Abstract

The two main agents of human malaria, Plasmodium vivax and Plasmodium falciparum, can induce severe anemia and provoke strong, complex immune reactions. To gain insight into the dynamics of parasitemia and anemia in malaria infections, we developed differential equation models of parasite and red blood cell (RBC) populations modulated by host immune and erythropoietic responses. The model immune responses incorporated a rapidly-responding paroxysm component and a slower-responding, long-term antibody component. The models compared dyserythropoietic (reducing RBC production during infection) and compensatory erythropoietic (boosting RBC production) responses to fixed, basal-rate RBC production. We consider how host regulation of parasitemia varies with the parasite development stages targeted by the immune responses. Infection outcomes over a wide range of immune-component targets and erythropoeitic behaviors showed several broad trends: (A) Dyserythopoiesis was associated with lower parasitemia but heightened risk of catastrophic anemia. (B) Compensatory erythropoietic response was associated with less severe anemia, but higher parasitemia when either the paroxysm or antibody responses were ineffective. (C) For both parasite species, sharp transitions between the schizont and merozoite stages of development (i.e., with standard deviation in intra-RBC development time <= 2.4 hours) were associated with lower parasitemia and less severe anemia. (D) P. vivax can induce catastrophic anemia as readily as P. falciparum, though P. vivax attacks a much smaller subset of RBCs. Our conclusions are (a) the hosts erythopoietic response affects infection outcome in the presence of immune responses. (b) Tight synchronization in asexual parasite development can benefit the host. (c) The marked immune response observed clinically in P. vivax malaria may be preventing a fatal outcome in this nonlethal but debilitating infection.



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