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Review
. 2021 Nov 5:25:100284.
doi: 10.1016/j.jctube.2021.100284. eCollection 2021 Dec.

A systematic review of potential screening biomarkers for active TB disease

James H Wykowski  1 , Chris Phillips  2 , Thao Ngo  2 , Paul K Drain  1   2   3
Affiliations
Review

A systematic review of potential screening biomarkers for active TB disease

James H Wykowski et al. J Clin Tuberc Other Mycobact Dis. .

Abstract

Introduction: The standard TB Four Symptom Screen does not meet the World Health Organization (WHO) ideal screening criteria for having greater than 90% sensitivity to identify active TB disease, regardless of HIV status. To identify novel screening biomarkers for active TB, we performed a systematic review of any cohort or case-control study reporting associations between screening biomarkers and active TB disease.

Methods: We searched PubMed and Embase for articles published before October 10, 2021. We included studies from high or medium tuberculosis burden countries. We excluded articles focusing on C-reactive protein and lipoarabinomannan. For all included biomarkers, we calculated sensitivity, specificity and 95% confidence intervals, and assessed study quality using a tool adapted from the QUADAS-2 risk of bias.

Results: From 8,062 abstracts screened, we included 79 articles. The articles described 302 unique biomarkers, including host antibodies, host proteins, TB antigens, microRNAs, whole blood gene PCRs, and combinations of biomarkers. Of these, 23 biomarkers had sensitivity greater than 90% and specificity greater than 70%, meeting WHO criteria for an ideal screening test. Among the eleven biomarkers described in people living with HIV, only one had a sensitivity greater than 90% and specificity greater than 70% for active TB.

Conclusion: Further evaluation of biomarkers of active TB should be pursued to accelerate identification of TB disease.

Keywords: Screening; Systematic review; Tuberculosis.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
PRISMA Diagram.
Fig. 2
Fig. 2
Sensitivity, specificity and 95% confidence intervals for tests meeting WHO Criteria.
Fig. 3
Fig. 3
Risk of Bias and Applicability Concerns for all included studies.
See this image and copyright information in PMC

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