Cytokine Profiling and Immunological Dysregulation in Children with Severe Plasmodium falciparum Malaria in Enugu State, South East Nigeria

The immunopathogenesis of severe Plasmodium falciparum malaria involves complex cytokine dysregulation that drives cerebral malaria, severe anaemia, and respiratory distress, yet the specific cytokine signatures in Nigerian children remain incompletely characterised. This study profiled serum cytokines and assessed immunological dysregulation in children with severe and uncomplicated falciparum malaria at Enugu State University Teaching Hospital, Enugu State, South East Nigeria. A case-control study enrolled 50 children with WHO-defined severe malaria, 50 with uncomplicated malaria, and 40 healthy community controls aged 6 months to 12 years. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-10, IL-12p70, and TGF-beta were measured by multiplex bead-based immunoassay. Full blood count, parasite density, and clinical severity scores were also obtained. Children with severe malaria had markedly elevated TNF-alpha, IL-6, and IFN-gamma compared to uncomplicated malaria and controls. IL-10 was elevated in both malaria groups but significantly higher in severe cases, suggesting a dysregulated anti-inflammatory response. The TNF-alpha to IL-10 ratio was a stronger predictor of severe disease than individual cytokine values alone. Cerebral malaria cases showed the most extreme pro-inflammatory profiles. Parasite density correlated modestly with cytokine levels. The study identifies cytokine profiles distinguishing severe from uncomplicated malaria and proposes the TNF-alpha to IL-10 ratio as a potential severity biomarker. Immunomodulatory adjunctive therapies targeting this imbalance warrant further investigation in the context of Nigerian childhood malaria. Keywords: cytokine profiling, severe malaria, TNF-alpha, IL-10, immunopathogenesis