A systematic review on correlates of risk of TB disease in children and adults

P S Siddhi, R Raveendranath, P Puligari, A Chinnaswamy, R Song, S B Welch

Research output: Contribution to journalReview articlepeer-review


Tuberculosis (TB) remains one of the leading causes of death in the world. Targeted treatment to prevent progression from TB exposure and infection to disease is a key element of WHO End-TB strategy. A systematic review to identify and develop correlates of risk (COR) of TB disease is timely. EMBASE, MEDLINE, PUBMED were searched using relevant keywords and MeSH terms published between 2000 and 2020 on COR of TB disease in children and adults. Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) framework was used for structuring and reporting of outcomes. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2). 4105 studies were identified. Following eligibility screening, 27 studies were quality assessed. Risk of bias was high in all studies. Broad variations in COR type, study population, methodology and result reporting were observed. Tuberculin skin test (TST) and interferon gamma release essays (IGRA) are poor COR. Transcriptomic signatures although promising require validation studies to assess wider applicability. Performance consistency of other CORs-cell marker, cytokines and metabolites are much needed. This review identifies the need for a standardized approach to identify a universally applicable COR signature to achieve the WHO END-TB targets. [Abstract copyright: Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.]
Original languageEnglish
Pages (from-to)197-213
Number of pages17
JournalThe Indian journal of tuberculosis
Issue number2
Early online date21 May 2022
Publication statusE-pub ahead of print - 21 May 2022


  • Child
  • Interferon-gamma Release Tests - methods
  • Adult
  • Tuberculin Test - methods
  • TB disease
  • Tuberculosis - diagnosis - epidemiology
  • Correlates of risk (COR)
  • Systematic review
  • Humans
  • Interferon-gamma - metabolism
  • Latent Tuberculosis - diagnosis - epidemiology


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