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人类非洲锥虫病的新进展。

New developments in human African trypanosomiasis.

作者信息

Brun Reto, Balmer Oliver

机构信息

Swiss Tropical Institute, Parasite Chemotherapy, Basel, Switzerland.

出版信息

Curr Opin Infect Dis. 2006 Oct;19(5):415-20. doi: 10.1097/01.qco.0000244045.93016.b1.

Abstract

PURPOSE OF REVIEW

To review recent literature on human African trypanosomiasis, focussing on genome sequencing, diagnosis and drug discovery, and typing of trypanosomes.

RECENT FINDINGS

The most important recent development has been the completion of the Trypanosoma brucei genome which will greatly facilitate the discovery of new drug targets and genetic markers. Correct staging of the disease is of key importance for treatment. The analysis of sleep patterns is a promising new method to this end and has advanced enough to begin thorough clinical trials. In terms of novel drug candidates, dicationic molecules show the most promise with one oral diamidine in phase 3 clinical trials. New targets and classes of molecules which show in vitro trypanocidal activity are also described. Two new methods - MGE-PCR and microsatellites - allow analyses without parasite cultivation, eliminating a major impediment to efficient sampling for population studies. The finding that several wild animal species harbour T. b. gambiense, and that parasite transmission is efficient even from very low parasitaemias, sheds a new light on the importance of animal reservoirs.

SUMMARY

The use of T. brucei as model system for molecular and cell biology is regularly producing new technologies exploitable for diagnosis and new drugs. Drug discovery and development experience a revival through new public-private partnerships and initiatives. The challenge remains to translate this progress into improvements for affected people in disease endemic areas.

摘要

综述目的

综述近期关于人类非洲锥虫病的文献,重点关注基因组测序、诊断、药物研发以及锥虫分型。

近期发现

最近最重要的进展是布氏锥虫基因组测序的完成,这将极大地促进新药物靶点和遗传标记的发现。疾病的正确分期对治疗至关重要。分析睡眠模式是实现这一目标的一种有前景的新方法,并且已经发展到足以开始全面的临床试验。就新型候选药物而言,双阳离子分子最具潜力,其中一种口服双脒正处于3期临床试验阶段。还描述了显示出体外杀锥虫活性的新靶点和新分子类别。两种新方法——MGE-PCR和微卫星——无需培养寄生虫即可进行分析,消除了群体研究高效采样的一个主要障碍。发现几种野生动物携带布氏冈比亚锥虫,并且即使在极低的寄生虫血症水平下寄生虫传播也很有效,这为动物宿主的重要性提供了新的认识。

总结

将布氏锥虫用作分子和细胞生物学的模型系统不断产生可用于诊断的新技术和新药物。通过新的公私合作伙伴关系和倡议,药物研发正在复兴。挑战仍然是将这一进展转化为疾病流行地区受影响人群状况的改善。

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