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

Abstract

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 Duffyindependent P. vivax invasion of human erythrocytes.erythrocyte | evolution | DARC | Madagascar

Population genetics of malaria resistance in humans

“…The low frequency of FY*A ES appears to be the result of its recent origin, which is reflected in its association with specific alleles at two microsatellite loci about 3 cM from FY (Zimmerman et al, 1999). Recently, Ménard et al (2010) also showed that there is about half as much expression in a sample from Madagascar for FY*A/FY*B ES heterozygotes as that for for normal homozygotes (FY*A/FY*A) or heterozygotes (FY*A/ FY*B). In other words, it does not appear that either the expression or the protection from ES alleles is recessive, but is intermediate between ES homozygotes and genotypes with two normal alleles.…”

“…Perhaps the most definitive study is that of Ménard et al (2010) in Madagascar, a nation where endemic P. vivax is prevalent and a diverse ethnic population with both Duffynegative (FY*B ES /FY*B ES ) and Duffy-positive (having at least one allele that is FY*A or FY*B) individuals. In the sample examined of 476 asymptomatic Duffy-negative Population genetics of malaria resistance PW Hedrick individuals from eight locations, P. vivax was found in 8.8%.…”

Population Genetic Analysis of the DARC Locus (Duffy) Reveals Adaptation from Standing Variation Associated with Malaria Resistance in Humans

“…It has been proposed that due to the near-fixation of FY Ã O, P. vivax infection in humans is largely absent from equatorial Africa. An important recent discovery suggests low levels of P.vivax infection in FY Ã O homozygotes [13][14][15][16][17], which indicates that P. vivax might be evolving escape variants able to overcome the protective effect of FY Ã O. Phenotypic effects of the FY Ã A mutation are less clear than FY Ã O; however, there is evidence of natural selection and reduced P. vivax infection in individuals with this genotype ( [18,19], with conflicting reports in the Brazilian Amazon however [12,20,21]). …”

Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

“…DBP-II is a three-subdomain (SD) protein, with SD2 contributing key residues for dimerization and receptor binding (19). Duffy-independent invasion has been reported for certain isolates of P. vivax (29); however, these isolates contain a gene duplication of DBP, suggesting that increased expression of DBP may facilitate Duffy-negative invasion (30).…”