Evaluation of Interferon-Gamma Release Assay Testing and Tuberculin Skin Test for Early Diagnosis of Tuberculosis in Children and Adolescents

Background: This study aimed to evaluate the diagnostic value of interferon-γ release assay (IGRA), a sensitive microbiological diagnostic method, in children and adolescents with suspected tuberculosis in a country with a high burden of tuberculosis. Method: This study included 581 children and adolescents aged 4 - 19 years who were suspected of having tuberculosis, were latently infected with Mycobacterium tuberculosis, and had received at least one dose of BCG vaccine between April 17, 2019, and February 24, 2021. The study evaluated the TST results of 106 patients who had a positive Quantiferon test and were suspected of having tuberculosis. Results: The study included 581 patients aged between 4 and 19 years. Of these, 106 patients tested positive for the Quantiferon test, while 19 were indeterminate and 456 were negative. The Quantiferon test positivity rate was 18.24%. Among the 106 QFT-Plus-positive cases, 23 patients also tested positive for TST. The difference in distribution was found to be statistically significant. Conclusion: The QFT-Plus test is considered an alternative to TST and other microbiological diagnostic methods for early tuberculosis diagnosis, particularly in children and adolescents.

Investigation of the cell composition and gene expression in the delayed-type hypersensitivity tuberculin skin test

Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].

原发性颈淋巴结结核诊治分析

目的探讨原发性颈淋巴结结核的临床特征、确诊方式及诊疗方案。方法回顾性分析宁波市医疗中心李惠利医院确诊的39例原发性颈淋巴结结核患者临床资料,总结其临床特点、治疗方法及随访情况。结果所有患者均以颈部无痛性质韧肿块为首发症状,肿块多位于颈部Ⅲ、Ⅳ、Ⅴ区,部分位于Ⅰ、Ⅱ区,均完善CT、MRI或B超等检查。根据影像学检查和临床经验,21例患者行结核菌素试验(PPD)或结核感染T细胞斑点试验(T-SPOT),其中2例PPD阳性,13例T-SPOT阳性,15例均经穿刺病理结果确诊,6例经手术病理确诊;1例经细针穿刺细菌培养发现结核杆菌确诊;17例影像学考虑肿瘤性病变,经颈淋巴结清扫或肿块部分切除术后病理确诊结核。39例患者均予标准抗结核治疗半年,随访1年未见复发。结论原发性颈淋巴结结核缺乏特异性症状,初步诊断可借助T-SPOT检查,确诊仍需结核杆菌培养阳性、穿刺细胞学或组织病理结果,治疗应采用世界卫生组织(WHO)推荐的6个月治疗方案,当伴有脓肿、窦道或溃疡型结核时,应结合手术治疗,可有效缩短术后抗结核治疗时间、减少药物用量及不良反应。

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with or exposed to tuberculosis

Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children.Methods:A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis.QuantiFERON-TB Gold,T-SPOT.TB and tuberculin skin test were performed in each patient.Results:Of the 60 children,median age 3.3 years,17 had tuberculosis and 43 had recent tuberculosis exposure.Overall,15(25.0%)children had tuberculin skin test reaction≥10 mm;8(13.3%)were positive by QuantiFERON-TB Gold In-Tube test,and 12(20.0%)by T-SPOT.TB.Nineteen(31.7%)children had at least one positive test.There was a moderate agreement between interferon gamma release assays and tuberculin skin test.Conclusions:The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis,supporting the management strategy of not testing children younger than 5 years.

Performance and correlation of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution

Objective:To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution.Methods:A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes>25%or>500 cells/mm3 for at least 6 months.QuantiF ERON-TB Gold,T-SPOT.TB,and tuberculin skin test were performed in each patient.Results:A total of 50 patients were enrolled with median age of 13.7 years,CD4 counts of 753(IQR:587-989)cells/mm3.Among 27 patients with tuberculosis(16)or tuberculosis exposure(11),8(29.6%)were positive to at least one test,2(7.4%)were positive QuantiFERON-TB Gold,3(11.1%)positive T-SPOT.TB,and 7(25.9%)had tuberculin skin test≥5 mm.Among 23 patients without history of tuberculosis or exposure,all had negative interferon gamma release assays,while 2(8.7%)had positive tuberculin skin test.Conclusions:All tests had low sensitivity despite immune reconstitution.

Comparison between Quanti-FERON-TB Gold In-Tube test and tuberculin skin test for diagnosis of latent tuberculosis in children: A cross-section study

Objective: To compare Quanti-FERON-TB Gold In-Tube (QFT-GIT) test and tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection in children. Methods: In this cross-sectional study, 64 participants who were between 3 months and 14 years old and had close contact with smear-positive pulmonary tuberculosis were included. Both QFT-GIT test and TST were done and the results were analyzed by SPSS software and Kappa test. Results: The distribution of gender and age according to QFT-GIT and TST results were matched (P>0.05). Overall agreement between QFT-GIT and TST for diagnosis of latent tuberculosis infection in children was 75%. In addition, the contingency coefficient was 0.257, and the Kappa measure of agreement was 0.246 (P=0.034). Conclusions: Compared to TST, QFT-GIT shows no apparent advantage for diagnosis of latent tuberculosis infection in children.

Indications, Interpretation and Clinical Consequences of Tuberculin Skin Tests in Resource Limited Settings

Objective: to evaluate the policy of TST testing in Suriname. As there is no gold standard to diagnose latent tuberculosis infection (LTBI), the tuberculin skin test (TST) is used to diagnose LTBI. However, internationally, the cut-off values of the TST are not uniform and depend on local tuberculosis (TB) epidemiology and guidelines for test initiation. In Suriname, where currently several indications exist for TSTs, cut-off values are set at 5 mm or 10 mm, depending on the age and/or medical history of the patient. LTBI classification is performed by pulmonologists primarily based on the American Thoracic Society targeted TB testing guidelines. Method: retrospective analysis of outpatient TST data between 2011 and 2019 from Suriname’s sole pulmonary medicine clinic. Result: 1373 patients were evaluated. 590 patients were from the screening group of whom 253 had a positive TST result, 46 of whom were classified as LTBI. In the contact tracing group of 649 patients, 616 had a positive TST, 352 of whom were classified as LTBI. In the medical condition group of 134 patients, 96 had a positive TST, 38 of whom were classified as LTBI. Eventually, positive TST results were found for 965 tested patients: 436 patients were classified as LTBI and 529 non-LTBI patients were not prescribed chemoprophylaxis. None of the non-LTBI TST-positive patients were diagnosed with active TB, including 174 patients with a TST result of 15 mm or greater and in need of IPT, but not prescribed by judgement of the pulmonologist or because of loss to follow-up. Conclusion: the overrepresentation of positive TST results in Suriname is attributable to stringent cut-off values, especially among patients who do not disclose TB risk factors. In our opinion the TST cut-off value for such patients in Suriname and other similar settings could be set at 15 mm. We also promote that for all patients with a TST result of 15 mm or greater, offering IPT should be considered (after excluding active TB).

Performance of Comparative Cervical Tuberculin Test and Serological Methods with Culturing of Nasal Swab in Diagnosis of Bovine Tuberculosis in Cross Breed Cattle Baghdad Iraq: A Comparative Evaluation

This study was designed to assess the diagnostic value of Rapid Antigen bovine TB antibody test kit (RAT) and any association with cervical comparative tuberculin test (CCTT), (iELISA) and nasal swabs culturing, among based detection of M. bovis infection. A herd of 21 animals aged 1 - 8 years cross bread cattle of college of veterinary medicine. 19 (90.47%) animals had good body condition scores, two bulls included, and 2 (9.52%) cows were fair. Serum samples were collected, analyzed for anti-bovine TB antibody using RAT and iELISA. Also the herd was screened by CCTT. The tests were carried out twice, more than ten month interval, and twelve nasal swabs were taken within second survey. The first survey results revealed prevalence rate: 4 (19.04%) animals considered positive results (one positive and 3 suspected results) for CCTT, while the prevalence rate according to RAT was 10 (47.61%). The difference between the two prevalence rate was significant (McNemar chi-statistic = 4.50, p-value = 0.03) Kappa = 0.215 95% confidence interval: from -0.128 to 0.558;the strength of agreement is considered to be “fair”. The study interprets: sensitivity 30%;specificity 99%. The second survey results revealed prevalence rate according to CCTT was 4 (36.36%), while prevalence rate according to RAT was 5 (45.45%). The difference between the two prevalence was not significant (McNemar chi-statistic = 0.33, p-value = 0.56). Kappa = 0.441 95% confidence interval: from -0.087 to 0.968;the strength of agreement is considered to be “moderate”;sensitivity: 60%;specificity: 83%. All serum samples and nasal swabs gave negative results for iELISA and culturing respectively. The study concluded that RAT was highly specific, easy, labor and time saving, suggesting its use as screening test in bovine tuberculosis, and CCTT could be used to confirm positive animals screened by RAT, while there was no association between RAT, CCTT with body condition scores, iELISA and nasal swabs culture results.

Latent tuberculosis infection in health-care workers in the government sector in Brunei Darussalam:A cross-sectional study

Objective:Health-care workers(HCWs)are known to be at high risk for occupational biological hazards,and this includes exposure to mycobacterium tuberculosis(TB)which can result in either active or latent TB infection(LTBI).This study aims to provide an overview of the incidence of LTBI among HCWs in Brunei Darussalam,to examine associated risk factors,and to evaluate LTBI treatment compliance.Materials and Methods:This is a retrospective cross-sectional study which was conducted using data from January 2018 to December 2021,on notified cases of LTBI in HCWs which identified 115 cases.Demographic data,underlying medical conditions,and compliance to treatment were assessed through reviews of their electronic health records.Results:The incidence of LBTI was 14.6/year/1000 HCWs.The incidence rate reached a high of 24.6/1000 in 2020,and majority of cases were in the older age groups.There was good treatment acceptance and compliance(82.6%),and this was observed to be significantly higher in females than males(P=0.02).Conclusion:This study showed an average incidence of LTBI of 14.6/1000 HCWs over 4 years and high LTBI treatment acceptance(82.6%)and compliance.Emphasis on infection prevention and control measures in health-care settings and actions to increase awareness of LTBI are crucial interventions toward reducing the burden of LTBI.

Does “Latent Tuberculosis Infection” (LTBI)” Really Exist? Genealogy of a Medical Nosology

Introduction: The diagnosis of latent tuberculosis infection (LTBI) is based on secular ways: chest radiography and tuberculin skin test (TST). In front of a recent enthusiasm for LTBI, this paper reports a historical perspective of this concept. Method: Bibliometric analysis and literature review from medical databases, using the terms “latent tuberculosis infection (“LTBI”), “primary tuberculosis”, “tuberculin skin test”, “tuberculosis”, and from reference books on tuberculosis. Results: In the PubMED/MEDLINE search for LTBI, a total of 7787 articles were found between 1901 and 2020, 95% from 2000 to 2020. In the first part of the 20th century, LTBI term was used for sub-clinical tuberculosis disease, the latency being also called “primary tuberculosis” or “abortive tuberculosis infection”. From 1960, randomized prospective therapeutic studies mentioned “tuberculosis chemoprophylaxis”. By the end of the 20th century, the epidemic of AIDS impeded tuberculosis decrease, making LTBI search more efficient. In 2000, the American Thoracic Society and the Centers for Disease Controls and Prevention proposed the systematic used of LTBI, relayed through public health policies. A significant higher scientific production about LTBI was noted, supported by IGRA tests commercialization. Conclusion: In the recent years, health public policies, combined with epidemiologic and economic factors, strengthened the use of LTBI terminology.

Prevalence of Bovine Tuberculosis in Sheep at Sadar and Parbatipur Upazila under Dinajpur District in Bangladesh

Tuberculosis is Zoonotic disease and infected animals continue to spread the disease to other animals and humans by excreting the germs in milk, meat, feces, and respiratory droplets, this study used bPPD (Bovine purified protein derivative) to observe TST (Tuberculin skin test) reactivity in the Sheep population in the Sadar and Parbatipur Upazilas of Dinajpur District. The research conducted from January to June of 2018. There is no history for sheep tuberculosis in the study area. Overall, 5 percent (7/140) of 140 sheep were positive, 15% (21/140) were doubtful, and 80% (112/140) were negative based on sex, age, breed, and body condition score, while lactation stage and reproduction status prevalence was 6.4 percent, 14.9 percent, and 78.7% positive, doubtful, and negative, respectively. Our findings suggest the presence of a skin test reaction response when employing the bPPD reagent, but this needs to be validated by pathological and serological techniques. Nevertheless, my preliminary investigation suggests that abattoirs must implement effective control systems and raise public awareness.

Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette-Guerin booster vaccination： subgroup analysis of a population-based cross-sectional study

The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette-Guerin （BCG） booster vaccination in China was estimated using tuberculin skin testing （TST） and QuantiFERON-TB Gold assay （QFT） to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5-15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST （induration ≥ 10 mm） and QFT positivity were 9.3% （264/2827） and 2.5% （71/2831）, respectively. The rate of QFT indeterminate result was 2.2% （62/2831）. The overall agreement between TST and QFT was low （concordance = 88.0%; K coefficient = 0.125）. Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26-2.31 ]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a two- step approach might be considered for TB infection testing among adolescents in China.

Epidemiological investigation of Histoplasma capsulatum infection in China

Objectives To provide reliable information concerning the presence or the absence of Histoplasma capsulatum (H. capsulatum) infection in China, and data concerning this respect.Methods Three hundred normal people and 435 hospitalized patients, who lived in Hunan and Jiangsu provinces, and the Xinjiang Autonomous Region, were tested with yeast-phase histoplasmin (ALK/Berkerley Biologicals Laboratories, USA) and human pure protein derivative of tuberculin (PPD) on the volar surface of the forearm. Any reaction to the antigens over 5.0?mm in diameter of induration at 48-72?hours was considered positive. Results A total of 138 subjects (18.8%) in 735 patients reacted to histoplasmin with 5.0-45.0 (9.1±4.3)?mm indurations. Significant differences of positive skin reaction rates in normal subjects were found in Hunan, Jiangsu and Xinjiang (8.9% vs 15.1% vs 2.1%). The overall positive rate of patients was 25.5%. Patients with tuberculosis [31.7% (78/246)] had a significantly higher positive skin reaction rate in comparison with those suffering from pneumonia [17.7% (11/62)], lung cancer [20.9% (9/43)], chronic obstructive pulmonary disease [17.3% (9/52)] and other diseases [12.5% (4/32)] (P<0.01). Of 562 cases, 292 cases (52.0%) reacted to PPD with indurations of 5-50 (13.7±4.9)mm in diameter, 63 cases (11.2%) reacted to both histoplasmin and PPD, while 38 cases (6.9%) reacted to histoplasmin but not to PPD.Conclusions The data suggest that there is H. capsulatum herd infection in China. The infection rate in Southeast China is higher than that in the Northwest, and the infection rate of patients with pulmonary tuberculosis is higher than that of normal persons and other pneumonopathy patients.

A prospective longitudinal study for latent tuberculosis infection in hospital in Beijing evaluating a T-cell-based assay health-care workers in a general

Background The health-care workers （HCWs） are at high risk of acquiring infection with Mycobacterium tuberculosis. The objectives of this study were to compare the performance of the T-SPOT.TB and tuberculin skin test （TST） for latent tuberculosis infection （LTBI）, evaluate diagnostic concordance and risk factors for LTBI, and observe the progression to active tuberculosis （TB） disease among HCWs in a general hospital in Beijing. Methods The prospective cohort study enrolled HCWs in a tertiary general hospital in Beijing, China, to evaluate LTBI with T-SPOT.TB and TST. The subjects were evaluated every 12 months during the 60-month follow-up. Results Of 101 participating HCWs, 96 and 101 had valid TST and T-SPOT.TB results, respectively. Twenty-nine （28.7%, 95% confidence interval （C/）, 19.9%-37.5%） were defined as positive by T-SPOT.TB and 53 （55.2%, 95% CI, 45.2%-64.9%） were defined as positive by TST （using a ≥10 mm cutoff）. An agreement between the two tests was poor （57.3%, K=0.18, 95% CI, 0.01%-0.52%）. In multJvariate analysis, direct exposure to sputum smear-positive TB patients was a significant risk factor for a positive T-SPOT.TB （OR 5.76; 95% CI 1.38-24.00）. Pooled frequency of antigen- specific IFN-y secreting T-cells for subjects who reported direct contact with sputum smear-positive TB patients was significantly higher than that for participants without direct contact （P=0.045）. One of 20 participants with positive result of T-SPOT.TB and TST developed active TB at 24-month follow-up.Conclusion T-SPOT.TB is a more accurate, targeted method of diagnosing LTBI than TST.

A mathematical model to predict the risk of hepatitis B infection through needle/syringe sharing in mass vaccination

Background:The Japanese Government settled a class litigation case with hepatitis B virus(HBV)carriers who claim to have been infected through needle/syringe sharing in childhood mass vaccination with a blanket compensation agreement.However,it is difficult to estimate how many of the present HBV carriers were infected horizontally from mass vaccination and how many were infected vertically from mothers.Methods:A mathematical model to predict the risk of infection through needle/syringe sharing in mass vaccination was proposed and a formula was developed.The formula was presented in a logarithmic graph enabling users to estimate how many people will be infected if a needle/syringe is shared by how many people for how many times under certain probability of infection.The formula was then applied to the historical data of mass tuberculin skin tests(TSTs)and BCG inoculation,from which a best estimate of how much needle/syringe sharing was practiced in different birth cohorts was determined.Results:For the oldest cohort born between 1951 and 1955,the prevalence of HBV carriers-0.65%at birth through vertical transmission-more than doubled in 1995(1.46%)through horizontal transmission.If the probability of infection through needle/syringe sharing is assumed to be 10%,it is theoretically likely that an average of five or more people shared a needle/syringe four times to achieve the prevalence of HBV carriers in 1995.However,for the youngest cohort born between 1981 and 1985,the effects of needle/syringe sharing were negligible because the later prevalence of HBV carriers was lower than the prevalence at birth.Conclusions:More than half of the HBV carriers born in the early 1950s might have contracted the disease by mass vaccinations.Japan’s experience needs to be shared with other countries as a caution in conducting mass vaccination programs under scarce needle/syringe supply(291 words).