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.

Although rare, subclinical tuberculosis disease can be missed during evaluations for latent tuberculosis infection, and can manifest with symptoms during latent tuberculosis treatment. Among over 8000 patients treated for latent tuberculosis we found no evidence of acquired drug resistance, underscoring the safety of rifampin monotherapy for latent tuberculosis.

Pediatric patients were significantly more likely to complete LTBI treatment using a 4R than with a 9-month isoniazid regimen. Better completion rates of 4R may increase efficacy of tuberculosis prevention and decrease demand on public health resources.