Evidence map›Paper›PMID 39855750›Full record

SynthesisThe Lancet. Child & adolescent health2025

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, Maria Garcia-Cremades, Vivian Cox, Tamara Kredo, Rory Dunbar, H Simon Schaaf, James A Seddon, Jennifer Furin, Jay Achar, Kendra Radke and 93 more

Erratum issuedAbstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in The Lancet. Child & adolescent health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

103 authors.

Anthony J Garcia-PratsUniversity 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.
Maria Garcia-CremadesUniversity 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.
Vivian CoxStellenbosch 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.
Tamara KredoSouth African Medical Research Council, Health Systems Research Unit, Cape Town, South Africa.
Rory DunbarStellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
H Simon SchaafStellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
James A SeddonStellenbosch 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.
Jennifer FurinHarvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA.
Jay AcharKarolinska 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.
Kendra RadkeUniversity of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA.
Tina SachsStellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
Amanzhan AbubakirovNational Scientific Center of Phthisiopulmonology of the Ministry of Health of the Republic of Kazakhstan, Almaty, Kazakhstan.
Saman AhmedInteractive Research & Development, Karachi, Pakistan.
Onno W AkkermanUniversity 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.
Nadia Abdulkareem Al AniIraq National TB Programme, Drug-resistant Tuberculosis Unit, Baghdad, Iraq.
Farhana AmanullahTufts Medical Center, Department of Pediatrics, Boston, MA, USA.
Nafees AhmadUniversity of Balochistan, Department of Pharmacy Practice, Quetta, Pakistan.
Laura F AndersonWorld Health Organization, Global Malaria Programme, Geneva, Switzerland.
Meseret AsfawPartners in Health, Maseru, Lesotho.
Funeka BangoSouth African Medical Research Council, Health Systems Research Unit, Cape Town, South Africa.
Torsten BauerHelios Klinik Emil von Behring, Respiratory Diseases Clinic Heckeshorn, Berlin, Germany.
Mercedes BecerraHarvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA.
Martin BoereeRadboud University Medical Center, Department of Lung Disease, Nijmegen, Netherlands.
Folke BrinkmannUniversity Hospital Schleswig-Holstein, Campus Lübeck, Pediatric Pneumology, Lübeck, Germany; Airway Research Center North, Deutsches Zentrum für Lungenforschung, Großhansdorf, Germany.
Rosemary BrownStellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
James BrustAlbert Einstein College of Medicine, Department of Medicine, Bronx, NY, USA.
Jonathon R CampbellMcGill University, Departments of Medicine & Global and Public Health, Montreal, QC, Canada.
Anna Cristina CarvalhoOswaldo Cruz Institute, Fiocruz, Laboratory of Innovations in Therapies, Education and Bioproducts, Rio de Janeiro, Brazil.
Isabel CarvalhoVila Nova de Gaia Hospital Centre, Pediatric Department, Vila Nova de Gaia, Portugal.
J Peter CegielskiEmory University Rollins School of Public Health, Department of Epidemiology, and Emory Tuberculosis Center, Atlanta, GA, USA.
Rosella CentisIstituti Clinici Scientifici Maugeri, IRCCS, Servizio di Epidemiologia Clinica delle Malattie dell'apparato Respiratorio, Tradate, Italy.
Edward D ChanNational Jewish Hospital, Denver, CO, USA.
Sandeep ChauhanWorld Health Organization, National Tuberculosis Elimination Programme, Technical Support Network, Central TB Division, New Delhi, India.
Silvia S ChiangAlpert Medical School of Brown University, Pediatrics, Providence, RI, USA; Rhode Island Hospital, Center for International Health Research, Providence, RI, USA.
Pei-Chun ChanTaiwan Centers for Disease Control, The Division of Chronic Infectious Diseases, Taipei City, Taiwan.
Lia D'AmbrosioPublic Health Consulting Group, Lugano, Switzerland.
Margareth DalcolmoFiocruz, Reference Center Hélio Fraga, Rio De Janeiro, Brazil.
Narine DaneilyanMedecins Sans Frontieres, Medical Department, Paris, France.
Gerard de VriesNational Institute for Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, Netherlands.
Heather R DraperStellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
endTB Study Group
Lee FairlieWits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany.
Joshua R FrancisMenzies School of Health Research, Charles Darwin University, Global and Tropical Health Division, Darwin, Australia; Royal Darwin Hospital, Department of Paediatrics, Darwin, Australia.
Molly FrankeHarvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA; Harvard T H Chan School of Public Health, Epidemiology, Boston, MA, USA.
Medea GegiaWorld Health Organisation, Global TB Programme, Geneva, Switzerland.
Camilo Gomez RestrepoMedecins Sans Frontieres, Medical Coordination, Tashkent, Uzbekistan.
Annette GuentherHelios Klinik Emil von Behring, Klinik fuer Kinder- und Jugenmedizin, Berlin, Germany.
Tatyana GurevaNorthern State Medical University, Department of Phthisiopulmonology, Arkhangelsk, Russia.
Brit HaeckerGerman Central Committee against Tuberculosis, Berlin, Germany.
Elizabeth HarauszUpstate Medical University, Department of Infectious Disease, Syracuse, NY, USA.
Catherine HewisonMedecins Sans Frontieres, Medical Department, Paris, France.
Robert M HicksMills-Peninsula Medical Center, Department of Radiology, Burlingame, CA, USA.
Helena HuergaEpicentre, Field Epidemiology, Paris, France.
Jennifer HughesStellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.
Petros IsaakidisMedecins 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.
Syed M KadriDepartment of Health, Epidemiology and Public Health, Kashmir, India.
Mazhar Ali KhanProgrammatic Management of Drug Resistant TB Unit, Lady Reading Hospital, Peshawar, Pakistan; Peshawar Medical College, Riphah International University, Islamabad, Pakistan.
Tinatin KotrikadzeMedecins Sans Frontieres France, Medical Coordination, Tbilisi, Georgia.
Liga KuksaRiga East University Hospital, Tuberculosis and Lung Disease Clinic, Riga, Latvia.
Nathalie LachenalMedecins Sans Frontieres, Medical Department, Geneva, Switzerland.
Christoph LangeRespiratory 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.
Leonid LeccaSocios En Salud, Lima, Peru.
Elisa Lopez-VarelaStellenbosch 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.
Sheila LucenaHospital Municipal Raphael de Paula Souza, Department of Pneumology, Rio de Janeiro, Brazil.
Andrei MariandyshevNorthern State Medical University, Department of Phthisiopulmonology, Arkhangelsk, Russia; Northern Arctic Federal University, Scientific Department, Arkhangelsk, Russia.
Sanjay MattooGovernment of India, Ministry of Health and Family Welfare, Central TB Division, National TB Elimination Program, New Dehli, India.
Ana Mendez-EchevarriaHospital Universitario La Paz, Pediatric Infectious Diseases Unit, Madrid, Spain.
Giovanni Battista MiglioriIstituti Clinici Scientifici Maugeri, IRCCS, Servizio di Epidemiologia Clinica delle Malattie dell'apparato Respiratorio, Tradate, Italy.
Carole MitnickHarvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA.
Erika Mohr-HollandMedecins Sans Frontieres, Epidemiology Department, Khayelitsha, South Africa.
Winston MulandaMedecins Sans Frontieres - Holland, Medical Department, Kulob, Tajikistan.
Totugul MurzabakovaKNCV, Bishkek, Kyrgyz Republic.
Bakyt MyrzalieveKNVC, Technical Department, The Hague, Netherlands; Kyrgyz State Medical Academy, TB Department, Bishkek, Kyrgyzstan.
Norbert NdjekaNational Department of Health, South Africa, National Tuberculosis Programme, Pretoria, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
Stefan NiemannGerman Center of Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; Research Center Borstel, Molecular and Experimental Mycobacteriology, Borstel, Germany.
Iveta OzereRiga East Clinical University Hospital, State Centre of Tuberculosis and Lung Diseases, Upeslejas, Latvia; Riga Stradiņš University, Infectology, Riga, Lativa.
Nesri PadayatchiUniversity of KwaZulu Natal, CAPRISA, Durban, South Africa.
Malik ParmarWorld Health Organization, Country Office for India, Communicable Diseases, Tuberculosis, New Dehli, India.
Nargiza ParpievaRepublican Specialized Scientific-Practical Medical Center of Phthisiology and Pulmonology, Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan.
Mohammad Manzur-Ul-AlamInteractive Research & Development, Dhaka, Bangladesh.
Natasha RybakThe Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, RI, USA.
Kuldeep Singh SachdevaMolbio Diagnostics, Strategy Department, Goa, India.
Kelly SalmonCentre Hospitalier Universitaire Saint-Pierre, Pediatric Department, Brussels, Belgium.
Begoña Santiago-GarciaHospital 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.
Dagmar SchaubDepartment of Clinical Infectious Diseases, Research Center Borstel, Leibniz Lung Centre, Borstel, Germany.
Ira ShahB J Wadia Hospital for Children, Pediatric TB Clinic, Department of Pediatric Infectious Diseases, Mumbai, India.
Sarita ShahEmory Rollins School of Public Health, Department of Epidemiology, Atlanta, GA, USA.
Vaibhav ShahWorld Health Organization, Information Support and Surveillance, Delhi, India.
Sangeeta SharmaNational Institute of Tuberculosis and Respiratory Diseases, Department of Pediatrics, New Delhi, India.
Tae Shun ShimUniversity of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, Seoul, South Korea.
Sonya ShinHarvard 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.
Animesh SinhaMedecins Sans Frontieres, Manson Unit, London, UK.
Alena SkrahinaThe Republican Scientific and Practical Center for Pulmonology and TB, Clinical Department, Minsk, Belarus.
Hardik SolankiWorld Health Organization, Department of Communicable Diseases, New Dehli, India.
Belen P SolansUniversity 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.
Antoni Soriano-ArandesHospital Universitari Vall d'Hebron, Pediatric Infectious Diseases and Immunodeficiencies Unit, Barcelona, Spain; Val d'Hebron Research Institute, Infection and Immunity in Children, Barcelona, Spain.
Atyrkul ToktogonovaNational TB Center, Scientific Department, Bishkek, Kyrgyzstan.
Tjip van der WerfUniversity of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, Netherlands.
Gustavo E VelásquezUniversity 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.
Bhanu WilliamsNorthwick Park Hospital, Department of Paediatrics, London, UK.
Jae-Joon YimSeoul National University College of Medicine, Department of Internal Medicine, Seoul, Republic of Korea.
Rada SavicUniversity 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.
Anneke HesselingStellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Tygerberg, South Africa.

Funding

Emory/Georgia TB Research Advancement Center (TRAC)P30AI168386 · NIAID · EMORY UNIVERSITY · PI Neel Rajnikant Gandhi · 2022 to 2026
$5.8M
Mentoring Multidisciplinary Patient-Oriented Research in TB, HIV, and Global HealthK24AI165099 · NIAID · EMORY UNIVERSITY · PI Nippie Sarita Shah · 2023 to 2026
$781k
NIAID NIH HHS K24 AI165099NIAID NIH HHS P30 AI168386World Health Organization 001
6 · The paper itself

Abstract

backgroundThere 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.

methodsWe 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).

findings1417 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.

interpretationYounger 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.

fundingUnitaid.

Indexed as

Antitubercular AgentsRifampinTuberculosis, Multidrug-ResistantAdolescentAntibiotics, AntitubercularChildChild, PreschoolFemaleHumansInfantMaleTreatment OutcomeAntibiotics, AntitubercularAntitubercular AgentsRifampin

Identifiers

PMID39855750
PMCPMC13289721

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.