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Trypanosomes which undergo complete cyclical development are capable of controlling their

growth rates at different points within their life cycle. In the tsetse fly vector, mature metacyclic

forms, which are infective for the mammalian host, are non-dividing. When an infected fly takes

a blood-meal from a mammalian host, the infective metacyclic forms which pass into the host

begin to differentiate into actively dividing bloodstream-forms. These actively proliferate in the

vascular system. Studies on Trypanosoma brucei brucei in rodents have shown that when aninfection has matured, the trypanosomes are capable of undergoing a differentiation event to

become non-dividing. These non-dividing forms can be cleared by the host immune system

through recognition of the surface coat of the parasite. The clearing of a wave of parasitaemia

allows trypanosomes which have a different surface coat, generated through a process termed

antigenic variation, to become established in the vascular system. The mechanisms of antigenic

variation by which trypanosomes evade the host immune system are well documented. At

present, there is no information available on how growth of the parasite is controlled, although

there is evidence to suggest that a decrease in growth rate can allow the host to control and

eliminate the infection. The available information on infections in trypanotolerant and

trypanosusceptible cattle suggests that trypanotolerant breeds control the infection, at least in

part, by reducing parasite load in the first wave of parasitaemia, with subsequent waves showingmarked reductions until the infection is eliminated. Susceptible animals show only slightly

higher parasite load in the first wave but are incapable of controlling subsequent waves. Immune

dysfunction is evident in the susceptible animals following the first wave of parasitaemia but not

in the tolerant animals.

The consensus opinion at present is that the control of parasitaemia occurs prior to the first peak

of parasitaemia and prior to control of parasite numbers through immune recognition of parasite

molecules. We believe that there must be signalling between the host and parasite, between

parasites and between parasite and host which influence the course of the infection. In exotic

breeds these signals are clearly wrong, and an unchecked trypanosome infection eventually

results in the death of the animal. We wish to understand how these signals work on parasite

proliferation in order to identify the signals and the parasite surface receptors they bind to. In the

establishment of an infection and in the first wave of parasitaemia, the differences in parasite

numbers could be due to control of parasite growth rates (e.g. cell division cycle) or death rates

(e.g. programmed cell death).

We are not sure whether either of these possibilities would influence the modelling of an

infection and whether it is important, or even possible, to determine experimentally which of the

two is occurring. Towards the peak of the first wave of parasitaemia there is an immune response

elicited by the host against the surface coat of the parasite which eliminates that antigenic type

from the bloodstream and allows re-invasion of the vascular system with parasites having a

different surface coat. At this time, susceptible animals start to display immune dysfunction

whereas tolerant animals do not.