首页> 外文期刊>Veterinary Parasitology >The use of the larval development assay for predicting the in vivo efficacy of levamisole against Haemonchus contortus and Trichostrongylus colubriformis
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The use of the larval development assay for predicting the in vivo efficacy of levamisole against Haemonchus contortus and Trichostrongylus colubriformis

机译:幼虫发育测定的使用预测Levamisole对Haemonchus incortus和Trichostrongylus colubriformis的体内疗效

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The larval development assay has been used for many years to measure the sensitivity of the free-living life stages of trichostrongylid nematodes to anthelmintics. The assay has applications in both drug discovery and the diagnosis of drug resistance. We revisited the usefulness of the larval development assay for diagnosis of resistance to levamisole using field-derived isolates of Haemonchus contortus and Trichostrongylus colubriformis showing varying levels of resistance to this drug in vivo. Each of the resistant isolates showed a plateau in their larval development assay dose-response at the highest drug concentrations tested, representing a highly-resistant fraction, amounting to between 6.9 and 55.1% of the populations. The remaining population fractions for the resistant isolates showed IC50 values from 1.4- to 17.8-fold higher than their corresponding susceptible isolate of the same species. We used a data set from the DrenchRite (R) test user manual to derive equations describing the relationship between the IC50 values for these low / moderate resistance components of each population and in vivo drug efficacy, and then used these equations to estimate the expected in vivo efficacy of levamisole against this population component of each isolate. A combination of this expected efficacy, with the known zero efficacy of the drug in vivo against the highly-resistant population fractions in each isolate, allowed us to calculate a predicted drug efficacy for the whole population for each isolate. The predicted levamisole efficacies for the three resistant H. contortus isolates were 88.8, 84.1 and 43.7%. These compared favourably with the actual efficacy of the drug against these isolates as determined in faecal egg count reduction tests or total worm count studies: 79, 66.3 and 40.6%, respectively. Similarly, for T. colubriformis, predicted efficacies of 82.0 and 1.8% compared favourably with the actual efficacies of 65-92% and 0%, respectively. This study illustrates the usefulness of the larval development assay as a diagnostic tool for predicting in vivo efficacy of levamisole against H. contortus and T. colubriformis.
机译:幼虫发展测定已被使用多年,以衡量TrichostrongylID线虫的自由生活寿命与Anthelmintics的敏感性。该测定在药物发现和耐药性诊断中具有应用。我们重新审视了幼虫开发测定的有用性,用于使用现场衍生的Haemonchus Contortus和Trichostrongylus Colubriformis诊断对Levamisole抗性的抗性的耐受性,显示在体内对该药物的变化水平的抗性。每个抗性分离株在其幼虫发育测定剂中显示出高原,其在测试的最高药物浓度下,代表高度耐药级分,占群体的6.9和55.1%之间。抗性分离物的剩余种群分数显示IC50值高于其相应物种的相应敏感分离物的1.4-至17.8倍。我们使用了从Drenchrite(R)测试用户手册中的数据,以导出描述每个人口的这些低/中等电阻分量的IC 50值与体内药物功效之间的关系,然后使用这些方程来估计预期的预期Levamisole对每个分离物的这种人群成分的体内疗效。这种预期疗效的组合,用药物在每种分离物中的高度抗性群体级分中具有已知的药物零功效,使我们能够计算每个分离物的全群的预测药物效果。预测的三种抗性H. intortus分离物的左嘌呤菌效率为88.8,84.1和43.7%。这些在粪便卵数减少试验或总蠕虫计数中测定的这些分离物的实际疗效相比,这些分离物的实际疗效分别分别测定了:79,66.3和40.6%。类似地,对于粗炭,对于菌丝,预测的82.0和1.8%的疗效有利地与实际效率分别为65-92%和0%。本研究说明了幼虫发育测定作为预测左旋吲哚对H.污染的诊断工具的诊断工具和T.Colubriormis。

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