Exploring the influence of alpha thalassemia on antibody responses to Plasmodium falciparum infections in Ghana

Alpha thalassemia, a common inherited haemoglobin disorder in Africa, has long been associated with protection against Plasmodium falciparum malaria, but the exact mechanisms remain unclear. This study explored whether this protective effect is linked to antibody responses against key P. falciparum blood-stage antigens, including Apical Membrane Antigen-1 (P f AMA-1), Erythrocyte-Binding Antigen-175 (P f EBA-175), Glutamate-Rich Protein (P f GLURP), Merozoite Surface Protein-1 (P f MSP-1), and Reticulocyte-Binding Protein homologue 5 (P f RH5). We conducted a cross-sectional study of 220 malaria symptomatic individuals aged 1–80 years. Alpha thalassemia was genotyped using multiplex PCR, while Plasmodium falciparum infections were confirmed by microscopy and nested PCR. Using indirect Enzyme-Linked Immunosorbent Assay (ELISA) we measured antigen-specific IgG levels and analysed their patterns across genotypes, infection status, season, gender, and age categories. Heterozygotes consistently mounted the strongest antibody responses, with PfAMA-1 showing the highest median concentration (98.63 ng/mL) and homozygous recessive individuals had the lowest responses, particularly to PfRH5 (17.66 ng/mL). Across all five antigens, antibody levels differed significantly between genotypes (P < 0.0001). These findings reveal that heterozygous alpha thalassemia may enhance immune defense by boosting antibody production. These findings provide a deeper understanding of malaria protection and offer valuable clues for innovative malaria control strategies.