To the Editors:
We read with interest the articles by Spicer et al1 and Howley et al2 evaluating tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) among immigrant and internationally adopted children screened for latent tuberculosis infection (LTBI). Both studies reported a high percentage of TST-positive results (23–26%), whereas IGRAs-positive results were infrequent (4.6–5.6%).1,2
In 2012, we published our experience within a National Reference Unit for the evaluation of immigrant and internationally adopted children on the interpretation of TST and IGRAs.3,4 We agree that TST may overestimate LTBI in these populations, as suggested by both articles. However, several aspects may require clarification.
Spicer et al1 reported that positive TST was not associated with Calmette-Guérin bacillus (BCG) vaccination. However, this assumption is based on a relatively small number of children. Results from a large meta-analysis, which included 117,507 subjects, concluded that BCG significantly increased the likelihood of a positive TST.5
We compared TST and QuantiFERON-TB Gold test (QFT) in 318 asymptomatic immigrant and internationally adopted children without known TB contact, showing that TST/QFT discordant results were more frequently observed among BCG-vaccinated cases.3 In children younger than 5 years, there were more discordant results in the BCG-vaccinated group (12.5%) than in the unvaccinated population (1.5%),3 suggesting that the effect of BCG on TST is stronger during the first years.3–53–53–5 The low rate of QFT-positive results observed in younger cases2,3 also reflects a lower tuberculosis exposure at this age, supporting that IGRAs are more accurate tests for screening LTBI.
We agree with both authors that concordance between the tests is better in high-risk situations and that the rate of false-positive TST results may be important in immigrant and internationally adopted children.1–31–31–3 However, agreement between both tests was good in our non–BCG-vaccinated asymptomatic immigrant screened for LTBI (κ = 0.73) but very poor among BCG- vaccinated cases (κ = 0.31),3 despite all the children having the same risk factors for LTBI.
Some authors have suggested that BCG vaccination could prevent LTBI in children after TB exposure.6 In our study, a positive QFT test was significantly associated with no prior BCG vaccination (odds ratio, 2.8),3 supporting the hypothesis that BCG may have an effect in preventing LTBI.6 This could explain why some authors do not observe differences in TST results between BCG-vaccinated children, who will show some rate of false-positive results, and non-vaccinated children, who will more easily develop LTBI.
Adopted children are commonly younger than 5 years,1 and there are still some concerns about the use of IGRAs in young children and infants. Despite including young children in our study, we observed a very low QFT indeterminate results (4.3%),3 with no differences when comparing children younger than and older than 5 years.3
Therefore, based on our results and on previous reported data,1–41–41–41–4 we recommend the use of IGRAs as a complementary diagnostic tool in the evaluation of BCG-vaccinated asymptomatic immigrant and internationally adopted children screened for LTBI, with TST <15 mm, to differentiate potential BCG interference from LTBI. This will result in an important reduction in unnecessary radiation exposure and chemoprophylaxis.2
Ana Méndez-Echevarría, MD, PhD
Talia Sainz, MD, PhD
Milagros García-Hortelano, MD
Fernando Baquero-Artigao, MD
Maria J. Mellado, MD, PhD
Internationally Adopted Children Unit
General Paediatrics and Infectious and Tropical Diseases Department
Hospital La Paz
1. Spicer KB, Turner J, Wang SH, et al. Tuberculin skin testing and T-SPOT.TB in internationally adopted children. Pediatr Infect Dis J. 2015;34:599–603
2. Howley MM, Painter JA, Katz DJ, et al.Tuberculosis Epidemiologic Studies Consortium. Evaluation of QuantiFERON-TB gold in-tube and tuberculin skin tests among immigrant children being screened for latent tuberculosis infection. Pediatr Infect Dis J. 2015;34:35–39
3. Méndez-Echevarría A, González-Muñoz M, Mellado MJ, et al.Spanish Collaborative Group for Study of QuantiFERON-TB GOLD Test in Children. Interferon-γ release assay for the diagnosis of tuberculosis in children. Arch Dis Child. 2012;97:514–516
4. Piñeiro R, Mellado MJ, Cilleruelo MJ, et al. Tuberculin skin test in bacille Calmette-Guérin-vaccinated children: how should we interpret the results? Eur J Pediatr. 2012;171:1625–1632
5. Wang L, Turner MO, Elwood RK, et al. A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements. Thorax. 2002;57:804–809
6. Eisenhut M, Paranjothy S, Abubakar I, et al. BCG vaccination reduces risk of infection with Mycobacterium tuberculosis as detected by gamma interferon release assay. Vaccine. 2009;27:6116–6120