Beyond Randomized Trials – TB Treatment in Children
(2010; 12 pages)

Abstract

Tuberculosis (TB) represents a major cause of morbidity and mortality in the paediatric population. Of the estimated 8.3 million new tuberculosis cases diagnosed worldwide in 2000, 884,019 (11%) were children. Due to the difficulty of establishing an accurate diagnosis of tuberculosis in children, exact figures are difficult to calculate. In endemic areas their contribution to disease burden has been estimated to be up to 14%.

The impact of TB is particularly devastating in young children as they are more likely than adults to develop TB disease following exposure to the bacterium Mycobacterium tuberculosis, are at increased risk for severe disease, including disseminated and meningeal TB and have disproportionately higher rates of morbidity and mortality. It is well recognized that for treatment of TB in adults, proper dosages and duration of treatment are key to reducing the risk of progression from latent to active TB disease, achieving high rates of cure and preventing development of drug-resistant disease. The same should be true for the treatment of TB in children.

The WHO guideline for national TB programmes in children was first published in 2006. This publication included revised recommendations on the use of ethambutol in children, following a review of efficacy and safety. The amended daily dose of ethambutol for children of all ages was 20 mg/kg, with a range of 15–25 mg/kg. The previously recommended daily dose of ethanbutol for children varied from 15 mg/kg (without range) to 15–20 mg/kg and 20 mg/kg (range 15–25 mg/kg), with advice not to use in children < 5 years of age. In undertaking that review, two issues were highlighted: first, that children metabolize TB medicines differently than do adults, and second, that there was evidence available to inform dosage recommendations about these ‘old’ drugs. Neither of these findings are new but the systematic consideration of the findings to inform WHO recommendations was important.

To update the WHO 2006 recommendations for the treatment of TB in children, a series of literature reviews of clinical studies were carried out. As there are very few randomized trials of TB treatment in children, it was decided to include observational and pharmacokinetic studies to inform treatment decisions and ensure that all available evidence was considered. This overview provides a summary of the reviews and key issues encountered when using the data to develop recommendations.

 
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