Chapter 10 : Battling Blood Stages

Abstract:

Identification of the surface antigens of Plasmodium falciparum can be traced to studies carried out by Monroe Eaton in the 1930s. Eaton showed that serum from monkeys infected with P. knowlesi could agglutinate schizontinfected red cells. This schizont-infected cell agglutination (SICA) reaction was a clear indication that the surface of the malaria infected red cell had been altered. Sequestration and immune evasion are linked to the finding that P. falciparum erythrocyte membrane protein 1 (PfEMP1) has three different adhesive domains: DBL (Duffy ligand binding), a CIDR (cysteine-rich interdomain region), and an acidic region, called the ATS (acidic terminal sequence), that is presumed to anchor the molecule to the red cell surface. Each year over 50 million women are exposed to the risk of malaria during pregnancy. Pregnancy malaria (PM) results in substantial maternal and especially fetal and infant morbidity and mortality, causing 75,000 to 200,000 infant deaths annually. Rosetting has also been observed in P. vivax, P. ovale, P. malariae, P. coatneyi in the rhesus monkey, and P. fragile in the toque monkey. Rosetting in some of these hosts may be benign, but in others, i.e., humans infected with P. falciparum, it may contribute to pathogenesis leading to severe malaria. The substances to which the rosetting red blood cells bind are heparan sulfate, blood group antigens, and complement receptor 1.