Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

Pai, Madhukar; Denkinger, Claudia M.; Kik, Sandra V.; Rangaka, Molebogeng X; Zwerling, Alice; Oxlade, Olivia; Metcalfe, John; Cattamanchi, Adithya; Dowdy, David W.; Dheda, Keertan; Banaei, Niaz

doi:10.1128/cmr.00034-13

Cited by 703 publications

(725 citation statements)

References 121 publications

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“…Traditionally, the tuberculin skin test has been used for latent tuberculosis testing, but IFN-g release assays (IGRAs) such as the QuantiFERON-TB Gold in-tube (QuantiFERON; Cellestis Limited/Qiagen, Valencia, CA), and the T-SPOT.TB (T-SPOT; Oxford Immunotec, Abingdon, UK) are more recently developed alternatives with both strengths and limitations (1). IGRAs are considered to be more specific than the tuberculin skin test.…”

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confidence: 99%

Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

Tagmouti¹,

Slater

Benedetti

et al. 2014

Annals ATS

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Rationale: Interferon gamma (IFN-g) release assays for latent tuberculosis infection result in a larger-than-expected number of conversions and reversions in occupational screening programs, and reproducibility of test results is a concern.Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, preanalytical, or analytical) could help optimize testing protocols. Methods:We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial IFN-g release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate withinsubject SD. Measurements and Main Results:We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions, and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only three studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of IFN-g response in QuantiFERON under identical conditions was 60.47 IU/ml (coefficient of variation, 13%) and 60.26 IU/ml (30%) for individuals with an initial IFN-g response in the borderline range (0.25-0.80 IU/ml). The estimated range of variability in noncontrolled settings was substantially larger (61.4 IU/ml; 60%). Blood volume inoculated into QuantiFERON tubes and preanalytic delay were identified as key sources of variability.Conclusions: This systematic review shows substantial variability with repeat IFN-g release assays testing even under identical conditions, suggesting that reversions and conversions around the existing cut-point should be interpreted with caution.

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confidence: 99%

Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

Tagmouti¹,

Slater

Benedetti

et al. 2014

Annals ATS

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“…Factors that contribute to within subject variability include incubation time, contamination, storage conditions, and so forth. 1,30 We have eliminated the between-run variability by analyzing all samples for the same patient within the same plate. As the IP-10 based test is not commercially available, this test has not been as extensively studied as the QFT test.…”

Section: Discussionmentioning

confidence: 99%

“…They have a high specificity, but are imperfect as they cannot differentiate between active and LTBI and have a sensitivity around 80%. 1 A series of immunosuppressive conditions are known to compromise the IGRA test performance including human immunodeficiency virus (HIV) infection and low CD4 cell count, [2][3][4][5] glucocorticoid treatment, 6 cigarette smoking, 7 severe disease in children, 8 and helminth infection. 9,10 So far, no systematic evaluation of the possible effect of malaria infection on IGRA test performance has been done.…”

Section: Introductionmentioning

confidence: 99%

Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania

Drabe

Vestergaard

Helleberg

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis. The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD ® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem ® ). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.

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“…Bu DNA bölgesinde iki protein kodlanmaktadır;"Early Secretory Antigenic Target-6" (ESAT-6) ve "Culture Filtrate Protein-10" (CFP-10). Bu antijenler M. marinum, M. kansasii, M. szulgai ve M. flavescens dışındaki tüberküloz dışı mikobakterilerin çoğunda ve BCG aşı kökeninde bulunmamaktadır [8].…”

Section: Introductionunclassified

Retrospective evaluation of T-Spot. TB test results that sent to our tuberculosis laboratory

2017

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ÖzAmaç: T-Spot.TB testi tüberkülozun tanısında kullanılan ve interferon gamma salınımına dayanan bir testtir. Bu testte hastanın lenfositlerinin tüberküloz spesifik antijenlerle (ESAT-6 ve CFP10) uyarımını takiben T-lenfositlerinden interferon gamma üretimi ölçülmektedir. Çalışmamızda Tüberküloz Laboratuvarına gönderilmiş olan serum örnek-lerinde T.Spot.TB sonuçlarının incelenmesi amaçlanmıştır. Gereç ve Yöntemler:Ondokuz Mayıs Üniversitesi Tıp Fakültesi Hastanesi Tüberküloz Laboratuvarına Aralık 2013-Mart 2015 yılları arasında gönderilmiş olan klinik örnekler retrospektif olarak incelenmiştir. Serum örnekleri heparinli tüpe 6 ml olacak şekilde alınmış ve laboratuvarımıza gönderilmiş ve üretici firma önerileri doğrultusun-da çalışılmıştır. Bu testte yıkanmış ve sayılmış periferal mononükleer hücrelerde, tüberküloz spesifik antijenlerle (ESAT-6 ve CFP10) uyarımını takiben interferon gamma üretimi ölçülmektedir. Spotlar sayılmakta, 6 ve üzeri pozitif olarak kabul edilmektedir. Bulgular:Toplam 141 hastanın serum örneği çalışılmıştır, serum örneği gönderilmiş olan hastaların yaş ortalaması 33.03 (9 aylık-83 yaş) olarak saptanmıştır. Bu örneklerden 28 hasta örneğinde T-Spot.TB pozitifliği görülmüştür. T-Spot.TB pozitifliği görülen hastalardan 18 (%64,2) hastada EZN boyama, tüberküloz kültürü ve polimeraz zincir reaksiyonu (PZR) testleri istenmemiş olup sadece T-Spot.TB çalışılmıştır. T-Spot.TB çalışılmış olan 141 örneğin 3 (%2,1) tanesinde kültür pozitifliği saptanmış olup, hem kültür hem T-Spot.TB pozitifliği sadece 2 (%1,4) hastada saptanmıştır.Sonuç: T-Spot.TB testinde BCG aşılanması ve çevresel mikobakterilerle maruziyete bağlı yalancı pozitiflik görülmemesi bu testi, tüberkülin deri testiyle kıyaslandığında ön plana çıkartmaktadır. Ayrıca latent tüberküloz infeksiyonu tanısında daha özgül ve duyarlı olduğu belirtilmektedir. Bu nedenle bu testin ilerleyen dönemlerde daha ön plana çıkacağını düşünmekteyiz.Anahtar kelimeler: Latent tüberküloz enfeksiyonu, tanı, T-Spot.TB, IGRA Retrospective evaluation of T-Spot. TB test results that sent to our tuberculosis laboratory

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Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

Cited by 703 publications

References 121 publications

Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

Reproducibility of Interferon Gamma (IFN-γ) Release Assays. A Systematic Review

Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania

Retrospective evaluation of T-Spot. TB test results that sent to our tuberculosis laboratory

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