Title : The role of the ABO blood group system in Plasmodium falciparum disease severity

Abstract:

Introduction: Malaria remains a major cause of morbidity and mortality in endemic regions, including Malawi. The ABO blood group system has been proposed as a genetic factor influencing disease severity. Evidence suggests that blood group O may confer relative protection against severe malaria; this is attributed to less rosetting, a known driver of cerebral malaria pathogenesis, among erythrocytes of blood type O. Whether this protection extends to other forms of P. falciparum infections requires further elucidation.

Objectives: The study aimed to investigate the prevalence of asymptomatic, uncomplicated, and cerebral malaria among these ABO blood phenotypes. Also, peripheral parasitemia and the parasite marker, Histidine-Rich Protein 2 (HRP-2), were used as markers of parasite invasion.

Methods: A cross-sectional study was conducted involving pediatric patients diagnosed with P. falciparum malaria classified as asymptomatic, uncomplicated, or cerebral. Peripheral parasitemia was quantified by real-time PCR, and plasma levels of HRP-2 were measured by ELISA. ABO blood groups were determined by microplate reverse grouping.

Results: Results showed that children with blood group AB had increased odds of presenting with asymptomatic malaria (OR=2.84, p=0.03) and cerebral malaria (OR=3.57, p=0.004) compared to those with blood group O. Levels of HRP-2 and peripheral parasitemia were similar between asymptomatic and uncomplicated malaria cases, regardless of blood group. However, cerebral malaria cases with blood group O exhibited significantly lower parasitemia and HRP-2 levels compared to other blood groups.

Conclusions: These findings support the hypothesis that ABO blood phenotypes influence the severity of P. falciparum infection. They show an equal protection provided by blood group O against asymptomatic malaria and cerebral malaria. This protection does not appear to be due to a difference in invasion and is unlikely to be explained by differences in rosetting. Further research is needed to determine the underlying mechanisms responsible for this protection.