The Role of Haemoglobin Variants and Red Blood Cell Polymorphisms in Asymptomatic Malaria: A Cross-Sectional Study

Human phenotypes, particularly blood group polymorphisms (ABO) and haemoglobin variants (HbAA and HbAS), have been widely studied in relation to clinical malaria. However, their role in asymptomatic malaria remains underexplored. This study therefore, investigated the association of these phenotypic variants with the burden of asymptomatic malaria among Ghanaians.

Community members without clinical signs of malaria were recruited from four endemic communities. Whole blood samples were screened for Plasmodium falciparum histidine-rich protein 2 (PfHRP2). ABO blood group and Rhesus D factor typing were then performed, followed by confirmation of haemoglobin phenotypes using alkaline electrophoresis (pH 8.6). A multivariate logistic regression model was applied to assess the association between asymptomatic malaria and phenotypic factors, while adjusting for potential confounders.

Haemoglobin variants (p = 0.021) and red cell polymorphisms (p < 0.001) were significantly associated with asymptomatic malaria, whereas RhD types were not (p = 0.877). However, a significant association was observed when RhD types were combined with red cell polymorphisms (p = 0.00009). Individuals with haemoglobin AA had significantly higher odds of asymptomatic malaria (AOR = 2.1, p = 0.02). Although higher odds were observed among individuals with O Rh D-positive (AOR = 2.39), Group O/HbAA (AOR = 1.15), and Group B/HbAS (AOR = 1.22), these associations were not statistically significant.

This study found a high prevalence of asymptomatic malaria among community members. Haemoglobin variants and ABO blood group polymorphisms were associated with asymptomatic malaria, with HbAA showing significantly higher odds of infection. Although higher odds were observed among individuals with O Rh D-positive, O/HbAA, and B/HbAS phenotypes, these associations were not statistically significant. These findings highlight the complex role of host genetic factors in asymptomatic malaria carriage and underscore the need for further studies with larger sample sizes to clarify these associations.