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Nat Commun. 2018 Dec 6;9(1):5208. doi: 10.1038/s41467-018-07635-7.

Metabolite changes in blood predict the onset of tuberculosis.

Author information

1
Max Planck Institute for Infection Biology, 10117, Berlin, Germany.
2
Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P. O. Box 273, Banjul, The Gambia.
3
The Center for Infectious Disease Research, Seattle, WA 98145-5005, USA.
4
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Division of Immunology, Department of Pathology, University of Cape Town, Rondebosch 7701, Cape Town, South Africa.
5
Leibniz Institute for ZOO and and Wildlife Research, 10315 Berlin, Germany.
6
Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland 44106-4921, OH, USA.
7
Translational Medicine & Global Health Consulting, 10115 Berlin, Germany.
8
Metabolon Inc., Durham, NC 27709, USA.
9
Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
10
Armauer Hansen Research Institute, P.O. Box 1005, Addis Ababa, Ethiopia.
11
Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
12
Department of Infectious Diseases, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands.
13
NRF-DST Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 8000, South Africa.
14
Max Planck Institute for Infection Biology, 10117, Berlin, Germany. kaufmann@mpiib-berlin.mpg.de.

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.

PMID:
30523338
PMCID:
PMC6283869
DOI:
10.1038/s41467-018-07635-7
[Indexed for MEDLINE]
Free PMC Article

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