Malaria and iron: history and review.

To cause infection, nearly all protozoa, fungi, and bacteria must obtain growth-essential iron from their hosts. To suppress infection, hosts have evolved iron-withholding defense systems. Enhancement of iron withholding is a potential target for the development of novel therapeutic agents. This review focuses on the association of iron with current and emerging antimalarial drugs. Proposed mechanisms of antimalarial action of (1) iron-requiring agents, the artemisinins, are compared with (2) a spectrum of compounds that withdraw iron by chelation. A novel approach to malarial chemotherapy might involve the sequential use of a member of each of the two categories.