The pathophysiology of malarial anaemia: where have all the red cells gone?

In the accompanying article, Odhiambo, Stoute and colleagues show how the age distribution of malarial anaemia and the haemolysis of red blood cells (RBCs) may be linked by an age-dependent increase in the capacity of RBCs to inactivate complement components absorbed or deposited directly on to the surface of the RBC [1]. The work raises not only a number of important new lines of research but also challenges malaria researchers to apply this basic work to develop new ways to prevent and treat malaria.Malaria remains an enormous problem in public health around the world [2]. Over 2 billion people live in malaria-endemic areas and up to 1 million children die each year of malaria. Severe falciparum malaria may present a variety of syndromes, but presents most frequently in childhood with severe malarial anaemia or coma. The difference in age distributions of children presenting with these syndromes is as striking as it is puzzling; the median age of children presenting with severe malarial anaemia is typically 1 to 3 years old, while the median age of children presenting with coma is significantly and consistently older, typically 3 to 5 years old [3].Furthermore, there remain major unsolved problems about the fundamental pathophysiology of all syndromes of severe malaria. The rapid drop in haemoglobin during acute infection and the slower decline in chronic infection appear to be due to increased extravascular haemolysis of RBCs with a concomitant failure of the bone marrow to increase red cell production to compensate for these losses [4].The increased clearance of infected cells is readily explained by the rupture of cells after completion of the parasite's intra-erythrocytic life cycle and opsonisation and clearance of intact infected RBCs. Rather less obvious is why and how uninfected cells are also cleared. It has been estimated that approximately 10 uninfected cells are cleared from the circulation for every infected cell and so the clearance of uninfected cel