Abstract

BackgroundLassa fever and Ebola are characterized by non-specific initial presentations that can progress to severe multisystem illnesses with high fatality rates. Samples from additional subjects are examined to extend and corroborate biomarkers with prognostic value for these diseases.MethodsLiquid Chromatography Mass Spectrometry metabolomics was used to identify and confirm metabolites disrupted in the blood of Lassa fever and Ebola patients. Authenticated standards are used to confirm the identify of key metabolites.ResultsWe confirm prior results by other investigators that the amino acid l-threonine is elevated during Ebola virus infection. l-Threonine is also elevated during Lassa virus infection. We also confirmed that platelet-activating factor (PAF) and molecules with PAF moiety are reduced in the blood of patients with fatal Lassa fever. Similar changes in PAF and PAF-like molecules were not observed in the blood of Ebola patients.ConclusionsMetabolomics may provide tools to identify pathways that are differentially affected during viral hemorrhagic fevers and guide development of diagnostics to monitor and predict outcome.

Highlights

  • Lassa fever and Ebola are characterized by non-specific initial presentations that can progress to severe multisystem illnesses with high fatality rates

  • Twentytwo subjects tested negative for Lassa virus (LASV) by all diagnostic tests and were classified as febrile non-Lassa

  • Twelve febrile subjects tested negative for Lassa virus (LASV) and Ebola virus (EBOV) by all diagnostic tests and were classified as febrile nonEbola

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Summary

Introduction

Lassa fever and Ebola are characterized by non-specific initial presentations that can progress to severe multisystem illnesses with high fatality rates. Select features within the metabolome may serve as biomarkers for disease severity/progression/outcome and lend themselves to the design of prognostic methods for viral diseases, such as Lassa fever and Ebola. We have previously characterized endogenous small molecules with prognostic value originating from the blood of febrile patients triaged to the Lassa fever ward in Kenema, Sierra Leone [1]. In an extraordinary multi-omics study Eisfeld and coworkers [2] demonstrated that levels of serum l-threonine were elevated in the blood of patients with Ebola, another severe viral hemorrhagic fever (VHF). Inspired by the results of Eisfeld and coworkers [2] we corroborate l-threonine as a biomarker of acute Lassa fever. We contrast levels of other select metabolites, including plate-activating factor (PAF) and PAF-like molecules, between Lassa fever and Ebola patients. Authenicate standards were used to confirm the identity of l-threonine and selected PAF-like molecules

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