Le diagnostic de tuberculose oculaire (TO) demeure difficile et la contribution du QuantiFERON® (QFT) reste à préciser malgré sa généralisation en France. L’objectif de cette étude est d’évaluer dans ...quelles situations d’inflammation oculaire (IO) le QFT doit être prescrit et l’intérêt du nouveau test QuantiFERON®-TB-Plus (QFT-Plus) dans la TO.
Étude monocentrique, observationnelle, effectuée en ophtalmologie sur une période de 5 mois. Les critères d’inclusion étaient l’existence d’une IO avec QFT-Plus demandé à visée étiologique. Sur 316 dossiers consécutifs, 72 ont été exclus (tests indéterminés, bilan préthérapeutique, données manquantes et mauvaise indication) et 244 retenus et répartis en deux groupes : groupe 1 (uvéite antérieure/épislérite, n=129), groupe 2 (uvéite intermédiaire/postérieure/névrite optique/myosite oculaire, n=115). Tous les patients QFT+ ont bénéficié d’un bilan étiologique avec imagerie thoracique.
Quarante-cinq patients, d’âge médian de 52±12 ans, avaient un QFT+ (18,5 %), incluant 18 patients dans le groupe 1 et 27 dans le groupe 2. Un voyage en pays d’endémie et un contage tuberculeux et des anomalies de l’imagerie thoracique étaient identifiés, respectivement dans 70 %, 27 % et 22 % des cas. L’IO était chronique chez 36 % des patients (groupe 1, n=4/18 ; groupe 2, n=12/27). Aucun des 18 patients du groupe 1, n’a reçu de quadrithérapie antituberculeuse, ni n’a présenté de rechute à 1 an de suivi. Un diagnostic alterne était retrouvé chez 15 % des patients du groupe 2. Parmi les 23 patients, sans étiologie identifiée, 13 (59 %) avaient au moins un élément sémiologique ophtalmologique prédictif de TO (synéchies postérieures, vascularite rétinienne, granulomes choroïdiens). Onze patients ont bénéficié d’un traitement antituberculeux (TAT) d’épreuve (rifampicine/isoniazide/pirilène/éthambutol) de six mois. La présence de granulomes à l’angiographie et d’anomalies radiologiques à l’imagerie thoracique était statistiquement plus fréquente parmi les patients ayant reçu un TAT (respectivement, p=0,001 et 0,03). Une guérison à 12 mois était observée pour 8 patients (73 %), considéré a posteriori comme TO. Neuf patients ont reçu trois mois de bithérapie (rifampicine/isoniazide) sans que l’on puisse déterminer l’impact sur l’IO. La comparaison des réponses lymphocytaires T entre la stimulation CD4 par peptides ESAT-6/CFP-10 ou la co-stimulation CD4/CD8 était similaire, ne retrouvant que 4 discordances sur 244 tests (1,5 %). Aucun de ces 4 patients n'avait de TO.
La fréquence de positivité du QFT est élevée parmi les patients consultant pour une IO postérieure. Les anomalies radiologiques et la présence de granulomes semblent être les éléments qui ont incités le clinicien à initier un TAT aux patients QFT+, avec guérison dans 73 % des cas. Le QFT-Plus ne semble pas plus pertinent que le QFT-TB-Gold dans l’exploration d’une IO. Des études prospectives restent nécessaires pour codifier l’utilisation du QFT dans le bilan étiologique des IO et définir les indications du TAT d’épreuve et de ses modalités.
Ocular tuberculosis (TB) diagnosisremains difficult and quantiferon (QFT) contribution needs still yet to be specified, despite its generalization in France. The purpose of this observational study is to assess in which ocular inflammation (OI) presentation QFT is prescribed and to evaluate the added value of new QuantiFERON®-TB Gold Plus (QFT-Plus) test for diagnosis ocular TB diagnosis.
Monocentric, observational study, carried out in an ophthalmology department over a period of 5 months. Inclusion criteria were defined as an existence of an OI for which a QFT-Plus test was part of the etiological investigations. Of the 316 consecutive files, 72 were excluded (indeterminate test, prescription before anti-TNFα or immunosuppressant initiation, missing data, wrong indication) and 244 were selected and divided into two groups: group one (anterior uveitis/episcleritis, n=129) and group two (intermediate/posterior uveitis/optic neuritis/ocular myositis, n=115). All positive QFT patients underwent an etiological investigation including thoracic imaging.
Forty-five patients, aged 52±12 years, had positive QFT (18.5%), including 18 patients for group 1 and 27 for group 2. Living in TB-endemic area, TB exposure and chest imaging abnormalities were identified in 70%, 27% and 22% of cases, respectively. OI was chronic in 36% of cases (group one, 4/18; group two, 12/27). None of the 18 patients, in group 1, received anti-tuberculosis treatment (ATT) or experienced a relapse during one-year follow-up. Four QFT+ patients, from group 2 (15%) had another associated disease explaining their uveitis. Among the 23 other patients without identified etiology, 13 had at least one relevant ophthalmological signs predictive of TB uveitis (posterior synechiae, retinal vasculitis and/or choroidal granuloma) (59%). Eleven patients received a 6-month ATT trial. Radiological abnormalities and granulomas at angiography were significantly more frequent among treated patients (p=0.03 and 0.001, respectively). A full OI recovery was observed for 8 patients (73%), considered ex-post as ocular TB. Nine patients in group 2 received rifampicin/isoniazid dual therapy for 3 months, but no conclusion could be drawn as to the benefit of such prescription on OI. QFT rate comparison, according to CD4 stimulation by ESAT-6/CFP-10 peptides or by CD4/CD8 co-stimulation, was comparable and found only 4 cases of discrepancy (1.6%). None of these 4 cases had ocular TB diagnosis.
Positive QFT frequency among patients consulting for posterior OI remains high. In this study, radiological abnormalities and granulomas at angiography seemed to be more closely related to clinician decision for starting ATT trial in QFT+ patients, which was effective in 73% of cases. QFT-Plus does not seem more relevant than QFT-TB in exploring an OI. Prospective studies are necessary to codify QFT management in the etiological assessment of OI and clearly define ATT trial indications as well as their modalities.
Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis ...(TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not TST5/15 mm) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17–25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82–7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58–7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48–11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23–2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98–3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p = 0.68 for QFT-GIT). Interpretation: IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results. Funding: YH, IA, and MXR were supported by the National Institute for Health and Care Research (NIHR), United Kingdom (RP-PG-0217-20009). MQ was supported by the Medical Research Council MC_UU_00004/07.
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.
The QuantiFERON-TB Gold plus (QFT-Plus) assay, an interferon gamma (IFN-γ) release assay (IGRA), was recently introduced as the next version of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay for ...diagnosing latent tuberculosis (TB). Whereas the QFT-GIT assay uses only one TB tube that induces a cell-mediated immune (CMI) response of CD4
T cells, the QFT-Plus has an additional TB antigen 2 tube (TB2) for the CMI response of CD8
T and CD4
T cells, in addition to a TB antigen 1 (TB1) tube for the CMI response of CD4
T cells only. We compared the results of the QFT-Plus and QFT-GIT assays as routine clinical tests for diagnosing TB. Samples from 220 patients referred for routine IGRA in various clinical departments were used. Correlations between IFN-γ levels in the QFT-GIT and QFT-Plus assays were strong and showed good agreement (kappa value = 0.69). Seven cases with positive QFT-GIT assay results and negative QFT-Plus assay results showed IFN-γ values near the cutoff value. However, 10 cases with active TB, recent TB, or immune problems showed discordance with the positive results only in the TB2 tube in QFT-Plus, unlike the negative results in TB1 and TB tubes. In these cases, IFN-γ levels in the TB2 tube were significantly higher than those in other tubes. This is the first study to compare these assays as routine IGRAs in the clinical setting. The QFT-Plus assay showed good agreement with the QFT-GIT assay and is presumably advantageous for patients with active TB, recent TB, and specific immune conditions involving CD8
T-cell responses.
In sepsis, personalized immunotherapy is being evaluated as a means of restoring immune function in the most severely affected patients. Biomarkers play a crucial role in this process, as there are ...no clear clinical indicators of immune dysfunction. Functional testing is considered a gold standard for assessing immune function, but this approach faces analytical challenges in terms of clinical implementation. The use of technician-dependent, time-consuming, home-made protocols often leads to poor standardization. This study represents the first beta testing of a fully automated interferon-γ release assay (IGRA) for monitoring the functionality of antigen-independent T lymphocytes. We observed a significant decrease in IFN-γ release capacity, which was associated with typical alterations in immunological cellular parameters (such as low mHLA-DR expression and decreased CD8 T lymphocyte count), in 22 patients with septic shock. Since the test is performed using whole blood and requires no technician intervention, with results available within 4 h, it may offer new possibilities for monitoring patients with immune alterations in routine clinical conditions. Further investigations in larger cohorts of patients are now needed to validate its clinical potential.
The fourth-generation QuantiFERON test for tuberculosis infection, QuantiFERON-TB Gold Plus (QFT-Plus) has replaced the earlier version, QuantiFERON-TB Gold In-Tube (QFT-GIT). A clinical need exists ...for information about agreement between QFT-Plus and other tests. We conducted this study to assess agreement of test results for QFT-Plus with those of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and the tuberculin skin test (TST). Persons at high risk of latent tuberculosis infection (LTBI) and/or progression to tuberculosis (TB) disease were enrolled at the 10 sites of the Tuberculosis Epidemiologic Studies Consortium from October 2016 through May 2017; each participant received all four tests. Cohen's kappa (κ) and Wilcoxon signed-rank test compared qualitative and quantitative results of QFT-Plus with the other tests. Test results for 506 participants showed 94% agreement between QFT-Plus and QFT-GIT, with 19% positive and 75% negative results. When the tests disagreed, it was most often in the direction of QFT-GIT negative/QFT-Plus positive. QFT-Plus had similar concordance as QFT-GIT with TST (77% and 77%, respectively) and T-SPOT (92% and 91%, respectively). The study showed high agreement between QFT-GIT and QFT-Plus in a direct comparison. Both tests had similar agreement with TST and T-SPOT.
The diagnosis of latent tuberculosis (TB) infection (LTBI) is critical to improve TB treatment and control, and the T-SPOT.TB test is a commercial enzyme-linked immunosorbent spot assay used for this ...purpose. The objective of the study was to increase automation and extend the time between blood collection and processing for the T-SPOT.TB test from 0 to 8 h to 0 to 54 h. The previous maximum time between blood collection and processing for the T-SPOT.TB test is 32 h using T-Cell Xtend. For this, we compared the T-SPOT.TB test using manual peripheral blood mononuclear cell (PBMC) isolation by density gradient separation at 0 to 8 h (reference method, control arm) to an automated PBMC isolation method using magnetic beads (T-Cell Select kit) at 0 to 55 h postcollection. A total of 620 subjects were enrolled from 4 study sites, and blood samples were collected from each volunteer, comprising 1,850 paired samples in total. Overall agreement between both methods was 96.8% (confidence interval CI, 95.9 to 97.6%), with 95.8% (CI, 93.5 to 97.5%) positive and 97.1% negative agreement (CI, 96.1 to 97.9%). In summary, there was a strong overall agreement between the automated and manual T-SPOT.TB test processing methods. The results suggest that the T-SPOT.TB test can be processed using automated positive selection with magnetic beads using T-Cell Select to decrease hands-on time. Also, this cell isolation method allowed for the time between blood collection and processing to range from 0 to 55 h. Additional studies in larger and diverse patient populations including immunocompromised and pediatric patients are needed.
The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination ...of its diagnostic accuracy is crucial before it is launched in Japan.
We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared.
The sensitivity of the QFT-Plus was 98.9% (95% confidence interval CI, 0.934–0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929–0.998) and T-SPOT (96.9%; 95% CI, 0.914–0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934–0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs.
The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan.
We established a set of atmospheric standard temperature and water vapor profiles and examined the characteristics of the tropopause over the Tibetan Plateau in summer using IGRA, COSMIC and ERA-5 ...datasets. We studied the temperature and water vapor profiles under clear sky, cloudy and “other” conditions and their diurnal variation. The atmosphere over the Central Tibetan Plateau is warmest and wettest in the lower to mid-troposphere, whereas the Western Tibetan Plateau is warmest and driest in the mid to high troposphere. The coldest and wettest air near the tropopause is over the Eastern Tibetan Plateau. The height of the tropopause decreases gradually from west to east over the plateau, although the difference in height is ≤0.5 km. Relative to clear sky conditions, cloudy conditions are characterized by warming and wetting anomalies in the lower to mid-troposphere and cooling and wetting anomalies in the tropopause and lower stratosphere. The largest vertical diurnal differences in temperature are at the surface and the difference decreases with increasing altitude from the surface to ~12 km. The difference between the six time periods of early morning, morning, noon, afternoon, evening and midnight are within −0.5 to 0.5 K above 12 km. The difference in water vapor between the six time periods is ≤0.2 g m−3. The lowest tropopause is at early morning. The height of the tropopause then increases followed by a decrease, with a sharp peak at noon. This establishment of a set of atmospheric standard profiles over Tibetan Plateau provides more accurate inputs for climate models.
•This establishment of a set of atmospheric standard profiles provides more accurate inputs for climate models.•We examine the differences of temperature and water vapor profiles between clear sky, cloudy and “other” conditions.•The characteristics for diurnal variation of temperature and water vapor profiles over Tibetan Plateau are quantified.•The height and temperature of tropopause under clear sky and cloudy conditions and their diurnal variations are revealed.
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.
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