Prichard R
Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, Que., Canada.
Vet Parasitol. 1994 Aug;54(1-3):259-68. doi: 10.1016/0304-4017(94)90094-9.
Anthelmintic resistance is widespread in nematode parasites of sheep, goats and horses. Resistance is also developing in nematode parasites of cattle and has been detected in pig parasites. Benzimidazole, levamisole/morantel and ivermectin resistances occur in nematodes of sheep and goats and closantel resistance has been found in Haemonchus contortus. Anthelmintic resistance is likely to develop wherever anthelmintics are frequently used and be detected if it is investigated. Worm count or egg count reduction after treatment are useful for the detection of all types of anthelmintic resistances. More economical, faster and more sensitive in vitro assays for the detection of anthelmintic resistance have been developed. Some, such as the egg hatch assay are specific for a particular class of anthelmintic, whilst others such as larval development assays can be used with most anthelmintics. Improvements in our understanding of the biochemistry and molecular genetics of anthelmintic actions should lead to the development of more sensitive assays for the detection of anthelmintic resistance in individual nematodes. Levamisole/morantel resistance appears to be associated with alterations in cholinergic receptors in resistant nematodes. Ivermectin appears to act by binding to a glutamate receptor of a membrane chloride channel. This receptor has been expressed in vitro so that further studies of the interaction of ivermectin with this receptor and its possible alteration in ivermectin resistance will be feasible. Benzimidazole resistance in nematodes and fungi appears to be associated with an alteration in beta-tubulin genes which reduces or abolishes the high affinity binding of benzimidazoles for tubulin in these organisms. This knowledge can be exploited for DNA probes for benzimidazole resistance/susceptibility in individual organisms.
抗蠕虫药耐药性在绵羊、山羊和马的线虫寄生虫中广泛存在。牛的线虫寄生虫也出现了耐药性,并且在猪的寄生虫中也检测到了耐药性。苯并咪唑、左旋咪唑/莫仑太尔和伊维菌素耐药性在绵羊和山羊的线虫中出现,而在捻转血矛线虫中发现了氯氰碘柳胺耐药性。只要频繁使用抗蠕虫药,就可能产生抗蠕虫药耐药性,并且如果进行调查就会被检测到。治疗后蠕虫计数或虫卵计数的减少对于检测所有类型的抗蠕虫药耐药性都很有用。已经开发出更经济、更快且更灵敏的体外检测抗蠕虫药耐药性的方法。一些方法,如虫卵孵化试验,对特定类别的抗蠕虫药具有特异性,而其他方法,如幼虫发育试验,可用于大多数抗蠕虫药。我们对抗蠕虫药作用的生物化学和分子遗传学的理解的改进应该会导致开发出更灵敏的检测单个线虫中抗蠕虫药耐药性的方法。左旋咪唑/莫仑太尔耐药性似乎与耐药线虫中胆碱能受体的改变有关。伊维菌素似乎通过与膜氯化物通道的谷氨酸受体结合而起作用。这种受体已在体外表达,因此对伊维菌素与该受体的相互作用及其在伊维菌素耐药性中可能的改变进行进一步研究将是可行的。线虫和真菌中的苯并咪唑耐药性似乎与β-微管蛋白基因的改变有关,这种改变会降低或消除苯并咪唑对这些生物体中微管蛋白的高亲和力结合。这些知识可用于开发针对单个生物体中苯并咪唑耐药性/敏感性的DNA探针。