Duffy-blood-group-negative human erythrocytes, FyFy, are resistant to invasion in vitro by Plasmodium knowlesi. The FyFy genotype is found predominantly in African and American blacks, who are the only groups completely resistant to infection by P. vivax. To determine if the FyFy genotype is the vivax resistance factor, we performed blood typing on 11 black and six white volunteers who had been exposed to the bites of P. vivax-infected mosquitoes. Only the five FyFy blacks were resistant to erythrocytic infection; the remaining six blacks and all whites had the Duffy-positive determinants (Fya or Fyb or both) and had contracted malaria. We conclude that Duffy determinants (Fya or Fyb or both) on the erythrocyte surface are required for invasion of erythrocytes by vivax merozoites.

Duffy blood group negative human erythrocytes (FyFy) are resistant to infection by Plasmodium knowlesi, a simian malaria that infects Duffy positive human erythrocytes. The P. knowlesi resistance factor, Duffy negative erythrocytes, occurs in high frequency in West Africa, where the people are resistant to vivax malaria. This suggests that Duffy blood group determinants (Fya or Fyb) may be erythrocyte receptors for P. vivax.

Duffy blood group negative erythrocytes from blacks are refractory to invasion by Plasmodium knowlesi merozoites in vitro, and blacks with this genotype are resistant to infection by P. vivax in vivo. In order to evaluate in a direct manner the role of Duffy blood group determinants in invasion by P. knowlesi merozoites, we studied erythrocytes from three rare non-black Duffy negative individuals, Fy(a-b-), in whom the Duffy negative phenotype probably represents a mutation and not the introduction of the black Fy gene. These cells were resistant to invasion by P. knowlesi in vitro indicating that resistance to invasion is mediated by the FyFy genotype and not another closely linked factor. The erythrocyte receptors for invasion, however, may not be the Fya or Fyb Duffy antigens themselves, or at least not restricted to these determinants, since refractory Duffy negative human erythrocytes were invaded after treatment with trypsin or neuraminidase although these enzyme-treated cells still lacked Fy a and Fy b determinants. Furthermore, new world monkey erythrocytes and chymotrypsinized chimpanzee and kra monkey erythrocytes were invaded, although there was no serologic evidence of Fya or Fyb determinants on these cells.