Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study

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Abstract

Background

In developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established.

Methods

This cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI.

Results

Among 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk ( P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI ( p < 0.001).

Conclusions

Compared to TST, IGRA positivity is consistent with the risk of TB infection and seems to be a better diagnostic tool for LTBI in HIV-infected patients.

Electronic supplementary material

The online version of this article (10.1186/s12879-018-3508-8) contains supplementary material, which is available to authorized users.

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Most cited references 19

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Tuberculosis.

Alimuddin Zumla, Mario Raviglione, Richard Hafner … (2013)

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Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research.

Dick Menzies, Madhukar Pai, George Comstock (2007)

Until recently, the tuberculin skin test was the only test for detecting latent tuberculosis (TB) infection, but 2 ex vivo interferon-gamma release assays (IGRAs) are now commercially licensed. To estimate sensitivity, specificity, and reproducibility of IGRAs (commercial or research versions of QuantiFERON [QFT] and Elispot) for diagnosing latent TB infection in healthy and immune-suppressed persons. The authors searched MEDLINE and reviewed citations of all original articles and reviews for studies published in English. Studies had evaluated IGRAs using Mycobacterium tuberculosis-specific antigens (RD1 antigens) and overnight (16- to 24-h) incubation times. Reference standards had to be clearly defined without knowledge of test results. DATA EXTRACTION AND QUALITY ASSESSMENT: Specific criteria for quality assessment were developed for sensitivity, specificity, and reproducibility. When newly diagnosed active TB was used as a surrogate for latent TB infection, sensitivity of all tests was suboptimal, although it was higher with Elispot. No test distinguishes active TB from latent TB. Sensitivity of the tuberculin skin test and IGRAs was similar in persons who were categorized into clinical gradients of exposure. Pooled specificity was 97.7% (95% CI, 96% to 99%) and 92.5% (CI, 86% to 99%) for QFT and for Elispot, respectively. Both assays were more specific than the tuberculin skin test in samples vaccinated with bacille Calmette-Guérin. Elispot was more sensitive than the tuberculin skin test in 3 studies of immune-compromised samples. Discordant tuberculin skin test and IGRA reactions were frequent and largely unexplained, although some may be related to varied definitions of positive test results. Reversion of IGRA results from positive to negative was common in 2 studies in which it was assessed. Most studies used cross-sectional designs with the inherent limitation of no gold standard for latent TB infection, and most involved small samples with a widely varying likelihood of true-positive and false-positive test results. There is insufficient evidence on IGRA performance in children, immune-compromised persons, and the elderly. New IGRAs show considerable promise and have excellent specificity. Additional studies are needed to better define their performance in high-risk populations and in serial testing. Longitudinal studies are needed to define the predictive value of IGRAs.

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Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010.

Gerald H. Mazurek, John Jereb, Andrew Vernon … (2010)

n 2005, CDC published guidelines for using the QuantiFERON-TB Gold test (QFT-G) (Cellestis Limited, Carnegie, Victoria, Australia) (CDC. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR;54[No. RR-15]:49-55). Subsequently, two new interferon gamma (IFN- gamma) release assays (IGRAs) were approved by the Food and Drug Administration (FDA) as aids in diagnosing M. tuberculosis infection, both latent infection and infection manifesting as active tuberculosis. These tests are the QuantiFERON-TB Gold In-Tube test (QFT-GIT) (Cellestis Limited, Carnegie, Victoria, Australia) and the T-SPOT.TB test (T-Spot) (Oxford Immunotec Limited, Abingdon, United Kingdom). The antigens, methods, and interpretation criteria for these assays differ from those for IGRAs approved previously by FDA. For assistance in developing recommendations related to IGRA use, CDC convened a group of experts to review the scientific evidence and provide opinions regarding use of IGRAs. Data submitted to FDA, published reports, and expert opinion related to IGRAs were used in preparing these guidelines. Results of studies examining sensitivity, specificity, and agreement for IGRAs and TST vary with respect to which test is better. Although data on the accuracy of IGRAs and their ability to predict subsequent active tuberculosis are limited, to date, no major deficiencies have been reported in studies involving various populations. This report provides guidance to U.S. public health officials, health-care providers, and laboratory workers for use of FDA-approved IGRAs in the diagnosis of M. tuberculosis infection in adults and children. In brief, TSTs and IGRAs (QFT-G, QFT-GIT, and T-Spot) may be used as aids in diagnosing M. tuberculosis infection. They may be used for surveillance purposes and to identify persons likely to benefit from treatment. Multiple additional recommendations are provided that address quality control, test selection, and medical management after testing. Although substantial progress has been made in documenting the utility of IGRAs, additional research is needed that focuses on the value and limitations of IGRAs in situations of importance to medical care or tuberculosis control. Specific areas needing additional research are listed.

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Author and article information

Contributors

Giselle Burlamaqui Klautau: gisellebk@hotmail.com

Nadijane Valéria Ferreira da Mota: nadijane.ferreira@gmail.com

Mauro José Costa Salles:

ORCID: http://orcid.org/0000-0002-5443-6024

+5511-21146262 , salles.infecto@gmail.com

Marcelo Nascimento Burattini: mnburattini@unifesp.br

Denise Silva Rodrigues: denise.rodrigues@saude.sp.gov.br

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 19 November 2018

Publication date PMC-release: 19 November 2018

Publication date Collection: 2018

Volume: 18

Electronic Location Identifier: 585

Affiliations

[1 ]ISNI 0000 0000 8872 5006, GRID grid.419432.9, Division of Infectious Diseases, Department of Internal Medicine Santa Casa de São Paulo School of Medical Sciences, Hospital da Irmandade da Santa Casa de Misericórdia de São Paulo, ; Rua Dr Cesáreo Mota Jr 112,, São Paulo, SP CEP: 01303-060 Brazil

[2 ]Clemente Ferreira Institute, Rua da Consolação 717, São Paulo, SP CEP: 01221-020 Brazil

[3 ]Emílio Ribas Institute of Infectious Diseases, Av Dr Arnaldo 165, São Paulo, SP CEP: 01246-900 Brazil

[4 ]ISNI 0000 0001 0514 7202, GRID grid.411249.b, Federal University of São Paulo (UNIFESP), ; Rua Sena Madureira 1500, São Paulo, CEP: 04021-001 Brazil

Author information

Mauro José Costa Salles http://orcid.org/0000-0002-5443-6024

Article

Publisher ID: 3508

DOI: 10.1186/s12879-018-3508-8

PMC ID: 6245697

PubMed ID: 30453903

SO-VID: 8c290608-ca6b-4c38-b3b3-890ded502bc7

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 15 April 2018

Date accepted : 8 November 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001807, Fundação de Amparo à Pesquisa do Estado de São Paulo;

Award ID: 2011/05805-1

Funded by: FundRef http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;

Award ID: 141705/2011-6

Award Recipient : Giselle Burlamaqui Klautau

Custom metadata

ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: hiv,latent tuberculosis infection,tuberculin skin testing,interferon-γ release assay,aids

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ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: hiv, latent tuberculosis infection, tuberculin skin testing, interferon-γ release assay, aids

Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study

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Abstract

Background

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Conclusions

Electronic supplementary material

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HIV Self-Testing

Most cited references 19

Tuberculosis.

Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research.

Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010.

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