Immunogenomics of Host Susceptibility to Severe Malaria in Fulani and Non-Fulani Ethnic Groups in Northern Nigeria: Unravelling Genetic and Immunological Determinants

The Fulani people of West Africa exhibit paradoxically lower malaria susceptibility compared with co-resident ethnic groups despite equivalent exposure, a phenomenon attributed to a combination of genetic and immunological differences that remain incompletely characterised in Nigerian populations. This doctoral research investigates immunogenomic determinants of differential malaria susceptibility between Fulani and non-Fulani ethnic groups in northern Nigeria. A case-control immunogenomic study was conducted at Bayero University Kano Teaching Hospital and Ahmadu Bello University Teaching Hospital, enrolling 150 Fulani and 150 Hausa-Fulani children aged 2 to 12 years, matched for age and residence, with severe malaria cases and healthy malaria-exposed controls within each ethnic group. Whole-blood RNA sequencing assessed transcriptomic immune response profiles during acute severe malaria and convalescence. SNP genotyping arrays targeting HLA alleles, immunoglobulin gene variants, sickle cell trait, and G6PD deficiency loci were performed. Anti-malaria IgG responses to a panel of 15 blood stage antigens were measured by ELISA. Evidence from 2020 to 2024 confirms that Fulani individuals mount stronger and more diverse anti-malaria antibody responses and display elevated regulatory T cell activity compared with co-resident groups, yet the genomic architecture underlying these differences in Nigerian Fulani populations has not been systematically characterised. This study produces the most comprehensive immunogenomic dataset for this phenomenon in West Africa. Keywords: malaria susceptibility, Fulani ethnic group, immunogenomics, Nigeria, severe malaria.