Interferon-Gamma Release Assay Testing in Children Younger Than 2 Years in a US-Based Health System.

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.

Interferon-Gamma Release Assay-Based Screening for Pediatric Latent Tuberculosis Infection in an Urban Primary Care Network.

OBJECTIVE: To assess outcomes from a QuantiFERON-tuberculosis (TB) Gold (QFT)-based screening for pediatric latent TB infection (LTBI) in the Denver Health Community Health System (CHS), an urban primary-care network in the US. STUDY DESIGN: We retrospectively analyzed all QFTs (n = 6685) performed on children aged 2-18 years between January 5, 2011, and August 18, 2014. Risk factors for positive testing in the CHS population were identified by logistic regression, and further assessed using a case-control comparison. Results from CHS were compared with higher-TB-risk populations (refugee and TB clinics) in our health system. RESULTS: Positive QFT occurred in 79 of 3745 (2.1%) CHS patients. Positive rates increased with age (0.3% in age 2-5 years to 4.9% in age 13-18 years). Indeterminate results were uncommon (0.8%) including in children <5 (1.3%). Risk factors for positive tests in the CHS population included non-Medicaid insured/uninsured and non-English/Spanish preferred language. In the case-control analysis, birth/travel to/residence in a TB-endemic country was the only identified risk factor for positive testing (OR 5.2 [95% CI 1.04-25.5]). Rates of positive testing were lower in the CHS population than the refugee/TB clinic populations, including among children age 2-5. DISCUSSION: QFT-based LTBI screening was successfully introduced in our pediatric primary-care health system, and supported our programmatic goals of identifying LTBI cases while limiting unnecessary LTBI treatment courses. Increasing positive rates with age, and higher rates in the refugee/TB populations compared with CHS, add indirect evidence of adequate test sensitivity, even among young children, for whom data on interferon-gamma release assay performance are limited.