TB preventive therapy in children: 4 months of isoniazid–rifampicin halved active TB against 9H

Design

Systematic review and network meta-analysis of RCTs

Population

11 trials of children and adolescents <18 with TB infection, HIV-negative

Primary outcome

Active TB incidence, adherence and adverse reactions

Effect

4HR vs 9H: RR 0.49 (0.32–0.76) for active TB; 4R vs 9H adverse reactions OR 0.34

A systematic review and network meta-analysis in BMJ Paediatrics Open included 11 randomised trials of preventive treatment in children and adolescents under 18 with TB infection or contact with drug-susceptible TB, excluding HIV.

Four months of isoniazid plus rifampicin (4HR) reduced active TB compared with nine months of isoniazid (9H) (RR 0.49, 95% CI 0.32–0.76). All three short regimens — 3HP, 4HR and 4R — had better completion than 9H (RR 1.07–1.12). Adverse reactions were less frequent with 4R than with 9H (OR 0.34) and more frequent with weekly isoniazid–rifapentine (3HP) than with 4HR (OR 4.56) or 4R (OR 6.37).

Shorter rifamycin-based regimens are already recommended by WHO for children, and India's programme offers shorter options alongside isoniazid. This analysis adds direct support for preferring them. The network was sparse and partly disconnected, so the comparisons between short regimens are less secure than their shared advantage over 9H. Check rifampicin interactions in any child on other long-term drugs.

• Where available, consider a short rifamycin-based regimen (3HP, 3HR/4HR or 4R) over prolonged isoniazid monotherapy for child contacts.
• 4R had the fewest adverse reactions; 3HP had more than other short regimens in this analysis.
• Warn families that rifampicin colours urine and tears orange.
• Follow national programme guidance on regimen and dosing for the child's age and weight.

Why it matters

Completion is the weak point of preventive therapy, and shorter regimens fix it without losing effect.

Don't overread it

The network was sparse; head-to-head differences between the short regimens are uncertain.

The statistics, in plain English

A risk ratio of 0.49 means about half as many children developed active TB on 4HR as on 9H. The adherence risk ratios of 1.07–1.12 mean completion was about 7–12% higher in relative terms.

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