Interferon-gamma Release Test Research Articles

P.333: Interferon-gamma release test results in organ transplant recipients and donors at Başkent University Faculty of Medicine Hospital.

P.333: Interferon-gamma release test results in organ transplant recipients and donors at Başkent University Faculty of Medicine Hospital.

Diagnostic approach of tuberculous lymphadenitis in a multicenter study.

Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults. Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study. A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05). Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.

Latent Tuberculosis Infection Management in Solid Organ Transplantation Recipients: A National Snapshot.

Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Turkey. Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n= 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines.

HTA38 Accuracy and Economic Evaluation of the Interferon Gamma Release Test (IGRA) for Detection of Latent Infection By Mycobacterium Tuberculosis in Patients with Immune-Mediated Diseases or Receptors of Solid Organ Transplants

Latent tuberculosis infection (LTBI) has a high global prevalence and can progress to its active form in immunocompromised patients. There is also considerable uncertainty about diagnostic tests accuracy because there is no gold standard. The purpose was to evaluate the accuracy of the interferon gamma release test (IGRA) to detect LTBI and predict the active tuberculosis in solid organ transplant candidates (1st group) and patients with immune-mediated inflammatory diseases (2nd group).

Reasons for requesting an interferon gamma release test from internal medicine and rheumatology clinics and evaluation of the results

Background/Aim: Tuberculosis is a disease involving many systems, such as the lung, gastrointestinal system, genitourinary system, etc. Detecting this disease in its latency significantly reduces the morbidity and mortality associated with tuberculosis. One of the tests used in latent TB screening is the interferon gamma release test. In rheumatology practices, it is routinely used to screen for latent tuberculosis infections before treatment with biological agents and Janus kinase (JAK) inhibitors, and it can also be used to exclude tuberculosis infection in clinical practice. In our study, we aimed to evaluate the reasons for requesting interferon gamma release tests and the results of this test in patients who requested it. Methods: Patients admitted to internal medicine and rheumatology outpatient clinics were retrospectively screened within the retrospective cohort study. In total, 364 patients who requested interferon gamma release testing were included in the study. Nine patients with unclear test results were excluded. Laboratory results, demographic data, reasons for requesting the interferon gamma release test, and results were evaluated. Results: The interferon gamma release test was requested by 355 patients. Of these, 266 patients (74.9%) asked for latent tuberculosis screening before treatment with biological agents and JAK inhibitors. This was followed by patients with peripheral lymphadenopathy-lung nodules, patients with unexplained elevated acute phase reactants, and patients with constitutional symptoms, respectively. Ten out of 107 patients (9.3%) had an active tuberculosis infection, while six out of ten patients (60%) had pulmonary tuberculosis, and four (40%) had extrapulmonary tuberculosis. Conclusion: The most common reason for requesting the interferon gamma release test in internal medicine and rheumatology clinics was screening for latent tuberculosis before treatment with biologic agents and JAK inhibitors. In internal medicine, it has been observed that this test can also be requested by patients with constitutional symptoms, unexplained elevated acute phase reactants, and a preliminary diagnosis of tuberculosis in order to rule out or strengthen the preliminary diagnosis.

Humoral and Cellular Immunity to Severe Acute Respiratory Syndrome Coronavirus-2 Vaccination in Patients with Sarcoidosis.

The coronavirus disease 2019 vaccine induces both antibody and T-cell immune responses and has been proven to be effective in preventing coronavirus disease 2019, including its severe disease form, in healthy individuals. However, the details of severe acute respiratory syndrome coronavirus-2 immunoglobulin-G antibody responses and severe acute respiratory syndrome coronavirus-2 specific T-cell responses in patients with sarcoidosis are unknown. To measure and compare antibody responses and T cell responses using enzyme-linked immunosorbent assays and interferon-gamma release assay in sarcoidosis patients infected with coronavirus disease 2019 and vaccinated with CoronaVac. A prospective cohort study. A total of 28 coronavirus disease 2019 polymerase chain reaction test-positive sarcoidosis patients who were infected with severe acute respiratory syndrome coronavirus-2 in the past 6 months and did not have coronavirus disease 2019 vaccination and 28 sarcoidosis patients who were administered with 2 doses of CoronaVac and never had coronavirus disease 2019 were included in this study. The immune response levels of patients were determined by measuring the severe acute respiratory syndrome coronavirus-2 immunglobulinG and interferon-gamma levels in the blood of the patients by the enzyme-linked immunosorbent assays method and interferon-gamma release assay tests, respectively. The mean age of the patients in the COVID-infected group was 48.1 ± 11.3, while the mean age of the patients in the vaccinated group was 55.6 ± 9.32. The mean time elapsed after infection was 97.32 ± 42.1 days, while 61.3 ± 28.7 days had passed since the second vaccination dose. In the COVID-infected group, immunoglobulin-G and interferon-gamma release tests were positive in 64.3% and 89.3% of the patients, respectively. In the vaccinated group, immunoglobulin-G was positive in 10.7% of the patients, and interferon-gamma release test was positive in 14.3%. Innate immune responses are better than adaptive immune responses in patients with sarcoidosis. The coronaVac vaccine is insufficient to generate humoral and cellular immunities in patients with sarcoidosis.

Performance of LTBI Screening in Patients with Rheumatic Diseases Using Two Different Interferon-Gamma Releasing Assays.

To evaluate the concordance between QuantiFERON-TB Gold in-tube test (QFT-GIT) and T-SPOT.TB test (T-SPOT) for the screening of latent tuberculosis infection (LTBI) in patients with rheumatic diseases (RDs). Patients diagnosed as rheumatic diseases (RDs) with clinical indications for test of interferon gamma release test (IGRA) were prospectively recruited from 2019 to 2020. The consistency of QFT-GIT and T-SPOT was assessed by Kappa analysis and the factors associated with the indeterminate results were explored by multivariable logistic analysis. A total of 108 patients with RDs were enrolled, including 64 patients with systemic lupus erythematosus (SLE) and 44 with inflammatory arthritis (26 with rheumatoid arthritis (RA) and 18 with ankylosing spondylitis (AS)). Poor concordance was confirmed between QFT-GIT and T-SPOT results in patients with SLE (K = 0.175, 95% confidence interval [95% CI] [-0.06, 0.40], p < 0.001), whereas concordance was moderate in patients with inflammatory arthritis (K = 0.539, 95% CI [0.11, 0.88], p < 0.001). Among SLE patients, the ratio of indeterminate results in detecting LTBI was significantly higher by QFT-GIT than by T-SPOT (18.8% vs. 4.7%, p = 0.013), while the statistical difference was not achieved in patients with inflammatory arthritis. The multivariable logistic analysis identified that the presence of lower lymphocyte counts (odds ratio [OR] = 0.81, 95% CI [0.68, 0.97], p = 0.020) was the independent predictor of an indeterminate result of the QFT-GIT in SLE patients. In patients with RDs, the result of screening of LTBI was more definitive by T-SPOT test than QFT, and the concordance was poor especially in the setting of SLE.

Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance.Clinical Trial Registration Number www.ClinicalTrials.gov, identifier: NCT04 905 862

Clinical Manifestations and Outcomes of Tubercular Uveitis in Taiwan-A Ten-Year Multicenter Retrospective Study.

Background andObjectives: This 10-year multicenter retrospective study reviewed the clinical manifestations, diagnostic tests, and treatment modalities of tubercular uveitis (TBU), including direct infection and indirect immune-mediated hypersensitivity to mycobacterial antigens in Taiwan. Materials and Methods: This retrospective chart review of patients with TBU was conducted at 11 centers from 1 January 2008 to 31 December 2017. We used a multiple regression model to analyze which factors influenced best-corrected visual acuity (BCVA) improvement. Results: A total of 79 eyes from 51 patients were included in the study. The mean age was 48.9 ± 16.4 years. The mean change of LogMAR BCVA at last visit was −0.21 ± 0.45. Diagnostic tools used include chest X-ray, chest computed tomography, Mantoux test, interferon gamma release test (QuantiFERON-TB Gold test), intraocular fluid tuberculosis polymerase chain reaction, and bronchial alveolar lavage. The clinical manifestations included 48% posterior uveitis and 37% panuveitis. In the sample, 55% of the cases were bilateral and 45% unilateral. There was 60.76% retinal vasculitis, 35.44% choroiditis, 21.52% serpiginous-like choroiditis, 17.72% vitreous hemorrhage, 12.66% posterior synechiae, 6.33% retinal detachment, and 3.80% choroidal granuloma. Treatment modalities included rifampicin, isoniazid, pyrazinamide, ethambutol, oral steroid, posterior triamcinolone, non-steroidal anti-inflammatory drugs, vitrectomy, and immunosuppressants. BCVA improved in 53.2% of eyes and remained stable in 32.9% of eyes. In the final model of multiple regression, worse initial BCVA, pyrazinamide, and receiving vitrectomy predicted better BCVA improvement. Ethambutol was associated with worse visual outcomes. Seven eyes experienced recurrence. Conclusions: This is the largest 10-year multicenter retrospective study of TBU in Taiwan to date, demonstrating the distribution of clinical manifestations and clinical associations with better treatment outcomes. The study provides a comprehensive description of TBU phenotypes in Taiwan and highlights considerations for the design of further prospective studies to reliably assess the role of ATT and vitrectomy in patients with TBU.

Interferon-γ release assays or tuberculin skin test for detection and management of latent tuberculosis infection: a systematic review and meta-analysis

Use of an interferon-γ (IFN-γ) release assay or tuberculin skin test for detection and management of latent tuberculosis infection is controversial. For both types of test, we assessed their predictive value for the progression of latent infection to active tuberculosis disease, the targeting value of preventive treatment, and the necessity of dual testing. In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions, on Oct 18, 2019, using the keywords ("latent tuberculosis" OR "latent tuberculosis infection" OR "LTBI") AND ("interferon gamma release assays" OR "Interferon-gamma Release Test" OR "IGRA" OR "QuantiFERON®-TB in tube" OR "QFT" OR "T-SPOT.TB") AND ("tuberculin skin test" OR "tuberculin test" OR "Mantoux test" OR "TST"). We included articles that used a cohort study design; included information that individuals with latent tuberculosis infection detected by IFN-γ release assay, tuberculin skin test, or both, progressed to active tuberculosis; reported information about treatment; and were limited to high-risk populations. We excluded studies that included patients with active or suspected tuberculosis at baseline, evaluated a non-commercial IFN-γ release assay, and had follow-up of less than 1 year. We extracted study details (study design, population investigated, tests used, follow-up period) and the number of individuals observed at baseline, who progressed to active tuberculosis, and who were treated. We then calculated the pooled risk ratio (RR) for disease progression, positive predictive value (PPV), and negative predictive value (NPV) of IFN-γ release assay versus tuberculin skin test. We identified 1823 potentially eligible studies after exclusion of duplicates, of which 256 were eligible for full-text screening. From this screening, 40 studies (50 592 individuals in 41 cohorts) were identified as eligible and included in our meta-analysis. Pooled RR for the rate of disease progression in untreated individuals who were positive by IFN-γ release assay versus those were negative was 9·35 (95% CI 6·48-13·49) compared with 4·24 (3·30-5·46) for tuberculin skin test. Pooled PPV for IFN-γ release assay was 4·5% (95% CI 3·3-5·8) compared with 2·3% (1·5-3·1) for tuberculin skin test. Pooled NPV for IFN-γ release assay was 99·7% (99·5-99·8) compared with 99·3% (99·0-99·5) for tuberculin skin test. Pooled RR for rates of disease progression in individuals positive by IFN-γ release assay who were untreated versus those who were treated was 3·09 (95% CI 2·08-4·60) compared with 1·11 (0·69-1·79) for the same populations who were positive by tuberculin skin test. Pooled proportion of disease progression for individuals who were positive by IFN-γ release assay and tuberculin skin test was 6·1 (95% CI 2·3-11·5). Pooled RR for rates of disease progression in individuals who were positive by IFN-γ release assay and tuberculin skin test who were untreated versus those who were treated was 7·84 (95% CI 4·44-13·83). IFN-γ release assays have a better predictive ability than tuberculin skin tests. Individuals who are positive by IFN-γ release assay might benefit from preventive treatment, but those who are positive by tuberculin skin test probably will not. Dual testing might improve detection, but further confirmation is needed. National Natural Science Foundation of China and Natural Foundation of Yunnan Province.

Evaluation of comparative intradermal tuberculin and interferon gamma release tests for prediction of tuberculous lesion development in slaughtered cattle

Bovine tuberculosis (BTB) is a chronic contagious disease of cattle which has economical, public health and veterinary importance worldwide. So far, test and slaughter is the most feasible method to control the disease but identification of lesions from slaughtered animals does not always coincide with ante-mortem test results. Fifty four animals which were found positive by comparative intradermal tuberculin test (CIDT) or INF-γ release assay or both were slaughtered and post mortem examination (PME) was conducted to identify tuberculous (TB) lesions. The animals were composed of four age groups (≤ 3; 4-6; 7-9 and ≥ 10 years) the two sexes and two breeds (Boran, Boran-Friesian cross). Out of all the slaughtered animals, lesions were detected from 70.3% (38/54) of them. No significant difference was observed among the four age groups and two sexes of both breeds of animals on the level of TB lesion detection. Higher proportion of the lesion was observed by mediastinal (40.4%) followed by bronchial (34.8%), retropharyngeal (17.9%) and lastly miliary form and mesenteric lymph nodes in equal proportion (3.3%). Among the CIDT positive animals, 59.2% of them had lesions. Similarly, 46.2% of INF-γ release assay positive animals had lesions during postmortem examination. Of the total CIDT (+) and INF-γ (-) animals, postmortem lesions were detected from 22.2% of them, and in the vice-versa, of the CIDT (-) and INF-γ (+) animals, 9.2% of them contain TB lesions. Using the PME as reference test, sensitivity of CIDT was 84.2% and the specificity was 6.2%. Similarly, the sensitivity and specificity of the INF-γ release assay was 65.7 and 37.5% respectively. It is concluded that, both tests predict the development of TB lesions. However, in our condition, CIDT was found more predictable for detection of TB lesions as compared to INF-γ release assay. Key words: Bovine tuberculosis (BTB), comparative intradermal tuberculin test (CIDT), interferon gamma (INF-γ) release, post mortem examination (PME), tuberculous (TB) lesion

Tumor infiltrating lymphocytes show in vitro cytotoxic activity against tumor cells in multiple cancers.

111 Background: There has been considerable research interest in recruiting immune cells of cancer patients to detect and destroy malignant cells. Various approaches have been attempted including activation of dendritic cells, chimeric antigen receptor T-cells, use of check point inhibitors and expansion and infusion of Tumor Infiltration Lymphocytes (TILs). TILs have however been successfully evaluated in only a few cancers such as Melanoma and Cervix. In order to explore the feasibility of using TILs for treatment of various solid organ cancers we hypothesized that their in vitro evaluation would establish preliminary viability of the approach. Methods: We isolated TILs from 3 patients with Ca Buccal Mucosa, 2 patients with Ca Cervix, 2 patients with Ca Breast and 1 patient each with Ca Bladder and Basal Cell Carcinoma. The explant cultures of primary/metastatic tumor tissues sections of minimum 3 mm3 size using appropriate growth medium in presence of T cell growth factor, interleukin 2 (IL2) was utilized for the propagation of TILs. TILs were expanded in meaningful numbers within three to four weeks of culture and characterized for in vitro cytotoxicity by live cell imaging and Interferon gamma release ((IGR) test. TCR gene repertoire sequencing was performed using Next Generation Sequencing (NGS) to accurately measure T cell diversity and clonal expansion. Results: TILs were isolated from 10 out of 10 patients with median number of TILs of 10 million / tissue section. The flow cytometric analysis revealed and confirmed the presence of various T cell markers in the TIL cultures generated. In vitro cytotoxicity analysis performed by live cell imaging and IGRs revealed high potency for tumor cell kill rate for the expanded TILs. TCR gene sequencing revealed clonal expansion in the TIL explant population. Conclusions: This study shows feasibility of TIL expansion from cohort of patients with multiple cancer types which can be utilized for large scale expansion and infusion in future clinical trials.

Screening for latent tuberculosis in patients with inflammatory bowel disease under antitumor necrosis factor: data from a Portuguese center

Portugal is one of the countries with the highest tuberculosis (TB) burden in the European Union. Patients who are receiving antitumor necrosis factor (TNF) treatment should be screened and treated for latent tuberculosis infection (LTBI). This study aimed to evaluate the prevalence of LTBI and the number of active TB cases in patients with inflammatory bowel disease (IBD) treated with anti-TNF agents. This was a retrospective study from a Portuguese center that included patients with IBD who started anti-TNF treatment between 2013 and 2017. LTBI screening was considered positive in case of positive tuberculin skin test, positive/indeterminate interferon gamma release test, or history of exposure to TB irrespective of the results of the screening. One hundred and seventeen patients were included, 56% female, mean age 40 years; 91% had Crohn's disease; infliximab was initiated in 79%, adalimumab in 21%, and golimumab in 1%. Of these, 37 (32%) presented LTBI - tuberculin skin test was positive in 18 (49%) patients; interferon gamma release test was positive in 14 (38%) patients and undetermined in seven (19%); and there was a history of exposure in 12 (32%) patients. All patients screened with LTBI were on isoniazid for 9 months. During follow-up (mean 21.6 months), one patient under infliximab developed pleural TB 5 years after receiving treatment with isoniazid. None of the patients with negative LTBI screening developed active TB. In this sample of patients with IBD, the prevalence of LTBI before starting anti-TNF treatment was significant (32%), but only one patient had active TB after LTBI treatment.

Application of enzyme-linked immunospot assay in the identification of culprit drugs in severe drug eruptions

Early identification of culprit drugs is crucial for the treatment and prevention of severe drug eruptions. At present, no accurate and effective methods are available for identifying the culprit drugs in severe drug eruptions. Commonly used tests include patch test, lymphocyte transformation test and so on. However, low sensitivity and specificity limit their clinical application. Enzyme-linked immunospot assay, an in vitro technique, can identify culprit drugs in cutaneous adverse drug reactions by detecting cytokines secreted by drug-specific T lymphocytes. It has high sensitivity and specificity in patients with severe drug eruptions, and can be carried out during the acute stage of disease or among immunocompromised patients. Therefore, enzyme-linked immunospot assay may be an effective method for identifying culprit drugs in severe drug eruptions. Key words: Drug eruptions; Enzyme-linked immunospot assay; Interferon-gamma release tests; Sensitivity and specificity; Culprit drugs

Evaluation of cases of pediatric extrapulmonary tuberculosis: a single center experience.

Aim:Extrapulmonary tuberculosis is observed more frequently and leads to complications with a higher rate in children compared with adults because the risk of lymphohematogen spread is higher. In this study, the clinical, laboratory, and radiologic findings and treatment outcomes were evaluated in pediatric patients who were followed up in our clinic with a diagnosis of extrapulmonary tuberculosis.Material and Methods:Seventy patients aged 0–18 years who were followed up with a diagnosis of extrapulmonary tuberculosis between 2008 and 2017 in the Division of Pediatric Infectious Diseases in our hospital were examined retrospectively.Results:The median age of the patients was 8,8 (range, 0,4–17) years and 47.1% were female (n=33). Twenty-seven patients (38.6%) were aged 0–4 years, 15 (21.4%) were aged 5–9 years, and 28 patients (40%) were aged 10–18 years. Forty-four patients (62.9%) were diagnosed as having extrapulmonary tuberculosis and 26 (37.1%) had pulmonary + extrapulmonary tuberculosis. The most common form of extrapulmonary tuberculosis was extrathoracic lymphadenopathy, which was found in 22 patients (31.4%). The other patients were diagnosed as having musculoskeletal system tuberculosis (n=10, 14.3%), gastrointestinal system tuberculosis (n=9, 12.9%), miliary tuberculosis (n=8, 11.4%), intrathoracic lymphadenopathy (n=7, 10%), renal tuberculosis (n=6, 8.6%), central nervous system tuberculosis (n=5, 7.1%), and pleural tuberculosis (n=3, 4.3%). Among a total of 58 patients in whom tuberculin skin test and interferon gamma release tests were studied together, tuberculin skin test positivity (n=37, 63.8%) was found with a higher rate compared with interferon gamma release test positivity (n=32, 55.2%), but the difference was not statistically significant (p=0.35). The median treatment period was 12 (range, 6–24) months. Among the patients whose treatments were terminated, improvement was observed in 52 patients (74.2%) and the development of sequela was observed in six patients (8.5%). Two patients who were diagnosed as having central nervous system tuberculosis (2.8%) died.Conclusion:Clinical, laboratory, and radiologic data should be evaluated together when making a diagnosis of extrapulmonary tuberculosis in children. Interferon gamma release tests alone are not superior to tuberculin skin test, but should be considered to be used in combination in the diagnosis.

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

BackgroundMultiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis.ObjectiveThe purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis.MethodsA panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed.ResultsTuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease.ConclusionLatent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates

Isoniazid daily for 9months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited. Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1month after treatment completion and at routine follow-up visits with their transplant providers. Eleven patients were men, and the median age was 60years (range 44-72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10-31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40months following transplantation. Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population.

The diagnostic efficiency evaluation of combination tuberculosis interferon-gamma release assay with human leukocyte antigen-G for tuberculosis

Objective To study the expression of IFN-γ by tuberculosis specific T cells(TB-IGRA)and Human Leukocyte Antigen-G(HLA-G) in the peripheral blood of tuberculosis patients and its diagnostic value in tuberculosis. Methods This was a retrospective cohort study. Study cases were all from Resparation Department of Shaoxing Municipal Hospital from January 2015 to December 2015. These patients were devided into tuberculosis group(TB) (34 cases), lung cancer group(LCa) (25cases) and non tuberculous pneumonia group(Non-TB pneumonia) (25cases) according to diagnosis, meanwhile, health group (35 cases) was set. IFN-γ and sHLA-G were detected by ELISA , and mHLA-G was detected by Flowcytometre. The receiver operating characteristic curve(ROC) was used to evaluate the diagnostic efficacy of TB-IGRA, sHLA-G and mHLA-G. Results The expression of TB-IGRA, sHLA-G and mHLA-G were higher in the TB group (with the median of 182.5 ng/L, 99.44 U/ml and 13.63%) than in the LCa group (117.0 ng/L, 82.3 U/ml and 9.12%), Non-TB pneumonia group(80.84 ng/L, 34.2 U/ml and 10.92%) and health group(30.5 ng/L, 31.28 U/ml and 8.18%)(P<0.05). The AUC-ROC of TB-IGRA, sHLA-G and mHLA-G were 0.842(95% CI, 0.761-0.922), 0.746(95% CI, 0.652-0.840) and 0.706(95% CI, 0.605-0.806). The sensitivity for TB-IGRA, sHLA-G and mHLA-G was 88.24%, 70.59% and 67.65%, and the specificity was 60%, 72.94% and 70.59% at the cutoff value of 35 ng/L, 60 U/ml and 10% respectively. The sensitivity and specificity of combination detection for TB-IGRA and HLA-G were 88.24% and 81.18%. Conclusions TB-IGRA, sHLA-G and mHLA-G were all increased in TB, while, the quantitative detection of TB-IGRA is more helpful for diagnosis. The combination detection of TB-IGRA, sHLA-G and mHLA-G can improve the sensitivity in the diagnosis of tuberculosis.(Chin J Lab Med, 2016, 39: 852-856) Key words: Tuberculosis, pulmonary; Mycobacterium tuberculosis; Interferon-gamma release tests; HLA-G antigens

Tuberculous uveitis in China

To assess tuberculous uveitis in Chinese patients. The hospital-based observational case series study included patients who attended a third-referral hospital and presented with chronic and recurrent uveitis without primarily detected aetiology. The patients underwent the tuberculin skin test (TST) and/or interferon gamma release test (IGRA). Patients with positive test results received standard antituberculous therapy. Patients who responded to the therapy and did not show recurrence of uveitis in the follow-up period were diagnosed as tuberculous uveitis and formed the study group. The remaining patients were diagnosed as non-tuberculous uveitis and formed the control group. The clinical characteristics were compared between both groups. The study group with tuberculous uveitis included 46 patients and the non-tuberculous group 38 patients. Multifocal choroiditis [n = 9 (20%) versus n = 1(3%); p = 0.04] and retinal vasculitis [n = 25(54%) versus 8 = (21.1%); p = 0.002] were significantly more common in the study group. Of 25 patients with retinal vasculitis in the study group, 11 patients (44%) additionally showed choroiditis lesions, compared with only one (13%) of eight patients in the control group (p = 0.01). In multivariate regression analysis, multifocal choroiditis [odds ratio (OR): 32.1], choroidal granuloma (OR: 21.4) and retinal vasculitis (OR: 11.2) were independent predictors of tubercular uveitis. About 50% of a group of 84 patients with primarily unexplained chronic posterior uveitis had tuberculosis and showed multifocal choroiditis, choroidal granuloma and retinal vasculitis. These features had a high predictive value for the diagnosis of tuberculous uveitis. Tuberculosis is an important part in the differential diagnosis of unexplained uveitis.

Interferon Gamma–induced Protein-10 Concentrations in Children With Previous Tuberculosis Infections and Disease

Interferon gamma-induced protein-10 is a diagnostic test for tuberculosis infection. There is no information on its concentrations over time. Interferon gamma-induced protein-10 was evaluated in 72 children formerly treated or in former contact with tuberculosis using Quantiferon Gold in-tube. Cases and contacts had similar interferon gamma-induced protein-10 concentrations. Concentrations varied with the tuberculin and interferon gamma release tests' concordance or discordance, and were independent of time.