Duffy Antigen Polymorphisms and Plasmodium vivax Malaria
Summary
The Duffy antigen, also known as the Duffy antigen receptor for chemokines (DARC), is a key erythrocyte membrane protein that mediates the entry of Plasmodium vivax merozoites into reticulocytes. Genetic variation at the DARC locus gives rise to alleles such as FY*A, FY*B and the null allele FY*O; the latter abolishes surface expression and confers marked resistance to P. vivax invasion in most sub-Saharan populations. However, increasing reports of clinical and subclinical infections in individuals lacking DARC have challenged the long-held view of absolute protection. These observations span molecular, structural and epidemiological domains: transient DARC expression during erythropoiesis may open windows of susceptibility in Duffy-negative hosts; parasite ligands such as the P. vivax Duffy-binding protein (PvDBP) evolve duplications or alternative binding modes; and low-density, asymptomatic reservoirs persist undetected in endemic regions. Together, these findings underscore the global significance of P. vivax, reveal unanticipated pathways of host–parasite interaction and highlight the need for species-specific diagnostics, surveillance and vaccine design targeting both canonical and DARC-independent invasion mechanisms.
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Duffy Antigen Polymorphisms and Plasmodium vivax Malaria publication trend
The graph below shows the total number of articles in duffy antigen polymorphisms and plasmodium vivax malaria across all publications each year (not limited to Nature Index journals).
Technical terms
DARC: Duffy antigen receptor for chemokines, a membrane glycoprotein on red blood cells that binds parasite ligands and host chemokines.
Reticulocyte: An immature erythrocyte that circulates briefly in the bloodstream and serves as the preferred host cell for P. vivax invasion.
PvDBP: Plasmodium vivax Duffy-binding protein, a parasite ligand that recognises the DARC ectodomain to mediate merozoite entry into reticulocytes.
Duffy-negative: A phenotype resulting from a promoter mutation of the DARC gene, leading to absence of Duffy antigen on mature erythrocytes.
References
- Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans. PLOS Genetics (2017).
- Unveiling P. vivax invasion pathways in Duffy-negative individuals. Cell Host & Microbe (2023).
- Potential hidden Plasmodium vivax malaria reservoirs from low parasitemia Duffy-negative Ethiopians: Molecular evidence. PLOS Neglected Tropical Diseases (2023).
- Genomic insights into Plasmodium vivax population structure and diversity in central Africa. Malaria Journal (2024).
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