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

TB-Epidemiology in GermanyC

ases

/100

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Incidence: all age groups

Cas

es/1

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00

Children <15 years

www.rki.de

Research questions:• How many contacts tested positive with an IGRA will develop

active TB later?• How do IGRA and TST compare regarding progression?

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

Study designDiel et al. AJRCCM, 2011

close contacts

offered preventive therapy*

TST positive (>5mm)

Study designDiel et al. AJRCCM, 2011

Both QFT and TST

QFT positive TST positive (>10mm)

* by doctors not involved in the study

1417 close contacts

21 refused preventive therapy

42 TST positive (5mm)

40 without preventive

therapy

Study recruitment profileDiel et al. AJRCCM, 2011

79 without TST, 3 indeterminate

381 moved

954 close contacts

23 QFT positive

106 children

104 untreated close contacts under 16 years

141 children < 16 years

21 TST positive (10mm)

20 without preventive

therapy

Median follow-up: 4.2 years (Min 0.3, Max 4.7)

ResultsDiel et al. AJRCCM, 2011

40 children+ TST 5mm

20 children+ TST 10mm

21children QFT +1 child

3 children

German born

yes 72%

no 28%

BCG vaccination

yes 35%

no 65%

Gender

male 46%

femal 54%

17 children

Mean age

10.2 years

SD 4.5

1417 close contacts

21 refused preventive therapy

Progression on the basis of QFT resultsDiel et al. AJRCCM, 2011

79 without TST, 3 indeterminate

381 moved

954 close contacts

23 QFT positive

106 children

141 children < 16 years

28.6%

83 QFT negative

0%

6 developed active TB

0 developed active TB

1417 close contacts

42 TST positive (5mm)

Progression on the basis of TST results: 5mm Diel et al. AJRCCM, 2011

79 without TST, 3 indeterminate

381 moved

954 close contacts 106 children

141 children < 16 years

40 without preventive therapy

15.0% ( 28.6%)

6 developed active TB

64 TST negative (5mm)

0 developed active TB

0% ( 0%)

1417 close contacts

21 TST positive (10mm)

Progression on the basis of TST results: 10mm Diel et al. AJRCCM, 2011

79 without TST, 3 indeterminate

381 moved

954 close contacts 106 children

141 children < 16 years

20 without preventive therapy

20.0% ( 15.0 28.6%)

4 developed active TB

85 TST negative (10mm)

2 developed active TB

2.4% ( 0% 0%)

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

0 1-5 6-10 11-15 >=16

0.00

0.25

0.50

0.75

1.001

4

7

10

(n= 313) (n= 78)(n= 363) (n= 163)(n= 37)

xx

xx

xx

x

x

x

xxx

x xxxxxx

TST induration (mm)

IFN

- R

esp

onse

(IU

/mL)

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

Key points

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.

Diel et al. AJRCCM, 2011

Thank you

for your attention!

www.dzk-tuberkulose.de

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