Febrile malaria and asymptomatic malaria parasitemia substantially decrease iron absorption in single-meal, stable isotope studies in women and children, but to date there is no evidence of decreased efficacy of iron-fortified foods in malaria-endemic regions. Without inadequate malarial surveillance or health care, giving iron supplements to children in areas of high transmission could increase morbidity and mortality. The most likely explanation is the appearance of non-transferrin-bound iron (NTBI) in the plasma. NTBI forms when the rate of iron influx into the plasma exceeds the rate of iron binding to transferrin. Two studies in women have reported substantially increased NTBI with the ingestion of iron supplements. Our studies confirm this, but found no significant increase in NTBI on consumption of iron-fortified food. It seems likely that the malarial parasite in hepatocytes can utilize NTBI, but it cannot do so in infected erythrocytes. NTBI however may increase the sequestration of parasite-infected erythrocytes in capillaries. Bacteremia is common in children with severe malaria and sequestration in villi capillaries could lead to a breaching of the intestinal barrier, allowing the passage of pathogenic bacteria into the systemic circulation. This is especially important as frequent high iron doses increase the number of pathogens in the intestine at the expense of the barrier bacteria.
