Utility of IGRAs in children when used as per Canadian Guidelines

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 lt 5 year olds
• Utility in childhood contacts in low incidence
  setting

Clin Infect Dis. 2007 Aug 145(3)322-8
Epidemiol Infect. 2008 Sep136(9)1179-87
3
Canadian IGRA Guidelines Briefly!

• Add on
• Suspected TB disease
• LTBI
• Immunocompromised
• Contacts
• gt probability of infection close contacts
• gt risk of progression esp. age lt5 yrs
• Rule out
• LTBI
• Contacts
• lt probability of LTBI eg. casual contact
• No high risk factors for progression
• Other Low risk gt5 with positive TST
• lt 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 lt5 years
• Rule out
• Non-household TB contact/no contact (reduced
  pre-test probability of LTBI)
• No risk factors for disease progression

5
Study population
305
88 excluded (TST-QFT interval gt 6 weeks)
217
No contact
contact
165(76)
52(24)
Household
Non-household
Screening
Diagnostic work up
Immunosuppression
142(86)
23(14)
25(48)
25(48)
2(4)
Place of Birth by TB incidence

6
QFT-TST concordance and discordance
Household Contacts (n 142)
77
Non-household Contacts (n 23)
62
3 (13)
No contacts (n 52)
38
10 (19)
7
Mutiple variable analysis contacts only (n 162)
QFT
Agelt5 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
Agelt5 OR 0.18(0.08-0.38)
BCG OR 2.98(1.45-6.22)
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 lt5 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)