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Isoniazid treatment of children: can genetics help guide treatment?
  1. N Cranswick1,
  2. K Mulholland2
  1. 1Australian Paediatric Pharmacology Research Unit, Royal Children’s Hospital and Murdoch Children’s Research Institute, University of Melbourne, Australia
  2. 2Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
  1. Correspondence to:
    Prof. K Mulholland
    Infectious Disease Epidemiology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (University of London), Keppel Street, London WC1E 7HT, UK;

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Commentary on the paper by Schaaf et al (see page 614)

Half of the world’s population are children, yet many of the most important developments in drug therapy ignore the needs of this most vulnerable population. With Mycobacterium tuberculosis as the cause of one of the most important chronic infectious diseases worldwide,1 it is gratifying to see research that describes the integration of modern molecular techniques to improve the delivery of the most important component of tuberculosis treatment for the world’s children. The study by Schaaf and colleagues,2 reported in this issue of the journal, focuses our attention on isoniazid therapy which is still the mainstay of tuberculosis therapy for both adults and children.

For most drugs, children need specific doses, usually defined in terms of body weight. Extrapolation of the dose from adult studies by body weight would result in the under-dosing of many drugs, as children are proportionally more efficient at clearing the drugs.3 Isoniazid is a good example. The study by Schaaf et al highlights the fact that not only are higher doses required in childhood to achieve the same levels as adults, but also that children are as metabolically heterogeneous as adults. Correct dosage is important to maximise the chances of effective treatment, and to minimise the chances of adverse effects, both serious and minor. Adherence in tuberculosis treatment of children is poor4 and may be improved by minimising adverse effects of therapy.

Where a drug is being used for the treatment of infections, the appropriate efficacious dose is defined by the characteristics of the organism as well as host factors such as absorption. Drug exposure must be adequate to control or eliminate the infection.5,6 Adverse effects are host dependent and may be dose related or idiosyncratic. Many of …

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  • Competing interests: none declared

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