Tuberculin Test

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Keith P. W. J. Mcadam - One of the best experts on this subject based on the ideXlab platform.

  • using elispot to expose false positive skin Test conversion in tuberculosis contacts
    PLOS ONE, 2007
    Co-Authors: Philip C Hill, Roger H Brookes, Dolly Jacksonsillah, Moses D Lugos, Simon Donkor, Bouke C De Jong, David Jeffries, Richard A. Adegbola, Tumani Corrah, Keith P. W. J. Mcadam
    Abstract:

    Background Repeat Tuberculin skin Tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. We evaluated whether an ELISPOT Test could identify tuberculosis (TB) contacts with boosting of immunity to non-tuberculous mycobacterial exposure. Methodology/Principal Findings We conducted Tuberculin and ELISPOT Tests in 1665 TB contacts: 799 were Tuberculin Test negative and were offered a repeat Test after three months. Those with Tuberculin Test conversion had an ELISPOT, chest X-ray and sputum analysis if appropriate. We compared converters with non-converters, assessed the probability of each of four combinations of ELISPOT results over the two time points and estimated boosting with adjustment for ELISPOT sensitivity and specificity. 704 (72%) contacts had a repeat Tuberculin Test; 176 (25%) had Test conversion, which increased with exposure to a case (p = 0.002), increasing age (p = 0.0006) and BCG scar (p = 0.06). 114 Tuberculin Test converters had ELISPOT results: 16(14%) were recruitment positive/follow-up positive, 9 (8%) positive/negative, 34 (30%) negative/positive, and 55 (48%) were negative/negative. There was a significant non-linear effect of age for ELISPOT results in skin Test converters (p = 0.038). Estimates of boosting ranged from 32%–41% of skin Test converters with increasing age. Three converters were diagnosed with TB, two had ELISPOT results: both were positive, including one at recruitment. Conclusions/Significance We estimate that approximately one third of Tuberculin skin Test conversion in Gambian TB case contacts is due to boosting of immunity to non-tuberculous mycobacterial exposure. Further longitudinal studies are required to confirm whether ELISPOT can reliably identify case contacts with Tuberculin Test conversion that would benefit most from prophylactic treatment.

S.j. More - One of the best experts on this subject based on the ideXlab platform.

  • using latent class analysis to estimate the Test characteristics of the γ interferon Test the single intradermal comparative Tuberculin Test and a multiplex immunoassay under irish conditions
    Veterinary Microbiology, 2011
    Co-Authors: T.a. Clegg, Margaret Good, Anthony Duignan, Clare Whelan, Eamonn Gormley, John Clarke, Nils Toft, S.j. More
    Abstract:

    Considerable effort has been devoted to improving the existing diagnostic Tests for bovine tuberculosis (single intradermal comparative Tuberculin Test [SICTT] and γ-interferon assay [γ-IFN]) and to develop new Tests. Previously, the diagnostic characteristics (sensitivity, specificity) have been estimated in populations with defined infection status. However, these approaches can be problematic as there may be few herds in Ireland where freedom from infection is guaranteed. We used latent class models to estimate the diagnostic characteristics of existing (SICTT and γ-IFN) and new (multiplex immunoassay [Enferplex-TB]) diagnostic Tests under Irish field conditions where true disease status was unknown. The study population consisted of herds recruited in areas with no known TB problems (2197 animals) and herds experiencing a confirmed TB breakdown (2740 animals). A Bayesian model was developed, allowing for dependence between SICTT and γ-IFN, while assuming independence from the Enferplex-TB Test. Different Test interpretations were used for the analysis: SICTT (standard and severe interpretation), γ-IFN (a single interpretation), and a range of interpretations for the Enferplex-TB (level-1 [high sensitivity interpretation] to level-5 [high specificity interpretation]). The sensitivity and specificity (95% posterior credibility intervals; 95% PCI) of SICTT[standard] relative to Enferplex-TB[level-1] and γ-IFN were 52.9-60.8% and 99.2-99.8%, respectively. Equivalent estimates for γ-IFN relative to Enferplex-TB[level-1] and SICTT were 63.1-70.1% and 86.8-89.4%, respectively. Sensitivity of Enferplex-TB[level-1] (95% PCI: 64.8-71.9%) was superior to the SICTT[standard], and specificity of the Enferplex-TB[level-5] was superior to γ-IFN (95% PCI: 99.6-100.0%). These results provide robust measures of sensitivity and specificity under field conditions in Ireland and suggest that the Enferplex-TB Test has the potential to improve on current diagnostics for TB infection in cattle. The extent of that potential will be assessed in further studies.

  • The comparative performance of the single intradermal comparative Tuberculin Test in Irish cattle, using Tuberculin PPD combinations from different manufacturers
    Veterinary Microbiology, 2011
    Co-Authors: M. Good, T.a. Clegg, F. Murphy, S.j. More
    Abstract:

    Ireland currently obtains its avian and bovine Tuberculin purified protein derivatives (PPDs) from a single source. Because problems of supply or quality cannot be discounted, it is prudent that Ireland identify alternative supplier(s) as part of a broad risk management strategy. Therefore, the aim of this study was to compare the performance of a number of different Tuberculin combinations (that is, pairings of bovine and avian PPD; with different manufacturers) in the single intradermal comparative Tuberculin Test (SICTT), as currently performed in Ireland. The study was randomised, controlled and double-blinded. A total of 2,172 cattle were used in the study. Each animal was Tested using two SICTTs, the first based on the Tuberculin combination in current use, and the second using one of six trial Tuberculin combinations. Analyses were conducted to compare both reactor-status and skin increase. For each control/trial Tuberculin combination, there was good agreement between the control and trial reactor-status. Differences in skin increases were mainly confined to animals categorised as either negative or severe inconclusive. However, the measured differences were minor, and unlikely to have a significant impact on the actual Test outcome, either for individual animals or for herds. In conclusion, while further studies determining sensitivity and specificity in Ireland would have to be done in the event of a change in Tuberculin PPD there should be minimal disruption of the national programme if alternative Tuberculin PPDs meeting WHO, OIE and EU regulations were used. In this study, the precision of the guinea pig bio-assay to assess Tuberculin potency was low and therefore Ireland should maintain its practice of periodically assessing potency in naturally infected cattle, even though this is not currently required under WHO, OIE or EU Regulations.

  • Using latent class analysis to estimate the Test characteristics of the interferon-γ Test, the single intradermal comparative Tuberculin Test and a multiplex immunoassay under Irish conditions
    Veterinary Microbiology, 2011
    Co-Authors: Tracy Clegg, Margaret Good, Anthony Duignan, Clare Whelan, Eamonn Gormley, John Clarke, Nils Toft, S.j. More
    Abstract:

    Considerable effort has been devoted to improving the existing diagnostic Tests for bovine tuberculosis (single intradermal comparative Tuberculin Test [SICTT] and γ-interferon assay [γ-IFN]) and to develop new Tests. Previously, the diagnostic characteristics (sensitivity, specificity) have been estimated in populations with defined infection status. However, these approaches can be problematic as there may be few herds in Ireland where freedom from infection is guaranteed. We used latent class models to estimate the diagnostic characteristics of existing (SICTT and γ-IFN) and new (multiplex immunoassay [Enferplex-TB]) diagnostic Tests under Irish field conditions where true disease status was unknown. The study population consisted of herds recruited in areas with no known TB problems (2,197 animals) and herds experiencing a confirmed TB breakdown (2,740 animals). A Bayesian model was developed, allowing for dependence between SICTT and γ-IFN, while assuming independence from the Enferplex-TB Test. Different Test interpretations were used for the analysis: SICTT (standard and severe interpretation), γ-IFN (a single interpretation), and a range of interpretations for the Enferplex-TB (level-1 [high sensitivity interpretation] to level-5 [high specificity interpretation]). The sensitivity and specificity (95% posterior credibility intervals; 95% PCI) of SICTT[standard] relative to Enferplex-TB[level-1] and γ-IFN were 52.9-60.8% and 99.2-99.8%, respectively. Equivalent estimates for γ-IFN relative to Enferplex-TB[level-1] and SICTT were 63.1-70.1% and 86.8-89.4%, respectively. Sensitivity of Enferplex-TB[level-1] (95% PCI: 64.8-71.9%) was superior to the SICTT[standard], and specificity of the Enferplex-TB[level-5] was superior to γ-IFN (95% PCI: 99.6-100.0%). These results provide robust measures of sensitivity and specificity under field conditions in Ireland and suggest that the Enferplex-TB Test has the potential to improve on current diagnostics for TB infection in cattle.

Philip C Hill - One of the best experts on this subject based on the ideXlab platform.

  • using elispot to expose false positive skin Test conversion in tuberculosis contacts
    PLOS ONE, 2007
    Co-Authors: Philip C Hill, Roger H Brookes, Dolly Jacksonsillah, Moses D Lugos, Simon Donkor, Bouke C De Jong, David Jeffries, Richard A. Adegbola, Tumani Corrah, Keith P. W. J. Mcadam
    Abstract:

    Background Repeat Tuberculin skin Tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. We evaluated whether an ELISPOT Test could identify tuberculosis (TB) contacts with boosting of immunity to non-tuberculous mycobacterial exposure. Methodology/Principal Findings We conducted Tuberculin and ELISPOT Tests in 1665 TB contacts: 799 were Tuberculin Test negative and were offered a repeat Test after three months. Those with Tuberculin Test conversion had an ELISPOT, chest X-ray and sputum analysis if appropriate. We compared converters with non-converters, assessed the probability of each of four combinations of ELISPOT results over the two time points and estimated boosting with adjustment for ELISPOT sensitivity and specificity. 704 (72%) contacts had a repeat Tuberculin Test; 176 (25%) had Test conversion, which increased with exposure to a case (p = 0.002), increasing age (p = 0.0006) and BCG scar (p = 0.06). 114 Tuberculin Test converters had ELISPOT results: 16(14%) were recruitment positive/follow-up positive, 9 (8%) positive/negative, 34 (30%) negative/positive, and 55 (48%) were negative/negative. There was a significant non-linear effect of age for ELISPOT results in skin Test converters (p = 0.038). Estimates of boosting ranged from 32%–41% of skin Test converters with increasing age. Three converters were diagnosed with TB, two had ELISPOT results: both were positive, including one at recruitment. Conclusions/Significance We estimate that approximately one third of Tuberculin skin Test conversion in Gambian TB case contacts is due to boosting of immunity to non-tuberculous mycobacterial exposure. Further longitudinal studies are required to confirm whether ELISPOT can reliably identify case contacts with Tuberculin Test conversion that would benefit most from prophylactic treatment.

P J Quinn - One of the best experts on this subject based on the ideXlab platform.

Ricardo U. Sorensen - One of the best experts on this subject based on the ideXlab platform.

  • Repeated Tuberculin Testing in Patients With Active Pulmonary Tuberculosis
    Chest, 1993
    Co-Authors: R.l. Sepulveda, Delfina Araya, X. Ferrer, Ricardo U. Sorensen
    Abstract:

    Objective : The proportion of Tuberculin reactors in a population and the intensity of Tuberculin reactions have been shown to increase with increasing exposure to mycobacterial infection, eg , repeated BCG immunization. These observations suggested that Tuberculin reactivity would become uniformly high in individuals with a high mycobacterial load who did not have a known cause of anergy. Since Tuberculin reactivity has been measured to evaluate the possible genetic regulation of responses to mycobacteria in humans, it is important to study its behavior under conditions of ongoing, maximal exposure to mycobacteria. In the present study, we determined the mean size of Tuberculin reactivity in BCG-immunized and unimmunized patients with pulmonary tuberculosis of recent onset, and the stability of Tuberculin reactions during and after treatment of pulmonary tuberculosis. Method : Serial Tuberculin Testing was performed on patients with newly diagnosed active pulmonary tuberculosis diagnosed over a period of 2 years at the National Institute for Respiratory Diseases in Santiago, Chile. The first Tuberculin Test was performed at the time of diagnosis in 58 patients. Repeated Tuberculin Testing was performed 2 weeks later in 15 patients with initial reaction sizes Results : Tuberculin reactions at entry had a unimodal distribution in patients both with and without BCG scars (14.8 ±5.0 mm and 16.5 ±5.2 mm, respectively). A second Tuberculin Test in patients with initial reaction sizes Conclusions : In the presence of an ongoing mycobacterial infection, patients without anergizing conditions express a Tuberculin reactivity that is relatively constant during and after treatment of pulmonary tuberculosis. The size and stability of the reactions seem to be determined by individual conditions that include the Tuberculin reactivity at the time of diagnosis and the BCG immunization status.