JPIDS Article Review: June 2016

Grinsdale JA. Interferon-Gamma Release Assays and Pediatric Public Health Tuberculosis Screening: The San Francisco Program Experience 2005 to 2008.

Written by: Christina Gagliardo, MD

Grinsdale et al. describe the experience of the San Francisco Department of Public Health’s (SFDPH) use of interferon-gamma release assays (IGRA) in a longitudinal retrospective pediatric cohort in a low TB-prevalence setting.

Latent tuberculosis infection (LTBI) was diagnosed in asymptomatic children with negative chest X-ray and positive QuantiFERON-TB Gold In-tube (QFT), regardless of tuberculin skin test (TST) results, if performed. A small subset of children with a prior or current positive TST and a negative QFT were treated for LTBI at the physician’s individual discretion. Indeterminate QFT tests were repeated and the subsequent test used to establish LTBI status, and for repeated indeterminate QFT tests, diagnosis of LTBI was based on the most recent TST result.

Inclusion criteria for the study were children <15 years of age with a QFT test performed March 1, 2005–December 31, 2008, with 1092 eligible children included. Children had varying risk factors for TB infection including contacts of active TB cases, immigrant children form high-prevalence TB countries who were also BCG vaccinated, and children born in the US being screened for school entry. The study population included 56 (5%) children <2 years of age and 292 (27%) < 5 years of age. QFT-negative/TST-positive discordant results were present in 158 (73%) of children.

976 (89%) of children in the cohort were not treated for LTBI, and observed for a median of 5.7 (range 4–7) years. No cases of active TB were seen in any untreated child during the 5587 person-years of follow-up, including among 146 TST-positive/QFT-negative children. Discordance between TST and QFT was most pronounced in BGC-vaccinated children born outside of the US who were <5 years old (93%) versus 73% in those > 5 years old, consistent with studies showing higher false positive TST results when BCG vaccine was given more recently. This highlights that widespread use of TST in foreign-born children inadvertently leads to increased and potentially unnecessary radiologic studies and LTBI treatment.

The findings of the study suggest that QFT has a high negative predictive value and supports use of IGRAs in screening BCG- and non-BCG vaccinated children, including those <5 years of age, and may prevent unnecessary imaging and treatment for LTBI in many children.

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