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.
Highlights
Human African Trypanosomiasis (HAT) is caused by infection with either of two subspecies of Trypanosoma brucei
Metabolic profiling of biofluids and tissues in disease and healthy individuals is a powerful approach to discover new markers for diagnosis. We have applied these techniques to the protozoan infection human African trypanosomiasis (HAT), otherwise known as sleeping sickness
We demonstrate that plasma metabolic profiles are characteristic for T. b. rhodesiense infection
Summary
Human African Trypanosomiasis (HAT) is caused by infection with either of two subspecies of Trypanosoma brucei. Trypanosoma brucei (T. b.) gambiense causes chronic disease (that can last months or years) and is endemic in Western Africa while T. b. Gambiense is routinely screened using the Card Agglutination Test for Trypanosomiasis (CATT) and a new generation of lateral-flow rapid diagnostic tests are being deployed based on the hostresponse to commonly expressed variant surface glycoproteins (VSG) [4]. No such serological approach has been successful for T. b. New diagnostic techniques are urgently needed for this disease in order to meet the World Health Organization (WHO) target of elimination by 2020 [5,6]
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