Frank, S. A. 1999. A model for the sequential dominance of antigenic variants in African trypanosome infections. Proceedings of the Royal Society of London B 266:1397-1401.

Trypanosoma brucei infects various domestic and wild mammals in equatorial Africa. The parasites' genome contains several hundred alternative and highly diverged surface antigens, of which only a single one is expressed in any cell. Individual cells occasionally change expression of their surface antigen, allowing them to escape immune surveillance. These switches appear to occur in a partly random way, creating a diverse set of antigenic variants. In spite of this diversity, the parasitemia develops as a series of outbreaks, each outbreak dominated by relatively few antigenic types. Host-specific immunity eventually clears the dominant antigenic types and a new outbreak follows from antigenic types that have apparently been present all along at low frequency. This pattern of sequential dominance by different antigenic types remains unexplained. I use a mathematical model of parasitemia 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 that randomly chosen switch rates do not provide sufficiently ordered parasitemias to match the observations. Instead, minor modifications of switch rates by natural selection are required to develop a sequence of ordered parasitemias.


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