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TOPLINE:

According to a recent meta-analysis, higher-dose tuberculosis treatment regimens in children, following 2010 World Health Organization (WHO) guidelines, were associated with significantly higher rates of adverse events than lower-dose treatment regimens.

METHODOLOGY:

• Researchers conducted a meta-analysis of 40 studies involving 5021 participants to evaluate adverse events in children and adolescents aged 19 years or younger receiving first-line tuberculosis treatment.
• Data were extracted from major databases, including MEDLINE, Embase, Scopus, the Cochrane Database, the WHO Global Index Medicus, and ClinicalTrials.gov, from March 2023 to July 2024.
• The proportion of children who experienced adverse events was compared between lower pre–WHO 2010 doses and higher WHO 2010–recommended doses of isoniazid, rifampin, pyrazinamide, and/or ethambutol.
• The primary outcome was the proportion of children who developed any adverse events while receiving first-line tuberculosis treatment across all doses, and secondary outcomes included drug-related adverse effects, specific adverse events, and mortality.

TAKEAWAY:

• Participants receiving WHO 2010 dosing experienced significantly more adverse events than those receiving pre–WHO 2010 dosing (26% vs 8%; P = .001).
• Severe adverse events increased significantly with WHO 2010 dosing compared with pre–WHO 2010 dosing (2% vs 0%; P = .04).
• The proportion of patients experiencing gastrointestinal adverse events was higher with WHO 2010 dosing than with pre–WHO 2010 dosing (14% vs 2%; P = .009).
• Drug-related adverse effects were also more common with WHO 2010 dosing than with pre–WHO 2010 dosing (10% vs 2%; P = .004); however, no deaths were attributable to the adverse events.

IN PRACTICE:

“Pediatric-specific counselling should be developed and evaluated to minimize severe AEs [adverse events], including advice to discontinue medication and seek care when encountering symptoms of hepatotoxicity. Patient education, a key factor in promoting adherence to TB [tuberculosis] treatment, should also include information about side effects and an action plan if they occur to ensure treatment safety,” authors of the study wrote.

SOURCE:

The study was led by Michael Prodanuk, Division of Infectious Diseases, The Hospital for Sick Children, Toronto, Ontario, Canada. It was published online on March 24, 2025, in Clinical Infectious Diseases.

LIMITATIONS:

The findings were limited by publication bias in observational trials, as well as substantial heterogeneity between studies, varying definitions of adverse events, and differing monitoring practices between studies. Additionally, the analysis was constrained by the low number of participants living with HIV and the limited reporting of comorbidities such as malnutrition.

DISCLOSURES:

This study was supported by the Canadian Paediatric Society’s Section on Respiratory Medicine trainee grant and the Edwin S.H. Leong Centre for Healthy Children, University of Toronto, Toronto, Ontario, Canada. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.