Performance of interferon-γ Release Assay for the Diagnosis of Active or Latent Tuberculosis in Children in the First 2 Years of Age

Garazzino, Silvia; Galli, Luisa; Chiappini, Elena; Pinon, Michele; Bergamini, Barbara Maria; Cazzato, Salvatore; Monte, Paola Dal; Dodi, Icilio; Lancella, Laura; Esposito, Susanna; Montagnani, Carlotta; Martino, Maurizio de; Tovo, Pier Angelo

doi:10.1097/inf.0000000000000353

Cited by 33 publications

(22 citation statements)

References 29 publications

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“…Results have been conflicting at times, with some studies showing comparable sensitivity and specificity to TST, whereas others found higher or lower sensitivity. 3,[26][27][28][29][30][31][32] Rates of indeterminate QFT tests have been higher in young children than in adults; 26,[33][34][35][36] although in this study, we noted a low rate of indeterminate tests (0·4% of all tests).…”

Section: Discussionmentioning

confidence: 39%

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

Andrews

Nemes

Tameris

et al. 2017

The Lancet Respiratory Medicine

123

113

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Background: The value of quantitative interferon-γ release assay results for predicting progression from Mycobacterium tuberculosis infection to active disease is unknown. Methods: We analysed data from a reported vaccine efficacy trial of MVA85A in South Africa. QuantiFERON-TB Gold In-Tube (QFT) negative, HIV uninfected infants aged 18–24 weeks were enrolled. We stratified participants by quantitative QFT result (IFN-γ <0.35, 0·35–4·00, >4·00 IU/ml) at the intermediate study visit (Day 336) and determined risk of progression to active tuberculosis disease over the subsequent 6–24 months. No QFT differences were observed between placebo and MVA85A groups; therefore, both groups were included in analyses. Study clinicians were not blinded to QFT values, but strict case definitions were used and excluded QFT results. Findings: Among 2,512 infants with QFT tests performed at Day 336, 172 (6·8%) were positive. Compared with QFT non-converters (disease incidence 0·7 per 100 person-years; 95% CI: 0·4–1·1), children with QFT conversion at IFN-γ values between 0·35–4·00 IU/ml did not have significantly increased risk of disease (2·5 per 100 person-years; 95% CI: 0·4–9·4; IRR 3·7; p=0·23). However, QFT conversion at IFN-γ values >4·00 IU/ml was associated with markedly increased disease incidence (28·0 per 100 person-years; 95% CI: 14·9–45·7) compared to nonconverters (IRR 42·5; p<0·0001); and compared to children with IFN-γ values between 0·35–4·00 IU/ml (IRR: 11·4; p=0·00047). Among 91 QFT converters with a repeat test, 53 (58·2%) reverted from positive to negative. QFT reversion risk was inversely associated with IFN-γ value at QFT conversion and was highest (47/61; 77·0%) with IFN-γ values <4·00 IU/ml. Interpretation: In young children, tuberculosis disease risk was not significantly elevated, and QFT reversion was common, following QFT conversion at IFN-γ values up to 10 times the recommended test threshold. By contrast, QFT conversion at very high IFN-γ values (>4·00 IU/ml) warrants intensified diagnostic and preventive intervention for extremely high risk of tuberculosis disease.

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Section: Discussionmentioning

confidence: 39%

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

Andrews

Nemes

Tameris

et al. 2017

The Lancet Respiratory Medicine

123

113

View full text Add to dashboard Cite

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“…Evaluation of IGRA performance in children remains limited due to small study sizes, resistance to phlebotomy, and difficulty in obtaining culture-confirmed results for reference (32). Sensitivity and specificity have been assessed in studies using either culture-confirmed cases or an exposure gradient as a surrogate for infection, but outcomes as well as proportion of indeterminate results are discordant, particularly in infants under 5 years (19,20,33,34). In our previous report, we showed good sensitivity (93.3%) and specificity (99.3%) of QFT-IT in comparison with TST for diagnosis of active TB (23).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis

et al. 2018

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The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to -specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.

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“…35 Prior guidelines have recommended the TST in children younger than 5 years of age, but increasingly the IGRA are being preferred in children of all ages who have likely been BCG vaccinated. 35 Studies which found comparable sensitivity and superior specificity of the QFT-GIT as compared with the TST, [36][37][38] as well as a longitudinal study of QFT-GIT conversions 39 are providing helpful data to guide care. Children younger than 2 years of age are at particularly high risk of progression to active TB.…”

Section: Guidelines For Use Of Tst/igra For Ltbi Testingmentioning

confidence: 99%

Latent tuberculosis infection: Opportunities and challenges

et al. 2018

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Diagnosing and treating latent tuberculosis (TB) infection (LTBI) is recognized by the World Health Organization as an important strategy to accelerate the decline in global TB and achieve TB elimination. Even among low-TB burden countries that have achieved high rates of detection and successful treatment for active TB, a number of barriers have prevented implementing or expanding LTBI treatment programmes. Of those infected with TB, relatively few will develop active disease and the current diagnostic tests have a low predictive value. LTBI treatment using isoniazid (INH) has low completion rates due to the long duration of therapy and poor tolerability. Both patients and physicians often perceive the risk of toxicity to be greater than the risk of reactivation TB. As a result, LTBI treatment has had a limited or negligible role outside of countries with high resources and low burden of disease. New tools have emerged including the interferon-gamma release assays that more accurately diagnose LTBI, particularly in people vaccinated with Bacillus Calmette-Guerin (BCG). Shorter, better tolerated treatment using rifamycins are proving safe and effective alternatives to INH. While still imperfect, TB prevention using these new diagnostic and treatment tools appear cost effective in modelling studies in the United States and have the potential to improve TB prevention efforts globally. Continued research to understand the host-organism interactions within the spectrum of LTBI is needed to develop better tools. Until then, overcoming the barriers and optimizing our current tools is essential for progressing toward TB elimination.

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Performance of interferon-γ Release Assay for the Diagnosis of Active or Latent Tuberculosis in Children in the First 2 Years of Age

Cited by 33 publications

References 29 publications

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study

Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis

Latent tuberculosis infection: Opportunities and challenges

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