CHEMOTHERAPEUTIC AND IMMUNOLOGICAL STUDIES ON STRAIN OF TRIPANOSOMA CONCOLENSE

Abstract

(l) The adaptation of two strains of T.congolense from cattle to rats is described. One of them, the Ibadan strain, showed the phenomenon of polymorphism after being transmitted for four and a half years in rats. (2) The pathogenicity of the two strains was studied. It was shown that the parasites are more pathogenic to younger rats than older ones and that a linear relationship exist between the size of the inoculum (number of parasites) and the prepatent period in rats and mice but not with the survival time of the rodents. A concurrent infection of P.berghei enhances the severity of T.congolense infection while that of T. brucei has no effect.

(3) In the case of these two strains of trypanosomes (Ibadan strain and Vom strain) excess Vitamin E had no effect on the parasitaemia. Glucose administered when the parasitaemia is very high does not affect the life span of the host but prolongs the survival time when given from the date of challenge or just after the prepatent period.

(4) In Infected rats, the clotting time of the tail blood increases rapidly from the third day after challenge with trypanosomes, while that of the heart blood is unaffected. The platelet count falls about 40-50% of the normal value before the death of the rat whiles the white blood cell count and the red blood cell count fall gradually until death. The packed cell volume and hemoglobin value fall off gradually as the parasitaemia increases. (5) Judging by the therapeutic indices obtained in the rat and the mouse, the safest of the currently used trypanocides is isometamidium, with ethidium, prothidium and berenil following respectively. (6) There is an inverse linear relationship between the weight of rats and mice and the average toxic dose of ethidium. (7) Of the six drugs studies in the project, berenil and M & B 2242 have a different mode of action when compared with the others which are phenanthridinum compounds (ethidium, prothidium, isometamidium & M & B 4596). This classification by their mode of action agrees with the classification proposed by Hawking and Sen (1960) also on the mode of action of trypanocidal compounds. The absorption coefficient of ethidium, isometamidium, prothidium and berenil were obtained. (8) Imuran and cortisone have no effect on the course of infection of the two strains of T. congolense used but ICI 47776 and dexamethasone suppress the immune response of rats and hence enhance the severity of the infections. ICI 47776 and dexamethasone have been shown in the present study to be contra-indicated in inflammatory and allergic conditions whenever there is a likelihood of trypanosomal infection.

(9) No apparent immunity has been shown to occur following therapeutic or prophylactic drug treatment to occur normal or relapsing trypanosomal infection.

(10) Berenil, ethidium, isometamidium given orally fourteen days before challenge at doses very considerably higher than the GD50 have no prophylactic effect. (11) Resistance to M & B 2242 is easily obtained in the laboratory while hundred fold resistance to ethidium was obtained after a long period of careful treatment. Resistance to isometamidium, berenil and prothidium was not obtained in the laboratory.

(12) T. congolense has been preserved in the frozen states with dimethyl-sulphoxide as a preservative at -179º C and remained viable after nine months of storage.