There is no confirmatory test for TB infection. Sensitivity of the TST or IGRA is measured in those with active TB disease as a proxy for TB infection. For practical purposes, a child with TB infection is considered to have no symptoms related to the infection, a positive TST or IGRA (see Chapter 4: Diagnosis of Tuberculosis Infection, Table 1, for TST interpretation guidelines), no clinical evidence of disease and a chest x-ray that is either normal or demonstrates evidence of remote infection, such as a calcified parenchymal nodule and/or a calcified intrathoracic lymph node.94,95
As with adults, the use of TST or IGRA needs to be interpreted in the clinical setting. This includes reason for testing, age, immunologic status, known contact with person(s) with infectious TB, place of residence, country of birth and foreign travel. The TST has been the most studied test in children that has some longitudinal data. Overall, the sensitivity of the TST or IGRA is similar, whereas the specificity of the IGRA is higher.96 Previous recommendations were to use IGRA only in children older than 5 years due to a lack of data. More recently, data has been published in the younger pediatric population (see Table 5).
Table 5. IGRA in young children.
Author/ Year | Total population | Design | Tests | Duration of follow- up | Population description | Outcomes |
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Ho 2021 99 | 2,088 children; 936 < 5 years of age | Prospective observational cohort | TST, QFT, T-SPOT in all | Cross sectional (Follow-up data for children is in Ahmed 2020, below) | US, at risk for TB | TST, QFT, T-SPOT + ve: All US-born: 11%, 12%, 8% Non-US born: 43%, 26%, 22% <5 years old US-born: 10%, 14%, 8% Non-US born 26%, 3.5%, 1.5% |
Ahmed 2020 100 | 3,593 children <15 years of age | Prospective cohort | TST, QFT, T-SPOT | 2 years then cross referenced with TB registry | Born outside of US, 25% less than 5 years |
|
Wendorf 2020101 | 3,371 children <5 years of age | Comparison of database with TB registry | TST 24%, IGRA 56% | 10,797 person-years, follow-up median 3 years in negative cases | California Refugee Health electronic information system; born in high-incidence countries |
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Kay 2018 97 | 778 patients <18 years with laboratory confirmed | Registry | TST, IGRA vs TB disease (50% laboratory confirmed) | California TB registry for children | IGRA vs TST (sensitivity)
|
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Lombardi 2019 102 | 226 children with TB disease | Retrospective multicenter study in Italy | QFT-IT vs TB disease (44% lab confirmed) | 9 years | Majority foreign-born | TB disease:
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Lab confirmed:
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Overall sensitivity:
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Abbreviations: TST, tuberculin skin test; QFT, quantiferon; T-SPOT, type of interferon-gamma release assay; IGRA, interferon-gamma release assay; QFT-GIT, Quantiferon Gold In-Tube type of IGRA; TB, tuberculosis.
TST should be used in children under 2 years of age; however, there are increasing data showing similar sensitivity and negative predictive value of IGRAs in this age group and some experts recommend their use instead.97 TST or IGRA can be used for children over 2 years of age. An IGRA is the preferred test in children who have received Bacille Calmette-Guérin (BCG) vaccine.
Recommendations
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We strongly recommend that either an interferon-gamma release assay or tuberculin skin test be used to test for TB infection in children older than 5 years of age (good evidence).
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We conditionally recommend that either an interferon-gamma release assay or tuberculin skin test be used to test for TB infection in children 2-5 years of age (poor evidence).
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We conditionally recommend that an interferon-gamma release assay can be used in place of a tuberculin skin test to test for TB infection in children less than 2 years of age (poor evidence).
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We strongly recommend that an interferon-gamma release assay be used to test for TB infection in children older than 2 years of age who have received the Bacille Calmette-Guérin vaccine (good evidence).
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