Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response

In the bloodstream of its mammalian host, the 'slender' form of Trypanosoma brucei replicates extracellularly producing a parasitaemia. At high densit y, the level of parasitaemia is limited at a sublethal level by differentia tion to the non-replicative 'stumpy' form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell ty pes and level of trypanosome parasitaemia, and compare the best fits,with e xperimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independen tly of one another. Best fits also favour a model in which the slender-to-s tumpy differentiation progresses in a manner that is essentially independen t of the cell cycle. Finally, these models also make the prediction that th e density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of t he immune system and are not due to antigenic variation.