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

BackgroundTrypanosoma 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 findingsThis 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/significanceWe 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.

背景：伊氏锥虫（Trypanosoma evansi）通过吸血蝇机械传播，可感染骆驼、马属动物及其他家养与野生动物，引发一种名为苏拉病（surra）的疾病。埃塞俄比亚境内目前至少存在两种伊氏锥虫流行株：A型伊氏锥虫分布于非洲、拉丁美洲与亚洲，B型伊氏锥虫则在东非地区广泛流行。截至目前，尚无关于埃塞俄比亚境内任何伊氏锥虫分离株药敏特性的公开研究数据。

材料与方法/主要结果：本研究旨在测定从埃塞俄比亚北部提格雷与阿法尔地区骆驼体内分离得到的2株A型伊氏锥虫分离株与2株B型伊氏锥虫分离株的体内药敏活性。本研究评估了4种抗锥虫药物对伊氏锥虫感染小鼠的治疗效果：盐酸美拉沙敏（melarsamine hydrochloride，Cymelarsan）、二乙酸二脒那嗪（diminazene diaceturate，商品名Veriben、Sequzene）、氯化异沙米啶（isometamidium chloride，Veridium）以及氯化胡米啶（homidium chloride，Bovidium）。实验每组设置6只小鼠，经腹腔接种锥虫，在首次虫血症峰值时每日给予药物注射，连续给药4天，随后对小鼠进行为期60天的跟踪观察。结果显示，2mg/kg剂量的盐酸美拉沙敏与20mg/kg剂量的Veriben可治愈所有受试伊氏锥虫分离株感染的小鼠；而20mg/kg剂量的Sequzene则会导致所有受试伊氏锥虫分离株感染出现复发。相较而言，1mg/kg剂量的Veridium与Bovidium无法治愈任何伊氏锥虫感染小鼠。

结论与意义：本研究证实，无论伊氏锥虫毒株类型如何，埃塞俄比亚来源的伊氏锥虫感染小鼠均可通过盐酸美拉沙敏与Veriben实现治愈。反之，Veridium与Bovidium对各型伊氏锥虫感染均无治疗效果。此前已有研究报道A型伊氏锥虫对菲啶类药物存在固有耐药性，但本研究首次证实该耐药现象同样存在于B型伊氏锥虫感染中。