Relative efficacy of melarsen oxide compared with mel Cy (Cymelarsan) when used in combination with difluoromethylornithine in the treatment of trypanosomiasis of the central nervous system.

A comparison was made between the efficacy of mel Cy (Cymelarsan) and melarsen oxide to cure central nervous system trypanosomiasis in a chronic Trypanosoma brucei mouse model. Combination treatment with difluoromethylornithine and arsenical was used and it was found that there was only a marginal advantage in using the water-soluble mel Cy in terms of the numbers of mice cured.

The possible use of Trypanosoma musculi infection in mice as a screening test for potential Trypanosoma cruzi-active drugs.

The ability of a range of trypanocidal drugs, including a number known to be active in Trypanosoma cruzi infections were tested against Trypanosoma musculi infections in the mouse. The ability of these drugs, particularly in their ability to eliminate the "cryptic phase" of T. musculi infections remaining in the kidneys, was investigated and their activity against this phase of T. musculi largely paralleled their known activity against T. cruzi infections. It is suggested that this could be used as a preliminary screening test for potential T. cruzi-active drugs.

Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. III. Studies in animals with acute infections.

Using trypanosomes labelled with [75Se]-methionine a series of experiments was conducted to investigate antibody production in mice with acute fulminating T. brucei infections. As measured by the hepatic uptake of radiolabelled parasites, we were unable to demonstrate any evidence of antibody-mediated uptake by the liver in such mice. It was concluded that this was not due to impaired macrophage function but was caused by the inability of antibody production to cope with the massive parasitaemias produced by rapidly-replicating infections so that effective opsonization of the parasites did not occur. In contrast, a train of trypanosome which causes a more chronic infection, although initially having a similar replication, although initially having a similar replication rate, subsequently switched t a slower one and thereby allowed antibody to reach levels which permitted effective opsonization. There was no evidence that the parasite caused any significant suppression of antibody responses in these acute infections since inoculation with trypanosomes of one stock at the same time as vaccination with irradiated organisms of a second stock did not prevent the development of antibody to the latter, as measured by the hepatic uptake of radiolabelled parasites.

Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. II. Mechanisms in immune animals.

Using trypanosomes labelled with [75Se]-methionine a series of experiments was conducted to investigate the respective roles of antibody, macrophage activtion and complement in the removal of trypanosomes from the circulation of immune mice. It was found that clearance in such animals is largely accomplished by antibody-mediated hepatic phagocytosis, which, at least in passively immunized animals, is dependent on opsonization involving C3. No evidence was found to suggest that intravascular lysis or activated macrophages are involved in immune clearance.

Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. I. Aspects of the radiolabelling technique.

A reliable and simple technique for the in vivo labelling of Trypanosoma brucei with [75Se]-methionine was developed. Between 97 and 99% of the radioactivity was protein bound in the trypanosomes and spontaneous elution in vitro was less than 10% over 4 h. The fate of the labelled trypanosomes after i.v. injection into normal and immune mice was studied. Whilst the vast majority of parasites remained in the circulation of normal animals they rapidly disappeared from the blood of immune animals. In the latter the liver was found to be the principal site of phagocytosis removing over 50% of the radiolabelled parasites within 15 min of injection.