Osman A S, Jennings F W, Holmes P H
University of Glasgow Veterinary School, U.K.
Acta Trop. 1992 Feb;50(3):249-57. doi: 10.1016/0001-706x(92)90081-8.
The effect of immunosuppression on the development of drug resistance by trypanosomes was investigated in mice infected with Trypanosoma evansi. As a result of frequent passage in immunosuppressed mice given subcurative drug treatments clones of T. evansi rapidly developed high levels of resistance to mel Cy, diminazene aceturate and isometamidium chloride. Similar protocols in normal immunocompetent mice infected with the same parent clones did not lead to the development of drug-resistance. The resistant populations developed in immunosuppressed mice maintained their high levels of resistance when tested in normal mice. The mel Cy resistant clone was tested for cross-resistance to other trypanocides and was found to be also highly resistant to diminazene and pentamidine. The results indicate that impairment of the host immune system may lead to the rapid development of drug-resistance by T. evansi under experimental conditions in mice and may possibly play a role in the development of drug resistance by trypanosomes in the field.
在感染伊氏锥虫的小鼠中研究了免疫抑制对锥虫耐药性发展的影响。在接受亚治疗剂量药物治疗的免疫抑制小鼠中频繁传代后,伊氏锥虫克隆迅速对美拉胂醇、乙酰氨基阿苯达唑和氯喹嘧胺产生了高水平耐药性。在感染相同亲本克隆的正常免疫活性小鼠中采用类似方案并未导致耐药性的产生。在免疫抑制小鼠中产生的耐药群体在正常小鼠中进行测试时仍保持其高水平耐药性。对美拉胂醇耐药克隆进行了对其他锥虫杀灭剂的交叉耐药性测试,发现其对乙酰氨基阿苯达唑和喷他脒也具有高度耐药性。结果表明,宿主免疫系统受损可能导致伊氏锥虫在小鼠实验条件下迅速产生耐药性,并且可能在野外锥虫耐药性的发展中发挥作用。