The Food and Environment Research Agency, Sand Hutton, York, YO41 1LZ, United Kingdom.
Vet Parasitol. 2012 Jun 8;187(1-2):244-53. doi: 10.1016/j.vetpar.2011.12.033. Epub 2012 Jan 5.
UK guidelines for the sustainable control of parasites in sheep (SCOPS) aim to delay further development of anthelmintic drug resistance. This study describes a computer model evaluation of resistance development with a novel oral formulation of derquantel-abamectin, to inform recommendations for use. Two different farm management scenarios, based on UK field data, were modelled to simulate low refugia (non SCOPS) or high refugia (SCOPS) worm populations. The effect on resistance allele frequencies and field efficacy of several treatment scenarios using the novel active derquantel (DQL), a spiroindole (SI), as either a single or multiple active formulation with abamectin (ABA), a macrocyclic lactone (ML), under the two farm management systems was evaluated. The initial resistance allele frequency for DQL was set at 0.0001, assuming that resistance in the UK is low, and for ML at 0.165 or 0.8, assuming that resistant nematode populations exist in the UK. DQL resistance reached a level at which a reduction in field efficacy might be detected (resistance allele frequency 0.25) by year 16 when used sequentially, and by year 31 when used in annual rotation (ABA) with SCOPS management inputs, and by year 5 (sequential) and by year 10 (annual rotation) with non SCOPS management inputs. ML resistance reached a level at which a reduction in ABA field efficacy might be detected (resistance allele frequency 0.25) by year 4 when used sequentially, and by year 8 when used in annual rotation with DQL and SCOPS management inputs, and by year 1 (sequential) and by year 2 (annual rotation) with non SCOPS management inputs. No detectable reduction in field efficacy was observed for DQL-ABA after 40 years of use with SCOPS management inputs for simulations using an initial ML resistance allele frequency of 0.165 and 0.8. A detectable reduction in field efficacy was observed for DQL-ABA by year 32 (initial ML resistance allele frequency=0.165) and by year 6 (initial ML resistance allele frequency=0.8) with non SCOPS management inputs. In summary, the results suggest that formulating DQL in combination with ABA confers a substantial advantage in delaying the development of both DQL and ML resistance, and the provision of adequate refugia further extends this advantage.
英国羊寄生虫可持续控制指南（SCOPS）旨在延缓抗寄生虫药物耐药性的进一步发展。本研究描述了一种新型口服双羟萘酸达氟沙星-阿维菌素制剂耐药性发展的计算机模型评估，为使用建议提供信息。根据英国田间数据，建立了两种不同的农场管理情景模型，以模拟低避难所（非 SCOPS）或高避难所（SCOPS）的蠕虫种群。评估了新型活性药物达氟沙星（DQL）、螺环吲哚（SI）作为单一或多种活性制剂与阿维菌素（ABA）、大环内酯（ML）组合，在两种农场管理系统下，对几种治疗方案的耐药等位基因频率和田间药效的影响。假设英国的耐药性较低，DQL 的初始耐药等位基因频率设定为 0.0001；假设英国存在耐药线虫种群，ML 的初始耐药等位基因频率设定为 0.165 或 0.8。当 DQL 连续使用时，到第 16 年，耐药等位基因频率可能达到检测到田间药效降低的水平（耐药等位基因频率 0.25）；当 DQL 与 SCOPS 管理输入一起每年轮换使用时，到第 31 年，耐药等位基因频率可能达到检测到田间药效降低的水平（耐药等位基因频率 0.25）；当 DQL 与非 SCOPS 管理输入一起连续使用时，到第 5 年（连续使用）和第 10 年（每年轮换），耐药等位基因频率可能达到检测到田间药效降低的水平（耐药等位基因频率 0.25）。当 ML 连续使用时，到第 4 年，耐药等位基因频率可能达到检测到 ABA 田间药效降低的水平（耐药等位基因频率 0.25）；当 ML 与 DQL 和 SCOPS 管理输入一起每年轮换使用时，到第 8 年，耐药等位基因频率可能达到检测到 ABA 田间药效降低的水平（耐药等位基因频率 0.25）；当 ML 与非 SCOPS 管理输入一起连续使用时，到第 1 年（连续使用）和第 2 年（每年轮换），耐药等位基因频率可能达到检测到 ABA 田间药效降低的水平（耐药等位基因频率 0.25）。在 SCOPS 管理输入情况下，模拟使用初始 ML 耐药等位基因频率为 0.165 和 0.8 时，DQL-ABA 在 40 年后的使用中没有观察到田间药效的可检测降低。在非 SCOPS 管理输入情况下，DQL-ABA 在第 32 年（初始 ML 耐药等位基因频率=0.165）和第 6 年（初始 ML 耐药等位基因频率=0.8）观察到田间药效的可检测降低。总之，结果表明，将 DQL 与 ABA 联合配制成药具有显著优势，可以延缓 DQL 和 ML 耐药性的发展，并且提供足够的避难所可以进一步延长这种优势。
