Lack of associations of α(+)-thalassemia with the risk of Plasmodium falciparum and Plasmodium vivax infection and disease in a cohort of children aged 3-21 months from Papua New Guinea.

Abstract Despite consistent evidence of a protective effect of α + -thalassemia against severe Plasmodium falciparum disease, the mechanisms underlying this protection remain unknown. An increase in risk of Plasmodium vivax malaria in early childhood resulting in a cross-species protection against severe P. falciparum malaria has been proposed as a possible mechanism in Melanesian children. The association of α + -thalassemia genotypes with a risk of P. falciparum and P. vivax infection and uncomplicated illness was reassessed in a cohort of 1,112 Papua New Guinean children, followed from 3 to 21 months of age. Three hundred and eighty-nine (35.0%) children were homozygous for α + -thalassemia (-α/-α), 506 (45.5%) heterozygous (αα/-α) and 217 (19.5%) homozygous for the wild-type allele. No significant differences in the incidence of P. falciparum ( Pf ) or P. vivax ( Pv ) malaria were observed between α + -thalassemia homozygote ( Pf : incidence rate ratio (IRR) = 1.13, CI 95 (0.82, 1.56), P  = 0.45, Pv : IRR = 1.15, CI 95 (0.88, 1.50), P  = 0.31), heterozygote ( Pf : IRR = 0.98, CI 95 (0.71, 1.34), P  = 0.93, Pv : IRR = 1.14, CI 95 (0.88, 1.48), P  = 0.33) and wild-type children. The prevalence of infection with either species did not differ between α + -thalassemia genotypes, although densities of P. vivax (but not of P. falciparum ) infections were significantly higher in α + -thalassemia homozygote and heterozygote children. An excessive risk of moderate-to-severe anemia (Hb  + -thalassemia homozygote children (IRR = 1.54, CI 95 (1.12, 2.11), P  = 0.008). This study therefore failed to confirm an increased risk of P. vivax or P. falciparum malaria in very young, α + -thalassemic children without significant levels of acquired immunity. This confirms the lack of protection by α + -thalassemia against uncomplicated P. falciparum and challenges the hypothesis of immunological cross-protection between P. falciparum and P. vivax as a mechanism underlying α + -thalassemia protection against severe P. falciparum disease in Melanesian children.