Parasite Therapeutics Research Group, School of Biological Sciences, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.
Vet Parasitol. 2011 Aug 4;180(1-2):133-43. doi: 10.1016/j.vetpar.2011.05.034. Epub 2011 May 27.
The liver fluke remains an economically significant parasite of livestock and is emerging as an important zoonotic infection of humans. The incidence of the disease has increased in the last few years, as a possible consequence of changes to the World's climate. Future predictions suggest that this trend is likely to continue. Allied to the changing pattern of disease, reports of resistance to triclabendazole (TCBZ) have appeared in the literature, although they do not all represent genuine cases of resistance. Nevertheless, any reports of resistance are a concern, because triclabendazole is the only drug that has high activity against the migratory and damaging juvenile stages of infection. How to deal with the twin problems (of increasing incidence and drug resistance) is the overall theme of the session on "Trematodes: Fasciola hepatica epidemiology and control" and of this review to introduce the session. Greater knowledge of fluke epidemiology and population genetics will highlight those regions where surveillance is most required and indicate how quickly resistant populations of fluke may arise. Models of disease risk are becoming increasingly sophisticated and precise, with more refined data analysis programmes and Geographic Information Systems (GIS) data. Recent improvements have been made in our understanding of the action of triclabendazole and the ways in which flukes have become resistant to it. While microtubules are the most likely target for drug action, tubulin mutations do not seem to be involved in the resistance mechanism. Rather, upregulation of drug uptake and metabolism processes appear to be more important and the data relating to them will be discussed. The information may help in the design of new treatment strategies or pinpoint potential molecular markers for monitoring fluke populations. Advances in the identification of novel targets for drugs and vaccines will be made by the various "-omics" technologies that are now being applied to Fasciola. A major area of concern in the current control of fasciolosis is the lack of reliable tests for the diagnosis of drug (TCBZ) resistance. This has led to inaccurate reports of resistance, which is hindering successful disease management, as farmers may be encouraged to switch to less effective drugs. Progress with the development of a number of new diagnostic tests will be reviewed.
肝片吸虫仍然是一种对家畜具有重要经济意义的寄生虫，并且正成为人类的一种重要人畜共患感染。由于世界气候的变化，近年来该病的发病率有所增加。未来的预测表明，这种趋势可能会持续下去。与疾病模式的变化相伴随的是，文献中出现了对三氯苯达唑（TCBZ）的耐药性报告，尽管并非所有报告都代表真正的耐药性。然而，任何耐药性报告都令人担忧，因为三氯苯达唑是唯一对感染的迁移和破坏性幼虫阶段具有高活性的药物。如何应对发病率增加和耐药性这两个问题是“吸虫：肝片吸虫流行病学和控制”会议的主题，也是本次综述介绍会议的主题。对吸虫流行病学和群体遗传学的更多了解将突出需要进行监测的那些地区，并表明耐药性吸虫群体可能会迅速出现。疾病风险模型变得越来越复杂和精确，具有更精细的数据分析程序和地理信息系统（GIS）数据。最近，我们对三氯苯达唑的作用方式以及吸虫对其产生耐药性的方式有了更多的了解。虽然微管是药物作用的最可能靶标，但微管蛋白突变似乎不参与耐药机制。相反，药物摄取和代谢过程的上调似乎更为重要，将讨论与之相关的数据。这些信息可能有助于设计新的治疗策略或确定监测吸虫群体的潜在分子标记。现在应用于 Fasciola 的各种“组学”技术将推动用于药物和疫苗的新靶标的识别方面的进展。目前在 Fasciola 控制中一个主要关注的问题是缺乏用于诊断药物（TCBZ）耐药性的可靠测试。这导致了耐药性的不准确报告，从而阻碍了成功的疾病管理，因为农民可能会被鼓励转而使用效果较差的药物。将回顾一些新诊断测试的开发进展。
