Abstract
The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).
Highlights
Tuberculosis (TB) remains one of the world’s major public health problems
On the road towards a POC test, host immune biomarkers should ideally be explored on platforms that can be translated to primary diagnostic centers
We have previously explored the diagnostic potential of this assay in Indian children < 3 years referred to a TB verification ward for suspected tuberculosis[17]
Summary
Tuberculosis (TB) remains one of the world’s major public health problems. Following the declaration of TB as a global emergency in 1993, the response focused almost exclusively on reducing the transmission of Mycobacterium tuberculosis (MTB)[1]. A microbiologically confirmed diagnosis of pediatric TB is challenging due to the paucibacillary nature of disease which results in 70–80% of clinical cases remaining culture-negative even under optimal study conditions. This implies that despite successful implementation of the GeneXpert MTB/RIF assay in 22 high-burden countries[5], even direct identification of MTB in specimens by nucleic acid amplification tests, like the GeneXpert MTB/RIF assay, will never meet the requirements of a POC test for pediatric TB6. Unstimulated WB was analyzed for transcriptional immune biomarkers direct ex-vivo applying dcRT-MLPA, whereas WB stimulated with MTB antigens were analyzed for translational immune biomarkers using an 18-plex multiplex bead array (bioplex)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
