Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New Guinea

In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobi nopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria pa rasites are holoendemic below 1500 meters in PNG. At this elevation, a prom inent condition characterizing Melanesians is alpha(+)-thalassemia. Interes tingly. recent epidemiological surveys have demonstrated that alpha(+)-thal assemia is associated with increased susceptibility to uncomplicated malari a among young children. It is further proposed that alpha(+)-thalassemia ma y facilitate so-called "benign" Plasmodium vivax infection to act later in life as a "natural vaccine" against severe Plasmodium falciparum malaria. H ere, in a P. vivax-endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of alpha(+)-thalassemia greater than or equal to 0.98, we have discovered the mutation responsible for ery throcyte Duffy antigen-negativity (Fy[a-b-]) on the FY*A allele. In this st udy population there were 23 heterozygous and no homozygous individuals bea ring this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric a nalysis illustrated a 2-fold difference in erythroid-specific Fy-antigen ex pression between heterozygous (FY*A/FY*A(null)) and homozygous (FY*A/FY*A) individuals, suggesting a gene-dosage effect, in further comparisons, we ob served a higher prevalence of P. vivax infection in FY*A/FY*A (83/508 = 0.1 63) compared with FY*A/FY*A(null) (2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47-8.91). Emergence of FY*A(null) in this population suggests that P. vivax is involved in selection of this erythro id polymorphism. This mutation would ultimately compromise alpha(+)-thalass emia/P. vivax-mediated protection against severe P. falciparum malaria.