Title
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(s)
Garcia-Prats, Anthony J
Garcia-Cremades, Maria
Cox, Vivian
Kredo, Tamara
Dunbar, Rory
Schaaf, H Simon
Seddon, James A
Furin, Jennifer
Achar, Jay
Radke, Kendra
Sachs, Tina
Abubakirov, Amanzhan
Ahmed, Saman
Akkerman, Onno W
Al Ani, Nadia Abdulkareem
Amanullah, Farhana
Ahmad, Nafees
Anderson, Laura F
Asfaw, Meseret
Bango, Funeka
Bauer, Torsten
Becerra, Mercedes
Boeree, Martin
Brinkmann, Folke
Brown, Rosemary
Brust, James
Campbell, Jonathon R
Carvalho, Anna Cristina
Carvalho, Isabel
Cegielski, J Peter
Centis, Rosella
Chan, Edward D
Chauhan, Sandeep
Chiang, Silvia S
Chan, Pei-Chun
D'Ambrosio, Lia
Dalcolmo, Margareth
Daneilyan, Narine
de Vries, Gerard
Draper, Heather R
Fairlie, Lee
Franke, Molly
Gegia, Medea
Restrepo, Camilo Gomez
Guenther, Annette
Gureva, Tatyana
Haecker, Brit
Harausz, Elizabeth
Hewison, Catherine
Hicks, Robert M
Huerga, Helena
Hughes, Jennifer
Isaakidis, Petros
Kadri, Syed M
Khan, Mazhar Ali
Kotrikadze, Tinatin
Kuksa, Liga
Lachenal, Nathalie
Lange, Christoph
Lecca, Leonid
Lopez-Varela, Elisa
Lucena, Sheila
Mariandyshev, Andrei
Mattoo, Sanjay
Mendez-Echevarria, Ana
Migliori, Giovanni Battista
Mitnick, Carole
Mohr-Holland, Erika
Mulanda, Winston
Murzabakova, Totugul
Myrzalieve, Bakyt
Ndjeka, Norbert
Niemann, Stefan
Ozere, Iveta
Padayatchi, Nesri
Parmar, Malik
Parpieva, Nargiza
Manzur-Ul-Alam, Mohammad
Rybak, Natasha
Sachdeva, Kuldeep Singh
Salmon, Kelly
Santiago-Garcia, Begoña
Schaub, Dagmar
Shah, Ira
Shah, Sarita
Shah, Vaibhav
Sharma, Sangeeta
Shim, Tae Shun
Shin, Sonya
Sinha, Animesh
Skrahina, Alena
Solanki, Hardik
Solans, Belen P
Soriano-Arandes, Antoni
Toktogonova, Atyrkul
van der Werf, Tjip
Velásquez, Gustavo E
Williams, Bhanu
Yim, Jae-Joon
Savic, Rada
Hesseling, Anneke
Abstract
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.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).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.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.Unitaid.
Publication information
Lancet Child Adolesc Health . 2025 Feb;9(2):100-111. doi: 10.1016/S2352-4642(24)00330-4.
Date Issued
2025-02-01
Type
Journal Article
Journal Title
The Lancet. Child & adolescent health
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