Shorter Antitubercular Regimens Versus 9 Months of Isoniazid for Latent Tuberculosis in Children: A Systematic Review and Meta-Analysis

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract; CI for primary outcome crosses 1.0, indicating p >0.05 for TB disease development

• Effect Size: OR 0.19 for TB disease development (favouring shorter regimens but imprecise); OR 0.51 for treatment completion (favouring shorter regimens, moderate certainty)

• Primary Outcome: Development of active TB disease: pooled OR 0.19 (95% CI 0.03–1.12) from 3 RCTs — moderate-certainty evidence; result crosses the null, indicating no statistically significant difference between shorter regimens and 9H

• Nnt Or Sensitivity: NNT not calculable from abstract data; treatment completion OR 0.51 (95% CI 0.42–0.62) represents approximately 49% lower odds of non-completion with shorter regimens — clinically significant adherence benefit

• Confidence Interval: TB disease: 95% CI 0.03–1.12; Treatment completion: 95% CI 0.42–0.62

Clinical Application

Shorter rifamycin-containing regimens (e.g., 3HP — weekly isoniazid plus rifapentine for 12 doses; 4R — 4 months of rifampicin) are feasible in outpatient paediatric settings. The demonstrated completion advantage is clinically important as non-completion is a major driver of LTBI treatment failure. Pill burden, weight-based dosing, and drug interactions (particularly with antiretrovirals) require consideration in individual patients. In Australia, LTBI management is guided by the Communicable Diseases Network Australia (CDNA) and informed by RACGP and Thoracic Society of Australia and New Zealand (TSANZ) recommendations. Rifampicin is available on the PBS (Pharmaceutical Benefits Scheme) for TB indications. Rifapentine (used in 3HP) does not currently have TGA registration in Australia, limiting the applicability of the 3HP regimen in Australian practice. The 4-month rifampicin (4R) regimen is the most feasible shorter alternative in the Australian context and is increasingly recommended. This meta-analysis provides supportive evidence for clinicians and public health units managing paediatric LTBI in Australia, particularly in communities with elevated TB burden including recent migrants, Aboriginal and Torres Strait Islander communities in high-incidence regions, and immunocompromised children. Clinicians should consult current CDNA guidelines and state/territory TB control programs when selecting regimens. Children aged 1–18 years diagnosed with LTBI, particularly those with recent TB exposure, household contacts of active TB cases, immunocompromised children, and those in high-burden settings. Findings are most directly applicable to children who would otherwise receive 9H monotherapy.

Abstract

BACKGROUND: We conducted a systematic review and meta-analysis to compare effectiveness and safety of 9 months of isoniazid (9H) versus shorter rifamycin-containing regimens for treating latent tuberculosis infection (TBI) in children. METHODS: We systematically searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials to June 2025 for randomized, controlled trials (RCTs) and cohort studies that compared regimens that were shorter than 9 months of isoniazid in children aged 1-18 years. Outcomes were development of TB disease, treatment completion, and adverse events. Risk of bias was assessed using RoB 2.0 and the Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool; certainty of evidence was graded using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Five RCTs and 7 nonrandomized studies that enrolled approximately 2950 children in trials and >25 000 in observational cohorts were included. In pooled analysis of 3 RCTs, shorter rifamycin-containing regimens resulted in little to no difference in development of TB disease compared with 9H (odds ratio [OR], 0.19; 95% confidence interval [CI], .03-1.12; moderate-certainty evidence). Treatment completion was probably higher with shorter regimens (OR, 0.51; 95% CI, .42-0.62; moderate-certainty evidence). Adverse events were similar between groups, but evidence is uncertain (low-certainty evidence). Observational data were consistent with these findings, showing higher completion rates and lower hepatotoxicity with shorter treatments. CONCLUSIONS: Shorter rifamycin-containing regimens for pediatric TBI probably increase treatment completion and have similar safety outcomes, with no important difference in development of TB disease compared with the standard regimen. These findings support current guideline recommendations that favor shorter regimens in children.

References

1. 1.Kosenko, M., Davtian, L., Iakovleva, E., Ashurov, M., Podgalo, D., Oganezova, J. G., Kondrikova, E., Bondarenko, E., Blandino, R., Sodero, G., Raffaelli, F., Martino, L., Munblit, D., & Buonsenso, D. (2026). Shorter antitubercular regimens versus 9 months of isoniazid for latent tuberculosis in children: A systematic review and meta-analysis. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. https://doi.org/10.1093/cid/ciag073