Table 4.

Questions for future translational research.

PARASITE

How does the malaria parasite regulate iron?

What host iron sources are utilized by the malaria parasite?

Does the malaria parasite store iron?

Are parasite virulence factors regulated by iron?

Can merozoites sense host intra-erythrocytic iron?

RELATIONSHIP BETWEEN PARASITE AND HOST

Is iron limited enough during iron deficiency or in such excess following iron supplementation to respectively inhibit and exacerbate erythrocytic stage P. falciparum infection?

Do iron deficiency and iron supplementation affect erythrocytic stage P. falciparum microvascular adhesion, or host endothelial cell activation?

Do iron deficiency or iron supplementation impact parasite var gene expression or PfEMP1 protein levels on the RBC membrane?

Are there specific strains of P. falciparum that are better equipped to infect people with iron deficiency?

What is the effect of host iron deficiency and iron supplementation on P. falciparum gametocytogenesis?

What are the effects of changing RBC population dynamics on malaria infection?

How are the host innate and adaptive immune responses to malaria affected by iron deficiency and iron supplementation?

Is anemia of inflammation protective against malaria?

How does the presence of iron deficiency anemia modify the effects of HbS, HbC, or HbE on parasite growth, maturation, microvascular adhesion, or endothelial cell activation?

How do other malaria-protective polymorphisms, such as type O blood group antigen and glucose-6-phosphate dehydrogenase (G6PD) deficiency, interact with iron deficiency in mitigating malaria pathogenesis?