Despite the availability of effective treatment regimens for cutaneous tuberculosis, challenges to disease control result from delayed diagnosis, infection with multidrug-resistant mycobacterial ...strains, and coinfection with HIV. Delayed diagnosis can be mitigated when dermatologists are sensitized to the clinical signs and symptoms of infection and by the incorporation of appropriate diagnostic tests. All cases of cutaneous tuberculosis should be confirmed with histopathology and culture with or without molecular testing. In each case, a thorough evaluation for systemic involvement is necessary. Mycobacteria may not be isolated from cutaneous tuberculosis lesions and therefore, a trial of antituberculosis treatment may be required to confirm the diagnosis. The second article in this 2-part continuing medical education series describes the sequelae, histopathology, and treatment of tuberculosis.
Latent tuberculosis infection (LTBI) is a subclinical mycobacterial infection defined on the basis of cellular immune response to mycobacterial antigens. The tuberculin skin test (TST) and the ...interferon gamma release assay (IGRA) are currently used to establish the diagnosis of LTB. However, neither TST nor IGRA is useful to discriminate between active and latent tuberculosis. Moreover, these tests cannot be used to predict whether an individual with LTBI will develop active tuberculosis (TB) or whether therapy for LTBI could be effective to decrease the risk of developing active TB. Therefore, in this article, we review current approaches and some efforts to identify an immunological marker that could be useful in distinguishing LTBI from TB and in evaluating the effectiveness of treatment of LTB on the risk of progression to active TB.
Detection of latent Mycobacterium tuberculosis (LTBI) in patients is important to prevent active infection and the spread of disease, particularly in vulnerable patient populations. In 2020, a kit on ...the high throughput Liaison XL (DiaSorin) became commercially available for the analysis of QuantiFERON-TB Gold Plus assay (Qiagen). Pilot testing indicated suboptimal repeatability of some samples with this assay. This study provides an extensive assessment of repeatability with DiaSorin system.
Repeat testing of 481 IGRA positive samples, demonstrated substantial variability upon repeat analysis. Repeat results for TB1 and TB2 tubes, showed 73.73% and 72.82% concordance with initial results, respectively. TB1 and TB2 tube values minus the nil (IU/mL) were significantly higher in samples that were repeat positive (p < 0.001). Repeat results had better concordance with initial results if both TB1 and TB2 tubes were positive. Samples with TB1 tube values minus the nil (IU/mL) ≥ 4.54 and TB2 tube values minus the nil (IU/mL) ≥ 4.78 were found to always repeat positive. Assigning a threshold of 1.55 IU/mL for the TB1 tube value minus the nil and 1.45 IU/mL for the TB2 tube value minus the nil yielded a positive predictive value ≥95%.
These results identified a potential role for retesting of select IGRA positive samples on the Diasorin Liaison XL platform due to the high proportion of samples that show a lack of repeatability. Additionally, we identified a threshold that would determine samples most likely to repeat test positive and which samples should be retested.
As a virulence factor, HupB plays important roles in the survival of MTB after infection and modulates the host immune response. In the current study, we aim to explore a new cellular immunological ...detection method for tuberculosis infection detection based on HupB protein.
HupB was used to stimulate PBMCs extracted from pulmonary tuberculosis (PTB) patients, and secreted cytokines was examined. Then, we constructed a single center and a multi-center clinical trials to collect PBMCs from PTB patients, nPTB patients, or healthy volunteers to verify our findings.
Cytokine's screening illustrated that IL-6 was the only cytokine released after HupB stimulation. Single-center and multi-center clinical trials showed that HupB stimulation significantly increased the level of IL-6 in the supernatant of PBMCs from PTB patients. Then we compared the specificity and sensitivity of HupB induced IL-6 release assay with ESAT-6 and CFP10 induced interferon γ release assay (IGRA), and found in smear positive PTB patients, the specificity and sensitivity of HupB induced IL-6 release assay was better than IGRA, and in smear negative PTB patients, the sensitivity was better. Combination of both assays provided an improved specificity and sensitivity for tuberculosis diagnosis.
This study explored an immunological detection method for tuberculosis infection cells based on HupB protein-induced IL-6 release test, which can be used to enhance the diagnosis diagnostic accuracy of TB.
•Tuberculosis (TB) infection accounts for 2 billion people worldwide•TB infection is defined by immune response detection without clinical active disease•Tests for TB infection diagnosis lack ...accuracy to identify progressors to disease•Preventive therapy is a strategy to control TB spread worldwide•A TB infection registry is crucial for public health issues of TB control
The World Health Organization estimated that a quarter of the global population is infected by Mycobacterium tuberculosis (Mtb). A better control of tuberculosis (TB) is based on the ability to detect Mtb infection, identifying the progressors to TB disease, undergoing to preventive therapy and implementing strategies to register the infections and treatment completion.
we reviewed the literature regarding the tests available for TB infection diagnosis, the preventive therapies options and the cascade of care for controlling TB at a public health level.
current tests for TB infection diagnosis as IFN-γ release assays or tuberculin skin tests are based on the detection of an immune response to Mtb in the absence of clinical disease. The main limit is their low accuracy to detect progressors to disease. New preventive treatments are available with short duration that are associated with better adherence. Options to register TB infections are presented.
Tests to diagnose TB infection are available but they lack accuracy to identify the progressors from infection to TB disease. Shorter preventive TB therapy are available but need to be implemented worldwide. A TB infection registry is crucial for improving the cascade of care leading to a better TB control.
BACKGROUNDSerpiginous-like choroiditis (SLC) denotes ocular tuberculosis (TB), in the presence of positive tuberculin skin test (TST) or interferon gamma release assay (IGRA). METHODSRetrospective ...review of SLC patients from a TB-endemic country, with negative TST and IGRA tests, but responsive to anti-TB therapy. RESULTSFifteen patients (13 bilateral) with active SLC were included. Eleven (73.3%) patients had received corticosteroids ± immunosuppressive therapy prior to presentation. Chest radiographic abnormalities were found in four (26.7%) patients. We treated all patients with a combination of anti-TB therapy (ATT) and corticosteroids. Paradoxical worsening was noted in nine (60%) patients, complete resolution of lesions in 12 (80%), persistent inflammation (post-ATT) in one, while two were yet to complete ATT. None had recurrence after complete resolution of lesions (median follow-up of 71 weeks range 15-676 weeks). CONCLUSIONSTB-SLC may present with negative TST and IGRA tests but may still have clinical appearance, and treatment response, like test-positive disease.
Introduction Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive ...strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx. Methods We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses. Results In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01). Conclusion Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients.
Interferon-γ release assays (IGRA) are designed for diagnosis of tuberculosis (TB) infection, and do not discriminate latent TB infection (LTBI) from active TB. Heparin-binding hemagglutinin antigen ...(HBHA) emerged as a promising antigen for TB diagnosis when used in IGRA format. Aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA to support TB diagnosis and TB therapy monitoring in children with TB infection or active TB disease.
Following clinical, microbiological and radiological assessment, children (0–14 years old) were tested by the QuantiFERON TB-Gold In tube (QFT) assay and an aliquot of whole-blood was stimulated with HBHA and IFNγ evaluated only in QFT-positive subjects.
Among the 550 children tested, 486 (88.4%) scored negative and 64 (11.6%) positive. None of the QFT-negative had active TB. Among the QFT-positive, 45 were with LTBI and 19 active TB. HBHA-IGRA scored positive in 41/45 children (91.1%) with LTBI and in 6/19 active TB children (31.6%) at diagnosis (p = 0.001); remarkably, 5 of these 6 children with active TB scoring HBHA-positive were asymptomatic. Moreover, following TB-specific therapy, most of the non-HBHA-responding children, gained an HBHA-positive response.
HBHA-based IGRA is a useful support in TB diagnosis and TB-therapy monitoring in children.
Anti-interferon- γ (IFN-γ) autoantibodies (anti-IFN-γ Abs) have been increasingly recognized as an important cause of disseminated nontuberculous mycobacterial (DNTM) infection, and identification of ...this immunodeficiency impacts clinical management. However, the protean disease manifestations and inaccessibility to diagnostic tests in clinical settings hamper its early diagnosis. Here, we sought to determine whether QuantiFERON-TB Gold In-tube (QFT-GIT), a commercialized IFN-γ release assay, could be used to screen for neutralizing anti-IFN-γ Abs among previously healthy adults with DNTM infection.
Non-HIV patients with DNTM infection were prospectively enrolled for the QFT-GIT assays. We measured their plasma concentration of anti-IFN-γ Abs and their neutralizing capacity through enzyme-linked immunosorbent assay and flow cytometry. We then analysed the correlation between QFT-GIT results and the presence of neutralizing anti-IFN-γ Abs among patients with and without previously recognized immunosuppression, respectively.
Irrespective of the autoantibody concentration or disease activity, all patients with neutralizing anti-IFN-γ Abs (100%, 30/30) had indeterminate QFT-GIT results because of extremely low or undetectable IFN-γ levels in the mitogen tubes. None of the four DNTM patients who were previously healthy and tested negative of anti-IFN-γ Abs had an indeterminate QFT-GIT result, and their IFN-γ levels in the mitogen tube were significantly higher than those of the patients with anti-IFN-γ Abs (8.28 IU/mL vs. 0.05 IU/mL, p 0.001).
An indeterminate QFT-GIT result because of undetectable or extremely low IFN-γ level in the mitogen tube suggests the presence of neutralizing anti-IFN-γ Abs in a previously healthy patient with DNTM infection.