A transcriptional blood signature distinguishes early tuberculosis disease from latent tuberculosis infection and uninfected individuals in a Vietnamese cohort

Jennifer Ho; Nilesh J Bokil; Phuong Thi Bich Nguyen; Thu Anh Nguyen; Michael Y Liu; Nathan Hare; Greg J Fox; Bernadette M Saunders; Guy B Marks; Warwick J Britton

doi:10.1016/j.jinf.2020.03.066

A transcriptional blood signature distinguishes early tuberculosis disease from latent tuberculosis infection and uninfected individuals in a Vietnamese cohort

J Infect. 2020 Jul;81(1):72-80. doi: 10.1016/j.jinf.2020.03.066. Epub 2020 Apr 21.

Authors

Affiliations

¹ Woolcock Institute of Medical Research, The University of Sydney, 431 Glebe Point Rd, Glebe NSW 2037, Australia; South Western Sydney Clinical School, University of New South Wales, Sydney, Australia; Centenary Institute, The University of Sydney, Sydney, Australia. Electronic address: jennifer.ho@sydney.edu.au.
² School of Life Sciences, University of Technology Sydney, Sydney, Australia.
³ Woolcock Institute of Medical Research, The University of Sydney, 431 Glebe Point Rd, Glebe NSW 2037, Australia.
⁴ The ithree Institute, University of Technology Sydney, Sydney, Australia.
⁵ Centenary Institute, The University of Sydney, Sydney, Australia.
⁶ Woolcock Institute of Medical Research, The University of Sydney, 431 Glebe Point Rd, Glebe NSW 2037, Australia; Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
⁷ Centenary Institute, The University of Sydney, Sydney, Australia; School of Life Sciences, University of Technology Sydney, Sydney, Australia.
⁸ Woolcock Institute of Medical Research, The University of Sydney, 431 Glebe Point Rd, Glebe NSW 2037, Australia; South Western Sydney Clinical School, University of New South Wales, Sydney, Australia.
⁹ Centenary Institute, The University of Sydney, Sydney, Australia; Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

PMID: 32330522
DOI: 10.1016/j.jinf.2020.03.066

Abstract

Objectives: Global tuberculosis (TB) control is restricted by the failure to detect an estimated 3.3 million TB cases annually. In the majority of TB endemic settings, sputum smear microscopy is used to diagnose TB, but this test is insensitive for TB in its early stages. The objective of this study is to establish a concise gene signature that discriminates between individuals with early TB disease, latent TB infection (LTBI) and those without infection.

Methods: This is a case control study nested within a cluster-randomised trial of population screening for active TB using Xpert MTB/RIF. Whole blood samples from 303 participants with active TB (97), LTBI (92) and uninfected individuals (114) were subject to transcriptomic analysis of selected target genes based on a systematic review of previous studies.

Results: Analysis of 82 genes identified a pattern of differentially expressed genes in TB disease. A seven gene signature was identified that distinguished between TB disease and no TB disease with an AUC of 0.86 (95% CI: 0.80-0.91), and between TB disease from LTBI with an AUC of 0.88 (95% CI: 0.82-0.93).

Conclusion: This gene signature accurately distinguishes early TB disease from those without TB disease or infection, in the context of community-wide TB screening. It could be used as a non-sputum based screening tool or triage test to detect prevalent cases of TB in the community.

Keywords: Active case finding; Biomarker; Gene signature; Tuberculosis diagnosis; Tuberculosis screening.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Asian People
Case-Control Studies
Humans
Latent Tuberculosis* / diagnosis
Mycobacterium tuberculosis* / genetics
Randomized Controlled Trials as Topic
Sensitivity and Specificity
Sputum
Tuberculosis*