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Factors Associated with False Negative Interferon-γ Release Assay Results in Patients with Tuberculosis: A Systematic Review with Meta-Analysis

54 Pages Posted: 2 Jan 2019

See all articles by Mari Yamasue

Mari Yamasue

Oita University - Department of Respiratory Medicine and Infectious Diseases

Kosaku Komiya

Oita University - Department of Respiratory Medicine and Infectious Diseases

Yuko Usagawa

Oita University - Department of Respiratory Medicine and Infectious Diseases

Kenji Umeki

Oita University - Department of Respiratory Medicine and Infectious Diseases

Shin-ichi Nureki

Oita University - Department of Respiratory Medicine and Infectious Diseases

Masaru Ando

Oita University - Department of Respiratory Medicine and Infectious Diseases

Kazufumi Hiramatsu

Oita University - Department of Respiratory Medicine and Infectious Diseases

Hideaki Nagai

National Hospital Organization (NHO) - Tokyo National Hospital

Jun-ichi Kadota

Oita University - Department of Respiratory Medicine and Infectious Diseases

More...

Abstract

Background: Although interferon-γ release assay (IGRA) is widely used for diagnosis of latent tuberculosis (TB) infection, which factors are related to false negative results are uncertain. The aim of this systematic review was to describe the risk factors associated with false negative IGRA results.

Methods: Two authors independently identified studies designed to evaluate risk factors for false negative IGRA results from PubMed, the Cochrane Register of Control Trial database, and EMBASE assessed on October 22, 2018. Meta-analyses were conducted with random-effect models and heterogeneity was calculated with the I2 method.

Findings: Of 1,377 titles and abstracts screened, 47 full texts were selected for review, and we finally included 17 studies in this systematic review. The most commonly studied risk factor (14 studies) was advanced age followed by low peripheral lymphocyte counts (7 studies), and these factors were associated with false negative results even under different TB prevalence (pooled odds ratio, 2.06; 95%CI, 1.68-2.52 in advanced age, and 7.93; 95%CI, 1.74-36.09 in low peripheral lymphocyte counts, respectively). However, detailed procedure of these assays were not clearly stated in many studies and the cut-off value of these factors were varied.

Interpretation: Advanced age and low peripheral lymphocyte counts may be common risk factors for false negative IGRA results, suggesting people with these factors need careful followed-up even if they have negative IGRA results. Standardization of the assay procedure and assessment of risk factors with common definition and the same cut-off value are needed.

Funding Statement: The authors state: "There was no funding source for this study."

Declaration of Interests: The authors declare declare no competing interests.

Keywords: tuberculosis, interferon-γ release assay, false negative

Suggested Citation

Yamasue, Mari and Komiya, Kosaku and Usagawa, Yuko and Umeki, Kenji and Nureki, Shin-ichi and Ando, Masaru and Hiramatsu, Kazufumi and Nagai, Hideaki and Kadota, Jun-ichi, Factors Associated with False Negative Interferon-γ Release Assay Results in Patients with Tuberculosis: A Systematic Review with Meta-Analysis (December 29, 2018). Available at SSRN: https://ssrn.com/abstract=3307647 or http://dx.doi.org/10.2139/ssrn.3307647

Mari Yamasue

Oita University - Department of Respiratory Medicine and Infectious Diseases

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

Kosaku Komiya (Contact Author)

Oita University - Department of Respiratory Medicine and Infectious Diseases ( email )

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

Yuko Usagawa

Oita University - Department of Respiratory Medicine and Infectious Diseases

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

Kenji Umeki

Oita University - Department of Respiratory Medicine and Infectious Diseases

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

Shin-ichi Nureki

Oita University - Department of Respiratory Medicine and Infectious Diseases

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

Masaru Ando

Oita University - Department of Respiratory Medicine and Infectious Diseases

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

Kazufumi Hiramatsu

Oita University - Department of Respiratory Medicine and Infectious Diseases

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

Hideaki Nagai

National Hospital Organization (NHO) - Tokyo National Hospital

3-1-1 Takeoka
Kiyose
Tokyo, 204-8585
Japan

Jun-ichi Kadota

Oita University - Department of Respiratory Medicine and Infectious Diseases

1-1 Idaigaoka
Hasama-machi, Yufu
Oita, 879-5593
Japan

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