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

Abstract

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.

Elevated L-Threonine is a Biomarker for Lassa Fever and Ebola

“…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]. Here, we corroborate biomarkers in samples from the most acutely ill Lassa fever patients and contrast select metabolites in patients with Ebola, another severe viral hemorrhagic fever (VHF).…”

Discovery and Predictive Modeling of Urine Microbiome, Metabolite and Cytokine Biomarkers in Hospitalized Patients with Community Acquired Pneumonia

“…Since the microbiome and metabolite profiles are influenced by the environment, nutrition, age, and lifestyle of the host, in addition to genetics, these concatenated profiles provide a unique snapshot of individual health. 19,22,31,[23][24][25][26][27][28][29][30] Indeed, while these complex profiles can be examined independently, changes in the collective abundance patterns of metabolites and microbes may indicate deeper homeostatic disturbances, which may be reflected through changes in interleukin signaling. The membership of the bodies microbial communities have dynamic interconnected relationships with one another and the host that change under states of disease and stress.…”

“…The metabolome and microbiome 21 are also unique portraits of the individual patient as they are not only influenced by genetics and disease state but also by the environment, nutrition, age, and lifestyle 19,22,31,[23][24][25][26][27][28][29][30] . Thus the microbiome and metabolome are very different from transcriptomic or proteomic biomarkers.…”

Whole exome sequencing in the diagnostic workup of patients with a bleeding diathesis

“…Novel strategies, such as proteomics, metabolomics and genomics, are slowly incorporated into clinical practice . Continued next‐generation sequencing (NGS) efforts have already significantly improved our understanding of the pathobiology in other diseases such as acute myeloid leukaemia and changed treatment towards more individualized therapy .…”

“…Novel strategies, such as proteomics, metabolomics and genomics, are slowly incorporated into clinical practice. [4][5][6] Continued next-generation sequencing (NGS) efforts have already significantly improved our understanding of the pathobiology in other diseases such as acute myeloid leukaemia and changed treatment towards more individualized therapy. 7 Routine diagnostic whole exome sequencing (WES) in our genetic department has shown to be an effective tool to elucidate the genetic defect underlying many different types of heterogeneous disorders and we hypothesize that such an approach would also benefit the diagnostics of bleeding disorders.…”