Comparison of Enzyme-Linked Immunospot Assay and Tuberculin Skin Test in Healthy Children Exposed to <i>Mycobacterium tuberculosis</i>

Hill, Philip C.; Brookes, Roger H.; Adetifa, Ifedayo; Fox, Annette; Jackson-Sillah, Dolly; Lugos, Moses D.; Donkor, Simon; Marshall, Roger; Howie, Stephen R. C.; Corrah, Tumani; Jeffries, David; Adegbola, Richard A.; McAdam, Keith P. W. J.

doi:10.1542/peds.2005-2095

Cited by 103 publications

(66 citation statements)

References 23 publications

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“…These data agree with findings in other studies that have investigated TB outbreaks and study contacts [4,11,[13][14][15][16][17][18]. These results also show the usefulness of IFN-c tests to diagnose LTBI in BCG-vaccinated children when they are screened as part of paediatric or epidemiological control.…”

Section: Discussionsupporting

confidence: 91%

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Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test

Altet-Gómez¹,

Souza-Galvão²,

Latorre³

et al. 2010

European Respiratory Journal

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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: Discussionsupporting

confidence: 91%

“…In published studies, this threshold can vary greatly, from 5, 10 and up to 15 mm of induration as indicative of TB infection [15,17,19,20,29], and generally depends on population groups (contacts and level of risk of development of active TB), and specific guidelines of the country.…”

Section: Discussionmentioning

confidence: 99%

Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test

Altet-Gómez¹,

Souza-Galvão²,

Latorre³

et al. 2010

European Respiratory Journal

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“…Although somewhat contradictory to reports from adult studies [6,30], the same has been reported from other paediatric cohorts in TB endemic countries [31,32], in which it was concluded that BCG vaccination was not an important cause of false-positive TST, except in communities with low TB prevalence. The findings of the present study are consistent with these observations.…”

Section: Discussioncontrasting

confidence: 81%

Interferon- release assays do not identify more children with active tuberculosis than the tuberculin skin test

Kampmann¹,

Whittaker²,

Williams³

et al. 2009

European Respiratory Journal

147

104

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Data are lacking on the performance of interferon-c release assays (IGRAs) in children. Although IGRAs are recommended for screening for latent tuberculosis infection (LTBI), many clinicians wish to employ them as a diagnostic test for active tuberculosis (TB). The objective of the present study was to compare the performance of the two commercially available IGRAs and the tuberculin skin test (TST) side-by-side in children with active TB and LTBI.In a prospective study, 209 children were investigated for active (n591) or latent TB (n5118). TST, QuantiFERON-TB Gold In-tube (QFG-IT; Cellestis, Carnegie, Australia) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK) assays were simultaneously used.For culture-confirmed active TB, the sensitivity of the TST was 83%, compared with 80% for QFG-IT and 58% for T-SPOT.TB. IGRAs did not perform significantly better than TST, although QFG-IT was significantly better than T-SPOT.TB. The agreement between QFG-IT and T-SPOT.TB in culture-confirmed TB was poor at 66.7%. In LTBI, the agreement between QFG-IT and T-SPOT.TB was very good (92%) with moderate agreement between TST and T-SPOT.TB (75%) and QFG-IT and TST (77%).A negative interferon-c release assay should not dissuade paediatricians from diagnosing and treating presumed active tuberculosis. If used for diagnosis of latent tuberculosis infection, interferon-c release assays could significantly reduce the numbers of children receiving chemoprophylaxis. Very good concordance between both tests was found.

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“…Notably, the results of a meta-analysis, involving more than 200,000 children in 24 studies, suggest that only 8.5% of individuals BCG-vaccinated in infancy develop a false-positive TST (defined as ≥ 10 mm induration), 43 indicating that BCG vaccination alone is unlikely to account for the large proportions of discordance reported in most pediatric IGRA studies. [44][45][46] In our study, we observed multiple statistically significant differences between the cytokine responses in the uninfected group and the common discordance group. Importantly, these differences were also detected in samples stimulated with ESAT-6 and CFP-10, which cannot be explained by antigenic cross-reactivity, as both peptides are absent from all BCG vaccine strains.…”

Section: Receiver Operating Characteristic Analysesmentioning

confidence: 46%

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

103

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Comparison of Enzyme-Linked Immunospot Assay and Tuberculin Skin Test in Healthy Children Exposed to Mycobacterium tuberculosis

Cited by 103 publications

References 23 publications

Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test

Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test

Interferon- release assays do not identify more children with active tuberculosis than the tuberculin skin test

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

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