Abstract

Background

Before August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown.

Methods

To inform a WHO guideline update, we undertook a systematic review and meta-analysis to evaluate outcomes from regimens of 6- to less than 12-months’ duration that included, at a minimum, isoniazid, rifampicin, and pyrazinamide. We included studies that applied rigorous diagnostic criteria and reported outcomes for ≥10 children or adolescents. Using generalized linear mixed models, we estimated the random effects pooled proportions of patients with key outcomes.

Results

Of 7 included studies, none compared regimens head-to-head. Three studies (724 patients) used a 6-month intensive regimen, which includes isoniazid and rifampicin at higher doses, pyrazinamide, and ethionamide instead of ethambutol (6HRZEto). Outcomes for this versus the 12-month regimen (282 patients, 3 studies) were, respectively, as follows: death, 5.5% (95% confidence interval [CI], 2.1%–13.4%) vs 23.9% (95% CI, 17.5%–31.7%); treatment success (survival with or without sequelae), 94.6% (95% CI, 73.9%–99.1%) vs 75.4% (95% CI, 68.7%–81.1%); and neurological sequelae among survivors, 66.0% (95% CI, 55.3%–75.3%) vs 36.3% (95% CI, 30.1%–43.0%). Relapse did not occur among 148 patients followed-up for 2 years after completing the 6-month intensive regimen.

Conclusions

Our findings are limited by the small number of studies and substantial potential for confounding. Nonetheless, the 6HRZEto regimen was associated with high treatment success and is now recommended by WHO as an alternative to the 12-month regimen.

Details

Title
Comparative Effectiveness of Regimens for Drug-Susceptible Tuberculous Meningitis in Children and Adolescents: A Systematic Review and Aggregate-Level Data Meta-Analysis
Author
Sulis, Giorgia 1 ; Tavaziva, Gamuchirai 2 ; Gore, Genevieve 3 ; Benedetti, Andrea 1 ; Solomons, Regan 4 ; Ronald van Toorn 4 ; Thee, Stephanie 5 ; Day, Jeremy 6 ; Verkuijl, Sabine 7 ; Brands, Annemieke 7 ; Viney, Kerri 7 ; Masini, Tiziana 7 ; Faiz Ahmad Khan 2 ; Chiang, Silvia S 8 

 Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, McGill University , Montreal , Canada 
 McGill International TB Centre , Montreal , Canada 
 Schulich Library, McGill University , Montreal , Canada 
 Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town , South Africa 
 Charité-Universitätsmedizin Berlin , Berlin , Germany 
 Nuffield Department of Medicine, University of Oxford , Oxford , United Kingdom 
 Global Tuberculosis Programme, World Health Organization , Geneva , Switzerland 
 Department of Pediatrics, Alpert Medical School of Brown University , Providence, Rhode Island , USA 
Publication year
2022
Publication date
Jun 2022
Publisher
Oxford University Press
e-ISSN
23288957
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3171170221
Copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is published under https://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.