Systematic Review: T-Cell–based Assays for the Diagnosis of Latent Tuberculosis Infection: An Update

Pai, Madhukar; Zwerling, Alice; Menzies, Dick

doi:10.7326/0003-4819-149-3-200808050-00241

Cited by 1,184 publications

(1,040 citation statements)

References 52 publications

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“…71,72 Unfortunately, technical and logistical challenges hinder use of TSTs, 73 and have been a barrier to scale-up of isoniazid therapy. Interferon-γ release assays that use ESAT-6 or CFP-10 antigens, or both, are an improvement on TSTs, but they are also associated with technical and fi nancial challenges, 74 and cannot yet be considered for routine use in resource-constrained settings.…”

Section: Isoniazid Preventive Therapymentioning

confidence: 99%

The HIV-associated tuberculosis epidemic—when will we act?

et al. 2010

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Journal LancetRights Reproduced on this site with permission of Elsevier Ltd. Please see [url] Tuberculosis 3The HIV-associated tuberculosis epidemic-when will we act? Anthony D Harries, Rony Zachariah, Elizabeth L Corbett, Stephen D Lawn, Ezio T Santos-Filho, Rhehab Chimzizi, Mark Harrington, Dermot Maher, Brian G Williams, Kevin M De Cock Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in aff ected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensifi ed tuberculosis case fi nding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be eff ective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

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Section: Isoniazid Preventive Therapymentioning

confidence: 99%

The HIV-associated tuberculosis epidemic—when will we act?

et al. 2010

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“…These one-visit, ex vivo blood tests avoid sensitization, the boosting of immune response, cross-reactivity with most nontuberculous mycobacteria, or loss to follow-up, as frequently observed with the TST (12,17). Recently, systematic reviews have shown that IGRAs have excellent specificity for the diagnosis of LTBI even in Bacillus Calmette-Guérin (BCG)-vaccinated populations (8,23). Furthermore, they correlate with occupational risk factors of TB exposure in low-incidence settings (37).…”

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confidence: 99%

Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

Ringshausen

Nienhaus

Costa

et al. 2011

Clin. Vaccine Immunol.

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Gamma interferon (IFN-␥) release assays (IGRAs) are used increasingly for the periodic tuberculosis (TB) screening of health care workers (HCWs), although data regarding the reproducibility and interpretation of serial testing results in countries with a low incidence of TB are scarce. The present study evaluated and compared the within-subject variability of dichotomous and continuous results of two commercial IGRAs, the QuantiFERON-TB Gold In-Tube (QFT) and the T-SPOT.TB (T-SPOT), in German HCWs during a 4-week period. Thirty-five immunocompetent HCWs with low or medium TB screening risk and without known recent TB exposure or tuberculin skin test application were tested repeatedly with both IGRAs at weekly intervals. A total of 158 valid results were obtained for each IGRA. Changes of about ؎70% (QFT) and ؎60% (T-SPOT) from the mean IFN-␥ response accounted for 95% of the within-subject variability. However, according to the manufacturers' cutoffs, inconsistent results were observed more frequently for the QFT (28.6%; four conversions, six reversions) than for the T-SPOT (8.6%; three reversions; P < 0.001). The overall agreement between the IGRAs was good. Regression toward the means accounted for a significant decline in mean IFN-␥ responses of about 25% between successive visits for both IGRAs. Although both assays were highly reliable and reproducible, we observed substantial within-subject variability and regression toward the means during a 4-week period, which should be considered when interpreting serial testing results in comparable populations and settings. Our data support the use of borderline zones for the interpretation of serial IGRA results and the retesting of borderline positive results before offering preventive chemotherapy.

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“…Until recently, tuberculin skin test (TST) has been the most frequently used screening method, leading to a high rate of false positive results in M. bovis BCG-vaccinated individuals, and false negative tests in immunosuppressed persons. The new interferon gamma release assays (IGRAs) employing RD-1 antigens specific for virulent mycobacteria have excellent specificity unaffected by BCG vaccination and increased sensitivity [ 3 ]. Yet IGRAs cannot discriminate between individuals with latent and active TBI either.…”

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confidence: 99%

Peripheral Blood CD8 T Cell Response in Different Phases of MTB Infection

Nikolova¹,

Muhtarova²,

Drenska³

et al. 2013

Proceeding BAS

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A reliable approach differentiating between active and latent TB infection (LTBI) is yet unavailable. Recent data suggest the involvement of CD8 T cells in protective response to mycobacterium tuberculosis (MTB). We compared the antigen-specific responses and subset composition of peripheral blood CD8 T cells in patients with active infection (ATB), recent household contacts (RC), highly-exposed health-care workers (HW), and BCG-vaccinated healthy controls (HC). Study groups included 20 ATB, 21 RH, 21 HW and 15 HC. Active TB was diagnosed according to microbiological and clinical criteria. RD1-specific CD4 and CD8 T cells were determined by intracellular cytokine staining (ICS). CD8 T subsets were defined as naïve (CD45RA+CD27+), memory (M, CD45RA-CD27+), effector (E, CD27-CD45RA-), and terminal effector (TE, CD27-CD45RA+), and analyzed by flow cytometry. The levels of RD-1-specific CD4 T cells were highest in ATB but not significantly different from LTBI groups. A significant RD-1-specific CD8 T cell IFNγ response (0.289%) differentiated RC from ATB, HE and HC subjects (0.053, 0.027 and 0.011, p < 0.05) and was associated with decreased M/TE ratio. Finally, an increased M/E CD8 T ratio distinguished HW from RC and ATB subjects (7.6 vs. 2.4 and 2.6, p < 0.05). The study of MTB-specific CD8 T-cell response in combination with CD8 T subset composition adds to the differentiation between active and latent TB.Key words: CD8 T-cell response, RD-1-specific T cells, ICS, MTB infection 587 Introduction. Mycobacterium tuberculosis (MTB) is one of the most frequent causes of infectious morbidity worldwide [ 1 ]. A large majority of M. tuberculosis-infected individuals remains asymptomatic while unable to clear the bacterium, with a lifelong probability to develop active TB of about 5-10% [ 2 ]. This probability is highest within the first two years after infection, and in subjects with recently-established LTBI preventive therapy can be effective. Thus the distinction between the different forms and stages of MTB infection is fundamental for the effective control of TB transmission.The correct diagnosis of LTBI remains a challenge. Until recently, tuberculin skin test (TST) has been the most frequently used screening method, leading to a high rate of false positive results in M. bovis BCG-vaccinated individuals, and false negative tests in immunosuppressed persons. The new interferon gamma release assays (IGRAs) employing RD-1 antigens specific for virulent mycobacteria have excellent specificity unaffected by BCG vaccination and increased sensitivity While CD4 Th1 cells are the well-known effectors of MTB-specific immune response, a lot of evidence from humans and from animal models indicate a critical role of CD8 T cells for MTB control as well [ 6-8 ]. However, data about the characteristics of CD8 T cell responses in individuals with LTBI and in patients with active tuberculosis are still scarce.In this study, using intracellular cytokine staining (ICS) and flow cytometry, we compared the CD8 T cell responses ...

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Systematic Review: T-Cell–based Assays for the Diagnosis of Latent Tuberculosis Infection: An Update

Cited by 1,184 publications

References 52 publications

The HIV-associated tuberculosis epidemic—when will we act?

The HIV-associated tuberculosis epidemic—when will we act?

Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

Peripheral Blood CD8 T Cell Response in Different Phases of MTB Infection

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