Potential immune mechanisms associated with anemia in Plasmodium vivax malaria: a puzzling question

Abstract

The pathogenesis of malaria is complex, generating a broad spectrum of clinical manifestations. One of the major complications and concerns in malaria is anemia, which is responsible for considerable morbidity in the developing world, especially in children and pregnant women. Despite its enormous health importance, the immunological mechanisms involved in malaria-induced anemia remain incompletely understood. Plasmodium vivax, one of the causative agents of human malaria, is known to induce a strong inflammatory response with a robust production of immune effectors, including cytokines and antibodies. Therefore, it is possible that the extent of the immune response not only may facilitate the parasite killing but also may provoke severe illness, including anemia. In this review, we consider potential immune effectors and their possible involvement in generating this clinical outcome during P. vivax infections.

FIG 1

Anemia in Plasmodium vivax malaria and possible immune mechanisms associated with destruction of infected and noninfected red cells. (A) During its intraerythrocytic cycle, P. vivax promotes extensive changes in the host reticulocyte, leading to its rupture. Parasites, antigens, and debris are released into the circulation. In response to these molecules, the host induces a strong immune response which may damage red blood cell (RBC) membranes or still lead to hemolysis or phagocytosis of both noninfected and infected erythrocytes. P. vivax has developed resistance to chloroquine, which may delay parasite clearance, therefore contributing to anemia. (B) Immune mediators may also act in the bone marrow and spleen, causing a toxic effect on erythroid lineages and leading to dyserythropoiesis. Moreover, P. vivax-infected RBCs seem to be able to cytoadhere to endothelial cells from these organs and also to the placental microvasculature. Another possible route of RBC loss is via rosetting. It has been suggested that these RBC aggregates may interfere negatively in erythropoiesis or that the noninfected RBCs attached to the infected one are destroyed in some way. However, the mechanisms that link cytoadherence/rosetting to anemia remain unknown. CSA, chondroitin sulfate A; HA, hyaluronic acid.