OBJECTIVES: Paediatric tuberculosis is often missed or overlooked due to non-specific symptoms and difficulties in diagnosis. Around 90% of the 205,000 children estimated to die from this disease every year are never treated. Our aim was to synthesize the available evidence on the efficacy and safety of different treatment regimens available for latent tuberculosis infection (LTBI) in children and adolescents.

METHODS: A systematic review with network meta-analysis was performed (PROSPERO-CRD142933). Searches were conducted in Pubmed and Scopus (May-2021) and complemented by manual searches. Randomized controlled trials comparing treatments for LTBI in patients up to 15 years, and reporting data on the incidence of the disease, death or any adverse event were included. Bayesian framework networks meta-analysis were built for each outcome of interest. Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Rank probabilities were calculated via the surface under the cumulative ranking analysis (SUCRA) (Addis v.1.16.8). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate evidence’s certainty.

RESULTS: Seven trials (n=8,696 patients) were included. Placebo was significantly associated with a higher incidence of tuberculosis compared to all active therapies. The combinations of isoniazid (15-25 mg/kg/week) plus rifapentine (300-900 mg/week), followed by isoniazid plus rifampicin (10 mg/kg/day) were ranked as best approaches with lower probabilities of disease incidence (10% and 19.5%, respectively in SUCRA) and death (both around 20%). However, higher doses of isoniazid monotherapy were significantly associated to more deaths (OR 18.28, 95% ICr [1.02, 48.60] of 4-6 mg/kg/day vs. 10 mg/kg/3x per week). Evidence was overall rated as moderate.

CONCLUSIONS: Combined short-term periods therapies (isoniazid plus rifapentine or rifampicin) for should be used as the first-line approach for treating LTBI in children and adolescents. The use of long-term isoniazid as monotherapy and at higher doses should be avoided for this population.