Safety and efficacy of iron supplements in malaria-endemic areas.

Where malaria surveillance and health care is inadequate, iron supplements given without food can increase the severity of malarial infections. The likely explanation is that the rate of iron influx into the plasma from high-dose oral supplements exceeds the rate of iron binding to transferrin and a quantity of non-transferrin-bound iron (NTBI) is formed. It is proposed that NTBI increases the intensity of malarial infections by increasing the sequestration of malaria-infected red cells in the capillaries of the brain and intestine, causing more cerebral malaria and further increasing the permeability of the intestinal barrier to the passage of pathogens. Bacteremia is frequently reported in children with severe malaria. At the same time, high iron doses stimulate the growth of pathogenic bacteria in the stool, further increasing the potential for bacteremia. The normal immune response to malaria, as well as other infections and inflammatory disorders, is to prevent further microbial growth by stimulating hepcidin synthesis and preventing the passage of iron into the plasma. Iron absorption is decreased and the efficacy of the iron interventions would be expected to be lower in the presence of infections.