1. Utility of IGRAs in children when used as per Canadian Guidelines Winsley Rose Wanatpreeya Phongsamart Kerry Chong Ray Lam Ian Kitai No conflicts of interest Funding: Pediatric Consultants, Hospital for Sick Children

2. Interferon Gamma Release Assays(IGRAs) Compared with TST – Higher specificity in low incidence setting – Correlate better with surrogate measures of MTB exposure – No cross reactivity with BCG and most NTM Questions remain! – Utility in < 5 year olds – Utility in childhood contacts in low incidence setting Epidemiol Infect. 2008 Sep;136(9):1179-87 Clin Infect Dis. 2007 Aug 1;45(3):322-8

3. Canadian IGRA Guidelines: Briefly! Add on Suspected TB disease LTBI – Immunocompromised – Contacts : > probability of infection – close contacts > risk of progression esp. age <5 yrs Rule out LTBI – Contacts: < probability of LTBI eg. casual contact No high risk factors for progression – Other Low risk >5 with positive TST < probability of infection No high/increased risk factors for progression CCDR June 2010, Vol 36

4. Methods Study population – All HIV negative children attending Paediatric TB clinic at SickKids, Toronto between March 2008 and September 2010 Screened as per Canadian guidelines – TST and IGRA (QFT G-IT) Add on Household TB contact (increased pre-test probabilty of LTBI) Risk factors for disease progression including age <5 years Rule out Non-household TB contact/no contact (reduced pre-test probability of LTBI) No risk factors for disease progression

5. Study population 217 165(76%)52(24%) 142(86%)23(14%)25(48%) 2(4%) No contactcontact HouseholdNon-householdScreening Diagnostic work upImmunosuppression 305 88 excluded (TST-QFT interval > 6 weeks) Place of Birth by TB incidence

6. QFT-TST concordance and discordance Household Contacts (n 142) Non-household Contacts (n 23) No contacts (n 52) 3 (13%) 10 (19%) 77% 62% 38%

7. QFT TST Age<5 OR 0.31(0.13-0.68) HHS- vs HHS+ OR 0.25 (0.09-0.62) TB disease OR 11.34(1.84-220.99) NHHS+ vs HHS+ OR 0.35(0.12-0.88 ) Age<5 OR 0.18(0.08-0.38) BCG OR 2.98(1.45-6.22) Mutiple variable analysis – contacts only (n 162)

8. Evaluation as per Canadian guidelines `Add on` Test Additional value in TB disease 11.1% Additional value in high risk contacts 5.3% All were household contacts None <5 or immunocompromised

9. Evaluation as per Canadian guidelines `Rule out` Test ‘Excluded’ LTBI in low risk contacts 60% ‘Excluded’ LTBI in children with no contact 72%

10. Conclusions Quantiferon produced no indeterminate results in our children. It correlates better with TST when surrogate markers of exposure are strong eg. Household smear positive contact When used as per Canadian guidelines – “Ruled out” latent TB in low risk contacts with positive TST (67.5%) Longitudinal studies required to validate the Canadian guidelines esp. of TST-QFT+ – Improved detection in TST negatives Of latent TB in high risk contacts (5.3%) Of disease (11.1%-- but numbers are small)