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1. Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa

Author

Elin Näsström, Christopher M Parry, Nga Tran Vu Thieu, Rapeephan R Maude, Hanna K de Jong, Masako Fukushima, Olena Rzhepishevska, Florian Marks, Ursula Panzner, Justin Im, Hyonjin Jeon, Seeun Park, Zabeen Chaudhury, Aniruddha Ghose, Rasheda Samad, Tan Trinh Van, Anders Johansson, Arjen M Dondorp, Guy E Thwaites, Abul Faiz, Henrik Antti, and Stephen Baker

Subjects
Metabolomics, mass spectrometry, two-dimensional gas chromatography, typhoid fever, diagnostics, biomarkers, Medicine, Science, Biology (General), QH301-705.5
Abstract

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

Published
2017
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2. Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa

Author

Olena Rzhepishevska, Nga Tran Vu Thieu, Christopher M. Parry, Masako Fukushima, Henrik Antti, Hanna K. de Jong, Florian Marks, Arjen M. Dondorp, Hyonjin Jeon, Justin Im, Seeun Park, Ursula Panzner, Guy E. Thwaites, Abul Faiz, Anders Johansson, Tan Trinh Van, Zabeen Chaudhury, Rapeephan R. Maude, Stephen Baker, Rasheda Samad, Aniruddha Ghose, Elin Näsström, Baker, Stephen [0000-0003-1308-5755], Apollo - University of Cambridge Repository, Center of Experimental and Molecular Medicine, and Other departments

Subjects
0301 basic medicine, wh_400, Metabolite, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), Salmonella typhi, Mass Spectrometry, chemistry.chemical_compound, Plasma, 0302 clinical medicine, diagnostics, Blood culture, Biology (General), Microbiology and Infectious Disease, Bangladesh, medicine.diagnostic_test, General Neuroscience, General Medicine, Senegal, 3. Good health, Cohort, Medicine, QH301-705.5, Science, infectious disease, 030231 tropical medicine, 030106 microbiology, two-dimensional gas chromatography, complex mixtures, General Biochemistry, Genetics and Molecular Biology, Typhoid fever, 03 medical and health sciences, medicine, Metabolomics, biochemistry, Humans, qy_400, Typhoid Fever, S. enterica serovar typhi, Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), General Immunology and Microbiology, business.industry, wc_270, microbiology, biomarkers, medicine.disease, bacterial infections and mycoses, chemistry, Infectious disease (medical specialty), Immunology, business, Research Advance, Validation cohort, Malaria
Abstract

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics. DOI: http://dx.doi.org/10.7554/eLife.15651.001

Published
2017

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