Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people.
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*B(ES)/*B(ES)) 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.
Ménard
Didier
D
Institut Pasteur de Madagascar, Unité de Recherche sur le Paludisme, Antananarivo 101, Madagascar. dmenard@pasteur.fr
Barnadas
Céline
C
Bouchier
Christiane
C
Henry-Halldin
Cara
C
Gray
Laurie R
LR
Ratsimbasoa
Arsène
A
Thonier
Vincent
V
Carod
Jean-François
JF
Domarle
Olivier
O
Colin
Yves
Y
Bertrand
Olivier
O
Picot
Julien
J
King
Christopher L
CL
Grimberg
Brian T
BT
Mercereau-Puijalon
Odile
O
Zimmerman
Peter A
PA
D000293:Adolescent; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D004375:Duffy Blood-Group System / Q000235:genetics / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D056726:Genetic Association Studies; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D008270:Madagascar / Q000453:epidemiology; D016780:Malaria, Vivax / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity
D017931:DNA Primers; D004375:Duffy Blood-Group System