Preeclampsia and eclampsia: the role of hemolytic protozoan iron

Organisms as well as pathogens require several transition metals including iron, copper, zinc, manganese, nickel and cobalt, for genetic replication and other cellular functions. Of these, iron is vital and plays a key role in DNA replication, transcription, synthesis of cofactors and other essential enzymes. During infection, iron deprivation, particularly sequestration thereof, represents a unique response against pathogen attack. The host sequesters ferrous (Fe²⁺) and ferric (Fe³⁺) iron via lactoferrin binding at mucosal surfaces, transferrin in blood and tissue and ferritin in blood and cytoplasm. Despite this protective mechanism, pathogens can be resilient in obtaining iron. For example, hemolytic protozoan parasites can obtain iron from heme by rupturing red blood cells. Furthermore, earlier pathogens, driven from active to inactive infections by iron deprivation, could now acquire sufficient iron to enable reactivation resulting in chronic inflammation, oxidative stress to organs and/or circulatory hypertension potentially leading to death. This review discusses the impact of hemolytic protozoan parasite infection in reactivation of latent iron-deprived pathogen infections thus explaining two puzzling pregnancy disorders, pre-eclampsia (PE) and eclampsia. The unknown causations of both disorders have created centuries of confusion and killed millions of women worldwide. Furthermore, reduction-oxidation reactions with iron promote additional oxidative stress damage to vital organs, particularly the kidneys, a common symptom in PE and eclampsia.