Paediatric TB: children under 25 kg were underexposed to ethambutol at WHO doses

Design

Individual patient data meta-analysis with population PK modelling

Population

220 children aged 0.2-15 years on first-line TB therapy, 3 studies

Primary outcome

Ethambutol exposure (AUC) vs adult target at WHO doses

Effect

Children under 25 kg below target; optimised bands raise dose in 40.5%

An individual patient data meta-analysis in The Journal of Infectious Diseases (September 2026) pooled 1,085 plasma ethambutol concentrations from 220 children aged 0.2 to 15 years (3.6 to 43 kg) in three studies, built a population pharmacokinetic model, and simulated exposure against the adult target (AUC 13.8 to 17.7 mg·h/L).

Clearance and volumes scaled with weight, and clearance matured with age. At current WHO-recommended doses, children under 25 kg had median exposures below the target range. Model-informed weight bands would increase the dose in about 40.5% of children, with a further 5% possibly benefiting.

This is modelling against a target derived in adults, not a trial showing better cure rates, and the authors note that toxicity — ethambutol's optic neuropathy — and practical issues with formulations must be weighed. Dosing should follow national programme guidance until it is revised.

The finding matters most where paediatric TB is common. It adds ethambutol to the list of TB drugs for which young children appear to be underdosed by weight-based tables built on adult pharmacokinetics.

• Dose ethambutol exactly to the current weight band — underdosing is already the risk in small children
• Reweigh children during TB treatment and move up a band as they gain weight
• Do not exceed programme doses on your own; await revised guidance
• Ask older children about blurred vision or colour change, and check visual acuity where they can cooperate
• Use dispersible fixed-dose combinations where available to avoid splitting errors

Why it matters

It suggests the youngest children with TB may be getting too little of a first-line drug.

Don't overread it

This is modelling against an adult-derived exposure target; it does not show better outcomes with higher doses.

The statistics, in plain English

AUC — area under the concentration-time curve — measures total drug exposure. A median below the target range means more than half of simulated children under 25 kg would fall short of the exposure associated with efficacy in adults.

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