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

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 Clin Infect Dis. 2007 Aug 1;45(3):322-8 Epidemiol Infect. 2008 Sep;136(9):1179-87

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

• •

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

Study population

305 217 88 excluded (TST-QFT interval > 6 weeks) contact 165(76%) No contact 52(24%) Household 142(86%) Non-household 23(14%)

Age distribution >10 years 43% <2 years 12% 2-5 years 21%

Screening Diagnostic work up Immunosuppression 25(48%) 25(48%) 2(4%)

Place of Birth by TB incidence High 38% low 62% Unvaccinated 51% BCG Vaccinated 49% 5-10 years 24%

QFT-TST concordance and discordance

Household Contacts (n 142)

60 50 40 30 20 10 0

52 (37%) 8 (6%)

QFT+TST-

77% 24 (17%) 58 (40%) Non-household Contacts (n 23)

QFT+TST+ QFT-TST+ QFT-TST 15 10 5 0

3 (13%) 62% 0 9 (38%) 11 (49%)

QFT+TST+ QFT+TST- QFT-TST+ QFT-TST-

No contacts (n 52)

30 25 20 15 10 5 0

38% 5 (10%) 27 (52%) 10 (19%) 10 (19%)

QFT+TST+ QFT+TST QFT-TST+ QFT-TST-

QFT Mutiple variable analysis – contacts only (n 162) Age<5

OR 0.31(0.13-0.68)

TB disease

OR 11.34(1.84-220.99)

HHS- vs HHS+

OR 0.25 (0.09-0.62)

NHHS+ vs HHS+

OR 0.35(0.12-0.88

)

TST Age<5

OR 0.18(0.08-0.38)

BCG

OR 2.98(1.45-6.22)

Evaluation as per Canadian guidelines `Add on` Test

Additional value in TB disease 11.1%

TB Disease (n 18) 12 4 2 0 QFT+TST+ QFT+TST- QFT-TST+ QFT-TST-

Additional value in high risk contacts 5.3%

52 High Risk Contacts(n 150) 56

All were household contacts None <5 or immunocompromised

24 8 QFT+TST+ QFT+TST QFT-TST+ QFT-TST-

Evaluation as per Canadian guidelines `Rule out` Test Low risk contacts (n 15) 9

‘Excluded’ LTBI in low risk contacts 60%

3 3 0 QFT+TST+ QFT+TST QFT-TST+ QFT-TST No known contact (n 25) 18

‘Excluded’ LTBI in children with no contact 72%

7 0 QFT+TST+ QFT+TST QFT-TST+ 0 QFT-TST-

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)