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Canadian Journal of Comparative... Dec 1947
Topics: Tuberculin
PubMed: 17648299
DOI: No ID Found -
Scientific Reports Feb 2023Bovine tuberculosis is a contagious bacterial disease of worldwide economic, zoonotic and welfare importance caused mainly by Mycobacterium bovis infection. Current...
Bovine tuberculosis is a contagious bacterial disease of worldwide economic, zoonotic and welfare importance caused mainly by Mycobacterium bovis infection. Current regulatory diagnostic methods lack sensitivity and require improvement. We have developed a multiplex serological test for bovine tuberculosis and here we provide an estimate of the diagnostic accuracy of the test in cattle. Positive and negative reference serum samples were obtained from animals from Europe and the United States of America. The diagnostic specificity estimate was 98.4% and 99.7% using high sensitivity and high specificity settings of the test respectively. Tuberculin boosting did not affect the overall specificity estimate. The diagnostic sensitivity in samples from Mycobacterium bovis culture positive animals following tuberculin boosting was 93.9%.The relative sensitivity following boosting in tuberculin test positive, lesion positive animals and interferon gamma test positive, lesion positive animals was 97.2% and 96.9% respectively. In tuberculin test negative, lesion positive animals and in interferon gamma test negative, lesion positive animals, the relative sensitivity following tuberculin boosting was 88.2% and 83.6% respectively. The results show that the test has high diagnostic sensitivity and specificity and can detect infected animals that are missed by tuberculin and interferon gamma testing.
Topics: Animals; Cattle; Tuberculosis, Bovine; Tuberculin; Interferon-gamma; Mycobacterium bovis; Tuberculin Test; Sensitivity and Specificity
PubMed: 36726018
DOI: 10.1038/s41598-023-28410-9 -
FEMS Immunology and Medical Microbiology Dec 2012The tuberculin skin test, which involves monitoring the immune reaction to an injection of purified protein derivative (PPD), has been the most widely used method for... (Review)
Review
The tuberculin skin test, which involves monitoring the immune reaction to an injection of purified protein derivative (PPD), has been the most widely used method for detecting infection with Mycobacterium tuberculosis since its development in 1930s. Until recently, the molecular composition of PPD was unknown. This thwarted the discovery of improved skin testing reagents and drastically hindered efforts to define the mechanism of action. Proteomic evaluation of PPD combined with a detailed analysis in the guinea pig model of tuberculosis led to further definition of the molecular composition of PPD. This communication reviews the history and current status of PPD, in addition to describing candidate next-generation PPD reagents, based on the use of an individual protein or protein cocktails.
Topics: Animals; Guinea Pigs; History, 20th Century; History, 21st Century; Humans; Tuberculin; Tuberculin Test; Tuberculosis; Tuberculosis Vaccines
PubMed: 22762692
DOI: 10.1111/j.1574-695X.2012.01002.x -
Proceedings of the National Academy of... Nov 2023Traditional understanding of the risk of progression from () infection to tuberculosis (TB) overlooks diverse presentations across a spectrum of disease. We developed a...
Traditional understanding of the risk of progression from () infection to tuberculosis (TB) overlooks diverse presentations across a spectrum of disease. We developed a deterministic model of infection and minimal (pathological damage but not infectious), subclinical (infectious but no reported symptoms), and clinical (infectious and symptomatic) TB, informed by a rigorous evaluation of data from a systematic review of TB natural history. Using a Bayesian approach, we calibrated the model to data from historical cohorts that followed tuberculin-negative individuals to tuberculin conversion and TB, as well as data from cohorts that followed progression and regression between disease states, disease state prevalence ratios, disease duration, and mortality. We estimated incidence, pathways, and 10-y outcomes following infection for a simulated cohort. Then, 92.0% (95% uncertainty interval, UI, 91.4 to 92.5) of individuals self-cleared within 10 y of infection, while 7.9% (95% UI 7.4 to 8.5) progressed to TB. Of those, 68.6% (95% UI 65.4 to 72.0) developed infectious disease, and 33.2% (95% UI 29.9 to 36.4) progressed to clinical disease. While 98% of progression to minimal disease occurred within 2 y of infection, only 71% and 44% of subclinical and clinical disease, respectively, occurred within this period. Multiple progression pathways from infection were necessary to calibrate the model and 49.5% (95% UI 45.6 to 53.7) of those who developed infectious disease undulated between disease states. We identified heterogeneous pathways across disease states after infection, highlighting the need for clearly defined disease thresholds to inform more effective prevention and treatment efforts to end TB.
Topics: Humans; Bayes Theorem; Communicable Diseases; Mycobacterium tuberculosis; Tuberculin; Tuberculosis
PubMed: 37963250
DOI: 10.1073/pnas.2221186120 -
Journal of Ayub Medical College,... 2018Childhood Tuberculosis remains one of the major public health concerns in developing countries like Pakistan and is responsible for high rates of morbidity and mortality...
BACKGROUND
Childhood Tuberculosis remains one of the major public health concerns in developing countries like Pakistan and is responsible for high rates of morbidity and mortality in children. Although tuberculin skin test is very commonly used by physicians all over the world, its interpretation always remains difficult and challenging. The objective of this study was to determine the frequency of positive tuberculin skin test in vaccinated and unvaccinated children suffering from tuberculosis.
METHODS
This Cross-sectional study was conducted in the department of Paediatric Ayub Teaching Hospital, Abbottabad from 1st February 2015 to 30th April 2016. A total of 150 patients were observed in this study. Children of either gender who were aged 1-15 years admitted in ward with tuberculosis were included in the study by using nonprobability convenient sampling technique. We injected 0.1 ml (10 units) of tuberculin purified protein derivative (PPD) into the anterior surface of the forearm and induration was read at 72 hours after administration. Data was entered and analysed using SPSS version 10.
RESULTS
Out of 150 children, 84 (56%) were males and 66 (44%) were females. The mean age was 7.8±3.84 years. Of these 75 (50%) were vaccinated and 75 (50%) were unvaccinated. In vaccinated Group 5.3% children had positive tuberculin skin test while in unvaccinated Group 2.7% children had positive tuberculin skin test and this difference was found statistically insignificant (pvalue= 0.40). Pulmonary TB was the diagnosis in 67 (44.7%), TBM in 65 (43.3%), abdominal TB in 7 (4.7%), disseminated TB in 4 (2.7%) and military TB in 7 (4.7%) patients.
CONCLUSIONS
The positivity of tuberculin skin test in vaccinated and unvaccinated children suffering from tuberculosis was found to be insignificant in our study. We conclude that Tuberculin Skin Test should not be used as a sole diagnostic tool for diagnosing the disease in children of our region..
Topics: Adolescent; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Male; Pakistan; Tuberculin; Tuberculin Test; Tuberculosis; Tuberculosis Vaccines; Vaccination
PubMed: 30632330
DOI: No ID Found -
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 -
Brazilian Journal of Microbiology :... Mar 2022Tuberculosis remains one of the most important infectious diseases with well-known zoonotic nature that affect humans, wildlife, and domestic animals, including goats....
Tuberculosis remains one of the most important infectious diseases with well-known zoonotic nature that affect humans, wildlife, and domestic animals, including goats. Nonetheless, no intradermal tuberculin test has been standardized for caprine diagnosis of tuberculosis. The present study investigated the intradermal comparative cervical tuberculin test (ICCTT) in the diagnosis of tuberculosis among 60 goats from farms with history of tuberculosis. The cutoff applied to goats was based on a study where goats had been experimentally infected with Mycobacterium bovis and Mycobacterium avium. Clinical examination, bacteriological culture, and histopathological staining were assessed to the diagnosis. Isolates compatible with mycobacteria were subjected for molecular diagnosis based on gyrB-restriction fragment length polymorphism (RFLP) analysis and PCR restriction-enzyme analysis (PRA) of hsp65 gene by BstEII and HaeIII, namely PRA-hsp65 assay. From all goats, 60% (n = 36/60), 3.3% (n = 2/60), and 36.7% (n = 22/60) showed positive, inconclusive, and negative reactions, respectively. Out of 36 goats with ICCTT positive, 75% (n = 27/36) had isolation of mycobacteria and were detected M. bovis by gyrB-RFLP. Molecular diagnosis and histopathological findings compatible with tuberculosis showed 86.1% (n = 31/36) concordance with the ICCTT. When compared ICCTT with M. bovis isolation, gyrB-RFLP, and histopathology, the better arithmetic means of sensitivity and specificity were 2.5 mm for ICCTT compared with M. bovis isolation and gyrB-RFLP, and 4.55 mm when compared with histopathology. Both receiver operating characteristic (ROC) curves presented statistical significance (P < 0.001). The identification of other mycobacteria, e.g., M. kansasii, M. flavescens, M. avium, M. florentinum, M. lentiflavum, M. simiae, and Corynebacterium pseudotuberculosis, not influenced positive results in ICCTT. The concordance between bacteriological, histopathological, and molecular identification with ICCTT findings indicate that the tuberculin test may be used as a valuable tool for diagnosis of caprine tuberculosis and reinforce the importance of association of methods to diagnostic of the disease from animal origin.
Topics: Animals; Goats; Mycobacterium bovis; Tuberculin; Tuberculin Test; Tuberculosis
PubMed: 34767242
DOI: 10.1007/s42770-021-00650-9 -
Clinical Infectious Diseases : An... Aug 2023Transcriptomic profiling of adults with tuberculosis (TB) has become increasingly common, predominantly for diagnostic and risk prediction purposes. However, few studies...
BACKGROUND
Transcriptomic profiling of adults with tuberculosis (TB) has become increasingly common, predominantly for diagnostic and risk prediction purposes. However, few studies have evaluated signatures in children, particularly in identifying those at risk for developing TB disease. We investigated the relationship between gene expression obtained from umbilical cord blood and both tuberculin skin test conversion and incident TB disease through the first 5 years of life.
METHODS
We conducted a nested case-control study in the Drakenstein Child Health Study, a longitudinal, population-based birth cohort in South Africa. We applied transcriptome-wide screens to umbilical cord blood samples from neonates born to a subset of selected mothers (N = 131). Signatures identifying tuberculin conversion and risk of subsequent TB disease were identified from genome-wide analysis of RNA expression.
RESULTS
Gene expression signatures revealed clear differences predictive of tuberculin conversion (n = 26) and TB disease (n = 10); 114 genes were associated with tuberculin conversion and 30 genes were associated with the progression to TB disease among children with early infection. Coexpression network analysis revealed 6 modules associated with risk of TB infection or disease, including a module associated with neutrophil activation in immune response (P < .0001) and defense response to bacterium (P < .0001).
CONCLUSIONS
These findings suggest multiple detectable differences in gene expression at birth that were associated with risk of TB infection or disease throughout early childhood. Such measures may provide novel insights into TB pathogenesis and susceptibility.
Topics: Child, Preschool; Humans; Infant; Infant, Newborn; Birth Cohort; Case-Control Studies; Fetal Blood; Latent Tuberculosis; South Africa; Transcriptome; Tuberculin; Tuberculin Test; Tuberculosis; Female
PubMed: 37144357
DOI: 10.1093/cid/ciad268 -
Tropical Medicine & International... Dec 2015To test the hypothesis that having a scar and a positive tuberculin skin test (TST) response after vaccination with Bacille Calmette-Guérin (BCG) is associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To test the hypothesis that having a scar and a positive tuberculin skin test (TST) response after vaccination with Bacille Calmette-Guérin (BCG) is associated with reduced infant mortality.
METHODS
We studied cohorts of 2709 normal-birthweight (NBW) and 1102 low-birthweight (LBW) infants in Guinea-Bissau. Children were enrolled in randomised trials between year 2002 and 2008 and received BCG vaccination at birth. BCG scars and TST responses were assessed at 2 and 6 months of age. The infants were followed for mortality to 12 months of age, and survival was analysed using Cox regression.
RESULTS
At age 2 months, 88% of NBW children and 91% of LBW children had a BCG scar, and 36% and 17% had a TST response, respectively. The LBW infants had nearly twofold higher mortality (4.5%) than the NBW infants (2.8%) between 2 and 12 months of age. In the LBW cohort, the adjusted mortality rate ratio (MRR) comparing children with a BCG scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05; 0.87). For NBW children, a scar and a positive TST were associated with 20% reductions in mortality, which did not reach statistical significance.
CONCLUSION
We confirmed previous observations that having a scar and a TST response after BCG vaccination is associated with lower mortality risk. The possibility of revaccinating scar-negative children should be considered.
Topics: BCG Vaccine; Birth Weight; Cicatrix; Cohort Studies; Female; Guinea-Bissau; Humans; Infant; Infant Mortality; Infant, Low Birth Weight; Infant, Newborn; Male; Proportional Hazards Models; Tuberculin; Tuberculin Test; Vaccination
PubMed: 26426863
DOI: 10.1111/tmi.12614 -
Scientific Reports Mar 2021Bovine tuberculosis (bTB) is a disease of livestock with severe and worldwide economic, animal welfare and zoonotic consequences. Application of test-and-slaughter-based...
Bovine tuberculosis (bTB) is a disease of livestock with severe and worldwide economic, animal welfare and zoonotic consequences. Application of test-and-slaughter-based control polices reliant on tuberculin skin testing has been the mainstay of bTB control in cattle. However, little is known about the temporal development of the bovine tuberculin skin test response at the dermal sites of antigen injection. To fill this knowledge gap, we applied minimally-invasive sampling microneedles (SMNs) for intradermal sampling of interstitial fluid at the tuberculin skin test sites in Mycobacterium bovis BCG-vaccinated calves and determined the temporal dynamics of a panel of 15 cytokines and chemokines in situ and in the peripheral blood. The results reveal an orchestrated and coordinated cytokine and local chemokine response, identified IL-1RA as a potential soluble biomarker of a positive tuberculin skin response, and confirmed the utility of IFN-γ and IP-10 for bTB detection in blood-based assays. Together, the results highlight the utility of SMNs to identify novel biomarkers and provide mechanistic insights on the intradermal cytokine and chemokine responses associated with the tuberculin skin test in BCG-sensitized cattle.
Topics: Animals; BCG Vaccine; Cattle; Cytokines; Needles; Tuberculin
PubMed: 33782422
DOI: 10.1038/s41598-021-86398-6