Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography

Nature Medicine volume 22, pages 1090–1093 (2016)Cite this article

Subjects

Abstract

Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers that are predictive of progression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Radiological and clinical findings in participants with evidence of subclinical pathology (infiltrates, scars or active nodules).
Figure 2: Radiological findings in participants with discrete nodules.

Similar content being viewed by others

References

  1. Rangaka, M.X. et al. Lancet Infect. Dis. 12, 45–55 (2012).

    Article  CAS  Google Scholar 

  2. Barry, C.E. III et al. Nat. Rev. Microbiol. 7, 845–855 (2009).

    Article  CAS  Google Scholar 

  3. Opie, E.L. J. Exp. Med. 25, 855–876 (1917).

    Article  CAS  Google Scholar 

  4. Golub, J.E., Mohan, C.I., Comstock, G.W. & Chaisson, R.E. Int. J. Tuberc. Lung Dis. 9, 1183–1203 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Corbett, E.L. & MacPherson, P. Int. J. Tuberc. Lung Dis. 17, 1125–1138 (2013).

    Article  CAS  Google Scholar 

  6. Koppaka, R. & Bock, N. in Toman's Tuberculosis Case Detection, Treatment and Monitoring: Questions and Answers (ed. T. Frieden) 51–60 (World Health Organization, Geneva, 2004).

  7. Oni, T. et al. Thorax 66, 669–673 (2011).

    Article  Google Scholar 

  8. Mamede, M. et al. Neoplasia 7, 369–379 (2005).

    Article  CAS  Google Scholar 

  9. Coleman, M.T. et al. Infect. Immun. 82, 2400–2404 (2014).

    Article  Google Scholar 

  10. Rybicki, B.A. & Iannuzzi, M.C. Semin. Respir. Crit. Care Med. 28, 22–35 (2007).

    Article  Google Scholar 

  11. Craven, S.A. & Benatar, S.R. S. Afr. Med. J. 55, 89–92 (1979).

    CAS  PubMed  Google Scholar 

  12. Steinbrück, P., Dănkovã, D., Edwards, L.B., Doster, B. & Livesay, V.T. Bull. Int. Union Tuberc. 47, 135–159 (1972).

    PubMed  Google Scholar 

  13. Stead, W.W. N. Engl. J. Med. 277, 1008–1012 (1967).

    Article  CAS  Google Scholar 

  14. Ghesani, N., Patrawalla, A., Lardizabal, A., Salgame, P. & Fennelly, K.P. Am. J. Respir. Crit. Care Med. 189, 748–750 (2014).

    Article  Google Scholar 

  15. Hunter, R.L. Tuberculosis (Edinb.) 91, 497–509 (2011).

    Article  Google Scholar 

  16. Dowdy, D.W., Basu, S. & Andrews, J.R. Am. J. Respir. Crit. Care Med. 187, 543–551 (2013).

    Article  Google Scholar 

  17. Tramontana, J.M. et al. Mol. Med. 1, 384–397 (1995).

    Article  CAS  Google Scholar 

  18. Kranzer, K. et al. Int. J. Tuberc. Lung Dis. 17, 432–446 (2013).

    Article  CAS  Google Scholar 

  19. Zak, D.E. et al. Lancet 387, 2312–2322 (2016).

    Article  CAS  Google Scholar 

  20. Samandari, T. et al. Lancet 377, 1588–1598 (2011).

    Article  CAS  Google Scholar 

  21. Centers for Disease Control and Prevention. Tuberculosis component of technical instructions for the medical examination of aliens in the United States. (US Department of Health and Human Services, Atlanta, Georgia, USA, 2008).

  22. Medlar, E.M. Am. Rev. Tuberc. 58, 583–611 (1948).

    CAS  PubMed  Google Scholar 

  23. Ghon, A. The Primary Lung Focus of Tuberculosis in Children (Paul B. Hoeber, New York, 1916).

Download references

Acknowledgements

This work was funded by the Wellcome Trust (grant no. 090170 (H.E.) and 104803 (R.J.W.)), the Bill and Melinda Gates Foundation–Wellcome Trust Grand challenges in Global Health (grant no. 37822; D.B.Y.), the US National Institutes of Health (NIH) (grant no. R01 HL106804; J.L.F.) and the intramural research program of the NIH–NIAID (C.E.B.). R.J.W. also received support from the European Union (grant no. FP& HEALTH F3-2012-305578), the National Research Foundation of South Africa (grant no. 96841), the Research Councils of the UK via the Francis Crick Institute (grant no. 10218 and U117565642) and the Medical Research Council of South Africa (Strategic Health Innovations partnership).

Author information

Authors and Affiliations

  1. Department of Medicine, Imperial College London, London, UK

    Hanif Esmail, Douglas B Young & Robert J Wilkinson

  2. Clinical Infectious Disease Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

    Hanif Esmail, Maia Lesosky, Katalin A Wilkinson, Anna K Coussens, Tolu Oni, Clifton E Barry III & Robert J Wilkinson

  3. Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    Hanif Esmail

  4. Francis Crick Institute Mill Hill Laboratory, London, UK

    Rachel P Lai, Katalin A Wilkinson, Christine M Graham, Douglas B Young, Anne O'Garra & Robert J Wilkinson

  5. Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa

    Maia Lesosky

  6. Department of Medical Imaging and Clinical Oncology, Stellenbosch University, Cape Town, South Africa

    James M Warwick

  7. Department of Radiology, Groote Schuur Hospital, Cape Town, South Africa

    Qonita Said-Hartley

  8. Department of Medicine, Stellenbosch University, Cape Town, South Africa

    Coenraad F Koegelenberg & Gerhard Walzl

  9. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

    Gerhard Walzl & Clifton E Barry III

  10. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    JoAnne L Flynn

  11. Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Clifton E Barry III

  12. Department of Pathology, University of Cape Town, Cape Town, South Africa

    Clifton E Barry III

  13. National Heart and Lung Institute, Imperial College London, London, UK

    Anne O'Garra

Authors
  1. Hanif Esmail
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel P Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maia Lesosky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katalin A Wilkinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christine M Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna K Coussens
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tolu Oni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. James M Warwick
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Qonita Said-Hartley
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Coenraad F Koegelenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gerhard Walzl
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. JoAnne L Flynn
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Douglas B Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Clifton E Barry III
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Anne O'Garra
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Robert J Wilkinson
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.E., A.O., C.E.B. and R.J.W. designed the study with input from K.A.W., D.B.Y. and J.L.F.; H.E., T.O. and Q.S.-H. screened participants for study entry; H.E., G.W. and C.F.K. collected samples and data, and provided clinical care for participants during follow-up; J.M.W. led the radiologists and nuclear medicine physicians who reported the [18F]FDG PET–CT scans; K.A.W. and H.E. processed samples; H.E., M.L. and R.P.L. analyzed data with advice and input from R.J.W., K.A.W., C.E.B., J.M.W., A.K.C., C.M.G., A.O. and J.L.F.; R.J.W. supervised data analysis; H.E. and R.J.W. wrote the manuscript, with early input from A.O., C.E.B., D.B.Y., M.L. and J.L.F., and subsequently all authors provided advice and approved the final manuscript.

Corresponding authors

Correspondence to Hanif Esmail or Robert J Wilkinson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 and Supplementary Table 1 (PDF 1878 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Esmail, H., Lai, R., Lesosky, M. et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nat Med 22, 1090–1093 (2016). https://doi.org/10.1038/nm.4161

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.4161

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research