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丁萘醌对亚临床感染牛中美国分离的池田基因型的短期疗效。

Transient efficacy of buparvaquone against the US isolate of Ikeda genotype in sub-clinically infected cattle.

作者信息

Bastos Reginaldo G, Hassan Amany, Onzere Cynthia K, Herndon David R, Villarino Nicolas F, Laughery Jacob M, Fry Lindsay M

机构信息

Animal Disease Research Unit, USDA-ARS, Pullman, WA, United States.

Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, United States.

出版信息

Front Vet Sci. 2024 Jul 26;11:1421710. doi: 10.3389/fvets.2024.1421710. eCollection 2024.

DOI:10.3389/fvets.2024.1421710
PMID:39132441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310158/
Abstract

INTRODUCTION

, an economically significant tick-borne hemoparasite, infects cattle globally. The Ikeda genotype, transmitted by ticks, is associated with clinical manifestations characterized by anemia, abortions, and mortality, although subclinical infections prevail. Despite the common occurrence of subclinical infections, therapeutic interventions targeting Ikeda in such cases are currently lacking, impeding effective parasite control measures. To address this critical knowledge gap, we assessed the efficacy of buparvaquone (BPQ) in eliminating the Ikeda, US isolate, in sub-clinically infected cattle.

METHODS

Twelve sub-clinically infected calves, identified by the presence of in peripheral blood alongside the absence of fever and anemia, were enrolled in the study. Six calves received two treatments of the BPQ label dose (2.5 mg/kg) at a 48-h interval, while additional three calves received the drug at a dosage of 6 mg/kg following the same regimen. Three untreated calves served as controls.

RESULTS AND DISCUSSION

Endpoint and quantitative PCR analyses revealed that BPQ exerted a transient effect on parasitemia. Parasites remained undetectable in peripheral blood until weeks 4 and 11 post-treatment in animals administered 2.5 mg/kg and 6 mg/kg of BPQ, respectively. Intriguingly, following recrudescence, administering 6 mg/kg to animals previously treated with 2.5 mg/kg did not result in a reduction in parasite load. Pharmacokinetic analysis data suggested that escalating the dosage led to a less than proportional increase in serum concentrations of BPQ. Moreover, a significant yet reversible decrease ( < 0.05) in blood urea nitrogen was observed in animals treated with the drug, irrespective of the dosage. Despite parasitemia relapse, animals treated with 6 mg/kg BPQ exhibited a noteworthy decrease ( < 0.05) in IgG levels specific to the major piroplasm surface protein compared to controls and animals treated with 2.5 mg/kg of the drug.

CONCLUSION

BPQ did not demonstrate efficacy in clearing subclinical Ikeda infection. Future investigations are warranted to explore innovative therapeutic modalities that, in synergy with vaccines and diagnostic assays, can facilitate the development of comprehensive programs aimed at controlling and eradicating this parasite.

摘要

引言

作为一种在经济上具有重要意义的蜱传血液寄生虫,在全球范围内感染牛群。由蜱传播的池田基因型与以贫血、流产和死亡为特征的临床表现相关,尽管亚临床感染较为普遍。尽管亚临床感染很常见,但目前缺乏针对此类情况下池田基因型的治疗干预措施,这阻碍了有效的寄生虫控制措施。为填补这一关键的知识空白,我们评估了布帕喹(BPQ)在清除亚临床感染牛体内美国分离株池田基因型方面的疗效。

方法

选取12头亚临床感染的犊牛,通过外周血中存在该病原体且无发热和贫血症状来确定。6头犊牛以48小时的间隔接受两次布帕喹标签剂量(2.5毫克/千克)的治疗,另外3头犊牛按照相同方案接受6毫克/千克剂量的药物治疗。3头未治疗的犊牛作为对照。

结果与讨论

终点分析和定量PCR分析表明,布帕喹对寄生虫血症产生了短暂的影响。在分别给予2.5毫克/千克和6毫克/千克布帕喹的动物中,外周血中直到治疗后第4周和第11周才检测不到寄生虫。有趣的是,复发后,对先前用2.5毫克/千克治疗的动物给予6毫克/千克剂量并未导致寄生虫负荷降低。药代动力学分析数据表明,增加剂量导致布帕喹血清浓度的增加小于成比例增加。此外,无论剂量如何处理,用该药物治疗的动物血液尿素氮均出现显著但可逆的下降(P<0.05)。尽管寄生虫血症复发,但与对照组和用2.5毫克/千克药物治疗的动物相比,用6毫克/千克布帕喹治疗的动物针对主要梨形虫表面蛋白的IgG水平显著下降(P<0.05)。

结论

布帕喹在清除亚临床池田基因型感染方面未显示出疗效。未来有必要进行研究,探索创新的治疗方式,与疫苗和诊断检测协同作用,以促进旨在控制和根除这种寄生虫的综合方案的制定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/589a0013561c/fvets-11-1421710-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/deb9921e50e8/fvets-11-1421710-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/5e9b52c6291b/fvets-11-1421710-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/8c25c40350f9/fvets-11-1421710-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/00aff44bddb2/fvets-11-1421710-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/589a0013561c/fvets-11-1421710-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/deb9921e50e8/fvets-11-1421710-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/5e9b52c6291b/fvets-11-1421710-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/8c25c40350f9/fvets-11-1421710-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/00aff44bddb2/fvets-11-1421710-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b14/11310158/589a0013561c/fvets-11-1421710-g005.jpg

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