Interferon-Gamma Release Assay Testing in Children Younger Than 2 Years in a US-Based Health System
James Gaensbauer1,2,3,4, Janine Young2,3,5, Cara Harasaki2,3,5
1From the Denver Metro Tuberculosis Clinic, Denver Public Health, Denver, CO.
Insights
Interferon-gamma releasing assays (IGRAs) show promise for diagnosing TB in children under two years old. Careful introduction of IGRA testing in this age group may be beneficial, especially for BCG-vaccinated children.
Area of Science:
- Pediatrics
- Infectious Diseases
- Immunology
Background:
- Interferon-gamma releasing assays (IGRAs) offer advantages over tuberculin skin tests (TST) in older children, but data for children under two years old are limited.
- Quantiferon-TB Gold/Gold Plus (QFT) has been used in select clinical scenarios for children under two years old since 2011.
Purpose of the Study:
- To evaluate the utility and safety of QFT testing in children under two years old.
- To analyze QFT test results, in vitro characteristics, and clinical outcomes in this pediatric population.
Main Methods:
- Retrospective analysis of 116 QFT tests performed on children aged 7-23 months between February 2011 and August 2019.
- Evaluation of incident tuberculosis (TB) cases, test results, and comparison with TST results.
Main Results:
- 93% of QFT tests were negative, with a low rate of indeterminate or failed tests.
- 13 patients were TST-positive; most were QFT-negative, and some received TB treatment based on TST or clinical findings.
- No TB disease was identified in QFT-negative patients during a median follow-up of 2.96 years.
Conclusions:
- IGRA use in children under two years old is feasible, with no significant barriers related to phlebotomy or indeterminate results.
- Careful introduction of IGRA testing in this age group could be considered, potentially amending current recommendations.
- Targeted treatment for high-risk individuals can mitigate the risk of missing infections in IGRA-negative patients.
Background:
Use of interferon-gamma releasing assays (IGRAs) in children <2 years old may derive many of the same advantages, which have led to preference over tuberculin skin test (TST) in older children, but data are limited. Since 2011, we have tested children <2 years old with Quantiferon-TB Gold/Gold Plus (QFT)) in select clinical scenarios at Denver Health, a health system encompassing a TB clinic, refugee and immigrant screening and primary care.
Methods:
We identified patients <2 years old tested with QFT between February, 2011 and August, 2019. The primary outcome measure was incident cases of TB among tested patients. Test results and in vitro characteristics were analyzed, as were demographic, epidemiologic and clinical outcomes.
Results:
We analyzed 116 QFTs ordered in children age 7-23 months. Two were positive, 3 indeterminate, 3 failed/refused phlebotomy and the remainder (93%) were negative. Mitogen tube results were robust. Thirteen patients were TST-positive: 11 were QFT-negative, 1 QFT-positive and 1 failed phlebotomy. Eight patients received some form of TB medication, including 4 QFT-negative patients who were treated for active TB or latent TB infection based on positive TST or clinical findings. Among QFT-negative patients, including 6 TST-positive, not treated for active TB or latent TB infection, no TB disease has been identified over a median follow-up time of 2.96 years.
Conclusions:
IGRA use was not limited by barriers of phlebotomy, indeterminate result or gamma-interferon production. The risk of missing an infected but IGRA-negative patient can be reduced by treatment of select patients at higher risk. Current recommendations against IGRA use in children <2 years old could be amended to allow careful introduction, particularly among well-appearing BCG-vaccinated patients.
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