Barnes E H, Dobson R J, Stein P A, Le Jambre L F, Lenane I J
CSIRO Livestock Industries, McMaster Laboratory, Locked Bag 1, Delivery Centre, Blacktown, NSW 2148, Australia.
Int J Parasitol. 2001 May 15;31(7):720-7. doi: 10.1016/s0020-7519(01)00174-6.
To understand the factors that influence selection for anthelmintic resistance, it is necessary to examine the impact of drug treatment, particularly persistent drugs, on all phases of the worm life cycle. The efficacy of various avermectin/milbemycin anthelmintics was determined against resident worms, incoming larvae (L3) and development of eggs in faecal culture. Homozygote-resistant and maternal and paternal F1-heterozygote genotypes of Haemonchus contortus were used to infect sheep before or after treatment with ivermectin (IVM) oral, IVM capsule, moxidectin (MOX) oral or MOX injectable. Total worm count and quantitative larval culture were used to determine efficacy against parasitic and free-living stages, respectively. Selection for resistance by IVM capsules occurred at the adult and L3 stages because of poor efficacy against these stages for all resistant genotypes. However, the selective advantage of these surviving worms was reduced due to the low development of their eggs to L3 in faecal culture. For MOX, selection for resistance predominantly occurred after treatment because of high efficacy against resident adult worms of all resistant genotypes but poor efficacy against resistant L3 ingested after drug administration. The results indicated no evidence of sex-linked inheritance for IVM resistance. Mean IVM efficacies against homozygous and heterozygous resistant adult worms were not different, and IVM capsule efficacy against incoming L3 was approximately 70% for all resistant genotypes, consistent with a dominant trait. MOX was highly effective against adults of all resistant genotypes and approximately 76% effective against incoming L3 regardless of resistance genotype, also consistent with a dominant trait. These results will enable the impact of persistent drugs on worm control and anthelmintic resistance to be estimated. The results indicate that IVM capsules should not be used in populations where avermectin/milbemycin resistance is present.
为了解影响抗蠕虫药耐药性选择的因素，有必要研究药物治疗，尤其是长效药物，对蠕虫生命周期各阶段的影响。测定了各种阿维菌素/米尔倍霉素抗蠕虫药对宿主体内蠕虫、进入的幼虫（L3）以及粪便培养物中虫卵发育的效果。用捻转血矛线虫的纯合抗性以及母本和父本F1杂合子基因型在口服伊维菌素（IVM）、IVM胶囊、莫昔克丁（MOX）口服剂或MOX注射剂治疗之前或之后感染绵羊。分别使用蠕虫总数和定量幼虫培养来确定对寄生阶段和自由生活阶段的疗效。IVM胶囊导致的耐药性选择发生在成虫和L3阶段，因为对所有抗性基因型的这些阶段疗效不佳。然而，由于其虫卵在粪便培养物中发育为L3的比例较低，这些存活蠕虫的选择优势有所降低。对于MOX，耐药性选择主要发生在治疗后，因为对所有抗性基因型的宿主体内成虫疗效高，但对给药后摄入的抗性L3疗效不佳。结果表明没有证据表明IVM耐药性存在性连锁遗传。IVM对纯合和杂合抗性成虫的平均疗效没有差异，并且对于所有抗性基因型，IVM胶囊对进入的L3的疗效约为70%，这与显性性状一致。MOX对所有抗性基因型的成虫都非常有效，并且无论抗性基因型如何，对进入的L3的有效性约为76%，这也与显性性状一致。这些结果将有助于评估长效药物对蠕虫控制和抗蠕虫药耐药性的影响。结果表明，在存在阿维菌素/米尔倍霉素耐药性的群体中不应使用IVM胶囊。
