Latent tuberculosis infection and screening method among close contacts in schools in Xuhui District，Shanghai from 2020 to 2022 / 上海预防医学

ObjectiveTo investigate the latent tuberculosis infection （LTBI） of close contacts in schools of Xuhui District， and to explore the tuberculin skin test （TST）- interferon-γ release assay （IGRA） two-step method in order to discover the screening strategy of tuberculosis in Xuhui District. MethodsClose contacts of tuberculosis in schools of Xuhui District from 2020 to 2022 were selected as research subjects. Screening was conducted using symptom questionnaire， TST， chest X-rays， IGRA， and the information including the etiological results and grade of the index cases， as well as gender， age， and relationship with the index cases of the research subjects were collected. ResultsTotally 615 close contacts of 32 tuberculosis cases occurred in the schools were finally included. Of the 609 close contacts who completed tuberculosis infection screening and underwent TST testing， 153 TST（+） individuals underwent IGRA testing. The final LTBI rate was 4.6%， and the pulmonary tuberculosis detection rate was 163 per 100 000. The relationship with the index cases was an influencing factor for LTBI. The IGRA positivity rate was higher among close contacts with TST ≥15 mm than among those with 10 mm≤ TST <15 mm （χ2=14.41， P<0.05）. ConclusionThe latent tuberculosis infection among close contacts of school tuberculosis cases in Xuhui District remains serious. TST-IGRA two-step method can assist in the accurate diagnosis of LTBI and pulmonary tuberculosis cases.

Early diagnosis value of peripheral blood PPARγ combined with IFN-γ detection for tuberculosis infection in patients with end-stage renal disease / 中国热带医学

@#Abstract: Objective　To explore the early diagnostic value of peripheral blood peroxisome proliferator-activated receptor γ (PPARγ) combined with γ-interferon (IFN-γ) release assay (IGRA) in the diagnosis of pulmonary tuberculosis in patients with end-stage renal disease (ESRD), and to provide reference for clinical diagnosis and treatment. Methods　From January 2019 to December 2021, 70 ESRD patients with suspicious symptoms of pulmonary tuberculosis were treated at Hebei Chest Hospital were selected as the research objects. According to the examination results, they were divided into ESRD group (40 cases) and ESRD complicated by pulmonary tuberculosis (40 cases, comorbidity group). In addition, 40 cases with pulmonary tuberculosis were used as the PTB group. All three groups of patients underwent IGRA test, and the peripheral blood PPARγ level was detected by enzyme-linked immunosorbent assay, and the diagnostic value of PPARγ combined with IGRA test for ESRD patients with pulmonary tuberculosis was explored. Results The expression level of PPARγ and IFN-γ content in the PTB group and the comorbidity group were obviously higher than those in the ESRD group (P<0.05), while the differences in PPARγ expression level and IFN-γ content between the PTB and comorbidity groups were not statistically significant (P>0.05). The ROC curve showed that the areas under the curve (AUC) of PPARγ and IGRA in the diagnosis of end-stage renal disease combined with tuberculosis were 0.823 (95%CI: 0.722-0.925) and 0.773 (95%CI: 0.662-0.883), respectively, and the AUC of combined detection was 0.928 (95%CI: 0.871-0.984), which was better than that of PPARγ and IGRA alone (Z/P=2.057/0.039, 2.843/0.005). The Kappa values of serum PPARγ and IGRA test compared with the clinical gold standard results in the diagnosis of ESRD complicated with pulmonary tuberculosis were 0.557 and 0.444 (P<0.05). The combined screening of ESRD with pulmonary tuberculosis was consistent with the clinical gold standard (Kappa=0.661, P<0.05). Among the 30 ESRD patients complicated with pulmonary tuberculosis, the sensitivity of PPARγ combined with IGRA test in diagnosis of ESRD complicated with pulmonary tuberculosis was 93.33% (28/30), which was higher than 70.00% (21/30) of PPARγ and 66.67% (20/30) of IGRA test alone (P<0.05). Conclusions Peripheral blood PPARγ and IGRA tests have certain diagnostic value for ESRD complicated with tuberculosis, and the combined detection of the two can improve the sensitivity and reduce the rate of missed diagnosis, which is worthy of clinical promotion.

Influencing factors of inconsistency between γ-interferon release test QFT-GIT and tuberculosis etiological test results / 中华临床感染病杂志

Objective:To evaluate the influencing factors of inconsistency between γ-interferon release test QFT-GIT and etiological results in tuberculosis patients.Methods:The clinical data of 1 398 patients with positive Mycobacterium tuberculosis infection confirmed by pathogen culture after QFT-GIT test who were admitted to Hangzhou Chest Hospital Affiliated to Zhejiang University School of Medicine from September 2017 to August 2021 were retrospectively analyzed. There were 1 242 cases in whom both the pathogenic culture and QFT-GIT results were positive(consistent result group) and 156 cases in whom the QFT-GIT test results were negative or indeterminate(inconsistent result group). Logistic regression was used to analyze the influencing factors of inconsistent results between QFT-GIT and tuberculosis pathogenic tests. SPSS 25.0 software was used to analyze the data. Results:The overall incidence of inconsistency between QFT-GIT and tuberculosis etiological results was 11.16% (156/1 398). The incidence of inconsistency was 0, 7.09% (63/889) and 19.58% (93/475) in patients aged <18, 18-<65 and ≥65 years old, respectively; the incidence of inconsistency in age group ≥65 was higher than that in age groups <18 and 18-<65 ( χ2=6.584 and 36.762, P<0.01). Multivariate Logistic regression analysis showed that age ( OR=1.026, 95% CI 1.016-1.037), smoking ( OR=1.649, 95% CI 1.159-2.347), chronic liver disease ( OR=1.868, 95% CI 1.213-2.876), cardiovascular disease ( OR=2.353, 95% CI 1.361-4.069) and blood albumin level ( OR=0.956, 95% CI 0.928-0.985) were independent influencing factors for the inconsistency between the results of QFT-GIT and tuberculosis etiology. Conclusion:Patients with advanced age, smoking, chronic liver disease, cardiovascular disease and low albumin level are more likely to have inconsistent results between QFT-GIT and tuberculosis etiological tests.

The diagnostic value of tuberculin skin test, tubercle bacillus-antibody, interferon-γ release assay, tubercle bacillus-DNA and bacterial collection centrifugal smear method in pneumoconiosis combined with tuberculosis / 中国医师进修杂志

Objective:To investigate five kinds of tuberculin skin test (TST), tubercle bacillus-antibody(TB-Ab), interferon-γ release assay(IGRA), tubercle bacillus-DNA (TB-DNA) and collection of bacterial centrifugal smears methods, the application value of combined detection in improving the diagnostic efficiency of pneumoconiosis complicated with tuberculosis.Methods:A total of 150 eligible patients with pneumoconiosis from January 2018 to January 2019 in Zhangjiakou Pulmonary Hospital were selected as the research subjects, and all of them underwent TST, TB-Ab, IGRA, TB-DNA and bacterial centrifugal smear detection. Compared the positive rates of five detection methods in pneumoconiosis and its different stages, and compare the proportion of tuberculosis infection and tuberculosis in different stages of pneumoconiosis.Results:Among the 150 patients with pneumoconiosis, 41 cases (27.33%) were with pneumoconiosis complicated with tuberculosis infection, 24 cases (16.00%) with pneumoconiosis complicated with clinically diagnosed pulmonary tuberculosis, 21 cases (14.00%) with pneumoconiosis complicated with confirmed pulmonary tuberculosis, and 45 cases (30.00%) with pneumoconiosis complicated with pulmonary tuberculosis; with the improvement of pneumoconiosis stage, the proportion of pneumoconiosis combined with tuberculosis infection and pulmonary tuberculosis increased significantly ( P<0.05). Compared with TB-Ab, TB-loop-mediated isothermal amplification(LAMP), and interlayered cup collection centrifuge smear method, the overall positive rate of IGRA detection and pneumoconiosis stage Ⅲ were higher ( P<0.05), but there was no significant difference compared with TST detection ( P>0.05). The positive rate of combined detection was higher, but there was no significant difference compared with IGRA detection ( P>0.05). With the increase of pneumoconiosis stage, the positive reaction intensity of TST decreased, and the positive value of TB-Ab and IGRA increased. Conclusions:The combined detection of TST, TB-Ab, IGRA, TB-DNA and bacterial centrifugal smear method can significantly improve the diagnostic efficiency of pneumoconiosis combined with tuberculosis.

Factors related to false negative results of interferon-γ release test in patients with confirmed pulmonary tuberculosis / 中华临床感染病杂志

Objective:To analyze the influencing factors related to false-negative results of interferon-γ release assay (IGRA) QFT-GIT in patients with confirmed pulmonary tuberculosis.Methods:Clinical data of 389 patients with bacteriologically confirmed pulmonary tuberculosis who underwent QFT-GIT in Quzhou Hospital Affiliated to Wenzhou Medical University between January 1 and December 31 2020 were retrospectively analyzed. Univariate and multivariate logistic regression were used to analyze the influencing factors related to the false-negative results of QFT-GIT.Results:Among 389 confirmed patients, 347 cases had positive QFT-GIT results and 42 cases had negative results. Univariate analysis showed that the false-negative results of QFT-GIT were associated with low BMI, reduced CD4 + T lymphocyte count, decreased lymphocyte count, increased C-reactive protein, negative sputum smear, anemia, diabetes mellitus, malignant tumor and sepsis ( P<0.05 or P<0.01). Multivariate conditional logistic regression analysis showed that BMI <18.5 kg/m 2( OR=1.585, 95% CI 1.076-2.336), complicated with diabetes( OR=5.157, 95% CI 2.340-11.365), malignant tumors ( OR=5.596, 95% CI 2.048-15.295)and sepsis ( OR=4.141, 95% CI 1.042-16.459) were independent risk factors for the false-negative results of QFT-GIT ( P<0.05 or P<0.01). Conclusion:When the pulmonary tuberculosis patients are extreme emaciation, complicated with diabetes, malignant tumor or sepsis, the QFT-GIT results will be false negative.

Different Quantitative Interferon-γ Response in Active Tuberculosis of Various Primary Infection Sites

Current status of treatment of latent tuberculosis infection in India

In view of the high burden of latency of tuberculosis (TB) in India, tackling latent TB in the right way is a menace. All latent TB’s infection (LTBI) are treated in countries having low burden such as the United States. However, this approach cannot be implemented in high burden countries like India until concrete evidence or consensus by experts on this subject is made. There are very specific risk groups where these patients are to be treated as far as current evidence-based medicine is concerned. Hence, the need to develop a document was felt, through which the treatment of LTBI becomes homogeneous by each and every physician who is practicing and treating TB. The last attempt to review the topic was made in 2015, after which there have been many changes and update in this subject.

Development of analytical method for quantification of antineoplastic in drug delivery systems

Nos últimos anos têm crescido cada vez mais o número de pesquisas envolvendo nanotecnologia para obtenção de medicamentos com liberação controlada, pois esses sistemas podem: proteger o fármaco de incompatibilidades tanto biológicas quanto físico-químicas assim como controlar a biodisponibilidade do fármaco. Embora com todas essas vantagens não existem métodos in vitro realmente capazes de prever com precisão a liberação dos fármacos por esses sistemas, por esse motivo, é muito importante o desenvolvimento de métodos de liberação in vitro para determinar a cinética de liberação desses sistemas.O presente trabalho teve como objetivo desenvolver e validar os métodos de eletroforese capilar (CE) e cromatografia líquida de alta eficiência (HPLC) para determinar a eficiência de encapsulação do fármaco imatinibe em nanopartículaspreviamente elaboradas e caracterizadas, assim como estudar sua liberação in vitro por CE. As nanopartículas foramdesenvolvidas pelo método de nanoprecipitaçãoe caracterizadas quanto ao tamanho, potencial zeta, morfologia e eficiência de encapsulação. A eletroforese capilar é uma técnica alternativa muito promissora em relação ao HPLC devido ao seu baixo custo, menor tempo de corrida e menos poluente ao meio ambiente. Os métodos de quantificação por CE e HPLCforam desenvolvidose validadossegundo as diretrizes do ICH, Farmacopeia Americana e ANVISA, permitindo desenvolver um estudo de liberação.As nanoesferas desenvolvidas apresentaram diâmetro médio próximo a 150nm, com índice de polidispersão menor que 0,1 e aproximadamente 90% de eficiência de encapsulação. Ambos métodos se mostraram lineares com coeficientes de determinação superiores a 0,99, os métodos se mostraram precisos (%DPR< 2), exatos(101,0±4,2% e 98,0±2,5% para HPLC e CE, respectivamente)e seletivos.O método de CE permitiu desenvolver um método de estudo de liberação independente das membranas de diálise

In recent years, there has been a growing number of researches involving nanotechnology to obtain controlled release drugs, these systems can: protect the drug against biological and physico-chemical incompatibilities; controlling the bioavailability of the drug. Although with all these advantages there are no in vitro methods really capable of accurately predicting drugs release by such systems, therefore, the development of in vitro release methods to determine the release kinetics of such systems is very important. The objective of the present work was to develop and validate capillary electrophoresis (CE) and HPLC methods to determine the encapsulation efficiency of the imatinib drug in previously elaborated and characterized nanoparticles, as well as to study its release in vitro by CE method. The nanoparticles were synthesized using the nanoprecipitation method and characterized by size, zeta potential, morphology and encapsulation efficiency. Capillary electrophoresis is a very promising alternative to HPLC because of its low cost, less runtime and less polluting environment. The CE and HPLC methodswere developed and validated according ICH, American Pharmacopoeia and ANVISA guidelines.Developed nanospheres had an average diameter close to 150nm, with polydispersity index less than 0.1 and approximately 90% encapsulation efficiency. Both methods were linear with determination coefficients higher than 0.99, the methods were precise (%RSD < 2), accurate (101.0±4,2% and 98.0±2,5% for HPLC and CE, respectively) and selective. Capillary electrophoresis method allowed to develop a drug release study independent of dialysis membranes

Application value of interferon gamma release assay combined with tuberculin skin test in diagnosis of intraocular tuberculosis and latent tuberculosis infection / 中国医师进修杂志

Objective To explore the application value of interferon gamma release assay (IGRA) combined with tuberculin skin test (TST) in diagnosis of intraocular tuberculosis and latent tuberculosis infection. Methods One hundred and ten patients with pulmonary tuberculosis (observation group) and 80 healthy persons (control group) in Hebei Chest Hospital from January 2016 to December 2018 were selected. Among the 110 patients with pulmonary tuberculosis, intraocular tuberculosis was in 35 cases, and latent tuberculosis infection was in 75 cases. All the patients were examined by ocular secretions IGRA and TST. Results The positive rates of IGRA and TST in observation group were significantly higher than those in control group: 88.18% (97/110) vs. 11.25% (9/80) and 83.64% (92/110) vs. 41.25% (33/80), and there were statistical differences (χ2=113.138 and 36.971, P﹤0.01). The positive rate of IGRA in patients with intraocular tuberculosis was significantly higher than that in latent tuberculosis infection: 97.14% (34/35) vs. 84.00% (63/75), and there was statistical difference (χ2=3.955, P﹤0.05). There was no statistical difference in the positive rate of TST between the patients with intraocular tuberculosis and patients with latent tuberculosis infection: 91.43% (32/35) vs. 80.00% (60/75), χ2 = 2.277, P＞0.05. The consistency rate of IGRA and TST was 89.90% (Kappa=0.867, P＞0.05). The sensitivity of IGRA combined with TST was significantly higher than the single detection of IGRA and TST (97.83% vs. 88.18% and 83.64% ), while the specificity of IGRA combined with TST was significantly lower than the single detection of IGRA and TST (61.11% vs. 92.31% and 83.33% ), and there were statistical differences (P﹤0.05). The receiver operating characteristic curve analysis result showed that the area under curve of IGRA in diagnosis of intraocular tuberculosis and latent tuberculosis infection was 0.781, area under curve of TST was 0.604, and area under curve of IGRA combined with TST was 0.679. Conclusions IGRA has high value in the diagnosis of intraocular tuberculosis and latent tuberculosis infection, and can be used as a diagnostic means of intraocular tuberculosis.

Application value of interferon gamma release assay combined with tuberculin skin test in diagnosis of intraocular tuberculosis and latent tuberculosis infection / 中国医师进修杂志

Objective@#To explore the application value of interferon gamma release assay (IGRA) combined with tuberculin skin test (TST) in diagnosis of intraocular tuberculosis and latent tuberculosis infection.@*Methods@#One hundred and ten patients with pulmonary tuberculosis (observation group) and 80 healthy persons (control group) in Hebei Chest Hospital from January 2016 to December 2018 were selected. Among the 110 patients with pulmonary tuberculosis, intraocular tuberculosis was in 35 cases, and latent tuberculosis infection was in 75 cases. All the patients were examined by ocular secretions IGRA and TST.@*Results@#The positive rates of IGRA and TST in observation group were significantly higher than those in control group: 88.18% (97/110) vs. 11.25% (9/80) and 83.64% (92/110) vs. 41.25% (33/80), and there were statistical differences (χ2 = 113.138 and 36.971, P<0.01). The positive rate of IGRA in patients with intraocular tuberculosis was significantly higher than that in latent tuberculosis infection: 97.14% (34/35) vs. 84.00% (63/75), and there was statistical difference (χ2 = 3.955, P<0.05). There was no statistical difference in the positive rate of TST between the patients with intraocular tuberculosis and patients with latent tuberculosis infection: 91.43% (32/35) vs. 80.00% (60/75), χ2 = 2.277, P>0.05. The consistency rate of IGRA and TST was 89.90% (Kappa = 0.867, P>0.05). The sensitivity of IGRA combined with TST was significantly higher than the single detection of IGRA and TST (97.83% vs. 88.18% and 83.64%), while the specificity of IGRA combined with TST was significantly lower than the single detection of IGRA and TST (61.11% vs. 92.31% and 83.33%), and there were statistical differences (P<0.05). The receiver operating characteristic curve analysis result showed that the area under curve of IGRA in diagnosis of intraocular tuberculosis and latent tuberculosis infection was 0.781, area under curve of TST was 0.604, and area under curve of IGRA combined with TST was 0.679.@*Conclusions@#IGRA has high value in the diagnosis of intraocular tuberculosis and latent tuberculosis infection, and can be used as a diagnostic means of intraocular tuberculosis.

Latent tuberculosis infection among medical students in Malaysia

Objective: This study aimed to determine prevalence of latent tuberculosis infection among medical students and tuberculosis exposure at the health facilities. Methods: A cross-section of study year 1 (n=68) and year 5 (n=75) medical students in a local university were recruited for latent tuberculosis infection testing using QuantiFERON-TB Gold Plus and a questionnaire analyzed for multivariate risk. Results: The majority of the study were vaccinated with BCG. None of year 1 medical students were positive for latent tuberculosis infection, however, six (8.0%) year 5 students were tested positive for latent tuberculosis infection. A higher incidence of year 5 medical students claimed to be exposed to tuberculosis at health facility (65.3% vs. 4.4%) and a higher percentage reported contact with tuberculosis case over the preceding year compared to year 1 students (30.7% vs. 8.8%). Conclusion: We observed a higher incidence of latent tuberculosis infection and higher exposure to tuberculosis in health facilities among year 5 medical students. Baseline screening and monitoring for progression to tuberculosis infection may benefit tuberculosis management programs.

Clinical Significance of Positive TB-IGRA in Patients With Crohn's Disease and Intestinal Tuberculosis / 胃肠病学

Background: Crohn's disease (CD) and intestinal tuberculosis (ITB) share similarities in disease manifestations, but their treatment methods are totally different. Thus, the differential diagnosis between CD and ITB is of great clinical importance. Aims: To investigate the significance of positive tuberculosis interferon-gamma release assay (TB-IGRA) in differential diagnosis and treatment of CD and ITB. Methods: Fifty-six consecutive patients with positive TB-IGRA and definite diagnosis of CD (n=23) or ITB (n=33) in the Tenth People's Hospital of Tongji University from Jan. 2015 to May 2018 were enrolled. All these patients have been proposed as CD at their first visit. The effects of TB-IGRA on diagnosis and treatment were analyzed. Results: ROC curve analysis demonstrated that the cut-off value, sensitivity and specificity of TB-IGRA for diagnosis of tuberculosis infection were 100 pg/mL, 88% and 74%, respectively. In patients with TB-IGRA≥100 pg/mL, 4 were CD and 29 were ITB, while in patients with TB-IGRA<100 pg/mL, 19 were CD and 4 were ITB (P<0.05); 75.0% (3/4) of the CD patients with TB-IGRA≥100 pg/mL and 5.3% (1/19) of the CD patients with TB-IGRA<100 pg/mL had a history of tuberculosis infection (P<0.05). Thirty-five patients received diagnostic anti-tuberculosis therapy, the efficacy of those with TB-IGRA≥100 pg/mL was significantly higher than those with TB-IGRA<100 pg/mL (96.2% vs. 22.2%, P<0.05). Conclusions: 100 pg/mL might be set as the cut-off value of TB-IGRA for differential diagnosis between CD and ITB. Diagnostic anti-tuberculosis therapy is preferred for patients with TB-IGRA≥100 pg/mL, while patients with TB-IGRA<100 pg/mL need comprehensive analysis. For patients with history of tuberculosis infection, false positive TB-IGRA is prone to occur.

Diagnosis and treatment of latent tuberculosis infection

In order to eliminate tuberculosis worldwide by 2050, effective management of latent tuberculosis infection is essential, and policy-makers have begun to recognize the importance of scaling up preventive therapy. The current guideline recommends targeted latent tuberculosis infection testing that identifies high-risk groups based on risk stratification for progression from latent infection to active disease. Both the tuberculin skin test and interferon-gamma releasing assay have a similar diagnostic efficacy for predicting progression to active tuberculosis. The Korean guideline recommends 9-month isoniazid monotherapy as the standard treatment; however, more evidence supports that short course rifampicin-based regimen is both more effective and tolerable than isoniazid monotherapy.

Screening for latent tuberculosis infection by an Aboriginal Community Controlled Health Service, New South Wales, Australia, 2015

Objective@#Ongoing transmission of tuberculosis (TB) continues in Indigenous communities in New South Wales (NSW), Australia. In a pilot project, a Public Health Unit TB team partnered with an Aboriginal Community Controlled Health Service (ACCHS) in a community with a cluster of TB to augment screening for latent TB infection (LTBI) using interferon-gamma release assay (IGRA). This study examined screening data and programme outcomes at 12 months post hoc to advise practice and policy formulation.@*Methods@#We conducted a retrospective, cross-sectional analysis of demographic and clinical data of ACCHS patients, stratified by IGRA testing status. Differences in sex and age distribution between the groups and cases of a genetically and epidemiologically linked TB cluster in Aboriginal people in NSW were assessed using non-parametric tests.@*Results@#Of 2019 Aboriginal and Torres Strait Islander people seen by general practitioners during the study period, 135 (6.7%) participated in the screening. Twenty-four (17.8%) participants were IGRA positive. One person was diagnosed with active TB. Twelve participants received a chest X-ray at the time of the positive test, and six participants had an additional chest X-ray within 12 months. None commenced preventive treatment for LTBI.@*Discussion@#ACCHS screening for LTBI reached individuals in the age group most commonly affected by TB in these Aboriginal communities. No conclusions can be made regarding the population prevalence due to the low screening rate. Further strategies need to be developed to increase appropriate follow-up and preventive treatment.

Latent tuberculosis infection among medical students in Malaysia

Objective: This study aimed to determine prevalence of latent tuberculosis infection among medical students and tuberculosis exposure at the health facilities. Methods: A cross-section of study year 1 (n=68) and year 5 (n=75) medical students in a local university were recruited for latent tuberculosis infection testing using QuantiFERON-TB Gold Plus and a questionnaire analyzed for multivariate risk. Results: The majority of the study were vaccinated with BCG. None of year 1 medical students were positive for latent tuberculosis infection, however, six (8.0%) year 5 students were tested positive for latent tuberculosis infection. A higher incidence of year 5 medical students claimed to be exposed to tuberculosis at health facility (65.3% vs. 4.4%) and a higher percentage reported contact with tuberculosis case over the preceding year compared to year 1 students (30.7% vs. 8.8%). Conclusion: We observed a higher incidence of latent tuberculosis infection and higher exposure to tuberculosis in health facilities among year 5 medical students. Baseline screening and monitoring for progression to tuberculosis infection may benefit tuberculosis management programs.

Research development of cytokine release syndrome induced by monoclonal antibody and cytokine release assays in vitro / 中国药理学通报

Cytokine-release syndrome (CRS) triggered by mon-oclonal antibodies ( mAbs) is characterized by rapid onset and severe damage, and difficulty in prediction and control. Recent years,it has been a research focus on establishing a reliable ani-mal model in vivo and cytokine release assay( CRA) in vitro to predict CRS for preclinical safety evaluation. In this paper we summarize matters related to CRA applicable objects, considera-tions of method design and method optimization, aiming to pro-vide suggestions for the optimization of CRA prediction platform.

A tuberculosis contact investigation involving a large number of contacts tested with interferon-gamma release assay at a nursing school: Kanagawa, Japan, 2012

@#In May 2012, a teacher of a nursing school with about 300 staff members and students in Japan was diagnosed with sputum smear-positive pulmonary tuberculosis (TB), leading to an investigation involving nearly 300 contacts. We describe the contacts’ closeness to the index TB patient and the likelihood of TB infection and disease. A case of TB was defined as an individual with positive bacteriological tests or by a physician diagnosis of TB. A latent TB infection (LTBI) case was defined as an individual who had a positive interferon-gamma release assay (IGRA). A total of 283 persons screened with IGRA were analysed. Eight persons (2.8%, 95% confidence interval [CI]: 1.2–5.4) tested positive by IGRA; one student who had intermediate (less than 10 hours) contact with the index patient was found to have pulmonary TB by chest X-ray. The positivity in IGRA among staff members with very close contact with the index patient (4 of 21, 19%, 95% CI: 5.4–42%) with a statistically significant relative risk of 17 (95% CI: 2.0–140) was high compared with that of the intermediate contacts (1 of 88, 1.1% [95% CI: 0.028–6.2]). There was a statistically significant trend in the risk of TB infection and closeness with the index patient among the staff members and students (P < 0.00022). In congregate settings such as schools, the scope of contact investigation may have to be expanded to detect a TB case among those who had brief contact with the index patient.

Diagnostic value of interferon-γ release assay of peripheral blood and pleural effusion for tuberculous pleurisy / 解放军医学杂志

Objective To evaluate the diagnostic value of interferon-γ release assay of blood and pleural effusion for tuberculous pleurisy.Methods Fifty-six adult patients with suspected tuberculous pleurisy were enrolled in our study.The blood and pleural effusion interferon-γ release assay were measured by T-SPOT.TB test in 38 pleural tuberculosis patients and 18 nontuberculous pleurisy controls.The diagnostic sensitivity,specificity,predictive value of T-SPOT.TB in pleural effusion mononuclear cells (PE-MC) and peripheral mononuclear cells (PBMC) were analyzed.Results The sensitivities and specificities,positive predictive values and negative predictive values,respectively,of the PE-MC and PBMC for diagnosing were as follows:86.5％(95％ confidence interval[CI] 71.2％-95.5％) and 100％(95％CI 90.5％-100％);52.9％(95％CI 27.8％-77.0％) and 35.3％(95％CI 14.2％-61.7％);80.0％(95％CI 64.4％-90.9％) and 77.1％(95％CI 62.7％-88.0％);64.3％(95％CI 35.1％-87.2％) and 100％(95％CI 54.1％-100％).By ROC curve analysis,a cut-off value of 47SFC/2.5 × 105 cells in PE-MC showed a sensitivity of 89.2％ and a specificity of 88.2％.Conclusion T-SPOT.TB in PE-MC could be an accurate diagnostic method for tuberculous pleurisy in TB endemic settings.Moreover,47SFC/2.5 × 105 cells might be the optimal cut-off value for diagnosing tuberculous pleurisy.

Clinical value of IGRA for pleural effusion in the diagnosis of tuberculous pleurisy / 国际检验医学杂志

Objective To investigate the clinical diagnosis value of interferon gamma release assay (IGRA ) for pleural effusion in patients with tuberculous pleurisy .Methods 68 patients with tuberculous pleurisy (tu-berculous group) were included as object of study in Ganzi state people′s hospital ,and selected 70 patients with pneumonic pleurisy(pneumonia group) and 70 patients with malignancy (malignant group) as controls . Enzyme linked immunosorbent assay (ELISA) was used to detect interferon gamma release assay for tubercu-losis infected T cells (TB-IGRA ) in pleural effusion ,and were in progress blood TB-IGRA for tuberculous group .Results The IFN-γ level of patients in tuberculous group[179 .3(158 .1 -276 .2)ng/L] was higher than that those in pneumonia group[86 .7(55 .1 -162 .2)ng/L] and malignant group[92 .7(48 .1 -178 .3) ng/L] ,the difference was statistically significant (P＜0 .05) .The IFN-γ level of TB-IGRA for blood was low-er than that TB-IGRA for pleural effusion ,the difference was statistically significant (P＝0 .012) .The sensi-tivity ,specificity ,positive predictive value ,and negative predictive value of TB-IGRA for pleural effusion high-er than that blood TB-IGRA ,the difference was statistically significant (P＜0 .05) .The AUC of TB-IGRA for pleural effusion was higher than that blood TB-IGRA .Conclusion TB-IGRA for pleural effusion is an impor-tant laboratory index for the diagnosis of tuberculous pleurisy ,and its diagnostic efficiency is higher than that of blood TB-IGRA .

Identification of novel Mycobacterium tuberculosis peptides as diagnostic reagents for tuberculosis among human immunodeficiency virus infected population / 中华传染病杂志

Objective To screen and validate the major histocompatibility complex class-Ⅰ(MHC-Ⅰ) restricted tuberculosis peptides as potential diagnostic reagents in tuberculosis interferon-gamma release assay (IGRA) used among human immunodeficiency (HIV)-infected population.Methods Candidate peptides were encoded by Mycobacterium tuberculosis (TB) RD (Region of difference).Computer software was used to predict and select CD8+ T cell epitopes restricted by MHC-Ⅰ molecules with high frequency and high affinity among HIV-infected people.Then peptides containing CD8+ T cell epitope were synthesized and screened in vitro.The sensitivity and specificity of IGRA using the above mixed peptides as stimulants were compared with those of IGRA using early secretory antigen target-6 (ESAT-6,molecular weight of 6 000) and culture filtrate protein-10 (CFP-10,molecular weight of 10 000) as stimulants among HIV-infected population.Results Eight overlapping peptides,including Rv0222176-191,Rv1980c122-138,Rv1985c105-120,Rv3425141-165,Rv3873133-151,Rv3873158-166,Rv387878-86,Rv3879c673-690,were obtained finally,which were able to stimulate the production of interferon-gamma from peripheral CD8+ T cells of tuberculosis patients,but not from peripheral blood mononuclear cells (PBMC) of healthy controls.Among the 25 patients with HIV/TB co-infection,the sensitivities of IGRA using the combination peptides (CP) and that using rESAT-6/CFP-10 (CE) were low (68％ vs 48％,x2 =2.052,P=0.152).However,the sensitivity increased to 92％ by using the combination of CP and CE,which was significantly higher than that using rESAT-6/CFP-10 alone (x2 =11.523,P ＜ 0.01),and the specificity was not affected.Conclusion These RD peptides with CD8+ T cell epitopes can increase the sensitivity of IGRA in detecting HIV/TB co-infection,which may improve the detection rate of tuberculosis in HIV infected population.