This thesis describes studies on curative and prophylactic effects
of diminazene aceturate and isometamidium chloride and development of
sterile immunity in rabbits infected with Trypanosoma congolense by
bites from infected Glossina morsitans morsitans or by intradermal
inoculation of cultured metacyclic trypanosomes.
It was shown that chemotherapy influences the development of the
trypanosome chancre. Rabbits treated with 7 mg/kg diminazene acetur¬
ate at up to three days after infective tsetse bite did not develop
chancres, while in animals treated 4-7 days post-infection, chancres
appeared but were reduced in size and persisted for a short while.
Treatment at 8-10 days after infection did not influence chancre size
There were indications that efficacy of chemotherapy was related
to the timing of treatment after infection and hence the stage of
development of parasites in the trypanosome chancre. Thus 50% of
rabbits treated with 7 mg/kg diminazene aceturate at 8-10 days post¬
infection had relapses in parasitaemia, whereas animals treated with
a similar dose of the drug at 0-7 or 12-42 days after infection were
There was indirect evidence that in drug treated rabbits in which
relapses in parasitaemia occurred, trypanosomes may have originated
from extravascular sites in the skin. This was indicated by develop¬
ment of secondary chancres in some treated animals which later showed
The mode of action of diminazene aceturate on chancre trypanosomes
was studied. There was no detectable increase in parasitaemia, following
treatment at the time of maximum trypanosome development in chancres.
This indicated that diminazene aceturate does not act on chancre
trypanosomes by causing their release into the circulatory system.
In addition, intact and degenerating trypanosomes could be detected
histologically in chancres removed at three hours and at 24 hours
post-treatment but not at 2-4 days post-treatment. As there was no
evidence of phagocytosis of trypanosomes it was concluded that diminazene aceturate kills chancre trypanosomes in situ.
Studies on the prophylactic effects of diminazene aceturate and
isometamidium chloride showed that 7 mg/kg diminazene aceturate has
no prophylactic effect against cyclically transmitted T. congolense
even at three hours after treatment, and isometamidium chloride had a
prophylactic effect of less than three weeks. In some animals under
isometamidium or diminazene prophylaxis, chancres developed without
subsequent development of parasitaemia.
Immunity to homologous challenge with T. congolense after infection
and treatment with diminazene aceturate was shown to depend on the tim¬
ing of treatment in relation to the primary infection. Rabbits treated
at day 0-12 days after infective tsetse bite were susceptible, whereas
those treated at 14 or more days after infective tsetse bite, when
parasitaemia was readily detectable, were immune. Similar results
were obtained using cultured metacyclic trypanosomes. It was shown
that effective immunity against homologous challenge by infected tsetse
flies developed in animals treated at 14 days but not at 7 days after
infection with cultured metacyclic trypanosomes. This development of
immunity following inoculation of cultured metacyclic trypanosomes points
to their potential use in immunisation against trypanosomiasis.