The Likelihood of an Indeterminate Test Result from a Whole-Blood Interferon-γ Release Assay for the Diagnosis of Mycobacterium tuberculosis Infection in Children Correlates With Age and Immune Status

Haustein, Thomas; Ridout, Deborah; Hartley, John C.; Thaker, U.; Shingadia, Delane; Klein, Nigel; Novelli, Vas; Dixon, Garth

doi:10.1097/inf.0b013e3181a16394

Cited by 154 publications

(128 citation statements)

References 18 publications

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“…These results have been associated with immunosuppression, young age (,5 yrs) and a negative TST [14,19,20,29]. Interestingly, new information from different studies suggests that the increased frequency of indeterminate results in young children reflects a performance characteristic of the in vitro tests rather than a responding impairment to specific antigens and PHA [17,30,31].…”

Section: Discussionmentioning

confidence: 96%

Diagnosing TB infection in children: analysis of discordances usingin vitrotests and the tuberculin skin test

Altet-Gómez¹,

Souza-Galvão²,

Latorre³

et al. 2010

Eur Respir J

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The aim of the present study was to compare the performance of the interferon (IFN)-c tests (QuantiFERON1-TB Gold In-Tube (QFT-G-IT) and T-SPOT1.TB) with the tuberculin skin test (TST) in diagnosing tuberculosis (TB) infection in children, and to analyse discordant results.This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations o5 mm recruited during public health screenings.Positive IFN-c tests results were associated with risk of exposure (p,0.0001). T-SPOT.TB was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against Mycobacterium avium were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5-9 mm in diameter and both IFN-c tests negative. In concordant IFN-c tests results, a positive correlation was found (p50.0001) between the number of responding cells and the amount of IFN-c released. However, in discordant IFN-c tests results this correlation was negative (p50.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-c released.The use of IFN-c tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.KEYWORDS: Agreement, children, interferon-c release assays, nontuberculous mycobacterial sensitins, tuberculin skin test, tuberculosis I n 2007, the estimated global incidence of tuberculosis (TB) cases was 9.27 million. Approximately 11% of these cases were children. In the developed world, the estimated proportion of children with TB is around 3-6%, but in developing countries this percentage can reach 15-20%, with an approximate mortality of 30% [1]. Latent TB infection (LTBI) treatment is an essential strategy to eliminate TB [2], although in order to achieve any epidemiological impact, this strategy must target groups with a high risk of infection and development of the disease if they become infected. Children merit special consideration, as they can develop the disease very quickly after primary infection, with the most severe forms prevailing in younger children [3].The advantages of techniques based on the detection of interferon (IFN)-c secreted by effector T-cells stimulated with specific Mycobacterium tuberculosis antigens to diagnose LTBI over the tuberculin skin test (TST) are the lack of cross-reactivity with vaccinal Mycobacterium bovis bacille Calmette-Guérin (BCG) strains and nontuberculous mycobacteria (NTM), and the absence of booster effect [4,5]. These antigens are the early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10 encoded in region of difference (RD)1, and TB7.7 encoded in RD11, which are absent in all BCG strains and in the majority of NTM. Two commercial in vitro assays based on this technology are currently availab...

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Section: Discussionmentioning

confidence: 96%

Diagnosing TB infection in children: analysis of discordances usingin vitrotests and the tuberculin skin test

Altet-Gómez¹,

Souza-Galvão²,

Latorre³

et al. 2010

Eur Respir J

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“…In our study, patients with hypoalbuminemia, but not malnutrition, tended to have an indeterminate response. In children, indeterminate results correlated with age and immune status (39). In dialysis patients, indeterminate results occurred in 8% of QFT and 11% of T-SPOT-TB (26), and up to 24.1% using QFT in those with suspected TB in Japan (27).…”

Section: Discussionmentioning

confidence: 99%

High Prevalence of Latent Tuberculosis Infection in Dialysis Patients Using the Interferon-γ Release Assay and Tuberculin Skin Test

Lee¹,

Chou²,

Dou³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…9 Furthermore, IGRA perform considerably worse in children, and significant rates of indeterminate results are an additional problem in this age group. [10][11][12][13][14] A further significant limitation of both TST and IGRA is their inability to discriminate between LTBI and active TB, a distinction that is highly relevant in geographic regions where TB prevalence is high and a large proportion of the population has LTBI. 6 This distinction is critical, as the treatment of LTBI and active TB differs.…”

Section: Introductionmentioning

confidence: 99%

Mycobacteria-Specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis

Tebruegge

Dutta

Donath

et al. 2015

Am J Respir Crit Care Med

107

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The Likelihood of an Indeterminate Test Result from a Whole-Blood Interferon-γ Release Assay for the Diagnosis of Mycobacterium tuberculosis Infection in Children Correlates With Age and Immune Status

Abstract: These data suggest that QFT-IT may not provide a determinate test result in a substantial proportion of children in a tertiary care setting due to the combination of young age and primary and acquired immune deficiencies.

Cited by 154 publications

References 18 publications

Diagnosing TB infection in children: analysis of discordances usingin vitrotests and the tuberculin skin test

Diagnosing TB infection in children: analysis of discordances usingin vitrotests and the tuberculin skin test

High Prevalence of Latent Tuberculosis Infection in Dialysis Patients Using the Interferon-γ Release Assay and Tuberculin Skin Test

Mycobacteria-Specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis

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