Abstract

Malaria remains one of the most significant parasitic diseases globally, exerting a disproportionate burden in sub
Saharan Africa, Asia, and Latin America. Host genetic factors play a critical role in determining susceptibility to 
malaria infection and severity, with evolutionary evidence showing that Plasmodium parasites have shaped human 
genetic diversity over centuries. Protective adaptations such as hemoglobinopathies, G6PD deficiency, and 
variations in erythrocyte surface antigens demonstrate the selective pressure malaria has exerted on human 
populations. Advances in genomics and molecular biology have expanded understanding of single-nucleotide 
polymorphisms (SNPs), copy number variations (CNVs), and immune-related polymorphisms that modulate host
parasite interactions. This paper reviews major genetic determinants of malaria susceptibility, explores their 
implications for pathophysiology, and highlights the role of modern genomic tools in uncovering novel protective 
and risk alleles. By integrating genetic insights with public health strategies, research in this field offers significant 
opportunities for vaccine development, targeted therapies, and precision medicine approaches in the global fight 
against malaria.