1. 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.
- Author
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Garcia-Prats AJ, Garcia-Cremades M, Cox V, Kredo T, Dunbar R, Schaaf HS, Seddon JA, Furin J, Achar J, Radke K, Sachs T, Abubakirov A, Ahmed S, Akkerman OW, Al Ani NA, Amanullah F, Ahmad N, Anderson LF, Asfaw M, Bango F, Bauer T, Becerra M, Boeree M, Brinkmann F, Brown R, Brust J, Campbell JR, Carvalho AC, Carvalho I, Cegielski JP, Centis R, Chan ED, Chauhan S, Chiang SS, Chan PC, D'Ambrosio L, Dalcolmo M, Daneilyan N, de Vries G, Draper HR, Fairlie L, Francis JR, Franke M, Gegia M, Restrepo CG, Guenther A, Gureva T, Haecker B, Harausz E, Hewison C, Hicks RM, Huerga H, Hughes J, Isaakidis P, Kadri SM, Khan MA, Kotrikadze T, Kuksa L, Lachenal N, Lange C, Lecca L, Lopez-Varela E, Lucena S, Mariandyshev A, Mattoo S, Mendez-Echevarria A, Migliori GB, 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 KS, Salmon K, Santiago-Garcia B, Schaub D, Shah I, Shah S, Shah V, Sharma S, Shim TS, Shin S, Sinha A, Skrahina A, Solanki H, Solans BP, Soriano-Arandes A, Toktogonova A, van der Werf T, Velásquez GE, Williams B, Yim JJ, Savic R, and Hesseling A
- Subjects
- Humans, Adolescent, Child, Treatment Outcome, Antitubercular Agents therapeutic use, Child, Preschool, Infant, Female, Male, Rifampin therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy
- 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., Competing Interests: 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., (Copyright © 2025 World Health Organization. Published by Elsevier Ltd. 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- 2025
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