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Vivax malaria has historically been absent in sub-Saharan Africa, as the parasite cannot penetrate Duffy-negative erythroblasts. However, a new study shows that P. vivax can penetrate erythrocytes during erythropoiesis due to the transitory expression of the protein.

Plasmodium vivax malaria was historically believed to be absent in sub-Saharan Africa due to the high prevalence of individuals lacking the Duffy antigen receptor for chemokines (DARC) on their red blood cells. The primary mechanism for invasion was assumed to be the interaction between the P. vivax Duffy binding protein (PvDBP) and DARC. However, the rising cases of vivax malaria in Duffy-negative individuals has raised intriguing questions about alternative invasion pathways. 

Hence, in this new study, researchers tried to identify alternative pathways by investigating the expression of DARC during the formation of red blood cells in both Duffy-positive (DP) and Duffy-negative (DN) individuals. Additionally, the study sought to determine if P. vivax could successfully invade red blood cells from both types of individuals in a controlled laboratory setting.The findings of this study were shared in a paper presented at the 65th ASH Annual Meeting & Exposition.

Vivax Can Penetrate Duffy-Negative Erythroblasts While The Cells Are Maturing

Through in vitro erythropoiesis assays, the research revealed that DP and DN erythroblasts exhibited very similar kinetics of terminal erythroid differentiation. Interestingly, a subset of DN erythroblasts transiently expressed DARC during erythropoiesis, a phenomenon detected through both flow cytometry and western blot analysis.

Subsequent in vitro invasion assays demonstrated that P. vivax merozoites were proficient in invading both DP and DN erythroblasts, indicating the existence of alternative invasion pathways beyond the PvDBP-DARC interaction. These findings challenge the conventional understanding of vivax malaria in Africa, suggesting that the parasite can exploit alternative routes to invade red blood cells. 

The mechanism unearthed in this exploration underscores the necessity for a more profound comprehension of these invasion mechanisms. Such insights are imperative for the development of effective strategies against malaria in regions where its presence was previously deemed improbable.

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The Bottom Line

This is one of the first studies to show that P. vivax can invade the red blood cells of people with DN erythroblasts. This invasion appears to occur in the early phases of erythrocyte development or maturation. This occurs due to transient expression of DARC during erythropoiesis. Such an alternative mechanism allows the parasite to penetrate the RBCs, but it is still unable to penetrate mature RBCs. This means that many people in the African population may serve as silent reservoirs of the parasite. Understanding this is vital to eliminating vivax malaria in sub-Saharan Africa.


Sara, E. H. (2023, December 9). The Darc Side of Vivax Malaria in Africa: Unveiling Invasion Pathways into Duffy-Negative Erythroblasts. https://ash.confex.com/ash/2023/webprogram/Paper184938.html