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Towards a point-of-care test for active tuberculosis: obstacles and opportunities

Key Points

  • Tuberculosis (TB) remains one of the world's most serious threats to public health. Limited access to diagnostic services and the poor performance of current tests result in a failure to detect millions of TB cases each year.

  • Unlike for other many other infectious diseases, there are as yet no affordable, rapid tests for active TB that are suitable for use at the point of care (POC) in developing countries. This article aims to give the non-expert an insight into the major issues relating to the development of POC diagnostic tests for TB.

  • The lack of biological markers capable of predicting active TB is a major obstacle to test development. Recent efforts to improve our knowledge of the markers available include attempts to discover novel markers and the use of combinations of markers.

  • There are also many technological challenges for detecting TB biomarkers at the POC in developing countries. Current strategies include the use of immunochromatography and PCR, as well as novel approaches such as nanotechnology, isothermal nucleic-acid amplification and optical detection methods.

  • In addition to these technical and knowledge-based problems, more general issues affecting test development are economic and commercial pressures, and logistical and geographical difficulties encountered when developing a test for TB disease.

Abstract

Limited access to diagnostic services and the poor performance of current tests result in a failure to detect millions of tuberculosis cases each year. An accurate test that could be used at the point of care to allow faster initiation of treatment would decrease death rates and could reduce disease transmission. Previous attempts to develop such a test have failed, and success will require the marriage of biomarkers that are highly predictive for the disease with innovative technology that is reliable and affordable. Here, we review the status of research into point-of-care tests for active tuberculosis and discuss barriers to the development of such diagnostic tests.

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Figure 1: Estimated number of tuberculosis cases that were not detected in 2009, by country.
Figure 2: An immunochromatographic device for detecting antibodies or antigens.
Figure 3: An example of nanosensor technology.

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Acknowledgements

During the preparation of this manuscript, R.M. received salary support from the UK Department for International Development (DFID), the UK Wellcome Trust and the UK Technology Strategy Board.

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Glossary

M. tuberculosis complex

A group of closely related mycobacteria that cause tuberculosis in humans and animals; these bacteria include Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium canetti, Mycobacterium bovis, Mycobacterium pinnipedia, Mycobacterium microti and Mycobacterium caprae.

Multiplex detection

The simultaneous detection of two or more targets within a single test.

Microfluidic

Pertaining to the control and movement of fluids within miniaturized devices that incorporate channels of a submillimetre scale, allowing the manipulation of submicrolitre volumes.

Isothermal amplification

Enzyme-based amplification of target nucleic acids using a single temperature, without a requirement to heat or cool the reaction.

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McNerney, R., Daley, P. Towards a point-of-care test for active tuberculosis: obstacles and opportunities. Nat Rev Microbiol 9, 204–213 (2011). https://doi.org/10.1038/nrmicro2521

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