Leathwick Dave M, Sauermann Christian W, Geurden Thomas, Nielsen Martin K
AgResearch Grasslands, Private Bag 11008, Palmerston North, 4442, New Zealand.
AgResearch Grasslands, Private Bag 11008, Palmerston North, 4442, New Zealand.
Vet Parasitol. 2017 Jun 15;240:75-81. doi: 10.1016/j.vetpar.2017.03.026. Epub 2017 Mar 30.
A previously described model for the dynamics of the parasitic stages of Parascaris spp. was modified to include eggs outside the host and the genetics of anthelmintic resistance before being used to address questions regarding the development of resistance. Three broad questions were addressed; i) How sustainable is the current common practice of treating foals monthly for their first year of life (i.e. 12 treatments/year)? ii) Does the timing of treatments have an effect on resistance development? (i.e. do certain treatments select for resistance more strongly than others?), and iii) How sustainable is the currently recommended strategy of targeting ascarid infections in foals with two treatments applied during the first five months of life? A range of variations within these broad questions were considered, such as the value in rotational deworming, whether larvicidal treatments are more selective for resistance, and whether combination anthelmintics should be introduced. Twelve anthelmintic treatments at monthly intervals resulted in the development of resistance to all the anthelmintics used, regardless of how they were used, indicating that such intensive treatment frequency is unlikely to be sustainable. The timing of a single annual treatment influenced resistance development with treatments at 3 and 4 months of age being more selective than treatments at other times. Treatments administered to foals older than 6 months of age did not select for resistance within the timeframe of these simulations. Treatments with activity against migrating third stage larvae (ivermectin and a programme of 5 daily treatments with fenbendazole) were more selective for resistance than those which only killed worms in the intestine. Restricting the number of treatments to young foals to two, administered at 2 and 5 months of age slowed the development of resistance by allowing a small contribution from susceptible genotype worms to subsequent generations. If the interval between treatments was reduced, resistance developed more rapidly demonstrating the importance of allowing some susceptible worms to reach patency before the second treatment is administered. Under a reduced treatment schedule with a clearly defined 'refugium' of susceptibility, the use of effective actives in combination appears to offer advantages for delaying resistance development. The model offers insights into more sustainable drug use strategies and has identified some priority questions for future research.
之前描述的用于副蛔虫属寄生虫阶段动态变化的模型，在用于解决抗寄生虫药耐药性发展相关问题之前，进行了修改，纳入了宿主体外的虫卵以及抗寄生虫药耐药性的遗传学因素。研究了三个主要问题：i）在驹出生后的第一年每月进行治疗（即每年12次治疗）这种当前常见做法的可持续性如何？ii）治疗时间对耐药性发展有影响吗？（即某些治疗比其他治疗更易导致耐药性产生吗？），以及iii）在驹出生后的前五个月进行两次治疗以针对蛔虫感染，这种当前推荐策略的可持续性如何？考虑了这些主要问题中的一系列变量，例如交替驱虫的价值、杀幼虫治疗对耐药性的选择性是否更高，以及是否应引入复方抗寄生虫药。每月进行12次抗寄生虫药治疗会导致对所有使用的抗寄生虫药产生耐药性，无论其使用方式如何，这表明如此密集的治疗频率不太可能持续。单次年度治疗的时间影响耐药性发展，3至4月龄时的治疗比其他时间的治疗更具选择性。在这些模拟的时间范围内，对6月龄以上的驹进行治疗不会导致耐药性产生。对移行期第三期幼虫有活性的治疗（伊维菌素以及芬苯达唑连续5天的治疗方案）比仅杀死肠道内蠕虫的治疗对耐药性的选择性更高。将幼驹的治疗次数限制为两次，分别在2月龄和5月龄时进行，通过允许易感基因型蠕虫对后代有少量贡献，减缓了耐药性的发展。如果治疗间隔缩短，耐药性发展更快，这表明在进行第二次治疗之前允许一些易感蠕虫发育成熟具有重要意义。在治疗方案减少且有明确界定的易感“庇护所”的情况下，联合使用有效的活性成分似乎在延缓耐药性发展方面具有优势。该模型为更可持续的药物使用策略提供了见解，并确定了一些未来研究的重点问题。
