Figure 1. The asexual life-cycle of blood-stage Plasmodium falciparum parasites.

As early ring-stage parasites (top center) mature, they traffic PfEMP1 and other knob-associated proteins to the surface of their host RBCs, enabling their late ring-stage forms to adhere to microvascular endothelial cells. While sequestered in microvessels, parasites continue to mature into trophozoite and segmented schizonts. Merozoites that egress from schizonts infect RBCs, producing a new brood of ring-stage parasites in the bloodstream. The sequestration of parasitized RBCs leads to multiple deleterious effects in humans. These are initiated by endothelial activation and include the co-sequestration of blood elements (RBCs, leukocytes and platelets), endothelial dysfunction and microvascular obstruction.