Distribution of HbS, HbC variants, ABO blood groups in relation to malaria infection among Saudi children in Jazan region.

Plasmodium falciparum remains a major public health challenge in the Jazan region, Saudi Arabia. This study investigated the influence of haemoglobin variants and ABO blood groups on malaria susceptibility, severity, and immune response among Saudi children. A total of 587 children were classified into malaria-free controls (MFC, n = 196), uncomplicated malaria (UM, n = 215), and severe malaria (SM, n = 176). Blood samples were analysed for P. falciparum infection, haemoglobin genotypes, ABO blood groups, and IgG levels using PCR, ELISA. The median age was 4 years for MFC and UM groups, and 5 years for SM. Blood group O predominated in MFC (49.5%), while blood group A was more frequent in UM (44.7%) and SM (41.5%). Carriers of the HbS allele had reduced odds ratio of SM versus MFC (OR=0.40, 95% CI: 0.22-0.72, P = 0.002). HbC allele carriers showed even stronger protective associations against SM versus MFC and UM in both unadjusted and adjusted models (P < 0.01). Blood group A was associated with higher susceptibility but did not reach statistical significance. Antibody analysis revealed higher total IgG and IgG subclass (IgG1-IgG4) levels in UM cases compared to MFC and SM (P < 0.001), suggesting a more effective immune response in UM. Hb S and C variants offer significant protection against severe malaria and high parasitaemia. Blood group A may be linked to increased susceptibility. These findings underscore the role of host genetic factors in malaria severity and may guide future prevention strategies in endemic areas.