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不同剂量莫昔克丁对大环内酯类药物耐药的犬恶丝虫 JYD-34 分离株的疗效。

Efficacy of moxidectin, using various dose regimens, against JYD-34, a macrocyclic lactone resistant isolate of Dirofilaria immitis.

机构信息

Boehringer Ingelheim Animal Health, 1730 Olympic Drive, Athens, GA, 30601, USA.

TRS Labs, Inc, 215 Paradise Blvd, Athens, GA, 30607, USA.

出版信息

Parasit Vectors. 2024 Apr 4;17(1):176. doi: 10.1186/s13071-024-06149-0.

Abstract

BACKGROUND

Macrocyclic lactones (MLs) are the only class of drugs currently commercially available that are effective for preventing heartworm disease. The data presented in this article provide information on the efficacy of oral moxidectin against JYD-34, a known ML-resistant Dirofilaria immitis isolate, when dogs are treated under various dosing regimens.

METHODS

Fifty-two purpose-bred Beagle dogs were used in five laboratory studies. All dogs were inoculated with 50 D. immitis third-stage larvae (L) (JYD-34 isolate) 30 days prior to the first treatment. Dogs were randomized to treatment (four to five animals in each group) with one, three, or five monthly doses of oral moxidectin ranging from 6 to 100 µg/kg body weight. In each study, control dogs were not treated. Five to 6 months after L inoculation, dogs were euthanized, and adult worms were counted to evaluate efficacy of the dosing regimens.

RESULTS

Adult heartworms were recovered from all control dogs, with an overall geometric mean of 29.7 worms (range 15.2 to 38.0, individual counts ranged from 8 to 51). Five monthly doses of 6 µg/kg provided 83.3% and 90.2%, efficacy, and the same number of monthly doses of 9 µg/kg demonstrated 98.8% and 94.1% efficacy. Three monthly doses of 30 and 50 µg/kg demonstrated 97.9% and 99.0% efficacy, respectively, while a single dose of 100 µg/kg demonstrated 91.1% efficacy.

CONCLUSIONS

Five monthly doses of 9 µg/kg provided similar or only marginally lower efficacy against JYD-34, a known ML-resistant isolate, compared to substantially higher doses administered for 3 months. This underscores the importance of duration of exposure to moxidectin when facing ML-resistant isolates. Repeated administration of lower doses of moxidectin are an alternative to higher doses in the prevention of heartworm disease associated with less susceptible or resistant isolates.

摘要

背景

大环内酯类(MLs)是目前唯一可有效预防心丝虫病的商业化药物。本文介绍了口服莫昔克丁在不同剂量方案下对 JYD-34(一种已知的 ML 耐药犬恶丝虫分离株)的疗效。

方法

在五项实验室研究中,使用了 52 只专门繁殖的比格犬。所有犬在首次治疗前 30 天接种 50 条犬恶丝虫第三期幼虫(L)(JYD-34 分离株)。将犬随机分组,接受一、三或五次每月剂量的口服莫昔克丁,剂量范围为 6 至 100μg/kg 体重。在每项研究中,对照组犬不进行治疗。L 接种后 5 至 6 个月,对犬进行安乐死,并计算成虫数量,以评估剂量方案的疗效。

结果

所有对照组犬均检出成虫心丝虫,总几何平均虫数为 29.7 条(范围 15.2 至 38.0,个体计数范围为 8 至 51)。5 次每月剂量 6μg/kg 提供了 83.3%和 90.2%的疗效,相同次数的每月 9μg/kg 剂量显示了 98.8%和 94.1%的疗效。3 次每月剂量 30 和 50μg/kg 分别显示了 97.9%和 99.0%的疗效,而单次 100μg/kg 剂量则显示了 91.1%的疗效。

结论

5 次每月剂量 9μg/kg 对已知的 ML 耐药分离株 JYD-34 的疗效与 3 个月内高剂量相比相似或略低。这突出了在面对 ML 耐药分离株时,莫昔克丁暴露时间的重要性。重复给予较低剂量的莫昔克丁是预防与低敏感性或耐药性分离株相关的心丝虫病的替代方案。

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本文引用的文献

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Heartworm disease - Overview, intervention, and industry perspective.心丝虫病-概述、干预和行业视角。
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Dirofilaria immitis JYD-34 isolate: whole genome analysis.犬恶丝虫JYD - 34分离株:全基因组分析
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