The dynamics of acute malaria infections. I. Effect of the parasite's red blood cell preference.

What determines the dynamics of parasite and anaemia during acute primary malaria infections? Why do some strains of malaria reach higher densities and cause greater anaemia than others? The conventional view is that the fastest replicating parasites reach the highest densities and cause the greatest loss of red blood cells (RBCs). Other current hypotheses suggest that the maximum parasite density is achieved by strains that either elicit the weakest immune responses or infect the youngest RBCs (reticulocytes). Yet another hypothesis is a simple resource limitation model where the peak parasite density and the maximum anaemia (percentage loss of RBCs) during the acute phase of infection equal the fraction of RBCs that the malaria parasite can infect. We discriminate between these hypotheses by developing a mathematical model of acute malaria infections and confronting it with experimental data from the rodent malaria parasite Plasmodium chabaudi. We show that the resource limitation model can explain the initial dynamics of infection of mice with different strains of this parasite. We further test the model by showing that without modification it closely reproduces the dynamics of competing strains in mixed infections of mice with these strains of P. chabaudi. Our results suggest that a simple resource limitation is capable of capturing the basic features of the dynamics of both parasite and RBC loss during acute malaria infections of mice with P. chabaudi, suggesting that it might be worth exploring if similar results might hold for other acute malaria infections, including those of humans.