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Tuberculosis Diagnostics: State of the Art and Future Directions

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  • Authors: Madhukar Pai1, Mark P. Nicol2, Catharina C. Boehme3
  • Editors: William R. Jacobs Jr.4, Helen McShane5, Valerie Mizrahi6, Ian M. Orme7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: McGill International TB Centre, McGill University, Montreal, QC H3A 1A2, Canada; 2: University of Cape Town, Cape Town 7700, South Africa; 3: FIND, 1202 Geneva, Switzerland; 4: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 5: University of Oxford, Oxford OX3 7DQ, United Kingdom; 6: University of Cape Town, Rondebosch 7701, South Africa; 7: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016
  • Received 04 May 2016 Accepted 04 July 2016 Published 21 October 2016
  • M. Pai, madhukar.pai@mcgill.ca
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  • Abstract:

    Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and the development of shorter TB drug regimens. Another concern is the relative absence of non-sputum-based diagnostics in the pipeline for children, and of biomarker tests for triage, cure, and latent TB progression. Increased investments are necessary to support biomarker discovery, validation, and translation into clinical tools. While transformative tools are being developed, high-burden countries will need to improve the efficiency of their health care delivery systems, ensure better uptake of new technologies, and achieve greater linkages across the TB and HIV care continuum. While we wait for next-generation technologies, national TB programs must scale up the best diagnostics currently available, and use implementation science to get the maximum impact.

  • Citation: Pai M, Nicol M, Boehme C. 2016. Tuberculosis Diagnostics: State of the Art and Future Directions. Microbiol Spectrum 4(5):TBTB2-0019-2016. doi:10.1128/microbiolspec.TBTB2-0019-2016.

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2016-10-21
2017-11-22

Abstract:

Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and the development of shorter TB drug regimens. Another concern is the relative absence of non-sputum-based diagnostics in the pipeline for children, and of biomarker tests for triage, cure, and latent TB progression. Increased investments are necessary to support biomarker discovery, validation, and translation into clinical tools. While transformative tools are being developed, high-burden countries will need to improve the efficiency of their health care delivery systems, ensure better uptake of new technologies, and achieve greater linkages across the TB and HIV care continuum. While we wait for next-generation technologies, national TB programs must scale up the best diagnostics currently available, and use implementation science to get the maximum impact.

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Image of FIGURE 1
FIGURE 1

Pipeline of TB diagnostics (source: FIND, Geneva; www.finddx.org).

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016
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Image of FIGURE 2
FIGURE 2

Classes of TB biomarkers under development and validation (source: FIND, Geneva; www.finddx.org).

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016
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FIGURE 3

How TB tests can potentially impact patient outcomes (source: Schumacher et al. [ 57 ]).

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016
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FIGURE 4

Timeline of availability of required elements for Xpert MTB/RIF implementation (from reference 58 with permission).

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016
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Tables

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TABLE 1

Technologies reviewed by WHO for TB case detection

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016
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TABLE 2

Technologies reviewed by WHO for drug-susceptibility testing

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016
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TABLE 3

Translational challenges for developing innovative TB technologies that can meet the needs

Source: microbiolspec October 2016 vol. 4 no. 5 doi:10.1128/microbiolspec.TBTB2-0019-2016

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