Adverse Events of First-Line Therapy for Pediatric Tuberculosis: A Systematic Review and Meta-Analysis.

Area of Science:

• Pediatric infectious diseases
• Pharmacovigilance
• Tuberculosis treatment

Background:

• In 2010, the World Health Organization (WHO) updated guidelines, increasing first-line tuberculosis (TB) drug dosages for pediatric patients.
• Concerns exist regarding the safety and tolerability of these higher pediatric TB treatment doses.

Purpose of the Study:

• To determine the incidence of adverse events (AEs) in children receiving first-line TB treatment.
• To evaluate if the 2010 WHO dosing recommendations have altered the toxicity profile of pediatric TB therapy.

Main Methods:

• A systematic review and meta-analysis of proportions were conducted.
• Searches included major databases (MEDLINE, Embase, Scopus, Cochrane) and clinical trial registries.
• Studies reporting AEs in children and adolescents (≤19 years) with TB receiving first-line drugs were included.

Main Results:

• Forty studies involving 5,021 participants were analyzed.
• The overall incidence of any AE was significantly higher with 2010 WHO dosing (26%) compared to pre-2010 dosing (8%).
• While overall hepatotoxicity showed no significant change, some subgroups experienced increased hepatotoxicity with 2010 dosing. AEs led to therapy changes in 1.2% of participants.

Conclusions:

• Increased first-line TB drug dosages in children are associated with a higher occurrence of adverse events.
• Caution is advised regarding further dose escalations in pediatric TB treatment, emphasizing the need for more research on treatment tolerability.
• Publication bias in observational studies may limit the generalizability of findings.