Eisler M C, Gault E A, Moloo S K, Holmes P H, Peregrine A S
University of Glasgow Veterinary School, UK.
Acta Trop. 1997 Feb;63(2-3):89-100. doi: 10.1016/s0001-706x(96)00602-x.
The relationship between serum concentrations of the prophylactic trypanocidal drug isometamidium chloride and protection against tsetse challenge with two populations of Trypanosoma congolense was investigated in Boran (Bos indicus) cattle, using an isometamidium-ELISA. Isometamidium chloride (Samorin) was administered to cattle at a dose rate of 1.0 mg/kg body weight by deep intramuscular injection. Thereafter, the animals were challenged at monthly intervals with either a drug-sensitive clone (T. congolense IL 1180) or a clone expressing a moderate level of resistance to isometamidium (T. congolense IL 3343). Untreated control cattle were used to confirm the infectivity of each challenge. Of ten drug-treated cattle that were challenged with T. congolense IL 3343, all were refractory to infection at the first challenge. 1 month after drug administration. However, all ten animals succumbed to infection at either the second (seven cattle) or third (three cattle) monthly challenges. By contrast, all five drug-treated cattle challenged with T. congolense IL 1180 resisted four monthly challenges. The mean isometamidium concentration at the time of the first, 1 month, challenge was 5.6 +/- 2.8 ng/ml. At the time of the second monthly challenge the mean concentration was 2.0 +/- 0.86 ng/ml: at this time, concentrations were not significantly different between those cattle refractory to challenge with T. congolense IL 3343 and those cattle that were not. Thus, differences in susceptibility to challenge at this time would appear to be due to differences in the drug sensitivity of the parasite challenge. Finally, the mean isometamidium concentration in uninfected cattle at the time of the fourth monthly challenge was 0.4 +/- 0.18 ng/ml. These results indicate that when T. congolense infection occurs in cattle under isometamidium prophylaxis, the parasites may be considered at least moderately drug resistant if the concentration of isometamidium in serum is 2.0 ng/ml. At concentrations between 0.4 and 2.0 ng/ml a low level of drug resistance may be inferred. Below 0.4 ng/ml, however, no inference regarding drug resistance should be made.
在博拉安（瘤牛）中，使用异米丁酶联免疫吸附测定法（isometamidium - ELISA）研究了预防性杀锥虫药物氯异米丁血清浓度与针对两种刚果锥虫群体采采蝇攻击的保护作用之间的关系。通过深部肌肉注射以1.0毫克/千克体重的剂量率给牛施用氯异米丁（Samorin）。此后，每月用对药物敏感的克隆株（刚果锥虫IL 1180）或对异米丁具有中等抗性水平的克隆株（刚果锥虫IL 3343）对动物进行攻击。未处理的对照牛用于确认每次攻击的感染性。在用刚果锥虫IL 3343攻击的10头药物处理牛中，在给药后1个月的首次攻击时，所有牛均对感染具有抵抗力。然而，在第二次（7头牛）或第三次（3头牛）每月攻击时，所有10头牛均死于感染。相比之下，用刚果锥虫IL 1180攻击的所有5头药物处理牛抵抗了4次每月攻击。首次攻击（1个月时）时异米丁的平均浓度为5.6±2.8纳克/毫升。在第二次每月攻击时，平均浓度为2.0±0.86纳克/毫升：此时，对刚果锥虫IL 3343攻击具有抵抗力的牛与不具有抵抗力的牛之间的浓度没有显著差异。因此，此时对攻击易感性的差异似乎是由于寄生虫攻击的药物敏感性差异所致。最后，在第四次每月攻击时未感染牛中异米丁的平均浓度为0.4±0.18纳克/毫升。这些结果表明，在氯异米丁预防下牛发生刚果锥虫感染时，如果血清中氯异米丁的浓度为2.0纳克/毫升，则可认为寄生虫至少具有中等耐药性。在0.4至2.0纳克/毫升之间的浓度下，可推断出低水平的耐药性。然而，低于0.4纳克/毫升时，不应推断耐药性情况。
