Review

. 2024 Jun;12(6):484-498.

doi: 10.1016/S2213-2600(24)00028-6. Epub 2024 Mar 22.

Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise

Anna K Coussens¹, Syed M A Zaidi², Brian W Allwood³, Puneet K Dewan⁴, Glenda Gray⁵, Mikashmi Kohli⁶, Tamara Kredo⁵, Ben J Marais⁷, Guy B Marks⁸, Leo Martinez⁹, Morten Ruhwald⁶, Thomas J Scriba¹⁰, James A Seddon¹¹, Phumeza Tisile¹², Digby F Warner¹³, Robert J Wilkinson¹⁴, Hanif Esmail¹⁵, Rein M G J Houben¹⁶; International Consensus for Early TB (ICE-TB) group

Collaborators, Affiliations

Collaborators

International Consensus for Early TB (ICE-TB) group:
David Alland, Marcel A Behr, Busisiwe B Beko, Erlina Burhan, Gavin Churchyard, Frank Cobelens, Justin T Denholm, Ryan Dinkele, Jerrold J Ellner, Razia Fatima, Kate A Haigh, Mark Hatherill, Katherine C Horton, Emily A Kendall, Palwasha Y Khan, Peter MacPherson, Stephanus T Malherbe, Vidya Mave, Simon C Mendelsohn, Munyaradzi Musvosvi, Elisa Nemes, Adam Penn-Nicholson, Dharanidharan Ramamurthy, Molebogeng X Rangaka, Suvanand Sahu, Alvaro Schwalb, Divya K Shah, Dylan Sheerin, Donald Simon, Adrie J C Steyn, Nguyen Thu Anh, Gerhard Walzl, Charlotte L Weller, Caroline Ml Williams, Emily B Wong, Robin Wood, Yingda L Xie, Siyan Yi

Affiliations

¹ Infectious Diseases and Immune Defence Division, The Walter and Eliza Hall Institute of Medical Research (WEHI), Parkville, VIC, Australia; Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, and Department of Pathology, University of Cape Town, Cape Town, South Africa; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
² WHO Collaborating Centre on Tuberculosis Research and Innovation, Institute for Global Health, and MRC Clinical Trials Unit, University College London, London, UK; Department of Public Health, National University of Medical Sciences, Rawalpindi, Pakistan.
³ Division of Pulmonology, Department of Medicine, Stellenbosch University, Stellenbosch, South Africa.
⁴ Tuberculosis and HIV, Bill & Melinda Gates Foundation, Seattle, WA, USA.
⁵ Health Systems Research Unit, South Africa Medical Research Council, Cape Town, South Africa.
⁶ Health Programmes, FIND, Geneva, Switzerland.
⁷ Sydney Infectious Diseases Institute, University of Sydney, Sydney, NSW, Australia; WHO Collaborating Centre in Tuberculosis, University of Sydney, Sydney, NSW, Australia.
⁸ Department of Clinical Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁹ Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
¹⁰ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, and Department of Pathology, University of Cape Town, Cape Town, South Africa.
¹¹ Department of Infectious Disease, Imperial College London, London, UK; Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
¹² TB Proof, Cape Town, South Africa.
¹³ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, and Department of Pathology, University of Cape Town, Cape Town, South Africa.
¹⁴ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; Department of Infectious Disease, Imperial College London, London, UK; The Francis Crick Institute, London, UK.
¹⁵ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; WHO Collaborating Centre on Tuberculosis Research and Innovation, Institute for Global Health, and MRC Clinical Trials Unit, University College London, London, UK. Electronic address: h.esmail@ucl.ac.uk.
¹⁶ TB Modelling Group, TB Centre, and Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

PMID: 38527485
PMCID: PMC7616323
DOI: 10.1016/S2213-2600(24)00028-6

Review

Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise

Anna K Coussens et al. Lancet Respir Med. 2024 Jun.

. 2024 Jun;12(6):484-498.

doi: 10.1016/S2213-2600(24)00028-6. Epub 2024 Mar 22.

Authors

Collaborators

International Consensus for Early TB (ICE-TB) group:
David Alland, Marcel A Behr, Busisiwe B Beko, Erlina Burhan, Gavin Churchyard, Frank Cobelens, Justin T Denholm, Ryan Dinkele, Jerrold J Ellner, Razia Fatima, Kate A Haigh, Mark Hatherill, Katherine C Horton, Emily A Kendall, Palwasha Y Khan, Peter MacPherson, Stephanus T Malherbe, Vidya Mave, Simon C Mendelsohn, Munyaradzi Musvosvi, Elisa Nemes, Adam Penn-Nicholson, Dharanidharan Ramamurthy, Molebogeng X Rangaka, Suvanand Sahu, Alvaro Schwalb, Divya K Shah, Dylan Sheerin, Donald Simon, Adrie J C Steyn, Nguyen Thu Anh, Gerhard Walzl, Charlotte L Weller, Caroline Ml Williams, Emily B Wong, Robin Wood, Yingda L Xie, Siyan Yi

Affiliations

¹ Infectious Diseases and Immune Defence Division, The Walter and Eliza Hall Institute of Medical Research (WEHI), Parkville, VIC, Australia; Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, and Department of Pathology, University of Cape Town, Cape Town, South Africa; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
² WHO Collaborating Centre on Tuberculosis Research and Innovation, Institute for Global Health, and MRC Clinical Trials Unit, University College London, London, UK; Department of Public Health, National University of Medical Sciences, Rawalpindi, Pakistan.
³ Division of Pulmonology, Department of Medicine, Stellenbosch University, Stellenbosch, South Africa.
⁴ Tuberculosis and HIV, Bill & Melinda Gates Foundation, Seattle, WA, USA.
⁵ Health Systems Research Unit, South Africa Medical Research Council, Cape Town, South Africa.
⁶ Health Programmes, FIND, Geneva, Switzerland.
⁷ Sydney Infectious Diseases Institute, University of Sydney, Sydney, NSW, Australia; WHO Collaborating Centre in Tuberculosis, University of Sydney, Sydney, NSW, Australia.
⁸ Department of Clinical Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁹ Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
¹⁰ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; South African Tuberculosis Vaccine Initiative, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, and Department of Pathology, University of Cape Town, Cape Town, South Africa.
¹¹ Department of Infectious Disease, Imperial College London, London, UK; Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
¹² TB Proof, Cape Town, South Africa.
¹³ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, and Department of Pathology, University of Cape Town, Cape Town, South Africa.
¹⁴ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; Department of Infectious Disease, Imperial College London, London, UK; The Francis Crick Institute, London, UK.
¹⁵ Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa; WHO Collaborating Centre on Tuberculosis Research and Innovation, Institute for Global Health, and MRC Clinical Trials Unit, University College London, London, UK. Electronic address: h.esmail@ucl.ac.uk.
¹⁶ TB Modelling Group, TB Centre, and Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

PMID: 38527485
PMCID: PMC7616323
DOI: 10.1016/S2213-2600(24)00028-6

Abstract

The current active-latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.

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Conflict of interest statement

Declaration of interests AKC reports a grant (GNT2020750) from the Australian National Health and Medical Research Council. SMAZ reports personal support from the Commonwealth Scholarship Commission studentship. BWA reports funding for research, including salaries for group members, from the German Federal Ministry for Research and Education (BMBF). LM reports grant funding from the US National Institutes of Health (NIH). DFW reports grants to his institution from NIH, the US National Institute of Allergy and Infectious Diseases, the South African Medical Research Council, the Bill & Melinda Gates Foundation, and the Research Council of Norway. RJW reports a grant to his institution from Wellcome. HE reports a grant (MR/V00476X/1) from the UK Medical Research Council and participation on a data safety monitoring board for the StatinTB trial. RMGJH reports a European Research Council Starting Grant (action number 757699). PKD, GG, MK, TK, BJM, GBM, MR, TJS, JAS, and PT declare no competing interests.

Figures

**Figure 1. a-b: Meeting process (a) and delegate overview (b)**

**Figure 2**
a-b: Overview of Delphi consensus process and participantsFigure 2a-b: Conceptual Mtb infection and TB states identified with consideration of benefit resulting from diagnosis and treatment (2a) and pathways across infection and disease states (2b). Pathology = macroscopic pathology, Infectious = ability to cause new Mtb infections, Symptoms & Signs = TB symptoms and signs, Self-cleared = absence of viable Mtb after Mtb infection, never crossed disease threshold and not received treatment, Infected = persistence of Mtb infection, including after antibiotic or self cure from disease, remains at risk of developing disease. Full recovery = Both disease and infection fully resolved without post-TB impairment, with or without treatment, Post-TB = disease or disability due to damage caused by TB pathology after microbiological or self-cure. Figure created with Biorender.com

See this image and copyright information in PMC

References

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Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise

Collaborators

Affiliations

Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical