Interferon-γ Release Assays for Tuberculosis Infection Diagnosis in Refugees <5 Years Old

Abstract

BACKGROUND: New guidelines support using interferon-g release assays (IGRAs) in children $2 years for diagnosis of latent tuberculosis infection (LTBI). However, lack of experience in young children and concern that IGRAs are less sensitive than tuberculin skin tests (TSTs) limit their use. Our aim was to identify active tuberculosis (TB) cases among high risk children ,5 years and tested for LTBI with an IGRA. METHODS: . Retrospective review of domestic TB screening data from California's Refugee Health Electronic Information System for children ,5 years old who resettled in California between October, 2013 and December, 2016. Children were crossmatched with the California TB registry to identify cases of TB disease between October 2013 and December 2018.RESULTS: A total of 3371 children ,5 years were identified; the majority were born in countries with high TB incidence (.150 cases per 100 000). Half received IGRAs (n = 1878; 56%), a quarter received TSTs (n = 811; 24%); 1.4% of children were IGRA-positive (n = 26) and 13% were TST-positive (n = 106). Twenty-two IGRA results were indeterminate (1.2%). Sixteen children had both tests; 9 were discrepant (positive TST with negative IGRA). No cases of TB disease were identified during 10 797 person-years of follow-up.CONCLUSIONS: IGRA positivity was less than TST positivity in high risk children ,5 years old. Despite fewer LTBI diagnoses in the IGRA-tested population, no cases of TB disease among children who tested negative were identified, suggesting IGRA is valuable tool for identifying LTBI in this population.

Diagnostic Value of Interferon-Gamma Release Assays for Tuberculosis in the Immunocompromised Population

“…Different studies had different conclusions regarding the value of IGRAs and the TST for diagnosing LTBI. A cohort study of BCG-vaccinated children younger than 5 years showed that there was a high discordance (12.3%) between IGRAs and the TST, mostly TST+/IGRA− [ 40 ]; another study showed that for high-risk children aged 2–5 years old, IGRAs’ positivity was lower than that of the TST [ 41 ]. None of the TST+/IGRA− children developed into ATBI during the follow-up even without prophylactic treatment, demonstrating the false positivity of the TST that came from the cross-reaction with BCG [ 40 , 41 , 42 ].…”

“…A cohort study of BCG-vaccinated children younger than 5 years showed that there was a high discordance (12.3%) between IGRAs and the TST, mostly TST+/IGRA− [ 40 ]; another study showed that for high-risk children aged 2–5 years old, IGRAs’ positivity was lower than that of the TST [ 41 ]. None of the TST+/IGRA− children developed into ATBI during the follow-up even without prophylactic treatment, demonstrating the false positivity of the TST that came from the cross-reaction with BCG [ 40 , 41 , 42 ]. Using the TST as a standard, a meta-analysis showed that IGRAs had higher sensitivity and specificity, with the pooled sensitivity and specificity of ELISA being 84.1 and 89.5%, respectively, and the pooled sensitivity and specificity of ELISPOT were 93.1 and 76.7%, respectively [ 43 ].…”

Prevalence of Latent Tuberculosis Infection Among Healthy Young Children and Adolescents and a Two-step Approach for the Diagnosis of Tuberculosis Infection in Chengdu, China

“…27 Studies included children with different population features also support the use of IGRAs for children. [28][29][30] On the contrary, the Canadian Thoracic Society suspected that IGRA performed worse in young children than in adults. 31 However, studies of meta-analysis confirmed that IGRA was more specific in low-risk, BCG-vaccinated individuals.…”

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection

“…While for children aged ≥5–18 years, IGRAs had greater sensitivity than TST. Interestingly, several studies have shown that none of the untreated children with negative IGRA progressed to ATB even with discordant test results TST + /IGRA − , suggesting that clinicians can rely on IGRA negative results as TST might be causing overdiagnosis and unnecessary treatment [ 77 , 78 ]. Although repeated IGRA testing was required for indeterminate results, the percentage is lower than those who fail to return for TST reads [ 77 ].…”

“…In mycobacterial infections, IFN-γ released by CD4 + T cells is essential for host survival and enhances both CD4 + and CD8 + T cell activities [ 129 ]. However, false-negative IGRA results were detected in patients with TB infection with advanced age [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , …”