Paradoxical Reaction to Tuberculosis Therapy among HIV-Negative Children: A Systematic Review and Meta-Analysis

Area of Science:

• Pediatrics
• Infectious Diseases
• Clinical Research

Background:

• Paradoxical reactions (PR) are a concern during tuberculosis (TB) treatment, particularly in HIV-coinfected individuals.
• The prevalence and characteristics of PR in HIV-negative children are not well-defined.
• Understanding PR in this population is crucial for optimizing TB treatment outcomes.

Purpose of the Study:

• To systematically review and estimate the burden and clinical characteristics of paradoxical reactions (PR) in HIV-negative children.
• To identify potential risk factors, management strategies, and outcomes associated with PR in this demographic.
• To highlight knowledge gaps and the need for further research.

Main Methods:

• A systematic review was conducted using multiple databases (PubMed, Embase, Web of Science, etc.).
• Included studies were observational, including case series with at least five cases of PR in HIV-negative children (<18 years).
• Data on prevalence, clinical features, risk factors, management, and outcomes were extracted and pooled using random-effects meta-analysis.

Main Results:

• Ten studies describing 133 HIV-negative children with PR were included.
• The pooled prevalence of PR was estimated at 8.8% (95% CI: 2.9%, 14.6%).
• Limited data suggested younger age and neurological or lymph node TB were more common in children with PR; risk factors were not identifiable due to heterogeneity.

Conclusions:

• Paradoxical reactions impact approximately 8.8% of HIV-negative children undergoing tuberculosis treatment.
• Current data are insufficient to identify specific risk factors or optimal management strategies.
• There is a critical need for enhanced surveillance and dedicated studies to better characterize PR in HIV-negative pediatric populations.