Performance of Tuberculin Skin Tests and Interferon-γ Release Assays in Children Younger Than 5 Years

Abstract

Background: Available data to assess the optimal diagnostic approach in infants and preschool children at risk of tuberculosis (TB) are limited. Methods: We conducted a prospective observational study in children younger than 5 years undergoing assessment with both tuberculin skin tests (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays at 2 tertiary TB units in Barcelona, Spain. Results: A total of 383 children were included. One of 304 participants considered uninfected developed active TB during follow-up {median [interquartile range (IQR)]: 47 [30; 48] months}, compared with none of 40 participants with latent TB infection [follow-up since completion of anti-TB treatment: 42 (32; 45) months]. Overall test agreement between TST and QFT-GIT was moderate (κ = 0.551), but very good in children screened after TB contact (κ = 0.801) and in Bacillus Calmette-Guérin (BCG)-unvaccinated children (κ = 0.816). Discordant results (16.8%, all TST+/QFT-GIT−) were mainly observed in new-entrant screening and in BCG-vaccinated children. Children with indeterminate QFT-GIT results were on average younger than those with determinate results (median age: 12 vs. 30 months; P < 0.001). The sensitivity of TSTs and QFT-GIT assays in children with confirmed active TB was 100% (95% confidence interval: 79.4%–100%) and 93.7% (95% confidence interval: 69.8%–99.8%), respectively. In patients with latent TB infection or active TB, there was no correlation between age and antigen-stimulated interferon-γ responses (r = −0.044; P = 0.714). Conclusions: In young BCG-unvaccinated children with recent TB contact, a dual testing strategy using TST and QFT-GIT in parallel may not be necessary. However, TST+/QFT-GIT− discordance is common, and it remains uncertain if this constellation indicates TB infection or not. In active TB, QFT-GIT assays do not perform better than TSTs.

A Case of Miliary Perinatal Tuberculosis in a Preterm Newborn Infant Presenting as Peritonitis

“…Diagnostic workup should begin with obtaining sputum samples, most commonly via gastric aspiration for the detection of: TB DNA via polymerase chain reaction (PCR), TB culturing, and TB acid-fast staining. PCR detection yields the highest likelihood to be consistently positive (67%), while positive results for cultures and acid faststaining range between 24%-40% and 10%-50%, respectively, across various studies [16][17][18].…”

Tuberculosis infection in under‐2‐year‐old refugees: Should we be screening? A systematic review and meta‐regression analysis

“…There is conflicting evidence on the use of IGRA in children under 5 years old; some studies have found a high level of reproducibility with TST and high specificity, whereas others cite the problems of low reproducibility and low sensitivity . While noting the low‐quality evidence, the guidelines for diagnosing LTBI for under‐5‐year‐olds from the American Thoracic Society, Infectious Disease Society and Centre for Disease Control recommend the use of TST and accept both TST and IGRA results …”

Tuberculosis Transmission in a Primary School and a Private Language School. An Estimation of Infectivity

“…The reliability of IGRAs among young children are not yet welldefined and increased frequency of indeterminate results in children <5 years limits its use in the detection of LTBI in these children (29). TST+/QFT-discordant results are common, and it remains uncertain if this constellation indicates TB infection or not (30). To overcome misdiagnosis in BCG-vaccinated young children, tested for LTBI, Pavic et al recommended using both tests and considering the child infected if either or both are positive (31,32).…”