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
Garcia-Prats A.J. Garcia-Cremades M. Cox V. Kredo T. Dunbar R. Schaaf H.S. Seddon J.A. Furin J. Achar J. Radke K. Sachs T. Abubakirov A. Ahmed S. Akkerman O.W. Al Ani N.A. Amanullah F. Ahmad N. Anderson L.F. Asfaw M. Bango F. Bauer T. Becerra M. Boeree M. Brinkmann F. Brown R. Brust J. Campbell J.R. Carvalho A.C. Carvalho I. Cegielski J.P. Centis R. Chan E.D. Chauhan S. Chiang S.S. Chan P.-C. DAmbrosio L. Dalcolmo M. Daneilyan N. de Vries G. Draper H.R. Fairlie L. Francis J.R. Franke M. Gegia M. Restrepo C.G. Guenther A. Gureva T. Haecker B. Harausz E. Hewison C. Hicks R.M. Huerga H. Hughes J. Isaakidis P. Kadri S.M. Khan M.A. Kotrikadze T. Kuksa L. Lachenal N. Lange C. Lecca L. Lopez-Varela E. Lucena S. Mariandyshev A. Mattoo S. Mendez-Echevarria A. Migliori G.B. Mitnick C. Mohr-Holland E. Mulanda W. Murzabakova T. Myrzalieve B. Ndjeka N. Niemann S. Ozere I. Padayatchi N. Parmar M. Parpieva N. Manzur-Ul-Alam M. Rybak N. Sachdeva K.S. Salmon K. Santiago-Garcia B. Schaub D. Shah I. Shah S. Shah V. Sharma S. Shim T.S. Shin S. Sinha A. Skrahina A. Solanki H. Solans B.P. Soriano-Arandes A. Toktogonova A. van der Werf T. Velásquez G.E. Williams B. Yim J.-J. Savic R. Hesseling A.
February 2025Elsevier B.V.
The Lancet Child and Adolescent Health
2025#9Issue 2100 - 111 pp.
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.
Text of the article Перейти на текст статьи
University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Madison, WI, United States
Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa
University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, United States
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
University of Cape Town, Center for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Cape Town, South Africa
South African Medical Research Council, Health Systems Research Unit, Cape Town, South Africa
Imperial College London, Department of Infectious Diseases, London, United Kingdom
Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, United States
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
National Scientific Center of Phthisiopulmonology of the Ministry of Health of the Republic of Kazakhstan, Almaty, Kazakhstan
Interactive Research & Development, Karachi, Pakistan
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
Iraq National TB Programme, Drug-resistant Tuberculosis Unit, Baghdad, Iraq
Tufts Medical Center, Department of Pediatrics, Boston, MA, United States
University of Balochistan, Department of Pharmacy Practice, Quetta, Pakistan
World Health Organization, Global Malaria Programme, Geneva, Switzerland
Partners in Health, Maseru, Lesotho
Helios Klinik Emil von Behring, Respiratory Diseases Clinic Heckeshorn, Berlin, Germany
Radboud University Medical Center, Department of Lung Disease, Nijmegen, Netherlands
University Hospital Schleswig-Holstein, Campus Lübeck, Pediatric Pneumology, Lübeck, Germany
Airway Research Center North, Deutsches Zentrum für Lungenforschung, Großhansdorf, Germany
Albert Einstein College of Medicine, Department of Medicine, Bronx, NY, United States
McGill University, Departments of Medicine & Global and Public Health, Montreal, QC, Canada
Oswaldo Cruz Institute, Fiocruz, Laboratory of Innovations in Therapies, Education and Bioproducts, Rio de Janeiro, Brazil
Vila Nova de Gaia Hospital Centre, Pediatric Department, Vila Nova de Gaia, Portugal
Emory University Rollins School of Public Health, Department of Epidemiology, Emory Tuberculosis Center, Atlanta, GA, United States
Istituti Clinici Scientifici Maugeri, IRCCS, Servizio di Epidemiologia Clinica delle Malattie dellapparato Respiratorio, Tradate, Italy
National Jewish Hospital, Denver, CO, United States
World Health Organization, National Tuberculosis Elimination Programme, Technical Support Network, Central TB Division, New Delhi, India
Alpert Medical School of Brown University, Pediatrics, Providence, RI, United States
Rhode Island Hospital, Center for International Health Research, Providence, RI, United States
Taiwan Centers for Disease Control, The Division of Chronic Infectious Diseases, Taipei City, Taiwan
Public Health Consulting Group, Lugano, Switzerland
Fiocruz, Reference Center Hélio Fraga, Rio De Janeiro, Brazil
Medecins Sans Frontieres, Medical Department, Paris, France
National Institute for Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, Netherlands
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
Menzies School of Health Research, Charles Darwin University, Global and Tropical Health Division, Darwin, Australia
Royal Darwin Hospital, Department of Paediatrics, Darwin, Australia
Harvard T H Chan School of Public Health, Epidemiology, Boston, MA, United States
World Health Organisation, Global TB Programme, Geneva, Switzerland
Medecins Sans Frontieres, Medical Coordination, Tashkent, Uzbekistan
Helios Klinik Emil von Behring, Klinik fuer Kinder- und Jugenmedizin, Berlin, Germany
Northern State Medical University, Department of Phthisiopulmonology, Arkhangelsk, Russian Federation
German Central Committee against Tuberculosis, Berlin, Germany
Upstate Medical University, Department of Infectious Disease, Syracuse, NY, United States
Mills-Peninsula Medical Center, Department of Radiology, Burlingame, CA, United States
Epicentre, Field Epidemiology, Paris, France
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
Department of Health, Epidemiology and Public Health, Kashmir, India
Programmatic Management of Drug Resistant TB Unit, Lady Reading Hospital, Peshawar, Pakistan
Peshawar Medical College, Riphah International University, Islamabad, Pakistan
Medecins Sans Frontieres France, Medical Coordination, Tbilisi, Georgia
Riga East University Hospital, Tuberculosis and Lung Disease Clinic, Riga, Latvia
Medecins Sans Frontieres, Medical Department, Geneva, Switzerland
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 Childrens Hospital, Houston, TX, United States
Socios En Salud, Lima, Peru
ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
Hospital Municipal Raphael de Paula Souza, Department of Pneumology, Rio de Janeiro, Brazil
Northern Arctic Federal University, Scientific Department, Arkhangelsk, Russian Federation
Government of India, Ministry of Health and Family Welfare, Central TB Division, National TB Elimination Program, New Dehli, India
Hospital Universitario La Paz, Pediatric Infectious Diseases Unit, Madrid, Spain
Medecins Sans Frontieres, Epidemiology Department, Khayelitsha, South Africa
Medecins Sans Frontieres – Holland, Medical Department, Kulob, Tajikistan
KNCV, Bishkek, Kyrgyzstan
KNVC, Technical Department, The Hague, Netherlands
Kyrgyz State Medical Academy, TB Department, Bishkek, Kyrgyzstan
National Department of Health, South Africa, National Tuberculosis Programme, Pretoria, South Africa
Department of Medicine, University of Cape Town, Cape Town, South Africa
Research Center Borstel, Molecular and Experimental Mycobacteriology, Borstel, Germany
Riga East Clinical University Hospital, State Centre of Tuberculosis and Lung Diseases, Upeslejas, Latvia
Riga Stradiņš University, Infectology, Riga, Latvia
University of KwaZulu Natal, CAPRISA, Durban, South Africa
World Health Organization, Country Office for India, Communicable Diseases, Tuberculosis, New Dehli, India
Republican Specialized Scientific-Practical Medical Center of Phthisiology and Pulmonology, Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan
Interactive Research & Development, Dhaka, Bangladesh
The Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, RI, United States
Molbio Diagnostics, Strategy Department, Goa, India
Centre Hospitalier Universitaire Saint-Pierre, Pediatric Department, Brussels, Belgium
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
B J Wadia Hospital for Children, Pediatric TB Clinic, Department of Pediatric Infectious Diseases, Mumbai, India
Emory Rollins School of Public Health, Department of Epidemiology, Atlanta, GA, United States
World Health Organization, Information Support and Surveillance, Delhi, India
National Institute of Tuberculosis and Respiratory Diseases, Department of Pediatrics, New Delhi, India
University of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, Seoul, South Korea
Brigham and Womens Hospital, Division of Global Health Equity, Boston, MA, United States
Medecins Sans Frontieres, Manson Unit, London, United Kingdom
The Republican Scientific and Practical Center for Pulmonology and TB, Clinical Department, Minsk, Belarus
World Health Organization, Department of Communicable Diseases, New Dehli, India
University of California, San Francisco, UCSF Center for Tuberculosis, San Francisco, CA, United States
Hospital Universitari Vall dHebron, Pediatric Infectious Diseases and Immunodeficiencies Unit, Barcelona, Spain
Val dHebron Research Institute, Infection and Immunity in Children, Barcelona, Spain
National TB Center, Scientific Department, Bishkek, Kyrgyzstan
University of California, San Francisco, Division of HIV, Infectious Diseases, and Global Medicine, San Francisco, CA, United States
Northwick Park Hospital, Department of Paediatrics, London, United Kingdom
Seoul National University College of Medicine, Department of Internal Medicine, Seoul, South Korea
University of Wisconsin-Madison
Stellenbosch University
University of California
Complutense University of Madrid
Institute of Industrial Pharmacy
University of Cape Town
South African Medical Research Council
Imperial College London
Harvard Medical School
Karolinska Institute
Stellenbosch University
National Scientific Center of Phthisiopulmonology of the Ministry of Health of the Republic of Kazakhstan
Interactive Research & Development
University of Groningen
University of Groningen
Iraq National TB Programme
Tufts Medical Center
University of Balochistan
World Health Organization
Partners in Health
Helios Klinik Emil von Behring
Radboud University Medical Center
University Hospital Schleswig-Holstein
Airway Research Center North
Albert Einstein College of Medicine
McGill University
Oswaldo Cruz Institute
Vila Nova de Gaia Hospital Centre
Emory University Rollins School of Public Health
Istituti Clinici Scientifici Maugeri
National Jewish Hospital
World Health Organization
Alpert Medical School of Brown University
Rhode Island Hospital
Taiwan Centers for Disease Control
Public Health Consulting Group
Fiocruz
Medecins Sans Frontieres
National Institute for Public Health and the Environment
Wits Reproductive Health and HIV Institute
Respiratory Medicine & International Health
Menzies School of Health Research
Royal Darwin Hospital
Harvard T H Chan School of Public Health
World Health Organisation
Medecins Sans Frontieres
Helios Klinik Emil von Behring
Northern State Medical University
German Central Committee against Tuberculosis
Upstate Medical University
Mills-Peninsula Medical Center
Epicentre
Medecins Sans Frontieres
University of Ioannina School of Medicine
Department of Health
Programmatic Management of Drug Resistant TB Unit
Peshawar Medical College
Medecins Sans Frontieres France
Riga East University Hospital
Medecins Sans Frontieres
Department of Clinical Infectious Diseases
German Center of Infection Research
Baylor College of Medicine and Texas Childrens Hospital
Socios En Salud
ISGlobal
Hospital Municipal Raphael de Paula Souza
Northern Arctic Federal University
Government of India
Hospital Universitario La Paz
Medecins Sans Frontieres
Medecins Sans Frontieres – Holland
KNCV
KNVC
Kyrgyz State Medical Academy
National Department of Health
Department of Medicine
Research Center Borstel
Riga East Clinical University Hospital
Riga Stradiņš University
University of KwaZulu Natal
World Health Organization
Republican Specialized Scientific-Practical Medical Center of Phthisiology and Pulmonology
Interactive Research & Development
The Warren Alpert Medical School of Brown University
Molbio Diagnostics
Centre Hospitalier Universitaire Saint-Pierre
Hospital General Universitario Gregorio Marañón
CIBERINFEC ISCIII Centro de Investigación Biomédica en Red de Enfermedades Infecciosas
B J Wadia Hospital for Children
Emory Rollins School of Public Health
World Health Organization
National Institute of Tuberculosis and Respiratory Diseases
University of Ulsan College of Medicine
Brigham and Womens Hospital
Medecins Sans Frontieres
The Republican Scientific and Practical Center for Pulmonology and TB
World Health Organization
University of California
Hospital Universitari Vall dHebron
Val dHebron Research Institute
National TB Center
University of California
Northwick Park Hospital
Seoul National University College of Medicine
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026