Kita Kiyoshi
Graduate School of Medicine and Faculty of Medicine, The University of Tokyo.
Yakugaku Zasshi. 2016;136(2):205-11. doi: 10.1248/yakushi.15-00233-1.
EBOLA hemorrhagic fever, a typical emerging infectious disease, began in December 2013 in the southern part of Guinea, and killed more than 11000 people by the end of June, 2015. In addition to emerging/re-emerging diseases and the 3 major infectious diseases i.e. HIV/AIDS, tuberculosis and malaria, neglected tropical diseases (NTDs) have recently become important tropical diseases of the poor. It is remarkable that Japan succeeded in the eradication of malaria and other tropical diseases, which include lymphatic filariasis and schistosomiasis. However, despite these achievements, it is important to sustain our efforts when we consider global health. This review highlights the significance of elimination and/or control of NTDs, and then introduces the current situation of drug development activities in Japan, which are aimed towards combating tropical infectious diseases. They include studies on a novel drug target, the "mitochondrial NADH-fumarate reductase system (Fumarate respiration)" composed of complex I, rhodoquinone and complex II, which plays an important role in the anaerobic energy metabolism of many helminths such as Ascaris suum. An additional interesting finding highlighted herein is that ascofuranone, a recently developed anti-African trypanosome drug, shows specific inhibition of fumarate respiration in Echinococcus multilocularis mitochondria.
埃博拉出血热是一种典型的新发传染病，于2013年12月在几内亚南部爆发，截至2015年6月底已造成11000多人死亡。除了新发/再发疾病以及三大传染病，即艾滋病毒/艾滋病、结核病和疟疾外，被忽视的热带病（NTDs）最近已成为穷人面临的重要热带病。值得注意的是，日本成功根除了疟疾以及包括淋巴丝虫病和血吸虫病在内的其他热带病。然而，尽管取得了这些成就，但在考虑全球健康问题时，持续努力仍然很重要。本综述强调了消除和/或控制被忽视热带病的重要性，然后介绍了日本目前针对热带传染病的药物研发活动情况。这些活动包括对一种新型药物靶点的研究，即由复合体I、泛醌和复合体II组成的“线粒体NADH-延胡索酸还原酶系统（延胡索酸呼吸）”，该系统在许多蠕虫（如猪蛔虫）的无氧能量代谢中起重要作用。本文强调的另一个有趣发现是，最近开发的一种抗非洲锥虫药物阿斯科呋喃酮对多房棘球绦虫线粒体中的延胡索酸呼吸具有特异性抑制作用。
