A novel approach for combining the use of in vitro and in vivo data to measure and detect emerging moxidectin resistance in gastrointestinal nematodes of goats
A novel approach for combining the use of in vitro and in vivo data to measure and detect emerging moxidectin resistance in gastrointestinal nematodes of goats
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DOI：
10.1016/j.ijpara.2007.01.001
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发表时间：
2007-06-01
影响因子：
4
通讯作者：
Terrill, T. H.
中科院分区：
文献类型：
--
作者：
Kaplan, R. M.;Vidyashankar, A. N.;Terrill, T. H.
伊维菌素和莫昔克丁是与阿维菌素/米尔倍霉素驱虫药密切相关的药物，现有数据表明这两种药物会产生副作用。然而，由于莫昔克丁的效力较高，因此对许多种类的伊维菌素耐药蠕虫仍然有效。幼虫发育测定（LDA）通常用于诊断捻转血矛线虫的伊维菌素耐药性，但由于缺乏任何经过验证的体外测试，莫昔克汀耐药性的实验室诊断受到阻碍。本研究的目的是测量佐治亚州山羊养殖场中的 H. contortus 对莫昔克汀的相对敏感性/耐药性，并验证 DrenchRite (R) LDA 用于检测莫昔克汀耐药性。在五种不同的莫昔克丁剂量水平下进行粪便卵数减少试验 (FECRT)，并在美国佐治亚州的九个肉山羊养殖场重复进行 DrenchRite (R) LDA。为了提高我们推断农场之间相对耐药水平的能力，首先使用线性混合模型分析 FECRT 数据，然后使用 Tukey 的序贯趋势检验来评估不同剂量水平的反应趋势。使用对数剂量 Logit 响应和 Probit 模型分析 LDA 数据。利用这些统计结果，我们能够对九个农场从耐药性最低到最高进行排名，并制定一套解释 DrenchRite (R) LDA 结果的标准，以便该测定可用于诊断临床明显的莫昔克丁耐药性以及亚临床新出现的耐药性。这些结果表明，我们检查这些类型数据的新方法提供了一种获得更多信息的方法，从而可以更灵敏地检测耐药性。根据 LDA 的结果，与伊维菌素敏感农场相比，莫西菌素抗性农场的抗性比率为 32 至 128，与伊维菌素抗性/莫西菌素未接种农场相比，抗性比率为 6-24。在几乎一半的测试农场中，血矛线虫和毛圆线虫均诊断出莫昔克丁耐药，尽管这种药物仅在这些农场使用了 2-3 年。 (C) 2007 年澳大利亚寄生虫学协会。由 Elsevier Ltd 出版。保留所有权利。
Ivermectin and moxidectin are closely related avermectin/milbemycin anthelmintics and available data suggest that side resistance occurs with these two drugs. However, moxidectin remains effective against many species of ivermectin-resistant worms due to its higher potency. The larval development assay (LDA) is routinely used to diagnose ivermectin resistance in Haemonchus contortus but laboratory diagnosis of moxidectin resistance is hampered by the lack of any validated in vitro tests. The objective of this study was to measure the relative susceptibility/resistance of H. contortus to moxidectin on goat farms in Georgia, and to validate the DrenchRite (R) LDA for detecting resistance to moxidectin. Fecal egg count reduction tests (FECRT) were performed at five different moxidectin dose levels and DrenchRite (R) LDAs were performed in duplicate on nine meat goat farms in Georgia, USA. To improve our ability to make inferences on the relative levels of resistance between farms, FECRT data were first analysed using a linear mixed model, and then Tukey's sequential trend test was used to evaluate the trend in response across dose levels. LDA data were analysed using log-dose logit-response and probit models. Using these statistical results, we were able to rank the nine farms from the least to the most resistant, and to develop a set of criteria for interpreting DrenchRite (R) LDA results so that this assay can be used to diagnose both clinically apparent moxidectin resistance, as well as sub-clinical emerging resistance. These results suggest that our novel approach for examining these types of data provides a method for obtaining an increased amount of information, thus permitting a more sensitive detection of resistance. Based on results of the LDA, moxidectin-resistant farms had resistance ratios, compared with an ivermectin-sensitive farm, ranging from 32 to 128, and had resistance ratios of 6-24 compared with an ivermectin-resistant/moxidectin naive farm. Moxidectin resistance was diagnosed both in Haemonchus and Trichostrongylus on almost half of the farms tested, despite this drug only being used on these farms for 2-3 years. (C) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.