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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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, endTB Study Group, Fairlie Lee, Francis Joshua R, 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
Аннотация
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.