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多西环素剂量率和成虫前杀期对心丝虫相关病理和成虫质量的影响。

Effects of doxycycline dose rate and pre-adulticide wait period on heartworm-associated pathology and adult worm mass.

机构信息

Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.

Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.

出版信息

Parasit Vectors. 2023 Jul 25;16(1):251. doi: 10.1186/s13071-023-05858-2.

Abstract

BACKGROUND

The American Heartworm Society canine guidelines recommend treatment with doxycycline prior to adulticide administration to reduce levels of Wolbachia and its associated metabolites, which are known to be a leading cause of pulmonary pathology. Studies have determined that doxycycline administered at 10 mg/kg BID for 28 days is an effective dose for eliminating Wolbachia, but what has not been determined is the clinical relevance of this elimination. The current guidelines also recommend a 30-day wait period following administration of doxycycline to allow for clearance of metabolites, such as Wolbachia surface protein, and for further reduction in heartworm biomass before administration of adulticide. Reducing the doxycycline dose and eliminating the wait period may carry practical benefits for the animal, client, and practitioner.

METHODS

To investigate these treatment practices, Dirofilaria immitis adults were surgically transplanted into each of 45 dogs, which were divided into nine study groups of five dogs each. Seventy-five days after transplantation, two groups each were administered 5, 7.5, or 10 mg/kg BID doxycycline orally for 28 days and 6 µg/kg ivermectin monthly, with three untreated groups serving as controls. Study animals were necropsied and examined prior to treatment as well as 30 and 60 days post-treatment.

RESULTS

Mean worm weight was unaffected by dosage but exhibited a significant increase at 30 days and significant decrease at 60 days post-treatment, including in control groups. Histopathology lesion scores did not significantly differ among groups, with the exception of the lung composite score for one untreated group. Liver enzymes, the levels of which are a concern in doxycycline treatment, were also examined, with no abnormalities in alanine aminotransferase or alkaline phosphatase observed.

CONCLUSIONS

No consistent worsening of tissue lesions was observed with or without the AHS-recommended 30-day wait period, nor did reduced dosages of doxycycline lead to worsening of pathology or any change in efficacy in depleting worm weight. Mean worm weight did significantly increase prior to, and decrease following, the wait period. Future work that also includes adulticide treatment (i.e. melarsomine) will study treatment recommendations that may improve both animal health and owner compliance.

摘要

背景

美国心丝虫协会犬类指南建议在使用杀成虫剂之前用强力霉素治疗,以降低沃尔巴克氏体及其相关代谢物的水平,已知这些代谢物是导致肺部病理学的主要原因。研究表明,每天两次给予 10 毫克/千克强力霉素治疗 28 天是消除沃尔巴克氏体的有效剂量,但尚未确定这种消除的临床意义。目前的指南还建议在给予强力霉素后等待 30 天,以清除代谢物,如沃尔巴克氏体表面蛋白,并在给予杀成虫剂之前进一步减少心丝虫生物量。降低强力霉素剂量并消除等待期可能对动物、客户和从业人员有实际好处。

方法

为了研究这些治疗方法,将犬恶丝虫成虫手术移植到 45 只狗体内,将它们分为 9 个研究组,每组 5 只狗。移植后 75 天,每组 2 只狗分别给予 5、7.5 或 10 毫克/千克强力霉素口服,每天 2 次,28 天,每月给予 6 微克/千克伊维菌素,3 只未治疗的狗作为对照组。研究动物在治疗前以及治疗后 30 天和 60 天进行尸检和检查。

结果

平均虫体重量不受剂量影响,但在 30 天时有显著增加,在 60 天时有显著减少,包括对照组。各组之间的组织病变评分无显著差异,但有一组未治疗组的肺复合评分除外。还检查了肝酶,强力霉素治疗时需要关注这些酶的水平,未观察到丙氨酸氨基转移酶或碱性磷酸酶异常。

结论

在有或没有 AHS 推荐的 30 天等待期的情况下,未观察到组织病变的一致性恶化,也没有观察到强力霉素的低剂量导致病理学恶化或减轻虫体重量的疗效任何变化。平均虫体重量在等待期前显著增加,在等待期后显著减少。未来的工作还包括杀成虫剂(即美拉索明)治疗,将研究可能改善动物健康和主人依从性的治疗建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/10369763/f7558e2ca853/13071_2023_5858_Fig1_HTML.jpg

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