Genetic blood disorders and malaria presentation in individuals from Kalisizo and Kabira villages, Rakai, Uganda

Abstract

INTRODUCTION: Malaria caused by Plasmodium falciparum parasite, is a major public health concern in Sub-Saharan Africa with an estimated 229 million cases each year (1). Malaria parasites have exerted the strongest evolutionary pressure on the human genome causing genetic changes that either confer protection or susceptibility to malaria. Human genetic blood disorders (HbS, alpha thalassemia, CD36 polymorphism and G6PD deficiency) are highly prevalent in residents of tropical areas and offer protection against severe malaria. While most studies have indicated that all these genetic disorders are associated with protection against severe malaria, data about prevalence and association of genetic blood disorders with symptomatic or asymptomatic malaria is still limited. AIM; In this study, we determined the prevalence of genetic blood disorders and their association with symptomatic and asymptomatic malaria. METHODS: The cross sectional and longitudinal studies used DBS samples from rural populations in Rakai district and was conducted from January to April 2020. PCR, restriction enzyme digestion and electrophoresis were used to determine the prevalence of the five polymorphisms i.e. the sickle hemoglobin mutation (β globin E6V), Hemoglobin C mutation (β globin Glu6Lys or E6K), the α-thalassemia 3.7 kb deletion, glucose-6-phosphate dehydrogenase deficiency caused by the common African variant (G6PDD), and the CD36T188G mutation and their association with symptomatic and asymptomatic malaria. RESULTS: Generally, almost one in three residents of Rakai district had at least one genetic blood disorder. Alpha thalassemia dominated both the heterozygote and homozygote genetic blood disorders. The sickle cell trait (HBAS) was found in around one in every fourteen residents while the homozygous state (sickle cell disease) was detected in only 3% of the residents. The carrier states for sickle cell (HBAS) and alpha thalassemia (αα/-α) were significantly associated with asymptomatic malaria (p-value 0.049 and p-value 0.000), respectively while homozygous state of the G6PDD (A-/A-) was significantly associated with symptomatic malaria in children older than 5 years (p-value 0.042). No single resident was detected with the HBC genetic blood disorder. EXPECTED BENEFITS: Data about genetic blood disorders has the potential to inform about national strategies for genetic diseases including disease screening for better disease management. Our findings have the potential to improve on our understanding/give more insight of the impact of genetic blood disorders and malaria presentation. A greater understanding of factors that influence development of symptomatic and asymptomatic malaria in different individuals is essential for the rational development of novel interventions. Our findings have the potential to guide on prioritizing screening for genetic blood disorders since asymptomatic individuals with these disorders often act as malaria reservoirs and contribute to the 20%-50% of onwards transmission posing a challenge towards malaria control, prevention and treatment (2).