Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis

ObjectivesWe aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI).MethodsOn 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlan...

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Main Authors: Guozhong Zhou, Qingyi Luo, Shiqi Luo, Hongbo Chen, Shunli Cai, Xin Guo, Jian He, Yuan Xia, Hanse Li, Yingchen Zhou, Yazhou Zhang, Chao Song
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1170579/full
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author Guozhong Zhou
Qingyi Luo
Shiqi Luo
Hongbo Chen
Shunli Cai
Xin Guo
Jian He
Yuan Xia
Hanse Li
Yingchen Zhou
Yazhou Zhang
Chao Song
author_facet Guozhong Zhou
Qingyi Luo
Shiqi Luo
Hongbo Chen
Shunli Cai
Xin Guo
Jian He
Yuan Xia
Hanse Li
Yingchen Zhou
Yazhou Zhang
Chao Song
author_sort Guozhong Zhou
collection DOAJ
description ObjectivesWe aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI).MethodsOn 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators independently extracted the study data and assessed their quality using a modified quality assessment of diagnostic accuracy studies (i.e., QUADAS-2) tool. A random-effects model was used to calculate pooled results.ResultsWe included 403 studies involving 486,886 individuals and found that the pooled indeterminate rate was 3.9% (95% CI 3.5%–4.2%). The pooled indeterminate rate for QuantiFERON®-TB (QFT) was similar to that for T-SPOT®.TB (T-SPOT) [odds ratio (OR) = 0.88, 95% CI 0.59–1.32]; however, the indeterminate rate for a new generation of QFT (QFT-plus) was lower than that of T-SPOT (OR = 0.24, 95% CI 0.16–0.35). The indeterminate rate in the immunocompromised population was significantly higher than that in healthy controls (OR = 3.51, 95% CI 2.11–5.82), and it increased with the reduction of CD4+ cell count in HIV-positive patients. Children’s pooled indeterminate rates (OR = 2.56, 95% CI 1.79–3.57) were significantly higher than those of adults, and the rates increased as the children’s age decreased.ConclusionOn average, 1 in 26 tests yields indeterminate IGRA results in LTBI screening. The use of advanced versions of the QuantiFERON-TB assay (QFT-plus), may potentially reduce the occurrence of an indeterminate result. Our study emphasizes the high risk of immunosuppression and young age in relation to indeterminate IGRA, which should receive more attention in the management of LTBI.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.
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spelling doaj.art-74eb218d615d4b328c19f0969536234a2023-05-15T04:33:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11705791170579Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysisGuozhong Zhou0Qingyi Luo1Shiqi Luo2Hongbo Chen3Shunli Cai4Xin Guo5Jian He6Yuan Xia7Hanse Li8Yingchen Zhou9Yazhou Zhang10Chao Song11Department of Science and Research, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Medical Imaging, Yanan Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, Yunnan, ChinaSchool of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, ChinaSchool of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, ChinaSchool of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, ChinaSchool of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, ChinaThe School of Medicine, Kunming University, Kunming, ChinaDepartment of Gerontology 2, The Second People’s Hospital of Kunming, Kunming, ChinaDepartment of Medical Imaging, Anning First People’s Hospital Affiliated to Kunming University of Science and Technology, Kunming, Yunnan, ChinaObjectivesWe aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI).MethodsOn 15 November 2022, we searched the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Cochrane Library databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators independently extracted the study data and assessed their quality using a modified quality assessment of diagnostic accuracy studies (i.e., QUADAS-2) tool. A random-effects model was used to calculate pooled results.ResultsWe included 403 studies involving 486,886 individuals and found that the pooled indeterminate rate was 3.9% (95% CI 3.5%–4.2%). The pooled indeterminate rate for QuantiFERON®-TB (QFT) was similar to that for T-SPOT®.TB (T-SPOT) [odds ratio (OR) = 0.88, 95% CI 0.59–1.32]; however, the indeterminate rate for a new generation of QFT (QFT-plus) was lower than that of T-SPOT (OR = 0.24, 95% CI 0.16–0.35). The indeterminate rate in the immunocompromised population was significantly higher than that in healthy controls (OR = 3.51, 95% CI 2.11–5.82), and it increased with the reduction of CD4+ cell count in HIV-positive patients. Children’s pooled indeterminate rates (OR = 2.56, 95% CI 1.79–3.57) were significantly higher than those of adults, and the rates increased as the children’s age decreased.ConclusionOn average, 1 in 26 tests yields indeterminate IGRA results in LTBI screening. The use of advanced versions of the QuantiFERON-TB assay (QFT-plus), may potentially reduce the occurrence of an indeterminate result. Our study emphasizes the high risk of immunosuppression and young age in relation to indeterminate IGRA, which should receive more attention in the management of LTBI.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1170579/fullinterferon gamma release assay (IGRA)latent tuberculosis infection (LTBI)indeterminatediagnosismeta-analysis
spellingShingle Guozhong Zhou
Qingyi Luo
Shiqi Luo
Hongbo Chen
Shunli Cai
Xin Guo
Jian He
Yuan Xia
Hanse Li
Yingchen Zhou
Yazhou Zhang
Chao Song
Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis
Frontiers in Immunology
interferon gamma release assay (IGRA)
latent tuberculosis infection (LTBI)
indeterminate
diagnosis
meta-analysis
title Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis
title_full Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis
title_fullStr Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis
title_full_unstemmed Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis
title_short Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis
title_sort indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection a systematic review and meta analysis
topic interferon gamma release assay (IGRA)
latent tuberculosis infection (LTBI)
indeterminate
diagnosis
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1170579/full
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