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

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


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Area Under Curve
  • Biomarkers / metabolism
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • ROC Curve
  • Sputum / microbiology*
  • Tuberculosis / diagnosis*
  • Tuberculosis / drug therapy
  • Tuberculosis / genetics*


  • Antitubercular Agents
  • Biomarkers
  • RNA, Messenger