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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.

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Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Division of Infectious Diseases, St. John's Research Institute, Koramangala, Bangalore, India.
Department of Infectious Diseases Group, Immunology and Immunogenetics of Bacterial Infectious Disease, Leiden University Medical Center, Leiden, The Netherlands.
GlaxoSmithKline Vaccines, Wavre, Belgium.
Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
Department of Microbiology, Haukeland University Hospital, University of Bergen, Bergen, Norway.


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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