Metabolite changes in blood predict the onset of tuberculosis

January Weiner, Jeroen Maertzdorf, Jayne S. Sutherland, Fergal J. Duffy, Ethan Thompson, Sara Suliman, Gayle McEwen, Bonnie Thiel, Shreemanta K. Parida, Joanna Zyla, Willem A. Hanekom, Robert P. Mohney, W. Henry Boom, Harriet Mayanja-Kizza, Rawleigh Howe, Hazel M. Dockrell, Tom H. M. Ottenhoff, Thomas J. Scriba, Daniel E. Zak, Gerhard Walzl and Stefan H. E. Kaufmann ()
Additional contact information
January Weiner: Max Planck Institute for Infection Biology
Jeroen Maertzdorf: Max Planck Institute for Infection Biology
Jayne S. Sutherland: Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine
Fergal J. Duffy: The Center for Infectious Disease Research
Ethan Thompson: The Center for Infectious Disease Research
Sara Suliman: University of Cape Town
Gayle McEwen: Max Planck Institute for Infection Biology
Bonnie Thiel: Case Western Reserve University School of Medicine and University Hospitals Case Medical Center
Shreemanta K. Parida: Max Planck Institute for Infection Biology
Joanna Zyla: Max Planck Institute for Infection Biology
Willem A. Hanekom: University of Cape Town
Robert P. Mohney: Metabolon Inc.
W. Henry Boom: Case Western Reserve University School of Medicine and University Hospitals Case Medical Center
Harriet Mayanja-Kizza: Makerere University
Rawleigh Howe: Armauer Hansen Research Institute
Hazel M. Dockrell: London School of Hygiene & Tropical Medicine
Tom H. M. Ottenhoff: Leiden University Medical Centre
Thomas J. Scriba: University of Cape Town
Daniel E. Zak: The Center for Infectious Disease Research
Gerhard Walzl: Stellenbosch University
Stefan H. E. Kaufmann: Max Planck Institute for Infection Biology

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract New biomarkers of tuberculosis (TB) risk and disease are critical for the urgently needed control of the ongoing TB pandemic. In a prospective multisite study across Subsaharan Africa, we analyzed metabolic profiles in serum and plasma from HIV-negative, TB-exposed individuals who either progressed to TB 3–24 months post-exposure (progressors) or remained healthy (controls). We generated a trans-African metabolic biosignature for TB, which identifies future progressors both on blinded test samples and in external data sets and shows a performance of 69% sensitivity at 75% specificity in samples within 5 months of diagnosis. These prognostic metabolic signatures are consistent with development of subclinical disease prior to manifestation of active TB. Metabolic changes associated with pre-symptomatic disease are observed as early as 12 months prior to TB diagnosis, thus enabling timely interventions to prevent disease progression and transmission.

Date: 2018
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DOI: 10.1038/s41467-018-07635-7

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