Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

doi:10.1183/13993003.01245-2015

Review

. 2015 Dec;46(6):1563-76.

doi: 10.1183/13993003.01245-2015. Epub 2015 Sep 24.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Haileyesus Getahun¹, Alberto Matteelli², Ibrahim Abubakar³, Mohamed Abdel Aziz⁴, Annabel Baddeley², Draurio Barreira⁵, Saskia Den Boon⁶, Susana Marta Borroto Gutierrez⁷, Judith Bruchfeld⁸, Erlina Burhan⁹, Solange Cavalcante¹⁰, Rolando Cedillos¹¹, Richard Chaisson¹², Cynthia Bin-Eng Chee¹³, Lucy Chesire¹⁴, Elizabeth Corbett¹⁵, Masoud Dara¹⁶, Justin Denholm¹⁷, Gerard de Vries¹⁸, Dennis Falzon², Nathan Ford¹⁹, Margaret Gale-Rowe²⁰, Chris Gilpin², Enrico Girardi²¹, Un-Yeong Go²², Darshini Govindasamy²³, Alison D Grant²⁴, Malgorzata Grzemska², Ross Harris²⁵, C Robert Horsburgh Jr²⁶, Asker Ismayilov²⁷, Ernesto Jaramillo², Sandra Kik²⁸, Katharina Kranzer²⁴, Christian Lienhardt², Philip LoBue²⁹, Knut Lönnroth³⁰, Guy Marks³¹, Dick Menzies²⁸, Giovanni Battista Migliori³², Davide Mosca³³, Ya Diul Mukadi³⁴, Alwyn Mwinga³⁵, Lisa Nelson¹⁹, Nobuyuki Nishikiori³⁶, Anouk Oordt-Speets³⁷, Molebogeng Xheedha Rangaka³⁸, Andreas Reis³⁹, Lisa Rotz²⁹, Andreas Sandgren⁴⁰, Monica Sañé Schepisi²¹, Holger J Schünemann⁴¹, Surender Kumar Sharma³⁹, Giovanni Sotgiu⁴⁰, Helen R Stagg⁴², Timothy R Sterling⁴³, Tamara Tayeb⁴⁴, Mukund Uplekar², Marieke J van der Werf⁴⁰, Wim Vandevelde⁴⁵, Femke van Kessel³⁷, Anna van't Hoog⁴⁶, Jay K Varma²⁹, Natalia Vezhnina⁴⁷, Constantia Voniatis⁴⁸, Marije Vonk Noordegraaf-Schouten³⁷, Diana Weil², Karin Weyer², Robert John Wilkinson⁴⁹, Takashi Yoshiyama⁵⁰, Jean Pierre Zellweger⁵¹, Mario Raviglione²

Affiliations

¹ The Global TB Programme, World Health Organization, Geneva, Switzerland getahunh@who.int.
² The Global TB Programme, World Health Organization, Geneva, Switzerland.
³ Dept of Infection and Population Health, University College London, London, UK Public Health England, London, UK.
⁴ World Health Organization, Regional Office for Eastern Mediterranean, Egypt.
⁵ National TB Programme, Ministry of Health, Brasilia, Brazil.
⁶ Independent consultant, Switzerland.
⁷ Pedro Kourí Institute of Tropical Medicine, La Habana, Cuba.
⁸ Unit of Infectious Diseases, Dept of Medicine, Karolinska Institute Solna and Karolinska University Hospital, Stockholm, Sweden.
⁹ Dept of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Indonesia and Persahabatan Hospital, Jakarta, Indonesia.
¹⁰ Evandro Chagas National Institute of Infectious Diseases, FIOCRUZ, Rio de Janeiro, Brazil.
¹¹ Hospital Nacionale Rosales, San Salvador, El Salvador.
¹² Center for TB Research, John Hopkins University, Baltimore, MD, USA.
¹³ Tan Tock Seng Hospital, Singapore.
¹⁴ TB Advocacy Consortium, Nairobi, Kenya.
¹⁵ London School of Hygiene and Tropical Medicine, Blantyre, Malawi.
¹⁶ World Health Organization, Regional Office for Europe, Denmark.
¹⁷ Victorian Tuberculosis Program, Melbourne, Australia.
¹⁸ KNCV Tuberculosis Foundation, Den Haag, The Netherlands.
¹⁹ Dept of HIV and Global Hepatitis Programme, World Health Organization, Switzerland.
²⁰ Public Health Agency of Canada, Ottawa, ON, Canada.
²¹ Istituto Nazionale Malattie Infettive L. Spallanzani, Rome, Italy.
²² Dept of HIV/AIDS and TB Control Korea, Korea Centers for Disease Control and Prevention, Republic of Korea.
²³ Health Systems Research Unit, South African Medical Research Council, South Africa.
²⁴ Dept of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.
²⁵ Public Health England, London, UK.
²⁶ Dept of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
²⁷ Main Medical Department, Ministry of Justice, Azerbaijan.
²⁸ McGill International TB Centre, and Dept of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
²⁹ Centers for Disease Control and Prevention, USA.
³⁰ The Global TB Programme, World Health Organization, Geneva, Switzerland Dept of Public Health Sciences, Karolinska Institute, Solna, Sweden.
³¹ Woolcock Institute of Medical Research University of Sydney and UNSW Australia, Sydney, Australia.
³² WHO Collaborating Center for TB and Lung Diseases Fondazione S. Maugeri, Tradate, Italy.
³³ Migration Health Department, International Organization of Migration, Geneva, Switzerland.
³⁴ Infectious Disease Division, Bureau for Global Health, US Agency for International Development, Washington, DC, USA.
³⁵ Zambart Project, Lusaka, Zambia.
³⁶ World Health Organization, Regional Office for the Western Pacific, Philippines.
³⁷ Pallas Health Research and Consultancy BV, Rotterdam, The Netherlands.
³⁸ Dept of Infection and Population Health, University College London, London, UK Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
³⁹ Knowledge, Ethics and Research Department, World Health Organization, Switzerland.
⁴⁰ European Centre for Disease Prevention and Control, Stockholm, Sweden.
⁴¹ Dept of Clinical Epidemiology and Biostatistics and Dept of Medicine, GRADE Center, McMaster University, Hamilton, ON, Canada.
⁴² Dept of Infection and Population Health, University College London, London, UK.
⁴³ Vanderbilt University School of Medicine, Nashville, TN, USA.
⁴⁴ National TB Programme, Ministry of Health, Riyadh, Saudi Arabia.
⁴⁵ European AIDS Treatment Group, Brussels, Belgium.
⁴⁶ Academic Medical Centre, University of Amsterdam, Dept of Global Health, Amsterdam, The Netherlands.
⁴⁷ HIV/TB and Penal System Projects, Russian Federation.
⁴⁸ Clinical Laboratories, Ministry of Health, Nicosia, Cyprus.
⁴⁹ Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa Francis Crick Institute Mill Hill Laboratory, Dept of Medicine, Imperial College London, London, UK.
⁵⁰ Fukujuji Hospital, Japan Anti Tuberculosis Association, Tokyo, Japan.
⁵¹ Tuberculosis Competence Centre, Berne, Switzerland.

PMID: 26405286
PMCID: PMC4664608
DOI: 10.1183/13993003.01245-2015

Review

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Haileyesus Getahun et al. Eur Respir J. 2015 Dec.

. 2015 Dec;46(6):1563-76.

doi: 10.1183/13993003.01245-2015. Epub 2015 Sep 24.

Authors

Affiliations

¹ The Global TB Programme, World Health Organization, Geneva, Switzerland getahunh@who.int.
² The Global TB Programme, World Health Organization, Geneva, Switzerland.
³ Dept of Infection and Population Health, University College London, London, UK Public Health England, London, UK.
⁴ World Health Organization, Regional Office for Eastern Mediterranean, Egypt.
⁵ National TB Programme, Ministry of Health, Brasilia, Brazil.
⁶ Independent consultant, Switzerland.
⁷ Pedro Kourí Institute of Tropical Medicine, La Habana, Cuba.
⁸ Unit of Infectious Diseases, Dept of Medicine, Karolinska Institute Solna and Karolinska University Hospital, Stockholm, Sweden.
⁹ Dept of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Indonesia and Persahabatan Hospital, Jakarta, Indonesia.
¹⁰ Evandro Chagas National Institute of Infectious Diseases, FIOCRUZ, Rio de Janeiro, Brazil.
¹¹ Hospital Nacionale Rosales, San Salvador, El Salvador.
¹² Center for TB Research, John Hopkins University, Baltimore, MD, USA.
¹³ Tan Tock Seng Hospital, Singapore.
¹⁴ TB Advocacy Consortium, Nairobi, Kenya.
¹⁵ London School of Hygiene and Tropical Medicine, Blantyre, Malawi.
¹⁶ World Health Organization, Regional Office for Europe, Denmark.
¹⁷ Victorian Tuberculosis Program, Melbourne, Australia.
¹⁸ KNCV Tuberculosis Foundation, Den Haag, The Netherlands.
¹⁹ Dept of HIV and Global Hepatitis Programme, World Health Organization, Switzerland.
²⁰ Public Health Agency of Canada, Ottawa, ON, Canada.
²¹ Istituto Nazionale Malattie Infettive L. Spallanzani, Rome, Italy.
²² Dept of HIV/AIDS and TB Control Korea, Korea Centers for Disease Control and Prevention, Republic of Korea.
²³ Health Systems Research Unit, South African Medical Research Council, South Africa.
²⁴ Dept of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.
²⁵ Public Health England, London, UK.
²⁶ Dept of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
²⁷ Main Medical Department, Ministry of Justice, Azerbaijan.
²⁸ McGill International TB Centre, and Dept of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
²⁹ Centers for Disease Control and Prevention, USA.
³⁰ The Global TB Programme, World Health Organization, Geneva, Switzerland Dept of Public Health Sciences, Karolinska Institute, Solna, Sweden.
³¹ Woolcock Institute of Medical Research University of Sydney and UNSW Australia, Sydney, Australia.
³² WHO Collaborating Center for TB and Lung Diseases Fondazione S. Maugeri, Tradate, Italy.
³³ Migration Health Department, International Organization of Migration, Geneva, Switzerland.
³⁴ Infectious Disease Division, Bureau for Global Health, US Agency for International Development, Washington, DC, USA.
³⁵ Zambart Project, Lusaka, Zambia.
³⁶ World Health Organization, Regional Office for the Western Pacific, Philippines.
³⁷ Pallas Health Research and Consultancy BV, Rotterdam, The Netherlands.
³⁸ Dept of Infection and Population Health, University College London, London, UK Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
³⁹ Knowledge, Ethics and Research Department, World Health Organization, Switzerland.
⁴⁰ European Centre for Disease Prevention and Control, Stockholm, Sweden.
⁴¹ Dept of Clinical Epidemiology and Biostatistics and Dept of Medicine, GRADE Center, McMaster University, Hamilton, ON, Canada.
⁴² Dept of Infection and Population Health, University College London, London, UK.
⁴³ Vanderbilt University School of Medicine, Nashville, TN, USA.
⁴⁴ National TB Programme, Ministry of Health, Riyadh, Saudi Arabia.
⁴⁵ European AIDS Treatment Group, Brussels, Belgium.
⁴⁶ Academic Medical Centre, University of Amsterdam, Dept of Global Health, Amsterdam, The Netherlands.
⁴⁷ HIV/TB and Penal System Projects, Russian Federation.
⁴⁸ Clinical Laboratories, Ministry of Health, Nicosia, Cyprus.
⁴⁹ Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa Francis Crick Institute Mill Hill Laboratory, Dept of Medicine, Imperial College London, London, UK.
⁵⁰ Fukujuji Hospital, Japan Anti Tuberculosis Association, Tokyo, Japan.
⁵¹ Tuberculosis Competence Centre, Berne, Switzerland.

PMID: 26405286
PMCID: PMC4664608
DOI: 10.1183/13993003.01245-2015

Abstract

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.

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Conflict of interest statement

Conflict of interest: Disclosures can be found alongside the online version of this article at erj.ersjournals.com

Figures

**FIGURE 1**
Schematic approach for programmatic management of latent tuberculosis infection (LTBI). TB: tuberculosis.

See this image and copyright information in PMC

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References

1. World Health Organization. Guidelines on the Management of Latent Tuberculosis Infection. Geneva, World Health Organization, 2015. - PubMed
1. Mack U, Migliori GB, Sester M, et al. . LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J 2009; 33: 956–973. - PubMed
1. Getahun H, Matteelli A, Chaisson RE, et al. . Latent Mycobacterium tuberculosis infection. N Engl J Med 2015; 372: 2127–2135. - PubMed
1. Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974; 99: 131–138. - PubMed
1. Lobue P, Menzies D. Treatment of latent tuberculosis infection: an update. Respirology 2010; 15: 603–622. - PubMed

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[1] World Health Organization. Guidelines on the Management of Latent Tuberculosis Infection. Geneva, World Health Organization, 2015. - PubMed

[2] World Health Organization. Guidelines on the Management of Latent Tuberculosis Infection. Geneva, World Health Organization, 2015. - PubMed

[3] Mack U, Migliori GB, Sester M, et al. . LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J 2009; 33: 956–973. - PubMed

[4] Mack U, Migliori GB, Sester M, et al. . LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J 2009; 33: 956–973. - PubMed

[5] Getahun H, Matteelli A, Chaisson RE, et al. . Latent Mycobacterium tuberculosis infection. N Engl J Med 2015; 372: 2127–2135. - PubMed

[6] Getahun H, Matteelli A, Chaisson RE, et al. . Latent Mycobacterium tuberculosis infection. N Engl J Med 2015; 372: 2127–2135. - PubMed

[7] Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974; 99: 131–138. - PubMed

[8] Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 1974; 99: 131–138. - PubMed

[9] Lobue P, Menzies D. Treatment of latent tuberculosis infection: an update. Respirology 2010; 15: 603–622. - PubMed

[10] Lobue P, Menzies D. Treatment of latent tuberculosis infection: an update. Respirology 2010; 15: 603–622. - PubMed

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Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

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Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

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