期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-05057-x
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资金
- Research Council of Norway Global Health and Vaccination Research (GLOBVAC) [179342, 192534, 248042]
- University of Bergen (Norway)
- Aeras (USA)
- St. John's Research Institute, Bangalore
- All India Institute of Medical Sciences, New Delhi, India
- FP7 ADITEC [280873]
- EC HORIZON [643381]
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 nonsputum 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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