Disease Control, Moredun Research Institute, Pentlands Science Park, Edinburgh, EH26 0PZ, United Kingdom.
Animal and Plant Health Agency (APHA), Job's Well Road, Carmarthen, Carmarthenshire SA31 3EZ, United Kingdom.
Vet Parasitol. 2021 Jan;289:109319. doi: 10.1016/j.vetpar.2020.109319. Epub 2020 Nov 13.
The prevalence of anthelmintic resistance in the bovine nematode Cooperia oncophora has been well documented globally but lack of efficacy against the more pathogenic nematode species Ostertagia ostertagi is less common. The sensitivity of an O. ostertagi isolate to the benzimidazole class of anthelmintic was investigated using classical parasitological techniques following apparent clinical failure of controlled release fenbendazole capsule administration in first season grazers at pasture. A controlled efficacy test (CET) was conducted in conjunction with sequencing of the β-tubulin isotype 1 gene of larvae pre- and post-fenbendazole administration. Twelve helminth-naïve calves were infected experimentally with 20,000 third stage larvae; six received oral fenbendazole (7.5 mg/kg bodyweight) 28 days post infection. Total abomasal nematode burdens were compared between treatment and control groups to determine efficacy. Fenbendazole resistance in O. ostertagi was confirmed with a total treatment failure in reducing worm burden: efficacy of 0%. Sequence analysis of the β-tubulin isotype-1 gene from forty-five infective larvae from both control and treated groups was performed. The three commonest single nucleotide polymorphisms (SNPs) associated with benzimidazole resistance, namely F167Y, E198A and F200Y, were examined. The predominant resistance-associated SNPs were F200Y (78 % control and 79 % treated groups) and F167Y (remaining genotypes) and emphasises the importance of these SNPs in clinical disease in this isolate. The development of diagnostic molecular tools based on a characterised field-derived isolate of benzimidazole-resistant Ostertagia will enable future prevalence surveys to be undertaken to assess the possible risk posed by resistance in this economically important species.
在全球范围内，已充分记录了牛线虫 Coopreia oncophora 对驱虫药的耐药性，但针对更具致病性的线虫物种 Ostertagia ostertagi 的驱虫药疗效不佳的情况则较少见。在牧场放牧的第一季中，在首次使用控释型芬苯达唑胶囊进行驱虫后，疑似出现临床疗效不佳的情况下，使用经典寄生虫学技术对 O. ostertagi 分离株对苯并咪唑类驱虫药的敏感性进行了研究。在进行苯并咪唑类驱虫药处理前后幼虫β-微管蛋白同型 1 基因测序的同时，还进行了控制功效测试（CET）。12 头从未感染过寄生虫的小牛经口感染了 20,000 条第三期幼虫；感染后第 28 天，6 头小牛口服芬苯达唑（7.5mg/kg 体重）。通过比较治疗组和对照组的总胃线虫负荷来确定功效。由于用芬苯达唑处理未能降低虫体负荷，导致完全治疗失败，从而证实了 O. ostertagi 对驱虫药产生了耐药性：功效为 0%。对来自对照组和治疗组的 45 条感染性幼虫的β-微管蛋白同型 1 基因进行了序列分析。检查了与苯并咪唑耐药相关的三个最常见的单核苷酸多态性（SNP），即 F167Y、E198A 和 F200Y。主要的耐药相关 SNP 是 F200Y（78%的对照组和 79%的治疗组）和 F167Y（其余基因型），这突显了这些 SNP 在该分离株的临床疾病中的重要性。基于一个经过特征描述的野外来源的苯并咪唑耐药 Ostertagia 分离株开发的诊断分子工具，将能够进行未来的流行情况调查，以评估该经济上重要的物种中耐药性可能带来的风险。
