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Review
. 2022 Dec 7;14(12):e14088.
doi: 10.15252/emmm.202114088. Epub 2022 Oct 31.

Diagnostic biomarkers for active tuberculosis: progress and challenges

Betânia M F Nogueira #  1   2   3 , Sonya Krishnan #  4 , Beatriz Barreto-Duarte  3   5   6   7 , Mariana Araújo-Pereira  3   7   8 , Artur T L Queiroz  2   9 , Jerrold J Ellner  10 , Padmini Salgame  10 , Thomas J Scriba  11 , Timothy R Sterling  12 , Amita Gupta  4 , Bruno B Andrade  3   5   7   8   13   14
Affiliations
Review

Diagnostic biomarkers for active tuberculosis: progress and challenges

Betânia M F Nogueira et al. EMBO Mol Med. .

Abstract

Tuberculosis (TB) is a leading cause of morbidity and mortality from a single infectious agent, despite being preventable and curable. Early and accurate diagnosis of active TB is critical to both enhance patient care, improve patient outcomes, and break Mycobacterium tuberculosis (Mtb) transmission cycles. In 2020 an estimated 9.9 million people fell ill from Mtb, but only a little over half (5.8 million) received an active TB diagnosis and treatment. The World Health Organization has proposed target product profiles for biomarker- or biosignature-based diagnostics using point-of-care tests from easily accessible specimens such as urine or blood. Here we review and summarize progress made in the development of pathogen- and host-based biomarkers for active TB diagnosis. We describe several unique patient populations that have posed challenges to development of a universal diagnostic TB biomarker, such as people living with HIV, extrapulmonary TB, and children. We also review additional limitations to widespread validation and utilization of published biomarkers. We conclude with proposed solutions to enhance TB diagnostic biomarker validation and uptake.

Keywords: active TB; biomarkers; diagnostic biomarkers; tuberculosis.

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Figures

Figure 1
Figure 1. Wide range of available biomarkers within the spectrum of TB
Abbreviations: Mtb, Mycobacterium tuberculosis; TB, tuberculosis; TST+, tuberculin skin test positive; IGRA+, interferon‐gamma release assay positive.
Figure 2
Figure 2. Timeline of the TB diagnostic biomarkers endorsed by the World Health Organization
Figure 3
Figure 3. Spectrum of host and pathogen biomarkers that have been widely studied as TB diagnostics
Figure 4
Figure 4. Challenges to biomarker development and proposed solutions
See this image and copyright information in PMC

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