Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis

Sabrina D Lamour, Maria Gomez-Romero, Pangiotis A Vorkas, Vincent Pius Alibu, Jasmina Saric, Elaine Holmes, Jeremy M Sternberg (Corresponding Author)

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Abstract

Human African trypanosomiasis (HAT) remains a major neglected tropical disease in Sub-Saharan Africa. As clinical symptoms are usually non-specific, new diagnostic and prognostic markers are urgently needed to enhance the number of identified cases and optimise treatment. This is particularly important for disease caused by Trypanosoma brucei rhodesiense, where indirect immunodiagnostic approaches have to date been unsuccessful. We have conducted global metabolic profiling of plasma from T.b.rhodesiense HAT patients and endemic controls, using 1H nuclear magnetic resonance (NMR) spectroscopy and ultra-performance liquid chromatography, coupled with mass spectrometry (UPLC-MS) and identified differences in the lipid, amino acid and metabolite profiles. Altogether 16 significantly disease discriminatory metabolite markers were found using NMR, and a further 37 lipid markers via UPLC-MS. These included significantly higher levels of phenylalanine, formate, creatinine, N-acetylated glycoprotein and triglycerides in patients relative to controls. HAT patients also displayed lower concentrations of histidine, sphingomyelins, lysophosphatidylcholines, and several polyunsaturated phosphatidylcholines. While the disease metabolite profile was partially consistent with previous data published in experimental rodent infection, we also found unique lipid and amino acid profile markers highlighting subtle but important differences between the host response to trypanosome infections between animal models and natural human infections. Our results demonstrate the potential of metabolic profiling in the identification of novel diagnostic biomarkers and the elucidation of pathogenetic mechanisms in this disease.
Original languageEnglish
Article numbere0004200
Number of pages17
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number10
Early online date27 Oct 2015
DOIs
Publication statusPublished - 27 Oct 2015

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African Trypanosomiasis
formic acid
Infection
Lipids
Liquid Chromatography
Mass Spectrometry
Magnetic Resonance Spectroscopy
Trypanosoma brucei rhodesiense
Neglected Diseases
Amino Acids
Lysophosphatidylcholines
Trypanosomiasis
Sphingomyelins
Africa South of the Sahara
Phenylalanine
Histidine
Rodentia
Creatinine
Glycoproteins
Triglycerides

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Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis. / Lamour, Sabrina D; Gomez-Romero, Maria; Vorkas, Pangiotis A; Alibu, Vincent Pius; Saric, Jasmina; Holmes, Elaine; Sternberg, Jeremy M (Corresponding Author).

In: PLoS Neglected Tropical Diseases, Vol. 9, No. 10, e0004200, 27.10.2015.

Research output: Contribution to journalArticle

Lamour, Sabrina D ; Gomez-Romero, Maria ; Vorkas, Pangiotis A ; Alibu, Vincent Pius ; Saric, Jasmina ; Holmes, Elaine ; Sternberg, Jeremy M. / Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis. In: PLoS Neglected Tropical Diseases. 2015 ; Vol. 9, No. 10.
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