Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers

Résumé

Lassa fever afflicts tens of thousands of people in West Africa annually.The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management.The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry.Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level.Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation.Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients. Author summaryLassa fever afflicts tens of thousands of people in West Africa each year.The disease progresses rapidly, but there are no tests available to determine which patients are at high risk for dying.We measured the levels of small molecules in the blood of febrile patients with and without infection by LASV that presented to Kenema Government Hospital in Sierra Leone using Ultra High Performance Liquid Chromatography Mass Spectrometry (LCMS), which identifies compounds based on their precise mass.Computational analyses were used to identify compounds that differed in patients with an acute LASV infection, patients with evidence of prior exposure to LASV and patients with fever, but who did not have evidence of exposure to LASV.Several serum metabolites, including factors that are involved in blood clotting and breakdown products of heme, were identified that may prove useful in diagnostic assays that will inform better care of Lassa fever patients or development of therapeutic interventions.

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