Sangster N C, Bjorn H
Department of Veterinary Pathology, University of Sydney, N.S.W., Australia.
Int J Parasitol. 1995 Mar;25(3):343-8. doi: 10.1016/0020-7519(94)e0068-x.
Resistance to the anthelmintic levamisole is common amongst most genera of trichostrongylid nematodes of sheep, but is relatively rare in the species Haemonchus contortus. The level of resistance in at least one strain of this species varies during the life cycle. Investigation of this phenomenon, especially in parasitic stages of the parasite may reveal information on resistance mechanisms and factors affecting the selection of resistance. Compared with adult worms of the same resistant strain, immature worms are more susceptible to levamisole both in in vitro contraction assays and an in vivo efficacy experiment. To ascertain if immature parasitic worms of a susceptible strain could be selected for resistance, 3 lines of worms were selected with levamisole for 9 generations. Lines were selected with the same dose rate (2 mg kg-1) at the 4th and 24th day of infection. In addition, because levamisole is less active against immature worms a further line was selected at the 4th day with a higher dose (8 mg kg-1) but similar efficacy to the selection at day 24. In in vitro assays the line selected at day 4 with the lower dose of levamisole showed no resistance compared with an unselected line. The other 2 lines developed high levels of resistance indicating that resistance can develop after selection at either stage. In addition these data directly show that selection pressure is important in determining the rate of development of resistance.
对驱虫药左旋咪唑产生抗性在绵羊的大多数毛圆科线虫属中很常见，但在捻转血矛线虫中相对少见。该物种至少一个品系的抗性水平在生命周期中会发生变化。对这一现象的研究，尤其是对寄生虫寄生阶段的研究，可能会揭示抗性机制以及影响抗性选择的因素的相关信息。与同一抗性品系的成虫相比，在体外收缩试验和体内药效试验中，未成熟虫体对左旋咪唑更敏感。为了确定是否可以选择敏感品系的未成熟寄生蠕虫使其产生抗性，用左旋咪唑对3组蠕虫进行了9代选育。在感染后的第4天和第24天，以相同的剂量率（2毫克/千克）对各组进行选育。此外，由于左旋咪唑对未成熟虫体的活性较低，在第4天用更高剂量（8毫克/千克）但与第24天选育效果相似的剂量对另一组进行了选育。在体外试验中，与未选育组相比，第4天用较低剂量左旋咪唑选育的组未表现出抗性。另外两组产生了高水平的抗性，这表明在任一阶段进行选育后都可能产生抗性。此外，这些数据直接表明选择压力在决定抗性发展速度方面很重要。
