A model for the sequential dominance of antigenic variants in African trypanosome infections

Trypanosoma brucei infects various domestic and wild mammals in equatorial Africa. The parasite's genome contains several hundred alternative and high ly diverged surface antigens, of which only a single one is expressed in an y cell. Individual cells occasionally change expression of their surface an tigen, allowing them to escape immune surveillance. These switches appear t o occur in a partly random way, creating a diverse set of antigenic variant s. In spite of this diversity, the parasitaemia develops as a series of out breaks, each outbreak dominated by relatively few antigenic types. Host-spe cific immunity eventually clears the dominant antigenic types and a new out break follows from antigenic types that have apparently been present all al ong at low frequency This pattern of sequential dominance by different anti genic types remains unexplained. I use a mathematical model of parasitaemia and host immunity to show that small variations in the rate at which each type switches to other types can explain the observations. My model shows t hat randomly chosen switch rates do not provide sufficiently ordered parasi taemias to match the observations. Instead, minor modifications of switch r ates by natural selection are required to develop a sequence of ordered par asitaemias.