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Tuberculosis

Nature Reviews Disease Primers volume 2, Article number: 16076 (2016) Cite this article

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Abstract

Tuberculosis (TB) is an airborne infectious disease caused by organisms of the Mycobacterium tuberculosis complex. Although primarily a pulmonary pathogen, M. tuberculosis can cause disease in almost any part of the body. Infection with M. tuberculosis can evolve from containment in the host, in which the bacteria are isolated within granulomas (latent TB infection), to a contagious state, in which the patient will show symptoms that can include cough, fever, night sweats and weight loss. Only active pulmonary TB is contagious. In many low-income and middle-income countries, TB continues to be a major cause of morbidity and mortality, and drug-resistant TB is a major concern in many settings. Although several new TB diagnostics have been developed, including rapid molecular tests, there is a need for simpler point-of-care tests. Treatment usually requires a prolonged course of multiple antimicrobials, stimulating efforts to develop shorter drug regimens. Although the Bacillus Calmette–Guérin (BCG) vaccine is used worldwide, mainly to prevent life-threatening TB in infants and young children, it has been ineffective in controlling the global TB epidemic. Thus, efforts are underway to develop newer vaccines with improved efficacy. New tools as well as improved programme implementation and financing are necessary to end the global TB epidemic by 2035.

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Figure 1: The spectrum of TB — from Mycobacterium tuberculosis infection to active (pulmonary) TB disease.
Figure 2: Global incidence of active TB disease (pulmonary and extrapulmonary).
Figure 3: Mycobacterium tuberculosis infection.
Figure 4: Imaging tools for active TB disease.
Figure 5: The global TB drug pipeline.

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Acknowledgements

M.P. is a recipient of a Canada Research Chair award from the Canadian Institutes of Health Research (CIHR), and acknowledges grant support from the CIHR and the Bill & Melinda Gates Foundation. He also holds a TMA Pai Endowment Chair from Manipal University, India. M.A.B. acknowledges grant support from the CIHR, the Public Health Agency of Canada and the US National Institutes of Health (NIH). D.D. acknowledges grant support from the NIH, CIHR, US Centers for Disease Control and Prevention, US Agency for International Development and the Bill & Melinda Gates Foundation. K.D. acknowledges grant support from the European Developing Clinical Trials Partnership, the South African Medical Research Council and the South African National Research Foundation. M.D. is supported by the CIHR Foundation Grant (FDN-143273) as well as a CIHR New Investigator Award. C.C.B. acknowledges grant support for Foundation for Innovative New Diagnostics (FIND) from several governments (Australia, the Netherlands, the United Kingdom and Switzerland), the Bill & Melinda Gates Foundation and the NIH. A.G. is a full-time employee of Aeras, which has received current or past grant support from the Bill & Melinda Gates Foundation, the UK Department for International Development (DFID), the Dutch Ministry of Foreign Affairs (DGIS), the Australian Agency for International Development (AusAID), the Global Health Innovative Technology (GHIT) Fund, the US FDA and the US National Institute of Allergy and Infectious Diseases (NIAID) of the NIH. S.S. is a full-time employee of the Indian Council of Medical Research (ICMR), a Government of India agency. M.S. is a full-time employee of TB Alliance, which has received current or past grant support from AusAID, the Bill & Melinda Gates Foundation, DFID, DGIS, the European Commission (EC), GHIT, the Indonesia Health Fund, NIAID/NIH, UNITAID, the US Agency for International Development (USAID) and the FDA. D.M. acknowledges grant support from CIHR.

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Authors and Affiliations

  1. McGill International TB Centre, McGill University, 1020 Pine Avenue West, Montréal, Québec H3A 1A2, Québec, Canada

    Madhukar Pai, Marcel A. Behr, Maziar Divangahi & Dick Menzies

  2. Manipal McGill Center for Infectious Diseases, Manipal University, Manipal, India

    Madhukar Pai

  3. Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

    David Dowdy

  4. Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Keertan Dheda

  5. Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland

    Catharina C. Boehme

  6. Aeras, Rockville, Maryland, USA

    Ann Ginsberg

  7. Indian Council of Medical Research, New Delhi, India

    Soumya Swaminathan

  8. Global Alliance for TB Drug Development, New York, New York, USA

    Melvin Spigelman

  9. Global TB Programme, WHO, Geneva, Switzerland

    Haileyesus Getahun & Mario Raviglione

Authors
  1. Madhukar Pai
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  2. Marcel A. Behr
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  3. David Dowdy
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  4. Keertan Dheda
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  5. Maziar Divangahi
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  6. Catharina C. Boehme
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  7. Ann Ginsberg
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  8. Soumya Swaminathan
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  9. Melvin Spigelman
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  10. Haileyesus Getahun
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  11. Dick Menzies
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  12. Mario Raviglione
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Contributions

Introduction (M.P.); Epidemiology (D.D.); Mechanisms/pathophysiology (M.A.B. and M.D.); Diagnosis, screening and prevention (M.P., C.C.B., M.A.B. and A.G.); Management (D.M., M.S., K.D., H.G. and S.S.); Quality of life (M.P., K.D. and M.R.), Outlook (M.R.); Overview of Primer (M.P.). M.P. and M.A.B. contributed equally to this work.

Corresponding author

Correspondence to Madhukar Pai.

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Competing interests

M.P. declares no financial conflicts. He serves as a consultant for the Bill & Melinda Gates Foundation, and on advisory committees of Foundation for Innovative New Diagnostics (FIND) and TB Alliance. M.A.B. receives royalties for an antigen used in one of the IGRA tests (QuantiFERON) but did not contribute to this section of the document. He serves on the Vaccine Advisory Committee for Aeras. K.D. has obtained speaker fees at industry-sponsored symposia and grants from FIND, eNose Company, Statens Serum Institut and bioMeriux, and grants and personal fees from ALERE, Oxford Immunotec, Cellestis (now Qiagen), Cepheid, Antrum Biotec and Hain Lifescience. In addition, K.D. has a patent Characterisation of novel tuberculosis specific urinary biomarkers pending, a patent A smart mask for monitoring cough-related infectious diseases pending and a patent Device for diagnosing EPTB issued. C.C.B. is employed by FIND, a not-for-profit organization driving the development and delivery of new diagnostics for tuberculosis (TB). FIND has contractual relationships with >20 in vitro diagnostic companies, several of which are mentioned in the article. M.R. declares no financial conflicts. He serves as observer on the Board of Directors of the TB Alliance and as External Clinical Research Expert for the US National Institute of Allergy and Infectious Diseases (NIAID) HIV/AIDS Clinical Trials Network Strategic Working Group, NIH. All other authors declare no competing interests.

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Pai, M., Behr, M., Dowdy, D. et al. Tuberculosis. Nat Rev Dis Primers 2, 16076 (2016). https://doi.org/10.1038/nrdp.2016.76

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