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Reducing the global burden of tuberculosis: the contribution of improved diagnostics

Nature volume 444, pages 4957 | Download Citation


We estimated the impact of hypothetical new diagnostic tests for tuberculosis (TB) in patients with persistent cough in developing countries. We found that a variety of new tests could help better identify TB cases and target treatment, thereby reducing the burden of disease.

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  1. 1.

    , , , & Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 282, 677–686 (1999).

  2. 2.

    & Modeling the impact of global tuberculosis control strategies. Proc. Natl Acad. Sci. USA 95, 13881–13886 (1998).

  3. 3.

    World Health Organization. Global Tuberculosis Control: Surveillance, Planning, Financing (WHO, Geneva, 2006).

  4. 4.

    World Health Organization. Toman's Tuberculosis. Case Detection, Treatment and Monitoring. 2nd edn (WHO, Geneva, 2003).

  5. 5.

    , , & Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Directly observed short-course therapy. Lancet 352, 1886–1891 (1998).

  6. 6.

    , & Interventions to reduce tuberculosis mortality and transmission in low- and middle-income countries. Bull. World Health Organ. 80, 217–227 (2002).

  7. 7.

    World Health Organization. Stop TB Partnership and World Health Organization. Global Plan to Stop TB (WHO, Geneva, 2006).

  8. 8.

    et al. 'Lost' smear-positive pulmonary tuberculosis cases: where are they and why did we lose them? Int. J. Tuberc. Lung Dis. 9, 25–31 (2005).

  9. 9.

    et al. Evaluation of new external quality assessment guidelines involving random blinded rechecking of acid-fast bacilli smears in a pilot project setting in Mexico. Int. J. Tuberc. Lung Dis. 9, 301–305 (2005).

  10. 10.

    et al. Care seeking behaviour and diagnostic processes in patients with smear-positive pulmonary tuberculosis in Malawi. Int. J. Tuberc. Lung Dis. 4, 327–332 (2000).

  11. 11.

    et al. Under-diagnosis of smear-positive pulmonary tuberculosis in Nairobi, Kenya. Int. J. Tuberc. Lung Dis. 5, 360–363 (2001).

  12. 12.

    , & Global survey of tuberculosis laboratory services. Int. J. Tuberc. Lung Dis. 8, S178 (2004).

  13. 13.

    World Health Organization. Treatment of Tuberculosis: Guidelines for National Programmes, 1–108 (WHO, Geneva, 2003).

  14. 14.

    et al. Useful clues to the presence of smear-negative pulmonary tuberculosis in a West African city. Int. J. Tuberc. Lung Dis. 6, 592–598 (2002).

  15. 15.

    & The utility of an antibiotic trial for diagnosis of AFB-negative tuberculosis. Int. J. Tuberc. Lung Dis. 7, 198 (2003).

  16. 16.

    , & Non-response to antibiotics predicts tuberculosis in AFB-smear-negative TB suspects, Botswana, 1997–1999. Int. J. Tuberc. Lung Dis. 5, S126 (2001).

  17. 17.

    et al. Trial-of-antibiotic algorithm for the diagnosis of tuberculosis in a district hospital in a developing country with high HIV prevalence. Int. J. Tuberc. Lung Dis. 4, 513–518 (2000).

  18. 18.

    et al. Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet 353, 444–449 (1999).

  19. 19.

    et al. Reducing the Global Burden of Tuberculosis: The Contribution of Improved Diagnosis. WR-422-HLTH (RAND Corporation, Santa Monica, 2006).

  20. 20.

    et al. Developing and interpreting models to improve diagnostics in developing countries. Nature S1, 3–8 (2006).

  21. 21.

    World Health Organization. Global Tuberculosis Control: Surveillance, Planning, Financing (WHO, Geneva, 2005).

  22. 22.

    et al. Completeness and timeliness of treatment initiation after laboratory diagnosis of tuberculosis in Gaborone, Botswana. Int. J. Tuberc. Lung Dis. 4, 956–961 (2000).

  23. 23.

    , , & Registration and treatment of patients with smear-positive pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 2, 944–945 (1998).

  24. 24.

    World Health Organization. Respiratory Care in Primary Care Services: A Survey in 9 Countries (WHO, Geneva, 2004).

  25. 25.

    et al. The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model. AIDS 20, 751–762 (2006).

  26. 26.

    & in Disease Control Priorities in Developing Countries. 2nd edn (eds Jamison, D.T. et al.) 289–309 (National Institutes of Health, Bethesda, Maryland, 2006).

  27. 27.

    et al. Screening pulmonary tuberculosis suspects in Malawi: testing different strategies. Trans. R. Soc. Trop. Med. Hyg. 91, 416–419 (1997).

  28. 28.

    et al. A comprehensive study of the efficiency of the routine pulmonary tuberculosis diagnostic process in Nairobi. Int. J. Tuberc. Lung Dis. 7, 186–189 (2003).

  29. 29.

    et al. Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence setting in Ethiopia: clinical, diagnostic and epidemiological characteristics. Scand. J. Infect. Dis. 34, 331–337 (2002).

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The authors thank M. Weinstein (Harvard School of Public Health, Massachusetts, USA) and M. Zignol (World Health Organization, Geneva, Switzerland) for their comments on an earlier draft of this paper.

Author information


  1. RAND Corporation, 1776 Main Street, PO Box 2138, Santa Monica, California 90407-2138, USA

    • Emmett Keeler
    • , Julia E. Aledort
    • , Lee Hillborne
    • , Maria E. Rafael
    •  & Federico Girosi
  2. Foundation for Innovative New Diagnostics, 71 Avenue Louis Casai, PO Box 93, 1216 Cointrin, Switzerland

    • Mark D. Perkins
  3. Bill & Melinda Gates Foundation, PO Box 23350, Seattle, Washington 98102, USA

    • Peter Small
  4. United States Agency for International Development, 1300 Pennsylvania Avenue North West, Washington DC 20523, USA

    • Christy Hanson
  5. Infectious Disease Research Institute, 1124 Columbia Street, Seattle, Washington 98104, USA

    • Steven Reed
  6. World Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland

    • Jane Cunningham
    •  & Christopher Dye


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Correspondence to Emmett Keeler.

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