Lipidomic Profiling and Platelet-Activating Factor Dysregulation in Patients with Severe Malaria in North East Nigeria

Platelet-activating factor, a potent phospholipid mediator of inflammation, has been implicated in the vascular pathology of severe Plasmodium falciparum malaria, yet comprehensive lipidomic characterisation of malaria-associated phospholipid dysregulation remains absent in the Nigerian literature. This study undertakes plasma lipidomic profiling and targeted PAF quantification in patients with severe malaria, uncomplicated malaria, and healthy controls in Adamawa and Borno States, North East Nigeria. A case-control design was employed, enrolling 60 severe malaria patients, 60 uncomplicated malaria patients, and 60 matched healthy controls. Untargeted lipidomics was performed by UHPLC-QTOF-MS, and PAF and lyso-PAF species were quantified by targeted LC-MS/MS. Serum PAF-acetylhydrolase activity, which inactivates PAF, was also measured. Clinical severity was assessed by WHO criteria, and markers of endothelial activation and organ dysfunction were simultaneously determined. Multivariate lipidomic models identified lipid species signatures discriminating severe from uncomplicated malaria. Causal mediation analysis examined whether PAF elevation mediates the relationship between parasitaemia and endothelial dysfunction. This work generates an original lipidomic framework for severe malaria pathophysiology and proposes novel biochemical targets for adjunct therapy. Keywords: lipidomics, platelet-activating factor, severe malaria, phospholipids, North East Nigeria.