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Sci Rep. 2017 Jul 19;7(1):5839. doi: 10.1038/s41598-017-05057-x.

Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children.

Author information

1
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
2
Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
3
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
4
Division of Infectious Diseases, St. John's Research Institute, Koramangala, Bangalore, India.
5
Department of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical Center, Leiden, The Netherlands.
6
GlaxoSmithKline Vaccines, Wavre, Belgium.
7
Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark. ritz@nexs.ku.dk.
8
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway. Harleen.Grewal@uib.no.
9
Department of Microbiology, Haukeland University Hospital, University of Bergen, Bergen, Norway. Harleen.Grewal@uib.no.

Abstract

Pediatric tuberculosis (TB) is challenging to diagnose, confirmed by growth of Mycobacterium tuberculosis at best in 40% of cases. The WHO has assigned high priority to the development of non-sputum diagnostic tools. We therefore sought to identify transcriptional signatures in whole blood of Indian children, capable of discriminating intra-thoracic TB disease from other symptomatic illnesses. We investigated the expression of 198 genes in a training set, comprising 47 TB cases (19 definite/28 probable) and 36 asymptomatic household controls, and identified a 7- and a 10-transcript signature, both including NOD2, GBP5, IFITM1/3, KIF1B and TNIP1. The discriminatory abilities of the signatures were evaluated in a test set comprising 24 TB cases (17 definite/7 probable) and 26 symptomatic non-TB cases. In separating TB-cases from symptomatic non-TB cases, both signatures provided an AUC of 0.94 (95%CI, 0.88-1.00), a sensitivity of 91.7% (95%CI, 71.5-98.5) regardless of culture status, and 100% sensitivity for definite TB. The 7-transcript signature provided a specificity of 80.8% (95%CI, 60.0-92.7), and the 10-transcript signature a specificity of 88.5% (95%CI, 68.7-96.9%). Although warranting exploration and validation in other populations, our findings are promising and potentially relevant for future non-sputum based POC diagnostic tools for pediatric TB.

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