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Frontiers in Immunology 2021Tuberculosis (TB) remains a worldwide problem. Despite the high disease rate, not all who are infected with () develop disease. Interferon-γ (IFN-γ) specific T cell... (Review)
Review
Tuberculosis (TB) remains a worldwide problem. Despite the high disease rate, not all who are infected with () develop disease. Interferon-γ (IFN-γ) specific T cell immune assays such as Quantiferon and Elispot, as well as a skin hypersensitivity test, known as a tuberculin skin test, are widely used to infer infection. These assays measure immune conversion in response to . Some individuals measure persistently negative to immune conversion, despite high and prolonged exposure to . Increasing interest into this phenotype has led to multiple publications describing various aspects of these responses. However, there is a lack of a unified "resister" definition. A universal definition will improve cross study data comparisons and assist with future study design and planning. We review the current literature describing this phenotype and make recommendations for future studies.
Topics: Global Health; Humans; Interferon-gamma Release Tests; Mycobacterium tuberculosis; Phenotype; Population Surveillance; Tuberculin Test; Tuberculosis
PubMed: 33717116
DOI: 10.3389/fimmu.2021.619988 -
International Journal of... 2022Pregnant women who live in tuberculosis (TB)-affected households are more likely to develop latent TB infection (LTBI), which often escapes treatment. This study aims to...
BACKGROUND
Pregnant women who live in tuberculosis (TB)-affected households are more likely to develop latent TB infection (LTBI), which often escapes treatment. This study aims to determine if Interferon-gamma release (IGRA) is reliable in screening for LTBI in pregnant women, compare to the tuberculin skin test (TST).
METHODS
It was a cross-sectional study that involved 60 pregnant women with TB contact history as a proxy for LTBI and 30 pregnant women without contact history. Latent TB was detected using the TST 5 tuberculin units and IGRA using the QuantiFERON Gold Plus TB Test kit (QFT-Plus). The sensitivity and specificity of the two diagnostic methods and the agreement between them were estimated using SPSS version 20.0.
RESULTS
The sensitivity 95% (95% confidence interval [CI]: 86.08%-98.96%) and specificity 26.7% (95% CI: 12.28%-45.89%) of TST were compared to that of the IGRA with 60% (95% CI: 46.54%-72.44%) and 73.3% (95% CI: 54.11%-87.72%) sensitivity and specificity, respectively in detecting LTBI in pregnancy. Although there was a significant difference (P < 0.05) between TST and IGRA, the agreement was fair (kappa 0.39; 95% CI: 0.24-0.45).
CONCLUSION
TST assay is more sensitive than IGRA; however, the specificity of IGRA was superior to the TST method. In this study, a fair agreement of TST and IGRA was observed for detecting latent TB infection in pregnant women with household contact with TB patients.
Topics: Humans; Female; Pregnancy; Tuberculin Test; Interferon-gamma Release Tests; Latent Tuberculosis; Cross-Sectional Studies; Tuberculosis; Interferon-gamma
PubMed: 36510919
DOI: 10.4103/ijmy.ijmy_112_22 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Apr 2021Mucosal disease is one of the most common oral cavity diseases in children, among which mucosal erosion and ulceration account for about 50%. Oral mucosal erosion and... (Review)
Review
Mucosal disease is one of the most common oral cavity diseases in children, among which mucosal erosion and ulceration account for about 50%. Oral mucosal erosion and ulcer diseases in children are mostly acute with obvious pain, affecting speech, eating and swallowing. Some oral mucosal diseases are caused by infection and would result in epidemic among children. The onset age, sites, lesions size and quantity could vary, and some would have recurrence. The detailed medical history and comprehensive physical examination are necessary, some diseases can be diagnosed according to the medical history and clinical manifestations. If diagnosis can not be made, biopsy, blood test and immunofluorescence staining, immunohistochemistry, molecular biology detection, gene diagnosis, tuberculin test and other tests should be considered, and further investigation of systemic diseases should also be carried out if necessary. In some cases, multidisciplinary consultation should be sought. For those who still have no abnormal findings, therapeutic diagnosis can be tried out or secondary biopsy should be performed. In this article, the research progress of oral mucosal diseases in children is reviewed and our own clinical experiences of oral erosive and ulcerative diseases in children are summarized.
Topics: Child; Humans; Neoplasm Recurrence, Local
PubMed: 34137230
DOI: 10.3724/zdxbyxb-2021-0122 -
Journal of Acquired Immune Deficiency... Jan 2022HIV and pregnancy may affect latent TB infection (LTBI) diagnostics. Tuberculin skin test (TST) and newer generation QuantiFERON-TB Gold Plus (QFT-Plus) evaluations in...
BACKGROUND
HIV and pregnancy may affect latent TB infection (LTBI) diagnostics. Tuberculin skin test (TST) and newer generation QuantiFERON-TB Gold Plus (QFT-Plus) evaluations in pregnant women living with HIV (WLHIV) and without HIV are lacking.
METHODS
In this cross-sectional study, pregnant women underwent TST and QFT-Plus testing during antenatal care in Kenya. We estimated LTBI prevalence and TST and QFT-Plus performances. Diagnostic agreement was assessed with kappa statistic, participant characteristics associated with LTBI and HIV were assessed with generalized linear models, and QFT-Plus quantitative responses were assessed with Mann-Whitney U test.
RESULTS
We enrolled 400 pregnant women (200 WLHIV/200 HIV-negative women) at median 28 weeks gestation (interquartile range 24-30). Among WLHIV (all on antiretroviral therapy), the median CD4 count was 464 cells/mm3 (interquartile range 325-654); 62.5% (125) had received isoniazid preventive therapy. LTBI prevalence was 35.8% and similar among WLHIV and HIV-negative women. QFT-Plus testing identified 3-fold more women with LTBI when compared with TST (32% vs. 12%, P < 0.0001). QFT-Plus positivity prevalence was similar regardless of HIV status, although TB-specific antigen responses were lower in WLHIV than in HIV-negative women with LTBI (median QFT-TB1 1.05 vs. 2.65 IU/mL, P = 0.035; QFT-TB2 1.26 vs. 2.56 IU/mL, P = 0.027). TST positivity was more frequent among WLHIV than among HIV-negative women (18.5% vs 4.6%; P < 0.0001).
CONCLUSIONS
QFT-Plus assay had higher diagnostic yield than TST for LTBI in WLHIV and HIV-negative women despite lower TB-specific antigen responses in WLHIV. Higher TST positivity was observed in WLHIV. LTBI diagnostic performance in the context of pregnancy and HIV has implications for clinical use and prevention studies, which rely on these diagnostics for TB infection entry criteria or outcomes.
Topics: Cross-Sectional Studies; Female; HIV Infections; Humans; Interferon-gamma Release Tests; Latent Tuberculosis; Pregnancy; Pregnant Women; Tuberculin Test
PubMed: 34629414
DOI: 10.1097/QAI.0000000000002827 -
Vaccine Dec 2021In randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies.
METHODS
Observational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002-04, 2009-2013 and 2014-18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality.
RESULTS
Large post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2-12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19-1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6-12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27-2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39-0.90); for 6-month TST responses the MRR was 0.65 (0.43-1.00).
CONCLUSION
Among BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG's beneficial non-specific effects.
Topics: BCG Vaccine; Birth Cohort; Child; Humans; Infant; Infant, Newborn; Observational Studies as Topic; Tuberculin; Tuberculin Test; Vaccination
PubMed: 34226104
DOI: 10.1016/j.vaccine.2021.06.077 -
International Journal of... 2022Increasing the extensity of latent tuberculosis infection (LTBI) treatment which is one of the important parameters of tuberculosis (TB) control and completing the...
AIM
Increasing the extensity of latent tuberculosis infection (LTBI) treatment which is one of the important parameters of tuberculosis (TB) control and completing the treatment in success are important. The purpose of this study is to evaluate LTBI treatment indications and treatment outcomes of patients who received LTBI treatment in İstanbul between 2016 and 2018.
METHODS
The treatment outcomes of people who started LTBI treatment registered in TB dispensaries in Istanbul between 2016 and 2018 were analyzed retrospectively according to the variables of the age groups, gender, dispensary subgroups, and prevention treatment indications. Data collected from the health institutions were evaluated.
RESULTS
26.920 patients received LTBI treatment in all Istanbul TB dispensaries between 2016 and 2018. The evaluation of LTBI treatment indications; contact 15.696, Tuberculin skin test (TST) positivity 2224, immunosuppression 8746, TST conversion 58, sequelae lesion 15, and other indications are identified as 181. The groups which diagnosed with TB disease, mortality, transfer, other, and still in treatment are excluded from the analysis of LTBI treatment outcomes. A total of 25.253 patients were analyzed. 65 percent of the patients had completed LTBI treatment. Variables effective for treatment outcomes are analyzed with logistic regression. Treatment discontinuation was statistically significantly lower in 2017 (odds ratio [OR]: 0.906 confidence interval [CI] [95%] [0.849-0.968]) and 2018 (OR: 0.635 CI [95%] [0.594-0.679]) compared to 2016. Treatment lost to follow-up was statistically significantly lower in those receiving LTBI treatment with the indication of tuberculin skin test positivity (OR: 0.541 CI [95%] [0.487-0.600]) and the indication of immunosuppression (OR: 0.284 CI [95%] [0.142-0.569]) compared to those who received LTBI treatment due to contact. When the treatment results are evaluated according to the TB incidence of the region where the dispensaries are located, treatment lost to follow-up was higher in 101-200 per 100,000 incidence group (OR: 1.201 CI [95%] [1.123-1.285]) and incidence of 201-370 per 100,000 (OR: 1.461 CI [95%] [1.358-1.572]). Treatment lost to follow-up was higher in dispensaries on the European side (OR: 1.293 CI [95%] [1.203-1389]) and the 0-35 age group (OR: 1.248 CI [95%] [1.168-1.333]).
CONCLUSION
In conclusion, the treatment completion rate should be improved for an effective LTBI treatment which is one of the important parameters of targeted TB elimination. Particularly people under the age of 35 years and regions with high-TB incidence should receive special care and close follow-up.
Topics: Humans; Adult; Latent Tuberculosis; Tuberculin Test; Interferon-gamma Release Tests; Retrospective Studies; Tuberculosis
PubMed: 36510932
DOI: 10.4103/ijmy.ijmy_196_22 -
Frontiers in Public Health 2022Diabetes mellitus (DM) patients with latent tuberculosis infection (LTBI) have an increased risk of developing active tuberculosis (TB) due to impaired immunity. The...
Serial testing of latent tuberculosis infection in patients with diabetes mellitus using interferon-gamma release assay, tuberculin skin test, and creation tuberculin skin test.
BACKGROUND
Diabetes mellitus (DM) patients with latent tuberculosis infection (LTBI) have an increased risk of developing active tuberculosis (TB) due to impaired immunity. The performance of currently available immune response-based assays for identification of TB infection had been rarely evaluated in patients with type 2 DM (T2DM) in China.
METHODS
A prospective study was conducted to investigate the status of LTBI in patients with confirmed T2DM. At the baseline survey, the prevalence of LTBI was tested using interferon-gamma release assay (IGRA), tuberculin skin test (TST) and creation tuberculin skin test (C-TST) in parallel. After a 3-month interval, the participants were retested by the three assays to estimate their performance in the serial testing.
RESULTS
A total of 404 participants with T2DM were included in the study. At baseline, after excluding active TB, the prevalence of LTBI identified by TST (≥ 10 mm), C-TST (≥ 5 mm) and IGRA (≥ 0.35 IU/ml) were 9.65% (39/404), 10.40% (42/404) and 14.85% (60/404), respectively. The concordance of TST and C-TST results with IGRA results was 86.39% (349/404) and 92.08% (372/404) with a Kappa coefficient of 0.37 [95% confidence interval (CI): 0.24- 0.50] and 0.64 (95% CI: 0.53- 0.76), respectively. After a 3-month interval, the continuous results of TST, C-TST and IGRA were observed to be increased with testing conversion for 50, 26 and 27 patients, respectively. For TST and C-TST conversions, the distribution of their quantitative results in serial tests varied significantly when further classified by baseline IGRA dichotomous results.
CONCLUSION
In studied patients with T2DM, C-TST showed higher consistency with IGRA as compared to TST. The present of conversion observed in serial testing suggested that boosting effect of skin testing should be considered for identify of LTBI in patients with T2DM.
Topics: Humans; Interferon-gamma Release Tests; Tuberculin Test; Latent Tuberculosis; Prospective Studies; Diabetes Mellitus, Type 2
PubMed: 36530654
DOI: 10.3389/fpubh.2022.1025550 -
Colombia Medica (Cali, Colombia) 2022Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century.
BACKGROUND
Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century.
OBJECTIVE
This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years.
METHODS
All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration.
RESULTS
A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis.
CONCLUSION
While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.
Topics: Male; Humans; Female; Adult; Middle Aged; Tuberculin; Tumor Necrosis Factor Inhibitors; Tuberculosis; Tuberculin Test; Latent Tuberculosis
PubMed: 37152521
DOI: 10.25100/cm.v53i3.5055 -
Journal of Infection and Public Health Apr 2022Healthcare workers are considered to be at a higher risk of acquiring tuberculosis (TB) infection than the general population. Clinical medical students are part of the...
Prevalence of latent tuberculosis infection among pre-clinical and clinical medical students using QuantiFERON-TB gold plus and tuberculin skin test at a teaching hospital in Thailand: A cross-sectional study.
BACKGROUND
Healthcare workers are considered to be at a higher risk of acquiring tuberculosis (TB) infection than the general population. Clinical medical students are part of the healthcare team and clinical practice are done during their clinical rotation. They could be exposed to similar occupational risks as the healthcare workers. Most students who become infected have latent tuberculosis infection (LTBI) and may not exhibit any clinical symptoms. Some students with LTBI can progress to TB disease during clinical rotations in the hospitals. Therefore, screening for LTBI in this population represents hospital aspect of public health strategy and infection control in medical school in high TB burden countries.
OBJECTIVE
We aimed to determine the prevalence of LTBI among fourth-year medical students and sixth-year medical students by using QuantiFERON-TB Gold Plus (QFT-Plus) and Tuberculin Skin Test (TST).
METHODS
A cross-sectional study of fourth-year medical students (n = 73) and sixth-year medical students (n = 85) was conducted at the School of Medicine, Chulalongkorn University, Bangkok, Thailand. The medical students (n = 158) who met the eligibility criteria were recruited into the study. LTBI was detected by using QFT-Plus and some of the participants had a tuberculin skin test (TST). The TST was interpreted after 48-72 h. The participants who tested positive by QFT-Plus were considered to have LTBI. Demographic information and data on occupational TB exposure were collected via a questionnaire. A multivariate logistic regression was used to test for associations between independent variables and results of the QFT-Plus.
RESULTS
A total of 158 participants were included in this study. The overall prevalence of LTBI was 6.3% (n = 10) as determined by QFT-Plus. The LTBI prevalence was higher in the sixth-year medical students (9.4%) compared to the fourth-year medical students (2.7%). Higher risk of LTBI was associated with sixth-year medical students (odds ratio, 3.69 [95%CI, 0.75-17.96]), but this was not significant. Moreover, history of occupational TB exposure without PPE yielded an odds ratio of 2.98 [95%CI, 0.68-13.12] but it was not statistically significant due to the small sample size. One hundred thirty-nine (88%) participants were BCG vaccinated as per the national vaccination requirements. No abnormal chest X-rays were found for any of the positive participants. Of the 158 participants, 41 (25.9%) of them had TST. Of the 41 participants, 6 (14.6%) tested positive at a cut-off of ≥ 10 mm for TST, which was concordant with QFT-Plus results. The agreement between the two tests was 0.57 using kappa coefficients.
CONCLUSION
The screening of TB infection in new healthcare workers (HCWs), especially medical students, is essential to reduce future nosocomial TB incidences in the hospitals. This study showed that there was a high prevalence of LTBI among sixth-year medical students compared to fourth-year medical students. Our results suggest that tendency of higher LTBI prevalence might be associated with advanced clinical years, thus tailored public health education strategy and infection control in tertiary care hospitals for new healthcare workers in TB endemic countries may prevent nosocomial TB disease from developing in the future. Therefore, active surveillance should be done for all new HCWs, and TB preventive therapy should be administered to recent converters.
Topics: Cross Infection; Cross-Sectional Studies; Hospitals, Teaching; Humans; Interferon-gamma Release Tests; Latent Tuberculosis; Prevalence; Students, Medical; Thailand; Tuberculin Test
PubMed: 35325687
DOI: 10.1016/j.jiph.2022.02.010 -
American Journal of Ophthalmology Feb 2023To compare antigen-specific intraocular immune responses between different clinical phenotypes of tuberculin skin test (TST)-positive and TST-negative uveitis.
PURPOSE
To compare antigen-specific intraocular immune responses between different clinical phenotypes of tuberculin skin test (TST)-positive and TST-negative uveitis.
DESIGN
Single center, retrospective cross-sectional study.
METHODS
Patients requiring diagnostic or therapeutic vitrectomy for the management of intraocular inflammation were divided into 3 groups based on Standardization of Uveitis Nomenclature (SUN) classification criteria for tubercular uveitis. Group 1 included patients with ocular tuberculosis (OTB; n = 23) who were TST-positive patients, met the SUN criteria, and/or had a polymerase chain reaction (PCR)-positive test for TB. Group 2 included patients with uveitis of unknown origin (UNK; n = 24) who were undifferentiated TST-positive patients who had not met SUN criteria. Group 3 included non-TB uveitis patients (n = 24) who were TST-negative either with or without a well-defined non-TB diagnosis. Total vitreous cells were activated with Mycobacterium tuberculosis-specific Early Secreted Antigenic Target-6 (ESAT-6) or the retinal autoantigen, interphotoreceptor retinoid-binding protein peptide (pIRBP 1-20), stained for intracellular interferon gamma (IFNγ), tumor necrosis factor-alfa (TNFα), and interleukin 17 (IL-17), and analyzed by flow cytometry. Antigen-specific single and dual (polyfunctional) cytokine responses to ESAT-6 and IRBP were compared between the 3 groups.
RESULTS
All cytokine responses to ESAT-6 were higher in the UNK group compared with the non-TB control subjects, while all except IL-17 were comparable between the OTB and non-TB groups. Polyfunctional responses-IFNγ/IL-17 (P = .002), TNFα/IL-17 (P = .02), and TNFα/IFNγ (P = .01)-were significantly greater for UNK than the OTB group. Polyfunctional cells also produced more cytokine per cell than respective monofunctional cells. IRBP cytokine responses were comparable between different groups and were not affected by the clinical phenotype or duration of disease.
CONCLUSION
The intraocular polyfunctional cytokine response is stronger in undifferentiated TST-positive uveitis than in OTB patients, likely representing an exaggerated anti-TB immune response rather than active infection.
Topics: Humans; Cytokines; Tumor Necrosis Factor-alpha; Tuberculosis, Ocular; Interleukin-17; Retrospective Studies; Cross-Sectional Studies; Tuberculosis; Uveitis; Tuberculin Test; Mycobacterium tuberculosis
PubMed: 36087765
DOI: 10.1016/j.ajo.2022.08.029