Molecular aspects of Plasmodium falciparum Infection during pregnancy

Abstract

Cytoadherence of Plasmodium-falciparum-parasitized red blood cells (PRBCs) to host receptors is the key phenomenon in the pathological process of the malaria disease. Some of these interactions can originate poor outcomes responsible for 1 to 3 million annual deaths mostly occurring among children in sub-Saharan Africa. Pregnancy-associated malaria (PAM) represents an important exception of the disease occurring at adulthood in malaria endemic settings. Consequences of this are shared between the mother (maternal anemia) and the baby (low birth weight and infant mortality). Demonstrating that parasites causing PAM express specific variant surface antigens (VSA(PAM)), including the P. falciparum erythrocyte membrane protein 1 (P f EMP1) variant VAR2CSA, that are targets for protective immunity has strengthened the possibility for the development of PAM-specific vaccine. In this paper, we review the molecular basis of malaria pathogenesis attributable to the erythrocyte stages of the parasites, and findings supporting potential anti-PAM vaccine components evidenced in PAM.

Figure 1

Schematic diagram of knobs showing potential intermolecular interactions between parasites proteins exported on the surface of PRBC and receptors on the host cell surface. P f EMP, Plasmodium falciparum erythrocyte membrane protein; KHARP, knob-associated histidine-rich protein; RIFIN, repetitive-interspersed family proteins; CLAG, cytoadherence-linked asexual protein; CR1, complement receptor 1; ICAM1, intercellular adhesion molecule 1; PECAM1, platelet endothelial cell adhesion molecule 1; CSA, chondroitin sulphate A; UPP, uncharacterized parasite proteins. The question mark “?” means that the binding to hyaluronic acid is controversial.

Figure 2

Structure of different kinds of GAG disaccharides of physiological significance.

Figure 3

Schematic diagram illustrating var gene and P f EMP1 organization. Domains with known binding properties are specified. NTS, N-terminal sequence; DBL, Duffy-binding like; CIDR, cystein-rich interdomain; SVL, sequence of variable length; TM, transmembrane; ATs, acidic terminal sequence.