Meta-Analysis

. 2025 Feb;9(2):100-111.

doi: 10.1016/S2352-4642(24)00330-4.

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis

Anthony J Garcia-Prats¹, Maria Garcia-Cremades², Vivian Cox³, Tamara Kredo⁴, Rory Dunbar⁵, H Simon Schaaf⁵, James A Seddon⁶, Jennifer Furin⁷, Jay Achar⁸, Kendra Radke⁹, Tina Sachs⁵, Amanzhan Abubakirov¹⁰, Saman Ahmed¹¹, Onno W Akkerman¹², Nadia Abdulkareem Al Ani¹³, Farhana Amanullah¹⁴, Nafees Ahmad¹⁵, Laura F Anderson¹⁶, Meseret Asfaw¹⁷, Funeka Bango⁴, Torsten Bauer¹⁸, Mercedes Becerra⁷, Martin Boeree¹⁹, Folke Brinkmann²⁰, Rosemary Brown⁵, James Brust²¹, Jonathon R Campbell²², Anna Cristina Carvalho²³, Isabel Carvalho²⁴, J Peter Cegielski²⁵, Rosella Centis²⁶, Edward D Chan²⁷, Sandeep Chauhan²⁸, Silvia S Chiang²⁹, Pei-Chun Chan³⁰, Lia D'Ambrosio³¹, Margareth Dalcolmo³², Narine Daneilyan³³, Gerard de Vries³⁴, Heather R Draper⁵; endTB Study Group; Lee Fairlie³⁵, Joshua R Francis³⁶, Molly Franke³⁷, Medea Gegia³⁸, Camilo Gomez Restrepo³⁹, Annette Guenther⁴⁰, Tatyana Gureva⁴¹, Brit Haecker⁴², Elizabeth Harausz⁴³, Catherine Hewison³³, Robert M Hicks⁴⁴, Helena Huerga⁴⁵, Jennifer Hughes⁵, Petros Isaakidis⁴⁶, Syed M Kadri⁴⁷, Mazhar Ali Khan⁴⁸, Tinatin Kotrikadze⁴⁹, Liga Kuksa⁵⁰, Nathalie Lachenal⁵¹, Christoph Lange⁵², Leonid Lecca⁵³, Elisa Lopez-Varela⁵⁴, Sheila Lucena⁵⁵, Andrei Mariandyshev⁵⁶, Sanjay Mattoo⁵⁷, Ana Mendez-Echevarria⁵⁸, Giovanni Battista Migliori²⁶, Carole Mitnick⁷, Erika Mohr-Holland⁵⁹, Winston Mulanda⁶⁰, Totugul Murzabakova⁶¹, Bakyt Myrzalieve⁶², Norbert Ndjeka⁶³, Stefan Niemann⁶⁴, Iveta Ozere⁶⁵, Nesri Padayatchi⁶⁶, Malik Parmar⁶⁷, Nargiza Parpieva⁶⁸, Mohammad Manzur-Ul-Alam⁶⁹, Natasha Rybak⁷⁰, Kuldeep Singh Sachdeva⁷¹, Kelly Salmon⁷², Begoña Santiago-Garcia⁷³, Dagmar Schaub⁷⁴, Ira Shah⁷⁵, Sarita Shah⁷⁶, Vaibhav Shah⁷⁷, Sangeeta Sharma⁷⁸, Tae Shun Shim⁷⁹, Sonya Shin⁸⁰, Animesh Sinha⁸¹, Alena Skrahina⁸², Hardik Solanki⁸³, Belen P Solans⁸⁴, Antoni Soriano-Arandes⁸⁵, Atyrkul Toktogonova⁸⁶, Tjip van der Werf⁸⁷, Gustavo E Velásquez⁸⁸, Bhanu Williams⁸⁹, Jae-Joon Yim⁹⁰, Rada Savic⁸⁴, Anneke Hesseling⁵

Affiliations

¹ University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Madison, WI, USA; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa. Electronic address: garciaprats@wisc.edu.
² University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA; Complutense University of Madrid, Department of Pharmaceutics and Food Technology, School of Pharmacy, Madrid, Spain; Institute of Industrial Pharmacy, Complutense University of Madrid, Madrid, Spain.
³ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa; University of Cape Town, Center for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa.
⁴ South African Medical Research Council, Health Systems Research Unit, Cape Town, South Africa.
⁵ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
⁶ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa; Imperial College London, Department of Infectious Diseases, London, UK.
⁷ Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA.
⁸ Karolinska Institute, Department of Global Public Health, Stockholm, Sweden; Stellenbosch University, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Tygerberg, South Africa.
⁹ University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA.
¹⁰ National Scientific Center of Phthisiopulmonology of the Ministry of Health of the Republic of Kazakhstan, Almaty, Kazakhstan.
¹¹ Interactive Research & Development, Karachi, Pakistan.
¹² University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, Netherlands; University of Groningen, University Medical Center Groningen, TB Center Beatrixoord, Groningen, Netherlands.
¹³ Iraq National TB Programme, Drug-resistant Tuberculosis Unit, Baghdad, Iraq.
¹⁴ Tufts Medical Center, Department of Pediatrics, Boston, MA, USA.
¹⁵ University of Balochistan, Department of Pharmacy Practice, Quetta, Pakistan.
¹⁶ World Health Organization, Global Malaria Programme, Geneva, Switzerland.
¹⁷ Partners in Health, Maseru, Lesotho.
¹⁸ Helios Klinik Emil von Behring, Respiratory Diseases Clinic Heckeshorn, Berlin, Germany.
¹⁹ Radboud University Medical Center, Department of Lung Disease, Nijmegen, Netherlands.
²⁰ University Hospital Schleswig-Holstein, Campus Lübeck, Pediatric Pneumology, Lübeck, Germany; Airway Research Center North, Deutsches Zentrum für Lungenforschung, Großhansdorf, Germany.
²¹ Albert Einstein College of Medicine, Department of Medicine, Bronx, NY, USA.
²² McGill University, Departments of Medicine & Global and Public Health, Montreal, QC, Canada.
²³ Oswaldo Cruz Institute, Fiocruz, Laboratory of Innovations in Therapies, Education and Bioproducts, Rio de Janeiro, Brazil.
²⁴ Vila Nova de Gaia Hospital Centre, Pediatric Department, Vila Nova de Gaia, Portugal.
²⁵ Emory University Rollins School of Public Health, Department of Epidemiology, and Emory Tuberculosis Center, Atlanta, GA, USA.
²⁶ Istituti Clinici Scientifici Maugeri, IRCCS, Servizio di Epidemiologia Clinica delle Malattie dell'apparato Respiratorio, Tradate, Italy.
²⁷ National Jewish Hospital, Denver, CO, USA.
²⁸ World Health Organization, National Tuberculosis Elimination Programme, Technical Support Network, Central TB Division, New Delhi, India.
²⁹ Alpert Medical School of Brown University, Pediatrics, Providence, RI, USA; Rhode Island Hospital, Center for International Health Research, Providence, RI, USA.
³⁰ Taiwan Centers for Disease Control, The Division of Chronic Infectious Diseases, Taipei City, Taiwan.
³¹ Public Health Consulting Group, Lugano, Switzerland.
³² Fiocruz, Reference Center Hélio Fraga, Rio De Janeiro, Brazil.
³³ Medecins Sans Frontieres, Medical Department, Paris, France.
³⁴ National Institute for Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, Netherlands.
³⁵ Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany.
³⁶ Menzies School of Health Research, Charles Darwin University, Global and Tropical Health Division, Darwin, Australia; Royal Darwin Hospital, Department of Paediatrics, Darwin, Australia.
³⁷ Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA; Harvard T H Chan School of Public Health, Epidemiology, Boston, MA, USA.
³⁸ World Health Organisation, Global TB Programme, Geneva, Switzerland.
³⁹ Medecins Sans Frontieres, Medical Coordination, Tashkent, Uzbekistan.
⁴⁰ Helios Klinik Emil von Behring, Klinik fuer Kinder- und Jugenmedizin, Berlin, Germany.
⁴¹ Northern State Medical University, Department of Phthisiopulmonology, Arkhangelsk, Russia.
⁴² German Central Committee against Tuberculosis, Berlin, Germany.
⁴³ Upstate Medical University, Department of Infectious Disease, Syracuse, NY, USA.
⁴⁴ Mills-Peninsula Medical Center, Department of Radiology, Burlingame, CA, USA.
⁴⁵ Epicentre, Field Epidemiology, Paris, France.
⁴⁶ Medecins Sans Frontieres, Southern Africa Medical Unit, Cape Town, South Africa; University of Ioannina School of Medicine, Clinical and Molecular Epidemiology Unit Department of Hygiene and Epidemiology, Ioannina, Greece.
⁴⁷ Department of Health, Epidemiology and Public Health, Kashmir, India.
⁴⁸ Programmatic Management of Drug Resistant TB Unit, Lady Reading Hospital, Peshawar, Pakistan; Peshawar Medical College, Riphah International University, Islamabad, Pakistan.
⁴⁹ Medecins Sans Frontieres France, Medical Coordination, Tbilisi, Georgia.
⁵⁰ Riga East University Hospital, Tuberculosis and Lung Disease Clinic, Riga, Latvia.
⁵¹ Medecins Sans Frontieres, Medical Department, Geneva, Switzerland.
⁵² Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany; Department of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Centre, Borstel, Germany; German Center of Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
⁵³ Socios En Salud, Lima, Peru.
⁵⁴ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa; ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
⁵⁵ Hospital Municipal Raphael de Paula Souza, Department of Pneumology, Rio de Janeiro, Brazil.
⁵⁶ Northern State Medical University, Department of Phthisiopulmonology, Arkhangelsk, Russia; Northern Arctic Federal University, Scientific Department, Arkhangelsk, Russia.
⁵⁷ Government of India, Ministry of Health and Family Welfare, Central TB Division, National TB Elimination Program, New Dehli, India.
⁵⁸ Hospital Universitario La Paz, Pediatric Infectious Diseases Unit, Madrid, Spain.
⁵⁹ Medecins Sans Frontieres, Epidemiology Department, Khayelitsha, South Africa.
⁶⁰ Medecins Sans Frontieres - Holland, Medical Department, Kulob, Tajikistan.
⁶¹ KNCV, Bishkek, Kyrgyz Republic.
⁶² KNVC, Technical Department, The Hague, Netherlands; Kyrgyz State Medical Academy, TB Department, Bishkek, Kyrgyzstan.
⁶³ National Department of Health, South Africa, National Tuberculosis Programme, Pretoria, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁶⁴ German Center of Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Research Center Borstel, Molecular and Experimental Mycobacteriology, Borstel, Germany.
⁶⁵ Riga East Clinical University Hospital, State Centre of Tuberculosis and Lung Diseases, Upeslejas, Latvia; Riga Stradiņš University, Infectology, Riga, Lativa.
⁶⁶ University of KwaZulu Natal, CAPRISA, Durban, South Africa.
⁶⁷ World Health Organization, Country Office for India, Communicable Diseases, Tuberculosis, New Dehli, India.
⁶⁸ Republican Specialized Scientific-Practical Medical Center of Phthisiology and Pulmonology, Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan.
⁶⁹ Interactive Research & Development, Dhaka, Bangladesh.
⁷⁰ The Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, RI, USA.
⁷¹ Molbio Diagnostics, Strategy Department, Goa, India.
⁷² Centre Hospitalier Universitaire Saint-Pierre, Pediatric Department, Brussels, Belgium.
⁷³ Hospital General Universitario Gregorio Marañón, Instituto de Investigacion Sanitaria Gregorio Marañón, Pediatric Infectious Diseases Department, Madrid, Spain; CIBERINFEC ISCIII Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
⁷⁴ Department of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Centre, Borstel, Germany.
⁷⁵ B J Wadia Hospital for Children, Pediatric TB Clinic, Department of Pediatric Infectious Diseases, Mumbai, India.
⁷⁶ Emory Rollins School of Public Health, Department of Epidemiology, Atlanta, GA, USA.
⁷⁷ World Health Organization, Information Support and Surveillance, Delhi, India.
⁷⁸ National Institute of Tuberculosis and Respiratory Diseases, Department of Pediatrics, New Delhi, India.
⁷⁹ University of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, Seoul, South Korea.
⁸⁰ Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA; Brigham and Women's Hospital, Division of Global Health Equity, Boston, MA, USA.
⁸¹ Medecins Sans Frontieres, Manson Unit, London, UK.
⁸² The Republican Scientific and Practical Center for Pulmonology and TB, Clinical Department, Minsk, Belarus.
⁸³ World Health Organization, Department of Communicable Diseases, New Dehli, India.
⁸⁴ University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA; University of California, San Francisco, UCSF Center for Tuberculosis, San Francisco, CA, USA.
⁸⁵ Hospital Universitari Vall d'Hebron, Pediatric Infectious Diseases and Immunodeficiencies Unit, Barcelona, Spain; Val d'Hebron Research Institute, Infection and Immunity in Children, Barcelona, Spain.
⁸⁶ National TB Center, Scientific Department, Bishkek, Kyrgyzstan.
⁸⁷ University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, Netherlands.
⁸⁸ University of California, San Francisco, UCSF Center for Tuberculosis, San Francisco, CA, USA; University of California, San Francisco, Division of HIV, Infectious Diseases, and Global Medicine, San Francisco, CA, USA.
⁸⁹ Northwick Park Hospital, Department of Paediatrics, London, UK.
⁹⁰ Seoul National University College of Medicine, Department of Internal Medicine, Seoul, Republic of Korea.

PMID: 39855750
DOI: 10.1016/S2352-4642(24)00330-4

Meta-Analysis

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis

Anthony J Garcia-Prats et al. Lancet Child Adolesc Health. 2025 Feb.

. 2025 Feb;9(2):100-111.

doi: 10.1016/S2352-4642(24)00330-4.

Authors

Affiliations

¹ University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Madison, WI, USA; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa. Electronic address: garciaprats@wisc.edu.
² University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA; Complutense University of Madrid, Department of Pharmaceutics and Food Technology, School of Pharmacy, Madrid, Spain; Institute of Industrial Pharmacy, Complutense University of Madrid, Madrid, Spain.
³ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa; University of Cape Town, Center for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa.
⁴ South African Medical Research Council, Health Systems Research Unit, Cape Town, South Africa.
⁵ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
⁶ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa; Imperial College London, Department of Infectious Diseases, London, UK.
⁷ Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA.
⁸ Karolinska Institute, Department of Global Public Health, Stockholm, Sweden; Stellenbosch University, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Tygerberg, South Africa.
⁹ University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA.
¹⁰ National Scientific Center of Phthisiopulmonology of the Ministry of Health of the Republic of Kazakhstan, Almaty, Kazakhstan.
¹¹ Interactive Research & Development, Karachi, Pakistan.
¹² University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, Netherlands; University of Groningen, University Medical Center Groningen, TB Center Beatrixoord, Groningen, Netherlands.
¹³ Iraq National TB Programme, Drug-resistant Tuberculosis Unit, Baghdad, Iraq.
¹⁴ Tufts Medical Center, Department of Pediatrics, Boston, MA, USA.
¹⁵ University of Balochistan, Department of Pharmacy Practice, Quetta, Pakistan.
¹⁶ World Health Organization, Global Malaria Programme, Geneva, Switzerland.
¹⁷ Partners in Health, Maseru, Lesotho.
¹⁸ Helios Klinik Emil von Behring, Respiratory Diseases Clinic Heckeshorn, Berlin, Germany.
¹⁹ Radboud University Medical Center, Department of Lung Disease, Nijmegen, Netherlands.
²⁰ University Hospital Schleswig-Holstein, Campus Lübeck, Pediatric Pneumology, Lübeck, Germany; Airway Research Center North, Deutsches Zentrum für Lungenforschung, Großhansdorf, Germany.
²¹ Albert Einstein College of Medicine, Department of Medicine, Bronx, NY, USA.
²² McGill University, Departments of Medicine & Global and Public Health, Montreal, QC, Canada.
²³ Oswaldo Cruz Institute, Fiocruz, Laboratory of Innovations in Therapies, Education and Bioproducts, Rio de Janeiro, Brazil.
²⁴ Vila Nova de Gaia Hospital Centre, Pediatric Department, Vila Nova de Gaia, Portugal.
²⁵ Emory University Rollins School of Public Health, Department of Epidemiology, and Emory Tuberculosis Center, Atlanta, GA, USA.
²⁶ Istituti Clinici Scientifici Maugeri, IRCCS, Servizio di Epidemiologia Clinica delle Malattie dell'apparato Respiratorio, Tradate, Italy.
²⁷ National Jewish Hospital, Denver, CO, USA.
²⁸ World Health Organization, National Tuberculosis Elimination Programme, Technical Support Network, Central TB Division, New Delhi, India.
²⁹ Alpert Medical School of Brown University, Pediatrics, Providence, RI, USA; Rhode Island Hospital, Center for International Health Research, Providence, RI, USA.
³⁰ Taiwan Centers for Disease Control, The Division of Chronic Infectious Diseases, Taipei City, Taiwan.
³¹ Public Health Consulting Group, Lugano, Switzerland.
³² Fiocruz, Reference Center Hélio Fraga, Rio De Janeiro, Brazil.
³³ Medecins Sans Frontieres, Medical Department, Paris, France.
³⁴ National Institute for Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, Netherlands.
³⁵ Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany.
³⁶ Menzies School of Health Research, Charles Darwin University, Global and Tropical Health Division, Darwin, Australia; Royal Darwin Hospital, Department of Paediatrics, Darwin, Australia.
³⁷ Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA; Harvard T H Chan School of Public Health, Epidemiology, Boston, MA, USA.
³⁸ World Health Organisation, Global TB Programme, Geneva, Switzerland.
³⁹ Medecins Sans Frontieres, Medical Coordination, Tashkent, Uzbekistan.
⁴⁰ Helios Klinik Emil von Behring, Klinik fuer Kinder- und Jugenmedizin, Berlin, Germany.
⁴¹ Northern State Medical University, Department of Phthisiopulmonology, Arkhangelsk, Russia.
⁴² German Central Committee against Tuberculosis, Berlin, Germany.
⁴³ Upstate Medical University, Department of Infectious Disease, Syracuse, NY, USA.
⁴⁴ Mills-Peninsula Medical Center, Department of Radiology, Burlingame, CA, USA.
⁴⁵ Epicentre, Field Epidemiology, Paris, France.
⁴⁶ Medecins Sans Frontieres, Southern Africa Medical Unit, Cape Town, South Africa; University of Ioannina School of Medicine, Clinical and Molecular Epidemiology Unit Department of Hygiene and Epidemiology, Ioannina, Greece.
⁴⁷ Department of Health, Epidemiology and Public Health, Kashmir, India.
⁴⁸ Programmatic Management of Drug Resistant TB Unit, Lady Reading Hospital, Peshawar, Pakistan; Peshawar Medical College, Riphah International University, Islamabad, Pakistan.
⁴⁹ Medecins Sans Frontieres France, Medical Coordination, Tbilisi, Georgia.
⁵⁰ Riga East University Hospital, Tuberculosis and Lung Disease Clinic, Riga, Latvia.
⁵¹ Medecins Sans Frontieres, Medical Department, Geneva, Switzerland.
⁵² Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany; Department of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Centre, Borstel, Germany; German Center of Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
⁵³ Socios En Salud, Lima, Peru.
⁵⁴ Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa; ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
⁵⁵ Hospital Municipal Raphael de Paula Souza, Department of Pneumology, Rio de Janeiro, Brazil.
⁵⁶ Northern State Medical University, Department of Phthisiopulmonology, Arkhangelsk, Russia; Northern Arctic Federal University, Scientific Department, Arkhangelsk, Russia.
⁵⁷ Government of India, Ministry of Health and Family Welfare, Central TB Division, National TB Elimination Program, New Dehli, India.
⁵⁸ Hospital Universitario La Paz, Pediatric Infectious Diseases Unit, Madrid, Spain.
⁵⁹ Medecins Sans Frontieres, Epidemiology Department, Khayelitsha, South Africa.
⁶⁰ Medecins Sans Frontieres - Holland, Medical Department, Kulob, Tajikistan.
⁶¹ KNCV, Bishkek, Kyrgyz Republic.
⁶² KNVC, Technical Department, The Hague, Netherlands; Kyrgyz State Medical Academy, TB Department, Bishkek, Kyrgyzstan.
⁶³ National Department of Health, South Africa, National Tuberculosis Programme, Pretoria, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
⁶⁴ German Center of Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Research Center Borstel, Molecular and Experimental Mycobacteriology, Borstel, Germany.
⁶⁵ Riga East Clinical University Hospital, State Centre of Tuberculosis and Lung Diseases, Upeslejas, Latvia; Riga Stradiņš University, Infectology, Riga, Lativa.
⁶⁶ University of KwaZulu Natal, CAPRISA, Durban, South Africa.
⁶⁷ World Health Organization, Country Office for India, Communicable Diseases, Tuberculosis, New Dehli, India.
⁶⁸ Republican Specialized Scientific-Practical Medical Center of Phthisiology and Pulmonology, Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan.
⁶⁹ Interactive Research & Development, Dhaka, Bangladesh.
⁷⁰ The Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, RI, USA.
⁷¹ Molbio Diagnostics, Strategy Department, Goa, India.
⁷² Centre Hospitalier Universitaire Saint-Pierre, Pediatric Department, Brussels, Belgium.
⁷³ Hospital General Universitario Gregorio Marañón, Instituto de Investigacion Sanitaria Gregorio Marañón, Pediatric Infectious Diseases Department, Madrid, Spain; CIBERINFEC ISCIII Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
⁷⁴ Department of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Centre, Borstel, Germany.
⁷⁵ B J Wadia Hospital for Children, Pediatric TB Clinic, Department of Pediatric Infectious Diseases, Mumbai, India.
⁷⁶ Emory Rollins School of Public Health, Department of Epidemiology, Atlanta, GA, USA.
⁷⁷ World Health Organization, Information Support and Surveillance, Delhi, India.
⁷⁸ National Institute of Tuberculosis and Respiratory Diseases, Department of Pediatrics, New Delhi, India.
⁷⁹ University of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, Seoul, South Korea.
⁸⁰ Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA; Brigham and Women's Hospital, Division of Global Health Equity, Boston, MA, USA.
⁸¹ Medecins Sans Frontieres, Manson Unit, London, UK.
⁸² The Republican Scientific and Practical Center for Pulmonology and TB, Clinical Department, Minsk, Belarus.
⁸³ World Health Organization, Department of Communicable Diseases, New Dehli, India.
⁸⁴ University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA; University of California, San Francisco, UCSF Center for Tuberculosis, San Francisco, CA, USA.
⁸⁵ Hospital Universitari Vall d'Hebron, Pediatric Infectious Diseases and Immunodeficiencies Unit, Barcelona, Spain; Val d'Hebron Research Institute, Infection and Immunity in Children, Barcelona, Spain.
⁸⁶ National TB Center, Scientific Department, Bishkek, Kyrgyzstan.
⁸⁷ University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, Netherlands.
⁸⁸ University of California, San Francisco, UCSF Center for Tuberculosis, San Francisco, CA, USA; University of California, San Francisco, Division of HIV, Infectious Diseases, and Global Medicine, San Francisco, CA, USA.
⁸⁹ Northwick Park Hospital, Department of Paediatrics, London, UK.
⁹⁰ Seoul National University College of Medicine, Department of Internal Medicine, Seoul, Republic of Korea.

PMID: 39855750
DOI: 10.1016/S2352-4642(24)00330-4

Erratum in

Correction to Lancet Child Adolesc Health 2025; 9: 100-11.
[No authors listed] [No authors listed] Lancet Child Adolesc Health. 2025 Mar;9(3):e9. doi: 10.1016/S2352-4642(25)00038-0. Lancet Child Adolesc Health. 2025. PMID: 39978998 No abstract available.

Abstract

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis. Databases were searched from Oct 1, 2014, to March 30, 2020. To be eligible, studies must have included more than five children or adolescents (0-19 years of age) treated for microbiologically confirmed or clinically diagnosed MDR or RR tuberculosis within a defined treatment cohort, and reported on regimen composition and treatment outcomes. Abstracts were screened independently by two authors to identify potentially eligible records. Full texts were reviewed by two authors independently to identify studies meeting the eligiblity criteria. For studies meeting eligiblity criteria, anonymised individual patient data was requested and individiual level data included for analysis. The main outcome assessed was treatment outcome defined as treatment success (cure or treatment completed) versus unfavourable outcome (treatment failure or death). Multivariable logistic regression models were used to identify associations between clinical and treatment factors and treatment outcomes. This study is registered with Prospero (CRD42020187230).

Findings: 1417 studies were identified through database searching. After removing duplicates and screening for eligibility, the search identified 23 369 individual participants from 42 studies, mostly from India and South Africa. Overall, 16 825 (72·0%) were successfully treated (treatment completed or cured), 2848 died (12·2%), 722 (3·1%) had treatment failure, and 2974 (12·7%) were lost to follow-up. In primary analyses, the median age was 16 (IQR 13-18) years. Of the 17 764 (87·1%) participants with reported HIV status, 2448 (13·8%) were living with HIV. 17 707 (89·6%) had microbiologically confirmed tuberculosis. After adjusting for significant factors associated with treatment outcome, the use of two (adjusted odds ratio [OR] 1·41 [95% CI 1·09-1·82]; p=0·008) or three (2·12 [1·61-2·79]; p<0·0001) WHO-classified group A drugs (bedaquiline, moxifloxacin, levofloxacin, and linezolid) compared with the use of no group A drugs at all was positively associated with treatment success.

Interpretation: Younger and clinically diagnosed children are underrepresented among those treated for MDR and RR tuberculosis and should be a focus for case-finding efforts. Overall treatment outcomes in our analysis were better than in adults but lower than the international targets of 90% or more individuals successfully treated. Treatment with more group A drugs was associated with better treatment outcomes in children and adolescents, highlighting the need for more rapid access to these drugs and improved regimens.

Funding: Unitaid.

Copyright © 2025 World Health Organization. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

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Declaration of interests AJG-P reports that his institution receives grant funding from the US National Institutes of Health (NIH) and Unitaid for paediatric studies of bedaquiline, delamanid, pretomanid, clofazimine, moxifloxacin, and levofloxacin. J-JY reports donations of linezolid (Zyvox) from Pfizer, Delamanid (Deltyba) from Otsuka Pharmaceutical, and Rifampicin (Rifampcin) from Yuhan for the for the clinical trials, in which he served as a principal investigator. JF reports grant funding form the Stop TB Partnership's Global Drug Facility. JRC reports grant funding to his institution from the Canadian Institutes of Health, Fonds de recherche du Quebec-Sante, the National Sanatorium Association, and WHO; and consulting fees from WHO, the World Bank, and the Saskatchewan Auditors Office. BSG reports grant funding from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain). GEV reports grant funding from the NIH, US Agency for International Development (USAID), Unitaid, Medecins Sans Frontiers, and Partners in Health; and consulting fees from the Gates Medical Research Institute. RS reports grant funding from the NIH, the Bill and Melinda Gates Foundation, USAID, and from UNITE4TB (Academia and Industry United Innovation and Treatment for Tuberculosis). AS reports participating at the Research Lead at UK Academics and Professionals to end Tuberculosis. All other authors declare no competing interests.

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Timeliness and value of individual participant data meta-analyses in paediatric tuberculosis research.
Marais BJ, Coleman M, Larsson L, Kranzer K. Marais BJ, et al. Lancet Child Adolesc Health. 2025 Feb;9(2):78-79. doi: 10.1016/S2352-4642(24)00357-2. Lancet Child Adolesc Health. 2025. PMID: 39855754 No abstract available.

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Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis

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Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis

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