Epidemiological studies suggest iron deficiency protects against malaria and administering iron to iron-deficient individuals may increase malaria risk. Our previous work confirmed decreased P. falciparum growth in iron deficient red blood cells (RBCs) and increased infection susceptibility in young RBCs and reticulocytes.Our objective was to comprehensively evaluate P. falciparum pathogenesis in pregnant women and children with iron deficiency before, during, and after iron supplementation. We also sought to evaluate the hypothesis that malaria risk increases as erythropoiesis increases in response to iron supplementation.
We investigated P. falciparum in vitro growth characteristics in RBCs from 135 children (ages 6-24 months; hemoglobin levels < 11 g/dL) and 165 pregnant women (2nd and 3rd trimester) before, during, and upon completion of 12 weeks of iron supplementation (12 mg and 60 mg daily). Using flow cytometry-based assays, we separately examined effects of iron deficiency and iron supplementation on overall parasite growth and merozoite RBC invasion.
We demonstrate that P. falciparum erythrocytic stage growth in vitro increases directly in relation to increasing reticulocytes in circulation and mean corpuscular hemoglobin concentration in RBCs, the kinetics of which correlate with increased erythropoiesis. Additionally, we show merozoite invasion is reduced in iron deficient RBCs and increases during iron supplementation.
We conclude malaria growth in vitro corresponds with elevated erythropoiesis, an inevitable consequence of iron supplementation. Our findings imply iron supplementation in malarious regions should be accompanied by effective preventative measures against falciparum malaria.