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Stefanie Castell, MD, MSc Roland Diel German Central Committee against Tuberculosis (DZK)

Predictive Value of IGRAs for Progression to Active TB in Children: Results of a longitudinal study in Germany using IGRAs. Stefanie Castell, MD, MSc Roland Diel German Central Committee against Tuberculosis (DZK) 15 January, 2012. TB-Epidemiology in Germany. Incidence: all age groups.

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Stefanie Castell, MD, MSc Roland Diel German Central Committee against Tuberculosis (DZK)

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  1. Predictive Value of IGRAs forProgression to Active TB in Children: Results of a longitudinal study in Germany using IGRAs Stefanie Castell, MD, MSc Roland Diel German Central Committee against Tuberculosis (DZK) 15 January, 2012

  2. TB-Epidemiology in Germany Incidence: all age groups Cases/100,000 Children <15 years Cases/100,000 www.rki.de

  3. Research questions: • How many contacts tested positive with an IGRA will develop active TB later? • How do IGRA and TST compare regarding progression?

  4. Study designDiel et al. AJRCCM, 2011 • Study population: • Hamburg (Germany) • close contacts of smear + culture + index cases, recruited 5/2005 – 4/2008 (follow-up until 4/2010) • at least 40h of exposure time (shared air) indoors during the 3 months before the diagnosis of the index case • IGRA: QuantiFERON-TB Gold in-tube assay (QFT) • Outcome assessment: reporting of progression to active TB obligatory due to the German Infectious Diseases Law • Diagnosis of TB: based on history, symptoms, clinical findings, X-ray, CT scan, detection of M.tb. (microscopy, PCR: sputum, bronchoscopy, gastric lavage), TST/IGRA, response to TB treatment

  5. Study designDiel et al. AJRCCM, 2011 close contacts Both QFT and TST QFT positive TST positive (>5mm) TST positive (>10mm) offered preventive therapy* * by doctors not involved in the study

  6. Study recruitment profileDiel et al. AJRCCM, 2011 1417 close contacts 141 children < 16 years 79 without TST, 3 indeterminate 381moved 106 children 954 close contacts 23 QFT positive 42 TST positive (5mm) 21 TST positive (10mm) 40 without preventive therapy 20 without preventive therapy 21 refused preventive therapy 104 untreated close contacts under 16 years Median follow-up: 4.2 years (Min 0.3, Max 4.7)

  7. ResultsDiel et al. AJRCCM, 2011 21children QFT + 1 child 40 children + TST 5mm 20 children + TST 10mm 3 children 17 children

  8. Progression on the basis of QFT resultsDiel et al. AJRCCM, 2011 1417 close contacts 141 children < 16 years 79 without TST, 3 indeterminate 381moved 106 children 954 close contacts 23 QFT positive 83 QFT negative 21 refused preventive therapy 0 developed active TB 6 developed active TB 0% 28.6%

  9. Progression on the basis of TST results: 5mm Diel et al. AJRCCM, 2011 1417 close contacts 141 children < 16 years 79 without TST, 3 indeterminate 381moved 106 children 954 close contacts 42 TST positive (5mm) 64 TST negative (5mm) 40 without preventive therapy 6 developed active TB 0 developed active TB 15.0%( 28.6%) 0%( 0%)

  10. Progression on the basis of TST results: 10mm Diel et al. AJRCCM, 2011 1417 close contacts 141 children < 16 years 79 without TST, 3 indeterminate 381moved 106 children 954 close contacts 21 TST positive (10mm) 85 TST negative (10mm) 20 without preventive therapy 4 developed active TB 2 developed active TB 20.0%( 15.0  28.6%) 2.4%( 0%  0%)

  11. Results regarding different age groups Diel et al. AJRCCM, 2011 • Proportion of untreated QFT + contact persons who developed TB: • All children: 28.6% • children < 6 years: 50.0% (3 of 6 QFT+, 95%-CI 14.7-85.3) • children 6 – under 16: 20.0% (3 of 15 QFT+, 5.4-45.4) • adolescents and adults: 10.3% (13 of 126 QFT+, 5.9-16.6) • Mean time from testing to TB: • children: 4.5 months • adults: 12.5 months

  12. Progression to active TB and INF-gamma levels* Diel et al. AJRCCM, 2011 . *for the 954 subjects with both results available. The 19 individuals who developed TB disease are marked by X. Children under 16 years with active TB

  13. Key points Diel et al. AJRCCM, 2011 • High risk of progression to active TB in children if untreated, especially in young children. • The QFT is at least as good as the TST (5mm) to predict progression to active TB in children and teenagers < 16 years. • More education about preventive therapy is needed.

  14. Thank you for your attention! www.dzk-tuberkulose.de

  15. BCG vaccination: trendsDiel et al. AJRCCM, 2011 • Proportion of QFT + results in • BCG vaccinated children: 13.9% (5 of 36) • Non BCG vaccinated children: 26.5% (18 of 68) => possible protective effect of BCG vaccination regarding LTBI • Of the children who developed active TB, none were vaccinated. => possible protective effect of BCG vaccination regarding progression to active TB

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