Acknowledgements

The recommendations and remarks in the current module on the treatment of drug-resistant tuberculosis (DR-TB) are the result of collaborative efforts of professionals from a range of specialties who have extensive expertise and experience in public health policy, tuberculosis (TB) programme management, and the care and management of patients with DR-TB and multidrug-resistant TB (MDR-TB). The recommendations herein have been developed through several meetings of the Guideline Development Group (GDG) and have then been consolidated in the present module. The World Health Organization (WHO) acknowledges and is grateful for the time and support of all individuals who have contributed to these efforts.

The production and writing of this document – WHO consolidated guidelines on tuberculosis. Module 4: Treatment – drug-resistant tuberculosis treatment, 2022 update – was coordinated by Fuad Mirzayev, with the support of Medea Gegia, Linh Nguyen and Samuel Schumacher, under the guidance of Matteo Zignol and the overall direction of Tereza Kasaeva, Director of the WHO Global Tuberculosis Programme (WHO/GTB). WHO/GTB gratefully acknowledges the contribution of all experts involved in the production of these guidelines.

Recommendations for treatment of drug-resistant tuberculosis, 2022 update

Guideline Development Group

The chairs of the GDG were Holger J. Schünemann (Chair, Grading of Recommendations Assessment, Development and Evaluation [GRADE] methodologist: Cochrane Canada & McMaster University, Canada) and Jeremiah Muhwa Chakaya (technical expert, national TB programme [NTP], Kenya).

The following experts served as members of the GDG: Denise Arakaki (NTP, end user, clinician: Ministry of Health MDR-TB referral centre, Brazil); Padmapriyadarsini Chandrasekaran (researcher, end user: National Institute for Research in Tuberculosis, India); Daniela Maria Cirillo (laboratory specialist: San Raffaele Scientific Institute, Supranational TB Reference Laboratory, Italy); Charles Daley (pulmonologist, MDR-TB expert: National Jewish Health Hospital, United States of America [USA]); Gerry Davies (trials expert, pharmacologist: University of Liverpool, United Kingdom of Great Britain and Northern Ireland [United Kingdom]); Amita Gupta (scientist, maternal health medicine: Johns Hopkins University, USA); Elmira Gurbanova (Regional Green Light Committee [rGLC] member, clinician, end user: Lung Clinic, University of Tartu, Estonia); Anneke Hesseling (paediatrician, end user: Stellenbosch University, South Africa); Christoph Lange (clinician, researcher, end user: Research Center Borstel, Germany); Christian Lienhardt (researcher, end user: French Institute for Research on Sustainable Development, France); Leslie Christine Magsayo-Salon (NTP, clinician [TB/HIV], end user: NTP, Northern Mindanao Medical Center, the Philippines); Guy Marks (clinician, researcher: International Union Against Tuberculosis and Lung Disease); Graeme Meintjes (researcher, end user: University of Capetown, South Africa); Asif Mujtaba (clinician, end user: Asgar Ali Hospital, Bangladesh); Mahshid Nasehi (NTP, end user: NTP of Iran, Islamic Republic of Iran); Nguyen Viet Nhung (NTP, end user: NTP, Ministry of Health, Viet Nam); Andrew Nunn (researcher, end user: University College London, United Kingdom); Ingrid Schoeman (former MDR-TB patient: TB PROOF, South Africa); Sabira Tahseen (laboratory manager, NTP, end user: National TB Control Programme, Pakistan); Ye Tun (clinician, end user: Thingankyun General Hospital, University of Medicine, Myanmar); Debrah Vambe (NTP, end user: NTP, Eswatini); Andrew Vernon (trials expert, technical agency, end user: US Centers for Disease Control and Prevention [US CDC], USA); Paran Winarni (civil society representative: TB Civil Society Task Force, Indonesia Youth Movement Against TB, Indonesia) and Yanlin Zhao (NTP, end user: National Tuberculosis Control and Prevention Center, Chinese Center for Disease Control [China CDC], China).

External Review Group

We thank the External Review Group (ERG), which had the following members: Giovanni Battista Migliori (WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy); Anuj K. Bhatnagar clinician, researcher: Rajan Babu Institute for Pulmonary Medicine and Tuberculosis, India); Lisa Chen (clinician, academic: UCSF Curry International Tuberculosis Center, USA); Edwin H. Herrera-Flores (clinician, end user: Hospital Nacional MDR-TB Referral Centre, Arzobispo Loayza, Peru); Ivan Solovic (NTP, clinician, end user: National Institute for TB, Lung Diseases and Thoracic Surgery, Slovakia); Rafael Laniado (clinician, end user: NTP, Mexico); Anna Cristina C. Carvalho (clinician, researcher: Fiocruz Institute, Brazil) and Philipp du Cros (clinician, researcher: Burnet Institute, Australia).

Evidence reviewers

WHO would also like to acknowledge the work conducted by the following evidence reviewers: Greg Fox, Tasnim Hasan, Ellie Medcalf, Hannah Morgan and Timothy Schlubb from The University of Sydney, and Claudia Denkinger and Ioana Olaru from Heidelberg University.

Observers and external partners

Draurio Barreira Cravo Neto (technical manager, TB: Unitaid, Switzerland); Michael Campbell (senior director, Tuberculosis: Clinton Health Access Initiative, Inc.); Abdul Ghafoor (advisor MDR-TB: Ministry of National Health Services Regulations & Coordination, Pakistan); Mustapha Gidado (executive director: KNCV TB Foundation, Netherlands); Brian Kaiser (technical officer: Stop TB Partnership’s Global Drug Facility, Switzerland); YaDiul Mukadi (technical advisor: United States Agency for International Development [USAID], USA); Payam Nahid (Director: UCSF Center for Tuberculosis, University of California San Francisco); Fraser Wares (senior consultant: KNCV TB Foundation); Wojtek Wiercioch (GRADE methodologist: McMaster University, Canada) and Mohammed Yassin (senior disease advisor, TB: The Global Fund to Fight AIDS, Tuberculosis and Malaria [Global Fund], Switzerland).

WHO Guideline Steering Committee

The following staff served as the WHO Steering Committee for the development of the current policy guideline: Fuad Mirzayev (lead), Annabel Baddeley, Dennis Falzon, Medea Gegia, Nazir Ismail, Linh Nguyen, Samuel Schumacher, Sabine Verkuijl, Kerri Viney and Matteo Zignol from the WHO/GTB; Askar Yedilbayev from the WHO Regional Office for Europe; Corinne Simone Collette Merle from the WHO Special Programme for Research and Training in Tropical Diseases; Lorenzo Moja from the WHO Medicines Selection, Intellectual Property and Affordability / Essential Medicines; Andreas Alois Reis from WHO Health Ethics and Governance; and Olufunmilayo Lesi and Marco Vittoria from the WHO Global HIV, Hepatitis and Sexually Transmitted Infections Programmes / Treatment, Care and Service Delivery.

Funding

This update was funded by grants provided to WHO by USAID.

Recommendations for treatment of drug-resistant tuberculosis, 2020 update

Guideline Development Group

The chairs of the GDG were Holger J. Schünemann (Chair, GRADE methodologist: Cochrane Canada & McMaster University, Canada) and Rafael Laniado-Laborin (Co-chair, clinician, NTP, end user: NTP and rGLC, Mexico).

The following experts served as members of the GDG: Susan Abdel-Rahman (pharmacology, pharmacodynamics, pharmacokinetics: Children’s Mercy Hospital Kansas City, USA); Erlina Burhan (clinician, end user: Department of Respiratory and Pulmonology, Persahabatan Hospital, Indonesia); Daniela Maria Cirillo (laboratory specialist: San Raffaele Scientific Institute, TB Supranational Reference Laboratory, Italy); Charles Daley (pulmonologist, MDR-TB expert: National Jewish Health, USA); Geraint Gerry Rhys Davies (trials expert, pharmacologist: University of Liverpool, United Kingdom); Fernanda Dockhorn Costa Johansen (NTP, end user, clinician: Ministry of Health MDR-TB Referral Centre, Brazil); Kelly Dooley (clinical pharmacologist, researcher: Johns Hopkins University School of Medicine, USA); Bernard Fourie (clinical trials expert: University of Pretoria, South Africa); Agnes Gebhard (technical agency, end user, clinician: KNCV TB Foundation, Netherlands); Elmira Gurbanova (rGLC, clinician, end user: Lung Clinic, University of Tartu, Estonia, WHO Collaborating Centre on TB in Prisons, Azerbaijan); Muhammad Amir Khan (civil society representative; Association for Social Development, Pakistan); Yuhong Liu (clinician, end user: Clinical Center on TB, China CDC, Beijing Chest Hospital, WHO Collaborating Centre on TB Research and Training, China); Marian Loveday (specialist scientist, maternal health medicine: South African Medical Research Council, South Africa); Barend (Ben) Marais (paediatrician: University of Sydney School of Medicine, Australia); Iqbal Master (clinician, MDR-TB physician, end user: King George V Hospital, South Africa); Alberto Mendoza (clinician, end user: NTP, Peru); Beatrice Mutayoba (programme manager, end user: National TB and Leprosy Programme, United Republic of Tanzania); Payam Nahid (clinician, clinical trials expert: University of California San Francisco & American Thoracic Society, USA); Mahshid Nasehi (programme manager, end user: National TB and Leprosy Control Programme, Iran); Alberto Piubello (clinician, MDR-TB physician, end user: International Union Against Tuberculosis and Lung Disease, Niger); Maria Rodríguez (clinician, NTP, end user: Ministry of Health MDR-TB Referral Centre, Dominican Republic); Rohit Sarin (technical agency, end user: National Institute of TB & Respiratory Diseases, India); Ingrid Schoeman (former MDR-TB patient: TB PROOF, South Africa); Alena Skrahina (NTP, MDR-TB physician, end user: Republican Research and Practical Centre for Pulmonology and Tuberculosis, Belarus); Carrie Tudor (nursing specialist, technical agency, end user: International Council of Nurses, South Africa); Debrah Vambe (NTP, end user: NTP, Eswatini); Andrew Vernon (trials expert, technical agency, end user: US CDC, USA); and Nguyen Viet Nhung (NTP, end user: NTP, Ministry of Health, Viet Nam).

External Review Group

We thank the ERG, which had the following members: Heather Alexander (federal agency, technical partner: International Laboratory Branch, Division of Global HIV and Tuberculosis, US CDC, USA); Giovanni Battista Migliori (clinician, researcher: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy); Anuj K. Bhatnagar (clinician, researcher: Rajan Babu Institute for Pulmonary Medicine and Tuberculosis, India); Lisa Chen (clinician, academic: UCSF Curry International Tuberculosis Center, USA); Farhana Amanullah (paediatrician, paediatric nephrologist: Interactive Research and Development, Pakistan); Mildred Fernando-Pancho (civil society, former MDR-TB patient, Philippines); Anna Marie Celine Garfin (end user, clinician: NTP, Philippines); Edwin H. Herrera-Flores (clinician, end user: Hospital Nacional MDR-TB referral centre, Arzobispo Loayza, Lima, Peru); Mathilde Jachym (clinician, pneumologist: Sanatorium, France); Guy Marks (technical agency, end user, clinician, researcher: International Union Against Tuberculosis and Lung Disease, Australia); Andrei Maryandyshev (clinician: Northern State Medical University Arkhangelsk, Russian Federation); Lawrence Mbuagbaw (epidemiologist, biostatistician: McMaster University, Canada); Thato Mosidi (civil society, former MDR-TB patient, South Africa); Bhabana Shrestha (clinician, end user: Nepal Anti-TB Association, Nepal); Welile Sikhondze (clinician, researcher: NTP, Eswatini); Sarabjit Singh Chadha (technical agency: Global Drug Initiative Working Group, Foundation for Innovative New Diagnostics [FIND], India); Ivan Solovic (clinician, end user: National Institute for TB, Lung Diseases and Thoracic Surgery, Slovakia); Carlos Torres (technical agency, end user, clinician: Latin American Thoracic Society, Colombia); and Zarir Udwadia (clinician, end user: Hinduja Hospital MDR-TB Referral Centre, Breach Candy Hospital and Parsee General Hospitals, Mumbai, India).

Evidence reviewers

WHO would also like to acknowledge the work conducted by the following evidence reviewers: Richard Menzies (lead evidence reviewer: McGill University’s Faculty of Medicine, Canada); Jonathon R. Campbell (epidemiologist, health economist: McGill University’s Faculty of Medicine, Canada); Amrita Daftary (behavioural health scientist: Dahdaleh Institute for Global Health Research, York University, Canada); Gabriela Gomez (health economist: London School of Hygiene & Tropical Medicine; United Kingdom); Emily Ann Kendall (assistant professor of medicine: Johns Hopkins University School of Medicine, USA); Stephanie Law (qualitative researcher: McGill University, Canada); Rada Savic (bioengineering and pharmacokinetics/pharmacodynamics expert: University of California San Francisco, USA); and Nicholas Winters (research assistant: McGill University’s Faculty of Medicine, Canada).

Observers and external partners

Draurio Barreira Cravo Neto (technical manager, TB: Unitaid, Switzerland); Dan Everitt (vice president and senior medical officer: TB Alliance, USA); Christopher Gilpin (global laboratory coordinator: International Organization for Migration, Switzerland); Anisa Hajizadeh (GRADE methods trainee: McMaster University, Canada); Brian Kaiser (technical officer: Stop TB Partnership’s Global Drug Facility, Switzerland); Blessi Kumar (civil society representative: Global Coalition of TB Activists, India); Tamara Lotfi (GRADE methodologist: American University of Beirut, South Africa); YaDiul Mukadi (technical advisor: USAID, USA); Norbert Ndjeka (director, Drug-Resistant TB, TB & HIV: Department of Health of the Republic of South Africa, South Africa); Eugene Sun (head of Research & Development: TB Alliance, USA); Kitty Van Weezenbeek (executive director: KNCV TB Foundation, Netherlands); Francis Varaine (project lead, EndTB Project: Médecins Sans Frontières, France); and Mohammed Yassin (senior disease advisor, TB: Global Fund, Switzerland).

WHO Guideline Steering Committee

The following staff served as the WHO Steering Committee for the development of the current policy guideline: Fuad Mirzayev (lead), Dennis Falzon, Medea Gegia, Ernesto Jaramillo, Alexei Korobitsyn, Linh Nguyen, Kerri Viney, Matteo Zignol from the WHO Global Tuberculosis Programme; Corinne Simone Collette Merle from the WHO Special Programme for Research and Training in Tropical Diseases; Lorenzo Moja from the WHO Medicines Selection, Intellectual Property and Affordability / Essential Medicines; Andreas Alois Reis from WHO Health Ethics and Governance; and Satvinder (Vindi) Singh from the WHO Global HIV, Hepatitis and STIs Programmes / Treatment, Care and Service Delivery.

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