Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis.
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.
Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Sabrina D
SD
Lamour
Section of Hepatology and Gastroenterology, Department of Medicine, Imperial College London, London, United Kingdom.
Maria
M
Gomez-Romero
Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Panagiotis A
PA
Vorkas
Section of Hepatology and Gastroenterology, Department of Medicine, Imperial College London, London, United Kingdom.
Vincent P
VP
Alibu
Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Jasmina
J
Saric
Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Elaine
E
Holmes
Institute of Biological and Environmental Sciences, University Of Aberdeen, Aberdeen, United Kingdom.
Jeremy M
JM
Sternberg
D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara; D000596:Amino Acids / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D016833:Trypanosoma brucei rhodesiense / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000175:diagnosis* / Q000469:parasitology / Q000473:pathology*; D055815:Young Adult
D000596:Amino Acids; D015415:Biomarkers; D008055:Lipids