Specificity of QuantiFERON-TB Plus, a New-Generation Interferon Gamma Release Assay

ABSTRACT Interferon gamma release assays (IGRAs) are important tools in identifying prior tuberculosis exposure. The new-generation QuantiFERON-TB Gold Plus (QFT-Plus) assay, recently approved for use in the United States, differs from the current-generation QFT Gold-In-Tube (QFT-GIT) assay with the addition of a second antigen tube that also contains novel CD8+ T-cell-stimulating peptides. The QFT-Plus assay has increased sensitivity in immunocompromised populations, and we sought to assess the specificity of QFT-Plus compared to that of QFT-GIT in low-risk individuals. We enrolled adults without tuberculosis risk factors, including a subgroup with pulmonary nontuberculous mycobacterial (NTM) disease due to Mycobacterium avium complex (MAC) or Mycobacterium abscessus. The primary outcome measures included specificity, interassay concordance, and agreement between the QFT-Plus and QFT-GIT assays. Of 262 participants enrolled, 51 had pulmonary NTM. The median age was 39 years (age range, 18 to 78 years); 73% were female. Among the 262 individuals who were enrolled, 5 (1.9%) individuals had positive QFT-Plus results, and 3 of these individuals also had positive QFT-GIT results. The two individuals with discordant results (QFT-Plus positive/QFT-GIT negative) had only one tube positive in the QFT-Plus assay. The overall specificity of QFT-Plus and QFT-GIT was 98.1% (95% confidence interval [CI], 95.6, 99.4%) and 98.9% (95% CI, 96.7, 99.8%), respectively. The QFT-Plus specificity was similar in both the NTM (98.0% [95% CI, 89.4, 99.9%]) and non-NTM (98.1% [95% CI, 95.2, 99.5%]) groups. QFT-Plus has a high specificity, similar to that of the QFT-GIT assay, including in patients with pulmonary MAC or M. abscessus disease.

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Role of interferon gamma release assay in the diagnosis and management of Mycobacterium tuberculosis-associated uveitis: a review

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2020-000663 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000663

Author(s):

Samra Rahman ◽

Muhammad Irfan ◽

M A Rehman Siddiqui

Keyword(s):

Interferon Gamma ◽

Interferon Gamma Release Assay ◽

Limited Evidence ◽

Ocular Tuberculosis ◽

Diagnosis And Management ◽

Pubmed Database ◽

Interferon Gamma Release Assays ◽

Infectious Uveitis ◽

Release Assay

Tuberculosis (TB)-associated uveitis is a common cause of infectious uveitis in the developing world. Diagnosis of TB uveitis remains a challenge. The role of interferon gamma release assays (IGRAs) is uncertain. Herein we summarise the available literature on the utility of IGRAs in the diagnosis and management of TB uveitis. We searched PubMed database from 1 August 2010 to 31 July 2020 using the following keywords alone and in combination: ‘interferon-gamma release assay’, ‘QuantiFERON’, ‘T-SPOT.TB’, ‘TB uveitis’, ‘serpiginous like choroiditis’, ‘tuberculoma’, ‘TB vasculitis’, ‘TB panuveitis’ and ‘ocular tuberculosis’. Data from 58 relevant studies were collated. The review is focused on currently marketed versions of IGRA tests: QuantiFERON-TB Gold In-Tube assay, QuantiFERON-TB Gold Plus assay (QFT-Plus) and T-SPOT.TB. We found limited evidence regarding the diagnostic utility of IGRA in patients with uveitis. No study was identified evaluating the newer QFT test—the QFT-Plus—in patients with uveitis. Similarly, there is lack of data directly comparing QFT-Plus with T-SPOT.TB specifically for the diagnosis of TB uveitis.

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Short-Term Reproducibility of a Commercial Interferon Gamma Release Assay

Clinical and Vaccine Immunology ◽

10.1128/cvi.00168-09 ◽

2009 ◽

Vol 16 (8) ◽

pp. 1170-1175 ◽

Cited By ~ 47

Author(s):

A. K. Detjen ◽

L. Loebenberg ◽

H. M. S. Grewal ◽

K. Stanley ◽

A. Gutschmidt ◽

...

Keyword(s):

Interferon Gamma ◽

Health Care Workers ◽

Immune Memory ◽

Interferon Gamma Release Assay ◽

Short Term ◽

Care Workers ◽

Interferon Gamma Release Assays ◽

Release Assay ◽

Ifn Γ ◽

Storage Methods

ABSTRACT Interferon gamma release assays (IGRAs) have been shown to be sensitive and highly specific for the detection of immune memory against Mycobacterium tuberculosis. Little is known about the reproducibility and within-person variability of these assays. Various aspects of short-term reproducibility of a commercial IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, were assessed. The QFT-IT assay was performed twice within 3 days in 27 health care workers in Cape Town, South Africa. Two sets of tests were performed by different operators on day 1, and one set was performed on day 3. Aspects such as interoperator, intraoperator, day-to-day variability, and test-retest variability as well as different the storage methods of plasma were investigated. Seventeen of 27 (63%) of participants had at least one positive QFT-IT text; six had discordant results. The agreement of all aspects studied was high, with kappa values between 0.82 and 1.00 for dichotomous measures, and interclass correlations (ICC) of 0.809 to 0.965 were observed for continuous gamma interferon (IFN-γ) measures. The variability of the magnitude of response was highest comparing measures obtained from individuals on different days (ICC of 0.809). The magnitude of the IFN-γ responses between assays performed for individual participants was variable, with ranges from 0.03 to 11 IU/ml, resulting is discordant results for five participants. The results indicate that the QFT-IT assay is a robust and highly reproducible assay. Considerable intraindividual variability occurs in the magnitude of IFN-γ responses, which may influence the interpretation of serial measures.

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Association of Low Sputum Smear Positivity among Tuberculosis Patients with Interferon-Gamma Release Assay Outcomes of Close Contacts in Japan

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16193713 ◽

2019 ◽

Vol 16 (19) ◽

pp. 3713

Author(s):

Tsuyoshi Ogata ◽

Natsuki Nagasu ◽

Ritei Uehara ◽

Kunihiko Ito

Keyword(s):

Interferon Gamma ◽

Acid Fast Bacillus ◽

Sputum Smear ◽

Interferon Gamma Release Assay ◽

Tuberculosis Patients ◽

Interferon Gamma Release Assays ◽

Response Measures ◽

Release Assay ◽

Smear Negative ◽

Close Contacts

Risk prediction and response measures may differ in tuberculosis (TB) patients with low sputum smear positivity for acid-fast bacillus (AFB) compared to those who are smear negative. However, previous studies using the tuberculin skin test (TST) did not show that differences in measures are important. This study compared results of interferon-gamma release assays (IGRA) between contacts of pulmonary TB patients with AFB smear positivity and those with smear negativity using QuantiFERON®-TB Gold In-Tube (QFT) assays. Close contacts of TB patients with culture-confirmed infections between April 2010 and December 2012 in Ibaraki, Japan, were enrolled, and 439 Japanese contacts of 129 index TB patients were examined. Adjusted odds ratios of QFT in contacts were 0.68 (95% confidence interval: 0.17–2.8) for AFB scanty patients, 1.12 (0.45–2.8) for AFB 1+, 1.20 (0.48–3.0) for AFB 2+, and 4.96 (1.9–12.9) for AFB 3+, compared to those who were smear negative. Differences in IGRA positivity were not significant between close contacts of TB patients with low positive and negative smears.

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Tuberculin skin test and interferon-gamma release assay use among privately insured persons in the United States

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.16.0617 ◽

2017 ◽

Vol 21 (6) ◽

pp. 684-689 ◽

Cited By ~ 3

Author(s):

K. Owusu-Edusei ◽

E. L. Stockbridge ◽

C. A. Winston ◽

M. Kolasa ◽

R. Miramontes

Keyword(s):

United States ◽

Tuberculin Skin Test ◽

Skin Test ◽

Interferon Gamma ◽

The United States ◽

Interferon Gamma Release Assay ◽

Release Assay ◽

Privately Insured

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Risk Factors for Indeterminate Outcome on Interferon Gamma Release Assay in Non-US-Born Persons Screened for Latent Tuberculosis Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy184 ◽

2018 ◽

Vol 5 (8) ◽

Cited By ~ 7

Author(s):

Jody C Sharninghausen ◽

Adrienne E Shapiro ◽

David M Koelle ◽

H Nina Kim

Keyword(s):

United States ◽

Risk Factors ◽

Interferon Gamma ◽

Multivariable Analysis ◽

Latent Tuberculosis ◽

The United States ◽

Interferon Gamma Release Assay ◽

Foreign Born ◽

Asian Race ◽

Release Assay

Abstract Background Non-US-born individuals account for the majority of active tuberculosis (TB) in the United States. Interferon gamma release assay (IGRA) is the preferred diagnostic test for latent TB but can produce an indeterminate result. We investigated the prevalence and predictors of an indeterminate IGRA (IND-IGRA) in a diverse cohort of non-US-born individuals and evaluated outcomes after IND-IGRA. Methods We identified patient age ≥18 years who had an outpatient IGRA between 2010 and 2017 in our health system and whose primary language was not English. We used univariate and multivariable logistic regression to examine the association of IND-IGRA with a variety of clinical factors. Results Of 3128 outpatients with ≥1 IGRA done, 33% were Asian, 30% Hispanic, and 29% black; 44% were men, and the median age was 50 years. An initial IND-IGRA occurred in 118 (3.8%; 95% confidence interval [CI], 3.1%–4.5%); notably, Asian race (55%) and rheumatologic conditions (25%) were prevalent in this group. In multivariable analysis, Asian race was independently associated with IND-IGRA (adjusted odds ratio [aOR], 2.9; 95% CI, 1.9–4.3), in addition to the presence of anemia and hypoalbuminemia (aOR for interaction, 4.3; 95% CI, 1.3–14.3). Only 55% of patients with an initial IND-IGRA underwent repeat testing; of those who did, 66% had a determinate result. Conclusions Asian race and anemia/hypoalbuminemia were independent risk factors for an indeterminate IGRA outcome in foreign-born patients screened in the United States. Our study underscores the importance of following through on indeterminate results in these key subgroups.

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