In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax.

Abstract

All the clinical and pathologic features of malaria are solely attributable to the parasitic stages of the asexual erythrocytic cycle. The propagation of this cycle in a host is dependent upon extracellular merozoites attaching to and invading susceptible erythrocytes . This attachment and initiation of invasion by malaria merozoites is mediated through specific interactions between parasite receptors and ligand molecules on the erythrocyte plasma membrane (1, 2). The identification oferythrocyte liganns used by invading merozoites is important to understanding this biologic event at the molecular level. Furthermore, this knowledge can aid in the isolation ofmalaria parasite receptor antigens ; potential targets of vaccine induced immunity.Studies on Plasmodium knowlesi, a simian malaria that can invade human erythrocytes, have indicated that an erythrocyte membrane component associated with Duffy blood group determinants is used by this species as a ligand for merozoite invasion (3-5). These studies on a simian malaria became more relevant to human malaria when indirect and retrospective studies in vivo also correlated susceptibility to infection by Plasmodium vtvax, a human malaria parasite of major importance, with the presence of the Duffy blood group antigens (6, 7).Direct ligand studies with P. vivax could not be done, however, because these parasites were difficult to obtain and could not be cultured in vitro, as has been possible with Plasmodium falciparum and P. knowlesi . Here we describe a short term invasion assay in vitro for P. vivax parasites obtained from squirrel (Saimiri sciureus) monkeys. We have made use of this invasion assay to investigate the role of the Duffy blood group as an erythrocyte ligand for P. vivax merozoites using human and simian erythrocytes of varying Duffy phenotypes and a mAb against a new Duffy blood group determinant, Fy6 (8). Materials and MethodsParasites and Cultures. P. knowlesi (H strain) parasites were cryopreserved in liquid nitrogen as ring stage infected erythrocytes from rhesus monkeys (9).

Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people

“…vivax readily infects erythrocytes of the squirrel monkey (Saimiri boliviensis) (29,30). Whereas squirrel monkeys express an Fy6-positive Duffy antigen (29-31), the P. vivax DBP binds poorly, if at all, to squirrel monkey erythrocytes (32), suggesting a PvDBPindependent invasion mechanism.…”

Polymorphism at the merozoite surface protein-3alpha locus of Plasmodium vivax: global and local diversity.

“…Plasmodium vivax laboratory strains Belem originating from Brazil 26 and Sal I from El Salvador 27 were obtained by venipuncture from infections maintained in Saimiri monkeys. 28 Plasmodium falciparum isolates from Africa (3D7 29 ) and Papua New Guinea (Muz37.2, Muz12.2, Muw51, 25 and 1776 30 ) were grown in culture 31 and used in control samples as described below.…”

The Global Public Health Significance of Plasmodium vivax

“…The reader is again referred to a detailed review of the effect of the lacking Duffy antigen on resistance to P. vivax provided in this thematic issue of Advances in Parasitology (Chapter 2, Volume 81). The Duffy antigen refers to a receptor expressed on the surface of red blood cells, which P. vivax has been shown to be dependent upon for erythrocytic invasion (Miller et al, 1976;Barnwell et al, 1989;Wertheimer and Barnwell, 1989). Duffy-negative individuals, who lack the antigen, are therefore largely refractory to P. vivax infection and high frequencies of the phenotype are presumed to suppress P. vivax endemicity in areas that would otherwise be well suited for transmission.…”