Can iron supplementation be reconciled with benefits and risks in areas hyperendemic for malaria?

Malaria is associated with about a million fatalities annually, largely among young children in zones of intense malarial transmission. The last thing needed would be measures that might increase the severity of clinical malaria. Thus, the finding in a field trial on Pemba Island, Tanzania, that routine oral iron supplementation produced adverse effects in iron-sufficient subjects had a ripple effect throughout the international public health community; it has effectively paralyzed efforts to redress iron-deficiency anemia in malaria-endemic regions. From a Hippocratic perspective, we consider the de facto moratorium on oral supplementation in such circumstance as a prudent interim measure. Public health programs to combat iron-deficiency anemia cannot be denied indefinitely to malaria-endemic populations, but the universal campaigns of iron provision cannot simply resume in the manner of the past. Contemporary biological and epidemiological understanding of the coevolution of humans and their pathogens should be able to provide guidance within the context of the essential and harmful aspects of iron. From these evolutionary standpoints, we identify a series of unresolved dilemmas. Toward a way forward, we highlight the pros and cons, as well as possible directions toward short-term strengthening, within three domains: tailored oral iron compounds, iron administration targeted only to iron-deficient individuals through screening, and prudent use of antimalarial prophylaxis. Although the tension between the essentiality of iron for humans and its role in pathogen virulence looms through every consideration, this recognition is a starting point toward the weighing of appropriate options balancing benefits and safety.