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异三氮脒和羟脒芐在治疗感染埃塞俄比亚锥虫 A 型和 B 型的小鼠时均无效。

Isometamidium chloride and homidium chloride fail to cure mice infected with Ethiopian Trypanosoma evansi type A and B.

机构信息

College of Veterinary Medicine, Mekelle University, Mekelle, Ethiopia.

College of Veterinary Medicine, Samara University, Afar, Ethiopia.

出版信息

PLoS Negl Trop Dis. 2018 Sep 12;12(9):e0006790. doi: 10.1371/journal.pntd.0006790. eCollection 2018 Sep.

Abstract

BACKGROUND

Trypanosoma evansi is mechanically transmitted by biting flies and affects camels, equines, and other domestic and wild animals in which it causes a disease called surra. At least two types of Trypanosoma evansi circulate in Ethiopia: type A, which is present in Africa, Latin America and Asia, and type B, which is prevalent in Eastern Africa. Currently, no information is available about the drug sensitivity of any Ethiopian T. evansi type.

METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted with the objective of determining the in vivo drug sensitivity of two T. evansi type A and two type B stocks that were isolated from camels from the Tigray and Afar regions of Northern Ethiopia. We investigated the efficacy of four trypanocidal drugs to cure T. evansi infected mice: melarsamine hydrochloride (Cymelarsan), diminazene diaceturate (Veriben and Sequzene), isometamidium chloride (Veridium) and homidium chloride (Bovidium). Per experimental group, 6 mice were inoculated intraperitoneally with trypanosomes, treated at first peak parasitemia by daily drug injections for 4 consecutive days and followed-up for 60 days. Cymelarsan at 2 mg/kg and Veriben at 20 mg/kg cured all mice infected with any T. evansi stock, while Sequzene at 20 mg/kg caused relapses in all T. evansi stocks. In contrast, Veridium and Bovidium at 1 mg/kg failed to cure any T. evansi infection in mice.

CONCLUSIONS/SIGNIFICANCE: We conclude that mice infected with Ethiopian T. evansi can be cured with Cymelarsan and Veriben regardless of T. evansi type. In contrast, Veridium and Bovidium are not efficacious to cure any T. evansi type. Although innate resistance to phenanthridines was previously described for T. evansi type A, this report is the first study to show that this phenomenom also occurs in T. evansi type B infections.

摘要

背景

伊氏锥虫通过吸血蝇机械传播,影响骆驼、马和其他家养和野生动物,导致苏拉病。在埃塞俄比亚,至少有两种伊氏锥虫循环存在:A型,存在于非洲、拉丁美洲和亚洲;B 型,流行于东非。目前,尚无关于任何埃塞俄比亚 T. evansi 型药物敏感性的信息。

方法/主要发现:本研究旨在确定从埃塞俄比亚北部提格雷和阿法尔地区的骆驼中分离出的两种 T. evansi 型 A 和两种型 B 株的体内药物敏感性。我们研究了四种杀锥虫药物对感染伊氏锥虫的小鼠的疗效:盐酸喷他脒(Cymelarsan)、二乙酰对二甲苯脒(Veriben 和 Sequzene)、异咪脒盐酸盐(Veridium)和盐酸羟脒(Bovidium)。每个实验组,6 只小鼠通过腹腔接种锥虫,在第一次高峰寄生虫血症时,每天用药物注射治疗 4 天,然后随访 60 天。Cymelarsan 2mg/kg 和 Veriben 20mg/kg 治愈了所有感染任何 T. evansi 株的小鼠,而 Sequzene 20mg/kg 导致所有 T. evansi 株的复发。相比之下,Veridium 和 Bovidium 1mg/kg 未能治愈任何 T. evansi 感染的小鼠。

结论

我们的结论是,感染埃塞俄比亚 T. evansi 的小鼠可以用 Cymelarsan 和 Veriben 治愈,无论 T. evansi 型如何。相比之下,Veridium 和 Bovidium 对任何 T. evansi 型都没有疗效。虽然先前已经描述了对 T. evansi 型 A 的天然对菲啶类药物的抗性,但本报告是首次表明这种现象也发生在 T. evansi 型 B 感染中。

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