Packianathan Raj, Hodge Andrew, Wright Jacqueline, DeRosa Andrew A
Zoetis, Veterinary Medicine Research and Development, Level 6, 5 Rider Boulevard, Rhodes, NSW 2138, Australia.
Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI 49007, USA.
Vet Parasitol. 2023 Nov;323S:109998. doi: 10.1016/j.vetpar.2023.109998. Epub 2023 Aug 1.
Intensive farming practices and heavy reliance on anthelmintics have contributed significantly to the problem of macrocyclic lactone (ML) resistance in New Zealand. Farmers now have few options for effectively controlling cattle gastrointestinal nematodes (GINs) and regularly experience sub-optimal efficacy against economically important species. We present a novel fixed-dose combination injectable (FDCI) that simultaneously delivers 0.2 mg/kg doramectin and 6 mg/kg levamisole hydrochloride (HCl) to target a broad spectrum of cattle GINs in a single dose, providing an additional solution to endoparasite control in an environment of anthelmintic resistance. A dose confirmation study was conducted using naturally acquired infections of GINs in beef cattle in New Zealand. Cattle with GIN infections confirmed by fecal egg count (FEC) were randomly allocated (n = 12 per group) to the control (saline-treated), FDCI-treated or doramectin-treated group. On Day 0, cattle were weighed and administered a single subcutaneous injection of saline or endectocide. Rectal fecal samples were collected from each animal on Day 7 for individual duplicate fecal egg count (FEC) analysis, and coprocultures were conducted on pooled fecal samples within each treatment group. All animals were euthanized and necropsied for worm recovery on Days 14 through 16. Treatment efficacy was calculated based on reduction in FECs and worm burdens. All enrolled cattle were positive for GINs based on Day -5 FECs, with geometric mean (GM) FECs ranging from 337 to 521 eggs per gram (EPG). All saline-treated cattle remained positive for GIN infections for the study duration (Day 7 GM FEC = 427 EPG). Necropsy and worm recoveries revealed the presence of doramectin-resistant Cooperia oncophora, C. surnabada and Trichostrongylus longispicularis, as evidenced by ≤ 72.3 % efficacy of doramectin against these species. The new FDCI was ≥ 99.8 % effective against all GIN species, including ML-resistant C. oncophora, C. surnabada and T. longispicularis, providing broad-spectrum efficacy and eliminating economically important cattle GINs, including ML-resistant populations.
集约化养殖方式以及对抗蠕虫药的严重依赖，在很大程度上导致了新西兰大环内酯类（ML）耐药性问题。农民现在几乎没有有效控制牛胃肠道线虫（GINs）的办法，而且在对付具有经济重要性的线虫种类时，经常遭遇药效欠佳的情况。我们推出了一种新型的固定剂量组合注射剂（FDCI），它能以单次剂量同时递送0.2毫克/千克多拉菌素和6毫克/千克盐酸左旋咪唑，以针对多种牛GINs，在抗蠕虫药耐药的环境中为体内寄生虫控制提供了额外的解决方案。利用新西兰肉牛自然感染的GINs进行了一项剂量确认研究。通过粪便虫卵计数（FEC）确诊感染GINs的牛被随机分配（每组n = 12头）到对照组（生理盐水处理组）、FDCI处理组或多拉菌素处理组。在第0天，对牛进行称重，并皮下注射一次生理盐水或驱虫药。在第7天从每头动物采集直肠粪便样本，进行个体粪便虫卵计数（FEC）重复分析，并对每个处理组的混合粪便样本进行粪便培养。在第14天至16天，对所有动物实施安乐死并进行剖检以回收蠕虫。根据FECs和蠕虫负荷的降低情况计算治疗效果。根据第-5天的FECs，所有入组的牛GINs均呈阳性，几何平均（GM）FECs范围为每克337至521个虫卵（EPG）。在研究期间，所有生理盐水处理的牛GIN感染仍呈阳性（第7天GM FEC = 427 EPG）。剖检和蠕虫回收显示存在对多拉菌素耐药的牛仰口线虫、苏氏仰口线虫和长刺毛圆线虫，多拉菌素对这些线虫种类的疗效≤ 72.3%即证明了这一点。新的FDCI对所有GIN种类的有效性≥ 99.8%，包括对多拉菌素耐药的牛仰口线虫、苏氏仰口线虫和长刺毛圆线虫，具有广谱疗效，可消除具有经济重要性的牛GINs，包括耐药种群。
