Université du Maine, Laboratoire Mer-Molécules-Santé, F-72085 Le Mans, France.
Vet Parasitol. 2010 Aug 27;172(1-2):80-8. doi: 10.1016/j.vetpar.2010.04.023. Epub 2010 Apr 28.
The evolution of benzimidazoles (BZ) resistance in Teladorsagia circumcincta was investigated in a controlled trial with lambs, submitted to different treatment regimens. Four paddocks were seeded with a T. circumcincta strain constituted by 25% of BZ-resistant nematodes. Ten permanent lambs were allocated to each paddock, from April to November in order to renew the contamination of pasture. Monthly, three tracer lambs were allocated in each paddock. BZ-resistant nematode frequency was determined (PCR diagnosis). The faecal egg count reduction test (permanent lambs) and the number of nematodes in lambs were also determined (permanent and tracer lambs). Four different regimens of treatments were performed: control, levamisole (a non-BZ drug), fenbendazole (a BZ drug), and an alternation of levamisole and fenbendazole every second treatment. The same protocol was repeated on two consecutive grazing seasons, increasing the number of treatments (3 in first year and 5 in second year). The proportions of BZ-resistant nematodes did not change during all the study in both the control and the levamisole paddocks, supporting an equal global fitness of BZ-resistant and susceptible nematodes. Thus, no reversion of BZ resistance is to be expected. In the alternated drug group and in the BZ treated group, BZ-resistant nematodes increased from 25% to 47% and to 78%, respectively. BZ resistance increased proportionally to the selective pressure (number of BZ treatments). The drug alternation is not a good solution to delay importantly the evolution of resistance when more than 25% of nematodes are BZ-resistant. This study is the first evaluation of BZ-resistance evolution (using individual genotyping) in controlled conditions. It showed that when a monogenic anthelmintic resistance is established at 25% in a sexually reproducing nematode population, it seems to be impossible to prevent its increase even when using limited number of BZ treatments.
本研究采用控制试验，以绵羊为对象，研究了泰泽氏绦虫（Teladorsagia circumcincta）苯并咪唑（BZ）耐药性的进化。试验在四个围场内进行，每个围场内播种了 25%耐药性泰泽氏绦虫的虫株。从四月到十一月，每个围场内分配了 10 只绵羊，以更新牧场的污染。每个围场内每月分配 3 只示踪绵羊。通过聚合酶链反应（PCR）诊断确定 BZ 耐药性线虫的频率。还通过粪便卵计数减少试验（永久性绵羊）和绵羊体内线虫数量（永久性和示踪绵羊）确定 BZ 耐药性。进行了四种不同的治疗方案：对照组、左旋咪唑（非 BZ 药物）、芬苯达唑（BZ 药物）和每两次治疗交替使用左旋咪唑和芬苯达唑。该方案在连续两个放牧季节重复进行，增加了治疗次数（第一年 3 次，第二年 5 次）。在整个研究过程中，对照组和左旋咪唑组的 BZ 耐药线虫比例没有变化，这表明 BZ 耐药线虫和敏感线虫的整体适应性相等。因此，预计不会出现 BZ 耐药性的逆转。在交替药物组和 BZ 治疗组中，BZ 耐药线虫从 25%增加到 47%和 78%，分别。BZ 耐药性的增加与选择压力（BZ 治疗次数）成正比。当超过 25%的线虫对 BZ 耐药时，药物交替并不是一个很好的解决方案，可以显著延缓耐药性的进化。本研究首次在控制条件下评估了 BZ 耐药性的进化（使用个体基因分型）。结果表明，当一种单基因驱虫药在一个有性繁殖的线虫种群中达到 25%的耐药水平时，即使使用有限数量的 BZ 处理，似乎也不可能阻止其增加。
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