A transcriptional blood signature distinguishes early tuberculosis disease from latent tuberculosis infection and uninfected individuals in a Vietnamese cohort. Issue 1 (July 2020)

• Record Type: Journal Article
• Authors: Ho, Jennifer; Bokil, Nilesh J.; Nguyen, Phuong Thi Bich; Nguyen, Thu Anh; Liu, Michael Y.; Hare, Nathan; Fox, Greg J.; Saunders, Bernadette M.; Marks, Guy B.; Britton, Warwick J.
• Is Part Of: Journal of infection. Volume 81:Issue 1(2020)
• Page Start: 72
• Page End: 80
• Publication Date: 2020-07
• Subjects: Biomarker -- Gene signature -- Tuberculosis screening -- Active case finding -- Tuberculosis diagnosis; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2020.03.066
• Languages: English
• ISSNs: 0163-4453

Abstract

Highlights: Dramatic reduction in tuberculosis (TB) incidence are required to achieve TB elimination. The current tools we have for screening for TB are insensitive. A concise blood gene signature can diagnose early TB disease prior to symptoms. This sensitive test could be used to detect prevalent cases of TB in the community. Summary: 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.