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Performance of diagnostic and predictive host blood transcriptomic signatures for Tuberculosis disease: A systematic review and meta-analysis

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  • Humphrey Mulenga
  • Chambrez-Zita Zauchenberger
  • Erick W Bunyasi
  • Stanley Kimbung Mbandi
  • Simon C Mendelsohn
  • Benjamin Kagina
  • Adam Penn-Nicholson
  • Thomas J Scriba
  • Mark Hatherill

Abstract

Introduction: Host blood transcriptomic biomarkers have potential as rapid point-of-care triage, diagnostic, and predictive tests for Tuberculosis disease. We aimed to summarise the performance of host blood transcriptomic signatures for diagnosis of and prediction of progression to Tuberculosis disease; and compare their performance to the recommended World Health Organisation target product profile. Methods: A systematic review and meta-analysis of the performance of host blood mRNA signatures for diagnosing and predicting progression to Tuberculosis disease in HIV-negative adults and adolescents, in studies with an independent validation cohort. Medline, Scopus, Web of Science, and EBSCO libraries were searched for articles published between January 2005 and May 2019, complemented by a search of bibliographies. Study selection, data extraction and quality assessment were done independently by two reviewers. Meta-analysis was performed for signatures that were validated in ≥3 comparable cohorts, using a bivariate random effects model. Results: Twenty studies evaluating 25 signatures for diagnosis of or prediction of progression to TB disease in a total of 68 cohorts were included. Eighteen studies evaluated 24 signatures for TB diagnosis and 17 signatures met at least one TPP minimum performance criterion. Three diagnostic signatures were validated in clinically relevant cohorts to differentiate TB from other diseases, with pooled sensitivity 84%, 87% and 90% and pooled specificity 79%, 88% and 74%, respectively. Four studies evaluated signatures for progression to TB disease and performance of one signature, assessed within six months of TB diagnosis, met the minimal TPP for a predictive test for progression to TB disease. Conclusion: Host blood mRNA signatures hold promise as triage tests for TB. Further optimisation is needed if mRNA signatures are to be used as standalone diagnostic or predictive tests for therapeutic decision-making.

Suggested Citation

  • Humphrey Mulenga & Chambrez-Zita Zauchenberger & Erick W Bunyasi & Stanley Kimbung Mbandi & Simon C Mendelsohn & Benjamin Kagina & Adam Penn-Nicholson & Thomas J Scriba & Mark Hatherill, 2020. "Performance of diagnostic and predictive host blood transcriptomic signatures for Tuberculosis disease: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 15(8), pages 1-17, August.
    • Handle: RePEc:plo:pone00:0237574
    DOI: 10.1371/journal.pone.0237574
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    1. Matthew P. R. Berry & Christine M. Graham & Finlay W. McNab & Zhaohui Xu & Susannah A. A. Bloch & Tolu Oni & Katalin A. Wilkinson & Romain Banchereau & Jason Skinner & Robert J. Wilkinson & Charles Qu, 2010. "An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis," Nature, Nature, vol. 466(7309), pages 973-977, August.
    2. Shiying Li & Bin Liu & Mingli Peng & Min Chen & Wenwei Yin & Hui Tang & Yuxuan Luo & Peng Hu & Hong Ren, 2017. "Diagnostic accuracy of Xpert MTB/RIF for tuberculosis detection in different regions with different endemic burden: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-13, July.
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    1. Adrienne Chang & Conor J. Loy & Daniel Eweis-LaBolle & Joan S. Lenz & Amy Steadman & Alfred Andgrama & Nguyen Viet Nhung & Charles Yu & William Worodria & Claudia M. Denkinger & Payam Nahid & Adithya , 2024. "Circulating cell-free RNA in blood as a host response biomarker for detection of tuberculosis," Nature Communications, Nature, vol. 15(1), pages 1-8, December.

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