Plasmodium falciparum, responsible for hundreds of thousands of deaths annually, remains a pressing global health threat. Malaria merozoites invade erythrocytes by harnessing host factors, commonly erythrocyte antigens. Parasitized erythrocytes bind specific antigens on various host tissues facilitating cytoadhesion and rosetting, two properties critical for pathogenesis of severe disease. Antigen-negative individuals have reduced parasite binding, invasion, and cytoadhesion conferring a host survival advantage. Not surprisingly, co-evolution of the parasite and human erythrocytes is evident, with malaria considered the ‘greatest evolutionary force in history’.
We update investigations of malaria and its effects on geographic distribution of blood group antigens, focusing on ABO and CD36 blood group systems. We discuss recent advances in functional genetic screening for identification of critical host factors for Plasmodium falciparum malarial invasion, including CD55/Cromer and LAN blood group systems. Finally, we outline utilization of next-generation sequencing for exhaustive blood group genotyping and investigate malaria-associated variant distribution in 345 samples representing 164 diverse populations.
Elucidating Plasmodium spp. interactions with blood group antigens and resulting resistance may reveal valuable potential targets for future anti-malarial treatment.
Examine malaria as a historical selection pressure, focusing on its interaction with ABO and platelet glycoprotein IV (CD36) blood group systems.
Explain how forward genetic screening can identify new erythrocyte host factors for malaria.
Summarize how next-generation sequencing can be used to genotype for malaria-associated blood group antigen variants.