Iron deficiency is protective against erythrocytic stage malaria infection (2014)

Undergraduates: Marwa Elnagheeb, Martha A. Clark, Morgan M. Goheen Anthony Fulford, Raj S. Kasthuri, Andrew M Prentice, Nancy Fisher, Steve M Taylor, Carla Cerami

Faculty Advisor: Carla Cerami
Department: Biology

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Iron deficiency and malaria are co-morbidities in significant portions of the developing world. Iron deficiency is easily reversed by oral iron supplementation. WHO guidelines recommend universal iron supplementation. However, epidemiological evidence that iron deficiency is protective against malaria infection and that iron supplementation may increase the risk of malaria calls into question the recommendation. Despite clear evidence that iron deficiency is protective against malaria; the biological principles governing the protection have remained elusive. We hypothesize that the erythrocytic stage of malaria infection, which is responsible for all symptoms of disease, is affected by iron deficiency. To address our hypothesis, we compared the growth of the malaria parasite in RBCs donated by individuals with iron deficiency anemia to growth of the parasite in RBCs donated by iron-replete individuals. We observed that malaria growth was significantly reduced in iron deficient RBCs due to (i) decreased invasion of the malaria parasite into iron deficient RBCs and (ii) reduced production of infectious daughter merozoites by parasites within iron deficient RBCs. We conclude that malaria propagation is attenuated in iron deficient RBCs. This may contribute to protection from malaria associated with iron deficiency anemia.