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Interferon-Gamma Release Assays and Pediatric Public Health Tuberculosis Screening: The San Francisco Program
Jennifer A Grinsdale1, Shamim Islam2, Olivia Chang Tran3
1San Francisco Department of Public Health, Population Health Division, California.
Insights
The QuantiFERON-TB Gold test is effective for diagnosing latent tuberculosis infection in children, especially those vaccinated with BCG. Untreated children testing negative showed no progression to active TB, supporting its use in pediatric screening.
Area of Science:
- Pediatric infectious diseases
- Immunological assays
- Tuberculosis diagnostics
Background:
- Limited longitudinal data exists for interferon-gamma release assay (IGRA) utilization in pediatric tuberculosis (TB) screening.
- This is particularly true in populations with a low burden of TB.
Purpose of the Study:
- To evaluate the utility of QuantiFERON (QFT)-TB Gold assay in pediatric TB screening.
- To assess QFT-TB Gold's concordance with the tuberculin skin test (TST) and its predictive value for active TB development in children.
Main Methods:
- Retrospective review of QFT-TB Gold results in children under 15 years old in San Francisco (2005-2008).
- Analysis of QFT-TB Gold and TST concordance in a subset of children.
- Tracking of disease progression to active TB via TB registries.
Main Results:
- Of 1092 children, 7% tested positive by QFT. Positive rates varied by risk factors like foreign birth and TB exposure.
- Discordance between QFT-negative and TST-positive results was higher in foreign-born, BCG-vaccinated children under 5.
- No active TB cases were identified in untreated children with QFT-negative results during follow-up (100% negative predictive value).
Conclusions:
- QFT is a valuable tool for evaluating latent TB infection in children, including young BCG-vaccinated individuals.
- QFT positivity correlates with TB exposure risk, suggesting targeted testing is needed.
- The high negative predictive value supports the use of QFT in ruling out TB infection in children.
Background:
Interferon-gamma release assay utilization in pediatric tuberculosis (TB) screening is limited by a paucity of longitudinal experience, particularly in low-TB burden populations.
Methods:
We conducted a retrospective review of QuantiFERON (QFT)-TB Gold results in San Francisco children from 2005 to 2008. Concordance with the tuberculin skin test (TST) was analyzed for a subset of children. Progression to active disease was determined through San Francisco and California TB registry matches.
Results:
Of 1092 children <15 years of age, 853 (78%) were foreign-born, and 136 (12%) were exposed to active TB cases (contacts). QuantiFERON tests were positive in 72 of 1092 (7%) children; 15 of 136 (11%) recent contacts; 53 of 807 (7%) foreign-born noncontacts; and 4 of 149 (3%) US-born noncontacts. QuantiFERON-negative/TST-positive discordance was seen more often in foreign-born/bacille Calmette-Guerin (BCG)-vaccinated children <5 years of age (52 of 56, 93%) compared to those ≥ 5 years of age (90 of 123, 73%; P = .003). Foreign-born, BCG-vaccinated children were more than twice as likely to have a discordant (79%) result as US-born, non-BCG-vaccinated children (37%; P < .0001). During 5587 person-years of follow-up of untreated children, including 146 TST-positive/QFT-negative children, no cases of active TB were identified, consistent with a negative predictive value of 100%.
Conclusions:
Our experience supports the use of QFT to evaluate latent TB infection in children, particularly young BCG-vaccinated children. The proportion of QFT-positive results correlated with risk of exposure, and none of the untreated QFT-negative children developed TB. The low QFT-positive rate highlights the need for more selective testing based on current epidemiology and TB exposure risk.
