title: Red blood cell polymorphism and susceptibility to Plasmodium vivax.
abstract: Resistance to Plasmodium vivax blood-stage infection has been widely recognised to result from absence of the Duffy (Fy) blood group from the surface of red blood cells (RBCs) in individuals of African descent. Interestingly, recent studies from different malaria-endemic regions have begun to reveal new perspectives on the association between Duffy gene polymorphism and P. vivax malaria. In Papua New Guinea and the Americas, heterozygous carriers of a Duffy-negative allele are less susceptible to P. vivax infection than Duffy-positive homozygotes. In Brazil, studies show that the Fy(a) antigen, compared to Fy(b), is associated with lower binding to the P. vivax Duffy-binding protein and reduced susceptibility to vivax malaria. Additionally, it is interesting that numerous studies have now shown that P. vivax can infect RBCs and cause clinical disease in Duffy-negative people. This suggests that the relationship between P. vivax and the Duffy antigen is more complex than customarily described. Evidence of P. vivax Duffy-independent red cell invasion indicates that the parasite must be evolving alternative red cell invasion pathways. In this chapter, we review the evidence for P. vivax Duffy-dependent and Duffy-independent red cell invasion. We also consider the influence of further host gene polymorphism associated with malaria endemicity on susceptibility to vivax malaria. The interaction between the parasite and the RBC has significant potential to influence the effectiveness of P. vivax-specific vaccines and drug treatments. Ultimately, the relationships between red cell polymorphisms and P. vivax blood-stage infection will influence our estimates on the population at risk and efforts to eliminate vivax malaria.
authors: Center for Global Health & Diseases, Case Western Reserve University, Cleveland, Ohio, USA. paz@case.edu
authors: Peter A
authors: PA
authors: Zimmerman
authors: Marcelo U
authors: MU
authors: Ferreira
authors: Rosalind E
authors: RE
authors: Howes
authors: Odile
authors: O
authors: Mercereau-Puijalon
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism; D004198:Disease Susceptibility; D004375:Duffy Blood-Group System / Q000235:genetics / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D016780:Malaria, Vivax / Q000235:genetics*; D010966:Plasmodium vivax / Q000502:physiology; D011110:Polymorphism, Genetic; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
chemical_list: C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface
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