Effect of α+ Thalassemia on the Severity of Plasmodium falciparum Malaria in Different Sickle Cell Genotypes in Indian Adults: A Hospital-Based Study

There is a paucity of literature on the association of a(+)-thalassemia, sickle-cell hemoglobin disorders, and malaria in India. This study aimed to understand the effect of a(+)-thalassemia on the severity of Plasmodium falciparum malaria in adults with respect to sickle-cell genotypes. The study subjects were categorized into 'severe-malaria' and 'uncomplicated-malaria' and age-gender matched 'control' groups. Sickle-cell and a(+)-thalassemia were investigated in all the recruited subjects. The effect of a(+)-thalassemia on the severity of malaria was analyzed in HbAA and sickle-cell genotypes (HbAS and HbSS) separately. The prevalence of a(+)-thalassemia in various groups ranged from 41.5% to 81.8%. The prevalence of a(+)-thalassemia was lower (OR = 1.64; p = 0.0013) in severe malaria (41.5%) as compared to healthy controls (53.8%) with HbAA genotype. In contrast, in HbAS genotype, the prevalence of a(+)-thalassemia was higher (OR = 4.11; p = 0.0002) in severe malaria (81.8%) compared to controls (52.2%). In severe malaria with HbAA genotype, there was a significantly higher hemoglobin level and low MCV and MCH level in patients with a(+)-thalassemia compared to the normal a-globin genotype. Further, the incidence of cerebral malaria, hepatopathy, and mortality was lower in patients (HbAA) with a(+)-thalassemia as compared to normal a-globin genotype (HbAA). In severe malaria with either HbAS or HbSS genotype, only a few parameters showed statistical differences with respect to a(+)-thalassemia. Low prevalence of a(+)-thalassemia in severe malaria with HbAA genotype compared to healthy controls with HbAA genotype indicates the protective effect of a(+)-thalassemia against severe malaria. However, the high prevalence of a(+)-thalassemia in patients with HbAS genotype depicts its interference in the protective effect of sickle-cell against severe malaria.