Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children : a systematic review and meta-analysis

Meier, Noëmi R.; Volken, Thomas; Geiger, Marc; Heininger, Ulrich; Tebruegge, Marc; Ritz, Nicole

doi:10.21256/zhaw-3232

Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-3232

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children : a systematic review and meta-analysis
Authors:	Meier, Noëmi R. Volken, Thomas Geiger, Marc Heininger, Ulrich Tebruegge, Marc Ritz, Nicole
DOI:	10.21256/zhaw-3232 10.3389/fped.2019.00208
Published in:	Frontiers in Pediatrics
Volume(Issue):	7
Issue:	208
Issue Date:	2019
Publisher / Ed. Institution:	Frontiers Research Foundation
ISSN:	2296-2360
Language:	English
Subjects:	Clinical study; IGRA; Latent; Pediatrics; Risk difference; QuantiFERON; T-SPOT.TB; T cell response
Subject (DDC):	616: Internal medicine and diseases
Abstract:	Background: Interferon-gamma release assays (IGRA) are well-established immunodiagnostic tests for tuberculosis (TB) in adults. In children these tests are associated with higher rates of false-negative and indeterminate results. Age is presumed to be one factor influencing cytokine release and therefore test performance.The aim of this study was to systematically review factors associated with indeterminate IGRA results in pediatric patients. Methods: Systematic literature review guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) searching PubMed, EMBASE, and Web of Science. Studies reporting results of at least one commercially available IGRA (QuantiFERON-TB, T-SPOT.TB) in pediatric patient groups were included. Random effects meta-analysis was used to assess proportions of indeterminate IGRA results. Heterogeneity was assessed using the I2 value. Risk differences were calculated for studies comparing QuantiFERON-TB and T-SPOT.TB in the same study.Meta-regression was used to further explore the influence of study level variables on heterogeneity. Results: Of 1,293 articles screened, 133 studies were included in the final analysis. These assessed QuantiFERON-TB only in 77.4% (103/133), QuantiFERON-TB and T-SPOT.TB in 15.8% (21/133), and T-SPOT.TB only in 6.8% (9/133) resulting in 155 datasets including 107,418 participants. Overall 4% of IGRA results were indeterminate, and T-SPOT.TB (0.03, 95% CI 0.02-0.05) and QuantiFERON-TB assays (0.05, 95% CI 0.04-0.06) showed similar proportions of indeterminate results; pooled risk difference was – 0.01 (95% CI 0.03-0.00). Significant differences with lower proportions of indeterminate assays with T-SPOT.TB compared to QuantiFERON-TB were only seen in subgroup analyses of studies performed in Africa and in non-HIV-infected immunocompromised patients. Meta-regression confirmed lower proportions of indeterminate results for T-SPOT.TB compared to QuantiFERON-TB only among studies that reported results from non-HIV-infected immunocompromised patients (p < 0.001). Conclusion: On average indeterminate IGRA results occur in 1 in 25 tests performed. Overall, there was no difference in the proportion of indeterminate results between both commercial assays. However, our findings suggest that in patients in Africa and/or patients with immunocompromising conditions other than HIV infection the T-SPOT.TB assay appears to produce fewer indeterminate results.
URI:	https://digitalcollection.zhaw.ch/handle/11475/17228
Fulltext version:	Published version
License (according to publishing contract):	CC BY 4.0: Attribution 4.0 International
Departement:	School of Health Sciences
Organisational Unit:	Institute of Public Health (IPH)
Appears in collections:	Publikationen Gesundheit

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Meier, N. R., Volken, T., Geiger, M., Heininger, U., Tebruegge, M., & Ritz, N. (2019). Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children : a systematic review and meta-analysis. Frontiers in Pediatrics, 7(208). https://doi.org/10.21256/zhaw-3232

Meier, N.R. et al. (2019) ‘Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children : a systematic review and meta-analysis’, Frontiers in Pediatrics, 7(208). Available at: https://doi.org/10.21256/zhaw-3232.

N. R. Meier, T. Volken, M. Geiger, U. Heininger, M. Tebruegge, and N. Ritz, “Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children : a systematic review and meta-analysis,” Frontiers in Pediatrics, vol. 7, no. 208, 2019, doi: 10.21256/zhaw-3232.

MEIER, Noëmi R., Thomas VOLKEN, Marc GEIGER, Ulrich HEININGER, Marc TEBRUEGGE und Nicole RITZ, 2019. Risk factors for indeterminate interferon-gamma release assay for the diagnosis of tuberculosis in children : a systematic review and meta-analysis. Frontiers in Pediatrics. 2019. Bd. 7, Nr. 208. DOI 10.21256/zhaw-3232

Meier, Noëmi R., Thomas Volken, Marc Geiger, Ulrich Heininger, Marc Tebruegge, and Nicole Ritz. 2019. “Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children : A Systematic Review and Meta-Analysis.” Frontiers in Pediatrics 7 (208). https://doi.org/10.21256/zhaw-3232.

Meier, Noëmi R., et al. “Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children : A Systematic Review and Meta-Analysis.” Frontiers in Pediatrics, vol. 7, no. 208, 2019, https://doi.org/10.21256/zhaw-3232.