物氯喹在30多年里几乎是一种神奇的治愈方法,但氯喹抗性寄生虫的出现和传播已使其在世界大部分地区几乎无效。目前,青蒿素,一种植物源抗疟药物,是全球唯一对该寄生虫有效的药物。尽管在过去30年里引入了几种新药,但广泛或个别病例的耐药性表明它们的有效期限将是有限的。因此,迫切需要开发新的治疗方法和方案来控制疟疾。本文概述了目前可用的抗疟化疗选择,以及基于近期技术进步、对旧疗法的改进以及联合疗法来开发新药所做的努力。

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