Trypanosomiasis caused by the mechanically transmitted organism Trypanosoma evansi is the most widely distributed species of the genus Trypanosoma and affects a wide range of animal hosts. The control of the disease caused by this organism, surra, relies principally on chemotherapy since there is no effective control strategy against the biting flies which predominantly transmit the disease. The emergence of drug-resistant strains of T. evansi in the field is considered to be a major problem which could undermine the efficacy of the small number of trypanocidal drugs currently available. It was reported over 50 years ago that drug-resistance was more likely to develop in immunosuppressed animals than in hosts with an intact immune system. This observation was re-evaluated in the present study using modem trypanocides to treat mice infected with T. evansi. It was found that the efficacy of the trypanocidal drugs currently available for the treatment of trypanosomiasis is substantially reduced in mice immunosuppressant by Co-60 irradiation compared to normal immunocompetent mice. Moreover, continuous passage of clones of T. evansi in immunosuppressed mice treated with gradually increasing doses of mel Cy, isometamidium and diminazene was found to rapidly lead to the development of high levels of drug resistance close to the maximum tolerated dose. Furthermore the drug-resistance developed in immunosuppressed mice was a genuine resistance and the clones maintained the same level of resistance when transferred into normal mice. On the other hand it was not possible to produce drug-resistant organisms in immunocompetent mice. These findings highlight the need for further investigations on the role of the immune response in the development of drug resistance in the field as well the genetic basis of drug resistance in trypanosomiasis.
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Interactions between Host Immunity and the Efficacy of Chemotherapy in Mice Infected with Trypanosoma evansi
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