Direct and indirect effects of parasite on the development of malarial anemia. Severe malarial anemia is characterized by destruction of infected red blood cell (iRBC) following schizogony and clearance of both iRBCs and uninfected RBCs. During malarial infection, changes in membrane protein composition occur and the resultant immune complexes of RBCs, Ag, and immunoglobulin (Ig) (eg, RBC:RSP2:Ig) are cleared by macrophages to the spleen where they become activated (see Table 3 for more examples). Pigment-containing macrophages may release inflammatory cytokines and other biologically active mediators such as hydroxy-nonenal (HNE). It is possible that malarial pigment or other parasite products may have a direct inhibitory effect on erythropoiesis. Inhibition of erythropoiesis may be at one or more sites in the growth and differentiation of hematopoietic progenitors. Both indirect and direct effects may cause suppression of the bone marrow and spleen resulting in inadequate reticulocyte counts for the degree of anemia. The mechanisms of insufficient erythropoiesis in murine malaria have been summarized in Chang and Stevenson.154 Blue box indicates demonstrated in human infection; pink box, demonstrated in mouse infection; yellow box, demonstrated in both human and mouse infections. Hz indicates hemozoin; GPI, glycophosphatidylinositol anchors of merozoite proteins; Epo, erythropoietin; Epo-R, erythropoietin receptor; MΦ, macrophage; RSP-2, ring surface protein-2; and Ig, immunoglobulin. Figure modified with permission from Springer Science Business Media, Heidelberg, Germany.
