Fellow, Pediatric Infectious Diseases The Hospital for Sick Children Toronto, Ontario, Canada
Background: Appropriate dosing of anti-tuberculosis (TB) medications in children is a significant challenge for optimizing treatment. Children may experience a different spectrum, frequency, or severity of adverse events (AEs) compared to adults. AEs to TB therapy may contribute to morbidity and mortality, hospitalization, total duration of therapy and exposure to other medications with associated toxicities. From 2006-2010, the World Health Organization increased the recommended doses of first-line TB medications for children. It is unknown if these higher dose regimens have resulted in increased drug toxicities. Few high-quality data exist regarding the risks of AEs secondary to anti-TB therapy in children. Objective: The primary aim is to describe the proportion of children undergoing anti-TB therapy with first-line TB agents (i.e., isoniazid, rifampin, pyrazinamide, and ethambutol) who experience AEs. Secondary aims are to describe the proportion of different types and severity of AEs, and the proportion of children experiencing AEs in high- vs. low-dose regimens, high- vs. low-burden countries, and low- and middle-income vs. high-income countries. Design/Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Global Index Medicus were searched for articles published before March 22, 2023. Studies describing AEs in children aged 19 years or younger after initiating first-line TB therapy were identified. PRISMA guidelines for data abstraction were followed, with each step conducted by two reviewers. 60 of 6,058 articles identified met inclusion criteria. We will classify AEs according to the Common Terminology Criteria for Adverse Events v5.0. Outcome measures including the pooled risk of AEs as well as the absolute frequency of AEs will be summed across all studies and by AE-type. We will synthesize data in forest plots and generate pooled proportions of patients experiencing AEs using random effects meta-analysis. This review is registered with the International Prospective Register of Systematic Reviews (PROSPERO).
