Figure 5: Hypothesized impact of iron deficiency and iron supplementation on host RBC population dynamics and susceptibility to erythrocytic stage malaria infection.

Recovery from IDA is a complex process, which varies between individuals. Iron supplementation of an individual with IDA (0 weeks) will result in reticulocytosis and the production of young iron-replete RBCs (6 weeks). 12 weeks after the initiation of supplementation, the majority of the iron-deficient RBCs, will have been cleared from circulation (iron-deficient and iron-replete RBCs have 90 and 120 day lifespans respectively). After 16 weeks of iron supplementation, iron status has been corrected and the age structure of the RBC population will be restored. As shown above, we hypothesize that individuals with IDA will be less susceptible to erythrocytic stage malaria. The induction of erythropoiesis in these individual by iron supplementation and subsequent replacement of the iron-deficient RBCs with young iron-replete RBCs will increase the susceptibility of the individual to erythrocytic stage malaria infection. The susceptibility to infection is predicted to peak at the point when all iron-deficient RBCs have been replaced, but the age distribution of iron-replete RBCs is on average younger than a fully recovered iron-replete individual. Finally, restoration of the normal distribution of RBC age will return an individual’s susceptibility to a normal level.