Lack of associations of alpha(+)-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

Rosanas-Urgell, A; Senn, N; Rarau, P; Aponte, JJ; Reeder, JC; Siba, PM; Michon, P; Mueller, I

Author(s): Rosanas-Urgell, A; Senn, N; Rarau, P; Aponte, JJ; Reeder, JC; Siba, PM; Michon, P; Mueller, I;
Details: Publication Year 2012-11,Volume 42,Issue #12,Page 1107-1113
Journal Title: INTERNATIONAL JOURNAL FOR PARASITOLOGY
Publication Type: Journal Article
Abstract: Despite consistent evidence of a protective effect of alpha(+)-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 alpha(+)-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 alpha(+)-thalassemia (-alpha/-alpha), 506 (45.5%) heterozygous (alpha alpha/-alpha) 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 alpha(+)-thalassemia homozygote (Pf: incidence rate ratio (IRR) = 1.13, CI95 (0.82, 1.56), P = 0.45, Pv: IRR = 1.15, CI95 (0.88, 1.50), P = 0.31), heterozygote (Pf: IRR = 0.98, CI95 (0.71, 1.34), P = 0.93, Pv: IRR = 1.14, CI95 (0.88, 1.48), P = 0.33) and wild-type children. The prevalence of infection with either species did not differ between alpha(+)-thalassemia genotypes, although densities of P. vivax (but not of P. falciparum) infections were significantly higher in alpha(+)-thalassemia homozygote and heterozygote children. An excessive risk of moderate-to-severe anemia (Hb < 8 g/dl) was observed in alpha(+)-thalassemia homozygote children (IRR = 1.54, CI95 (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, alpha(+)-thalassemic children without significant levels of acquired immunity. This confirms the lack of protection by alpha(+)-thalassemia against uncomplicated P. falciparum and challenges the hypothesis of immunological cross-protection between P. falciparum and P. vivax as a mechanism underlying alpha(+)-thalassemia protection against severe P. falciparum disease in Melanesian children. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Publisher: ELSEVIER SCI LTD
Keywords: SICKLE-CELL TRAIT; ALPHA-THALASSEMIA; ENDEMIC AREA; UNCOMPLICATED MALARIA; HEMOGLOBIN-VARIANTS; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; POLYMORPHISMS; TANZANIA; EPIDEMIOLOGY
Research Division(s): Infection And Immunity
Publisher's Version: https://doi.org/10.1016/j.ijpara.2012.10.001

Creation Date: 2012-11-01 12:00:00