Iron chelators as anti-infectives; malaria as a paradigm

Malaria is the major life threatening parasitic disease and the cause of a global public health problem. The failure of vector eradication programs an d the appearance and spread of drug resistant parasites have posed the urge nt challenge of developing effective, safe and affordable anti-malarial dru gs. The design of such drugs is largely based on the targeting of agents to the parasite-based machinery for host digestion and to the products of hem oglobin catabolism. Iron chelators, by depriving intracellular parasites fr om essential iron, lead to selective suppression of parasite growth. Howeve r, by acting on parasite-impaired macrophages, chelators can also expedite resumption of phagocytosis and elimination of parasites. In order to be cli nically effective, chelators need to be maintained in the blood for extensi ve time periods. Therapeutic doses can be attained with appropriate drug co mbinations and formulations or delivery devices and these must be presented in a form well tolerated by the host. The early documentation that chelati on therapy has activity against human malaria has paved the road for the de sign of novel and more efficient remedies based on short-term iron deprivat ion. (C) 1999 Published by Elsevier Science B.V. All rights reserved.