Meta-analysis: New Tests for the Diagnosis of Latent Tuberculosis Infection: Areas of Uncertainty and Recommendations for Research

Menzies, Dick; Pai, Madhukar; Comstock, George W.

doi:10.7326/0003-4819-146-5-200703060-00006

Cited by 907 publications

(782 citation statements)

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“…In previous meta-analyses, similarly to data reported in adults, higher IGRA specificity with respect to TST has been reported. However, the reported IGRA sensitivity ranged between 62% and 89% for T-SPOT.TB and 66% and 83% for QFT-G-IT [1,5,9-11]. Differences between IGRA performance in low income and high income countries were evaluated only in one meta-analysis which considered only QFT-G-IT- (and not T-SPOT.TB-) based studies [1].…”

Section: Discussionmentioning

confidence: 99%

“…Some authors reported a sub-optimal IGRA sensitivity in children [14], but this finding has not been confirmed by others [8]. Five meta-analyses have previously assessed IGRA sensitivity and specificity in children but reported pooled estimates largely differ (Table 1) [1,5,9-11]. Such discordances may be due to different inclusion/exclusion criteria and, thus, different characteristics of the study populations (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…IGRAs allow detection of circulating T-cells responsive to specific Mycobacterium tuberculosis antigens, which are absent in BCG and many non-tuberculosis mycobacteria, and displayed similar sensitivity and higher specificity than TST in adults (table 1) [5-12]. However, IGRA performance in paediatric populations is still under debate and caution is recommended for their use and interpretation in children [13].…”

Section: Introductionmentioning

confidence: 99%

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Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis finfection in children: a 2013 update

et al. 2014

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BackgroundPrevious meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.MethodsWe systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children.ResultsOverall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%).ConclusionsBoth IGRAs showed no better performance than TST in low income countries.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis finfection in children: a 2013 update

et al. 2014

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“…In the general population, these 2 tests have good concordance for detecting latent TB. 11 One study compared QFT to PPD testing in 153 chronic liver disease patients awaiting liver transplantation. Concordance between the 2 tests was 85.1% (k ¼ 0.60), and this suggests that QFT was comparable to PPD for the diagnosis of latent TB in this population.…”

Section: Diagnosis Latent Tbmentioning

confidence: 99%

“…[14][15][16] Because both QFT and TST measure the cellular immune response to M. tuberculosis, testing with QFT is unlikely to be helpful in patients with a negative TST related to defective cellular immune responses. 11,12 The full evaluation of a patient with cirrhosis before liver transplantation should be thorough and include a detailed medical and exposure history and a review of chest radiography (see the section on the evaluation of transplant candidates and donors). In posttransplant recipients, the diagnosis of LTBI similarly involves the use of TST or interferon-c release assay testing.…”

Section: Diagnosis Latent Tbmentioning

confidence: 99%

Mycobacterium tuberculosis infection in liver transplantation

Yehia

Blumberg

2010

Liver Transpl

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Mycobacterium tuberculosis can cause significant infections in liver transplant candidates and recipients. Its nonspecific clinical features and prolonged growth time in culture make the diagnosis difficult, and treating tuberculosis (TB) remains challenging because of significant toxicities and drug-drug interactions. The diagnosis of a latent TB infection may be accomplished with tuberculin skin testing and with the newer interferon-c release assays, although this infection may be underrecognized because of host factors. Latent TB should be treated, but the degree of liver failure and the likelihood of progression to active TB will dictate whether this should occur before or after transplantation. Patients who have a history of TB, have used muromonab-CD3 or anti-T lymphocyte antibodies, or have experienced allograft rejection or coinfection with cytomegalovirus, Pneumocystis jiroveci, or Nocardia are at the greatest risk of developing active TB. Active TB in transplant patients is difficult to treat because of drug-induced hepatotoxicity and the significant interaction between rifampin and calcineurin inhibitors. In this article, we review the epidemiology, clinical features, and evaluation of transplant candidates and recipients. In addition, we offer recommendations on the appropriate diagnostic and treatment regimens for patients with latent and active TB infections. Liver Transpl 16:1129-1135, 2010. V C 2010 AASLD.Received April 5, 2010; accepted July 6, 2010.Tuberculosis (TB) is a serious global infection with an estimated prevalence of 13.7 million cases worldwide. 1 Transplant recipients have a 36-to 74-fold higher risk of developing TB versus the general population. 2 TB in liver transplant recipients presents unique challenges, including a delayed diagnosis secondary to insensitive testing and treatment complications due to antituberculous drug toxicities and interactions with immunosuppressive agents. This review focuses on the epidemiology, clinical features, diagnosis, clinical evaluation, and treatment of liver transplant patients infected with TB. EPIDEMIOLOGYRates of 0.47% to 2.3% for active TB in adult liver transplant recipients has been reported. [2][3][4][5] Because of the difficulty of accurately diagnosing symptomatic TB, these figures most likely underestimate the burden of the disease. In addition, the frequency of the disease varies geographically, with particular regions (Asia and Africa) having a higher prevalence than other areas of the world. 6 Several factors place transplant patients at greater risk of developing active TB.A previous TB infection increases the likelihood of TB developing after transplantation. 5 The RESITRA (Spanish Network of Infection in Transplantation) cohort documented a relative risk of 4.3 for the development of symptomatic TB when the purified protein derivative (PPD) test was positive instead of negative. 4 In a systematic review of 139 cases of active TB infection after liver transplantation, 37% had a positive tuberculin skin test (TST), 23% had abnorm...

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Usefulness of Interferon- γ Release Assays in the Diagnosis of Erythema Induratum

Vera‐Kellet

Peters²,

Elwood³

et al. 2011

Arch Dermatol

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Background: Erythema induratum (EI) manifests as tender indurated nodules on the lower legs. It may be associated with concomitant active tuberculosis (TB) and is considered a hypersensitivity reaction to mycobacterial antigens. However, the results of Mycobacterium cultures are rarely positive, and the tuberculin skin test is of limited usefulness in populations exposed to bacille Calmette-Gué rin (BCG). Interferon-␥ release assays (IGRAs) are alternatives to the tuberculin skin test and have high specificity. We explored the use of IGRAs as an adjunct in the diagnosis of EI. We describe 5 patients with positive tuberculin skin test results and a history of vaccination against BCG or TB in whom IGRAs supported the diagnosis of EI. Observations: All patients were initially seen with tender nodules on the lower legs and a history of BCG vaccination or TB. Tuberculin skin test results were positive, and chest radiographic results were normal. The results of Mycobacterium cultures were negative in all patients, and biopsy specimens were compatible with EI. Interferon-␥ release assays were performed in all patients and supported initiation of anti-TB treatment in 4 of 5 patients. Conclusion: Interferon-␥ release assays may have value as an adjunct in the diagnosis of EI, particularly in the setting of prior BCG exposure.

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Meta-analysis: New Tests for the Diagnosis of Latent Tuberculosis Infection: Areas of Uncertainty and Recommendations for Research

Abstract: 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.

Cited by 907 publications

References 70 publications

Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis finfection in children: a 2013 update

Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis finfection in children: a 2013 update

Mycobacterium tuberculosis infection in liver transplantation

Usefulness of Interferon- γ Release Assays in the Diagnosis of Erythema Induratum

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