Neuro-Immune Mechanisms of Cerebral Malaria Pathogenesis in Paediatric Patients: A Multi-Omics Investigation in Borno State, North East Nigeria

Cerebral malaria in children involves complex neuro-immune crosstalk including blood-brain barrier disruption, neuroinflammation, and sequestration of parasitised erythrocytes, but the molecular determinants of neurological injury and recovery in African children remain incompletely characterised. This research employs a multi-omics approach to dissect neuro-immune mechanisms of cerebral malaria pathogenesis in paediatric patients at the University of Maiduguri Teaching Hospital, Borno State, North East Nigeria. A longitudinal case-control design will enrol 60 children with cerebral malaria, 60 with severe non-cerebral malaria, 60 with uncomplicated malaria, and 40 healthy controls. CSF and plasma samples will be subjected to cytokine multiplex profiling, metabolomics by LC-MS/MS, and proteomics by data-independent acquisition mass spectrometry. Host genome-wide genotyping will identify susceptibility polymorphisms in blood-brain barrier integrity and complement genes. CSF neurofilament light and GFAP will serve as neuronal injury biomarkers. Integration of cytokine, metabolome, and proteome data will be achieved through multi-omics network analysis using MOFA. Longitudinal sampling at admission, 48 hours, and 28-day follow-up will capture dynamic neuro-immune trajectories linked to neurocognitive outcome. The research makes original theoretical contributions by proposing a unified neuro-immune-metabolic model of cerebral malaria injury. Findings will identify candidate intervention targets and prognostic biomarkers to guide neurocognitive rescue strategies in North East Nigerian paediatric malaria management. Keywords: cerebral malaria, neuro-immune, multi-omics, blood-brain barrier, neurofilament