Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 13; pp. 5967 - 5971
• Main Authors: Ménard, Didier, Barnadas, Céline, Bouchier, Christiane, Henry-Halldin, Cara, Gray, Laurie R, Ratsimbasoa, Arsène, Thonier, Vincent, Carod, Jean-François, Domarle, Olivier, Colin, Yves, Bertrand, Olivier, Picot, Julien, King, Christopher L, Grimberg, Brian T, Mercereau-Puijalon, Odile, Zimmerman, Peter A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 30.03.2010; National Acad Sciences
• Subjects: Adolescent; African Continental Ancestry Group; African Continental Ancestry Group - genetics; ancestry; Antigens; Asian Continental Ancestry Group; Asian Continental Ancestry Group - genetics; Base Sequence; Biological Sciences; Blood; Blood groups; Child; Child, Preschool; Cytometry; DNA Primers; DNA Primers - genetics; Duffy Blood-Group System; Duffy Blood-Group System - genetics; Duffy Blood-Group System - immunology; epidemiological studies; Epidemiology; Erythrocyte invasion; Erythrocytes; Erythrocytes - parasitology; Female; flow cytometry; gametocytes; Genetic Association Studies; genetic markers; Genotype & phenotype; genotyping; Host-Parasite Interactions; Host-Parasite Interactions - genetics; Host-Parasite Interactions - immunology; Human health and pathology; Humans; Infections; Infectious diseases; Life Sciences; Madagascar; Madagascar - epidemiology; Malaria; Malaria, Vivax; Malaria, Vivax - blood; Malaria, Vivax - epidemiology; Malaria, Vivax - genetics; Male; microscopy; Molecular Sequence Data; Molecules; Parasites; Parasitic protozoa; people; Plasmodium vivax; Plasmodium vivax - genetics; Plasmodium vivax - growth & development; Plasmodium vivax - pathogenicity; polymerase chain reaction; therapeutics; Vector-borne diseases; Madagascar
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0912496107

Malaria therapy, experimental, and epidemiological studies have shown that erythrocyte Duffy blood group-negative people, largely of African ancestry, are resistant to erythrocyte Plasmodium vivax infection. These findings established a paradigm that the Duffy antigen is required for P. vivax erythrocyte invasion. P. vivax is endemic in Madagascar, where admixture of Duffy-negative and Duffy-positive populations of diverse ethnic backgrounds has occurred over 2 millennia. There, we investigated susceptibility to P. vivax blood-stage infection and disease in association with Duffy blood group polymorphism. Duffy blood group genotyping identified 72% Duffy-negative individuals (FY*BES/*BES) in community surveys conducted at eight sentinel sites. Flow cytometry and adsorption-elution results confirmed the absence of Duffy antigen expression on Duffy-negative erythrocytes. P. vivax PCR positivity was observed in 8.8% (42/476) of asymptomatic Duffy-negative people. Clinical vivax malaria was identified in Duffy-negative subjects with nine P. vivax monoinfections and eight mixed Plasmodium species infections that included P. vivax (4.9 and 4.4% of 183 participants, respectively). Microscopy examination of blood smears confirmed blood-stage development of P. vivax, including gametocytes. Genotyping of polymorphic surface and microsatellite markers suggested that multiple P. vivax strains were infecting Duffy-negative people. In Madagascar, P. vivax has broken through its dependence on the Duffy antigen for establishing human blood-stage infection and disease. Further studies are necessary to identify the parasite and host molecules that enable this Duffy-independent P. vivax invasion of human erythrocytes.