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 an infection 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 showing marked 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.