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

Guozhong Zhou; Qingyi Luo; Shiqi Luo; Hongbo Chen; Shunli Cai; Xin Guo; Jian He; Yuan Xia; Hanse Li; Yingchen Zhou; Yazhou Zhang; Chao Song

doi:10.3389/fimmu.2023.1170579

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

Front Immunol. 2023 May 15:14:1170579. doi: 10.3389/fimmu.2023.1170579. eCollection 2023.

Authors

Guozhong Zhou¹, Qingyi Luo², Shiqi Luo³, Hongbo Chen⁴, Shunli Cai⁵, Xin Guo⁵, Jian He³, Yuan Xia⁵, Hanse Li⁵, Yingchen Zhou⁶, Yazhou Zhang⁷, Chao Song⁸

Affiliations

¹ Department of Science and Research, Anning First People's Hospital Affiliated to Kunming University of Science and Technology, Kunming, Yunnan, China.
² Department of Medical Imaging, Yanan Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, China.
³ Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
⁴ Department of Pulmonary and Critical Care Medicine, Anning First People's Hospital Affiliated to Kunming University of Science and Technology, Kunming, Yunnan, China.
⁵ School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China.
⁶ The School of Medicine, Kunming University, Kunming, China.
⁷ Department of Gerontology 2, The Second People's Hospital of Kunming, Kunming, China.
⁸ Department of Medical Imaging, Anning First People's Hospital Affiliated to Kunming University of Science and Technology, Kunming, Yunnan, China.

Abstract

Objectives: We aimed to evaluate the indeterminate rate of interferon gamma release assays (IGRAs) in the detection of latent tuberculosis infection (LTBI).

Methods: On 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.

Results: We 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.

Conclusion: On 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 registration: PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020211363, CRD42020211363.

Keywords: diagnosis; indeterminate; interferon gamma release assay (IGRA); latent tuberculosis infection (LTBI); meta-analysis.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Child
HIV Seropositivity*
Humans
Immunocompromised Host
Interferon-gamma Release Tests / methods
Latent Tuberculosis* / diagnosis
Latent Tuberculosis* / epidemiology
Mass Screening
United States

Grants and funding

This work was supported by the Talent Project of Kunming Health Science and Technology under grant number 2022-SW (Leading Talents)-001 and the Special Project “Spring City Plan” Famous Doctor under grant number C202012016.