The within-host cellular dynamics of bloodstage malaria: theoretical and experimental studies

The properties of a mathematical model of bloodstage infection with a single strain of malaria were investigated. Analysing the cell population dynamics in the absence of a host immune response we demonstrate a relationship between host and parasite parameters that defines a criterion for the successful invasion and persistence of the parasite. Important parameters are the rates of merozoite production and death and those of erythrocyte production, death and invasion. We present data from experiments designed to evaluate the erythrocyte invasion rate in a rodent malaria system. The model generates patterns of parasitaemia in good qualitative agreement with those seen in Plasmodium berghei infections. The sole force behind the rise and fall in parasitaemia in the model without immunity is the density of susceptible erythrocytes, suggesting that resource availability is an important determinant of the initial pattern of infection in vivo. When we incorporate a simple immune response into the model we find that immunity against the infected cell is much more effective at suppressing parasite abundance than immunity against the merozoite. Simulations reveal oscillating temporal patterns of parasite abundance similar to P. c. chabaudi infection, challenging the concept that antigenic variation is the sole mechanism behind recrudescing patterns of infection.