Pathophysiology of Severe Childhood Malaria-Associated Anaemia: A Translational Study of Haemolytic Mechanisms and Erythropoietic Suppression in Benue State, North Central Nigeria

Severe malarial anaemia (SMA) is a leading cause of paediatric mortality in sub-Saharan Africa, yet the relative contributions of haemolytic and dyserythropoietic mechanisms to its pathophysiology remain incompletely characterised in Nigerian children. This translational clinical research study investigates the mechanistic basis of SMA in children aged 6 months to 10 years admitted with Plasmodium falciparum malaria at Benue State University Teaching Hospital, North Central Nigeria, comparing children with SMA to those with non-severe malaria and healthy community controls. A total of 180 children across the three groups underwent comprehensive haematological profiling including reticulocyte production index, erythropoietin-to-haematocrit ratios, hepcidin levels, bone marrow aspirate morphology in a subset (n equals 45), and flow cytometric characterisation of red blood cell surface antigens. Plasma inflammatory cytokines (TNF-alpha, IL-6, IL-10) were measured by multiplex immunoassay. Children with SMA demonstrated paradoxically suppressed erythropoietin responses despite severe anaemia, with erythropoietin-to-haematocrit ratios significantly lower than non-severe malaria controls (p less than 0.001). Elevated hepcidin levels were found in 78.9% of SMA cases, suggesting iron sequestration as a co-mechanism of anaemia. Bone marrow aspirates revealed dyserythropoiesis in 71.1% of SMA cases. IL-6 correlated positively with hepcidin levels (r 0.63, p less than 0.001). This study contributes novel mechanistic insight into the pathophysiology of SMA, identifying hepcidin-mediated dyserythropoiesis as a therapeutic target and providing the first bone marrow data from north-central Nigerian paediatric malaria patients. Keywords: severe malarial anaemia, pathophysiology, hepcidin, dyserythropoiesis, North Central Nigeria.