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Issues in TB Drug Development For a Paediatric Indication PR Donald PR Donald Paediatrics and Child Health Tygerberg Children’s Hospital Stellenbosch University

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Issues in TB Drug Development for a Paediatric Indication 1.Importance of childhood tuberculosis 2.Features of childhood tuberculosis 3.Children are not just small adults 4.Examples of pharmacokinetic differences between adults and children 5.Examples of approach in previous evaluations of TB therapy in children 6.Conclusion

Text of Issues in TB Drug Development For a Paediatric Indication PR Donald PR Donald Paediatrics and Child...

Issues in TB Drug Development For a Paediatric Indication PR Donald PR Donald Paediatrics and Child Health Tygerberg Childrens Hospital Stellenbosch University Stellenbosch University Cape Town South Africa Reis FJC, Bedran MBM, Moura JAR, Assis I, Rodrigues MESM. Six-month isoniazid-rifampin treatment for pulmonary tuberculosis in children. Am Rev Respir Dis 1990; 142: It is very difficult to assess the outcome and efficacy of any regimen for treatment of tuberculosis in children because they rarely have positive sputum and gastric washings and the best criteria would be clinical findings, such as weight gain and radiologic follow-up studies. It is very difficult to assess the outcome and efficacy of any regimen for treatment of tuberculosis in children because they rarely have positive sputum and gastric washings and the best criteria would be clinical findings, such as weight gain and radiologic follow-up studies. Issues in TB Drug Development for a Paediatric Indication 1.Importance of childhood tuberculosis 2.Features of childhood tuberculosis 3.Children are not just small adults 4.Examples of pharmacokinetic differences between adults and children 5.Examples of approach in previous evaluations of TB therapy in children 6.Conclusion Importance of childhood tuberculosis 5% of the tuberculosis case load in developed communities5% of the tuberculosis case load in developed communitiesBUT Between 20-40% in developing communitiesBetween 20-40% in developing communities Donald PR, Int J Tuberc Lung Dis 2004;8: ) Features of Childhood Tuberculosis Mortality and morbidity is age relatedMortality and morbidity is age related The youngest children will often be the sickest children Miliary tuberculosisMiliary tuberculosis Tuberculous meningitisTuberculous meningitis Lymphobronchial tuberculosisLymphobronchial tuberculosis Features of Childhood Tuberculosis Cavitation is uncommon, lesions are thus usually paucibacillaryCavitation is uncommon, lesions are thus usually paucibacillary Organisms are dormant or intermittently activeOrganisms are dormant or intermittently active Frequently culture negative (at best 40% culture positive)Frequently culture negative (at best 40% culture positive) Seldom smear-positiveSeldom smear-positive Radiological extent of disease is not necessarily related to bacteriological burdenRadiological extent of disease is not necessarily related to bacteriological burden Features of Childhood Tuberculosis If evaluated shortly after infection: Gastric aspirate may yield a positive cultureGastric aspirate may yield a positive culture Culture of urine is reported positive in 20% or more of childrenCulture of urine is reported positive in 20% or more of children Chest radiograph may show adenopathy in up to 80% of individualsChest radiograph may show adenopathy in up to 80% of individuals Chest radiograph may be normal, but gastric aspirate culture positive and CT or MRI shows adenopathy !!Chest radiograph may be normal, but gastric aspirate culture positive and CT or MRI shows adenopathy !! Mortality in relation to age Age (yrs)Number infectedMortality (%) Young adults Wallgren A. Primary tuberculous infections in young adult life and in childhood. Am J Dis Child 1941; 61: Mortality in relation to age Age of child Mortality (%)