Specificity of two tests for the early diagnosis of bovine paratuberculosis based on cell-mediated immunity: the Johnin skin test and the gamma interferon assay

Kalis, C.H.J.; Collins, Michael T.; Hesselink, Jan Willem; Barkema, Herman W.

doi:10.1016/j.vetmic.2003.07.003

Cited by 63 publications

(60 citation statements)

References 17 publications

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“…Specificities have varied over 10% between lots, even with lots made from the same seed culture (data not shown). Our experience is consistent with previous studies [17,18]. When and if an antigen for skin testing becomes standardized, it may be possible to assign likelihood ratios and recommendations based on induration size, so a measurement may always be desirable.…”

Section: Discussionsupporting

confidence: 87%

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Sensitivity and specificity of the agar-gel-immunodiffusion test, ELISA and the skin test for detection of paratuberculosis in United States Midwest sheep populations

et al. 2006

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-Our objective was to estimate the sensitivity and specificity of the agar-gelimmunodiffusion test (AGID), the ELISA, and the skin test for the detection of Mycobacterium avium subspecies paratuberculosis (MAP) in sheep using Bayesian methods without a gold standard. Fourteen flocks (2 465 sheep) were used. Five flocks (450 sheep) were considered MAP non-infected and 9 flocks (2 015 sheep) had sheep infected with MAP. Sheep were skin tested and blood was collected for AGID and ELISA testing. Results were analyzed using a Bayesian 3-test in 1-population model fitted in WinBUGS. The model allowed for dependence (correlation) between the two serologic tests, but these two tests were assumed to be conditionally independent of the skin test. The estimated specificity was 99.5% (95% PI of 98.9-99.9%) for the AGID; 99.3% (98.4-99.8%) for the ELISA using an optical density measured cutoff of 0.20; 99.2% (98.1-99.8%) using a cutoff of 0.15; 97.5% (95.8-98.7%) using a cutoff of 0.10; and 98.7% (97.3-99.5%) for the skin test. The estimated sensitivities were 8.3% (6.2-10.7%) for the AGID; 8.0% (6.0-10.4%), 10.6% (8.3-13.1%), and 16.3% (13.5-19.4%) for the ELISA using the cutoffs 0.20, 0.15, and 0.10 respectively; and 73.3% (62.3-85.8%) for the skin test. The skin test was specific in non-infected populations and sensitive in infected populations, although in some cases a positive skin test might represent MAP exposure rather than infection. The AGID and ELISA were specific but lacked sensitivity. The AGID and ELISA consistently identified two different populations of infected sheep with only moderate overlap between positive test results.

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Section: Discussionsupporting

confidence: 87%

“…This finding is contrary to previous results in cattle, which vary as to what induration size must be present in order to consider an animal positive. Kalis et al [18] used an induration of ≥ 4 mm. If they used an induration size of ≥ 2 mm the specificity of the skin test decreased from 93 to 88%.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity and specificity of the agar-gel-immunodiffusion test, ELISA and the skin test for detection of paratuberculosis in United States Midwest sheep populations

et al. 2006

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“…12 To the authors' knowledge, widespread evaluation of specificity for the IFN-c ELISA in sheep has not been done. We were only able to include 2 noninfected flocks, as it is particularly difficult to know the true flock paratuberculosis status with the management practices in the USA.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Gamma Interferon ELISA in Sheep Subclinically Infected withMycobacterium AviumSubspeciesParatuberculosisUsing a Whole-Cell Sonicate or a Johnin Purified-Protein Derivative

2006

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Abstract. The aim of the study reported here was to estimate the sensitivity and specificity of the gamma interferon (IFN-c) ELISA for paratuberculosis in sheep using receiver-operating characteristic analysis. Bacteriologic culture of tissues was used to define the reference positive population (n 5 33). Two reference negative populations were used: culture-negative sheep from infected flocks (n 5 77), and sheep from noninfected flocks (n 5 358). We also evaluated the accuracy of 2 Mycobacterium avium subspecies paratuberculosis (MAP) antigen preparations, a whole-cell sonicate (MpS) and a johnin purified-protein derivative (PPDj). The source of the reference negative sheep used in the analysis affected overall accuracy of the IFN-c ELISA. The area under the curve was 0.683 (95% confidence interval 0.574-0.787), using culturenegative sheep from infected flocks, was 0.831 (0.764-0.889), using sheep from noninfected flocks for the MpS, and was 0.809 (0.726-0.881) and 0.897 (0.862-0.925) for the PPDj, respectively. Using the MpS, the cut point that classified the most sheep correctly was an optical density reading of 0.20, for sensitivity of 40.7% (19.4-57.6) and specificity of 88.7% (77.0-95.7) or 97.6% (93.04-99.5), depending on the reference negative population used. Using the PPDj, the cut point that classified the most sheep correctly was 0.25 for sensitivity of 66.7% (47.2-82.7) and specificity of 93.5% (85.5-97.9) or 98.3% (96.4-99.4), respectively. The PPDj was more accurate at identifying MAP-infected sheep than was the MpS (P 5 0.034).

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“…paratuberculosis infection, such as enzyme-linked immunosorbent assay, the gamma interferon release assay, and the agarose gel immunodiffusion assay, many of the antigens used are not specific for M. avium subsp. paratuberculosis (31). Most tests use complex, ill-defined mixtures of proteins derived from whole-cell or fractionated extracts of M. avium subsp.…”

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Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex

et al. 2009

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The Mycobacterium avium complex (MAC) comprises genomically similar but phenotypically divergent bacteria that inhabit diverse environments and that cause disease in different hosts. In this study, a wholegenome approach was used to examine the polymorphic PE (Pro-Glu) and PPE (Pro-Pro-Glu) gene families, implicated in immunostimulation and virulence. The four major groups of MAC organisms were examined, including the newly sequenced type strains of M. intracellulare and M. avium subsp. avium, plus M. avium subsp. paratuberculosis and M. avium subsp. hominissuis, for the purpose of finding genetic differences that could be exploited to design diagnostic tests specific to these groups and that could help explain their divergence in pathogenesis and host specificity. Unique and missing PPE genes were found in all MAC members except M. avium subsp. avium. Only M. intracellulare had a unique PE gene. Apart from this, most PE and PPE sequences were conserved, with average nucleotide sequence identities of 99.1 and 98.1%, respectively, among the M. avium subspecies, but only 82.9 and 79.7% identities with the PE and PPE sequences of M. intracellulare, respectively. A detailed analysis of the amino acid sequences was performed between M. avium subsp. paratuberculosis and M. avium subsp. hominissuis. Most differences were detected in the PPE proteins, with amino acid substitutions and frame shifts leading to unique amino acid sequences. In conclusion, several unique PPE proteins were identified in MAC organisms next to numerous polymorphisms in both the PE and PPE gene families. These substantial differences could help explain the divergence in phenotypes within the MAC and could lead to diagnostic tests with better discriminatory abilities.Mycobacterium avium and Mycobacterium intracellulare are collectively known as the Mycobacterium avium complex (MAC). For genotypic, phenotypic, and historical reasons, multiple subspecies of M. avium are recognized; these include Mycobacterium avium subsp. paratuberculosis, M. avium subsp. hominissuis, Mycobacterium avium subsp. avium, and M. avium subsp. silvaticum (50). All four M. avium subspecies and M. intracellulare possess a high degree of genetic similarity but are capable of infecting a diverse range of host species.M. avium subsp. paratuberculosis is the causative organism of Johne's disease (paratuberculosis), a debilitating chronic enteritis in ruminants (49), and has been implicated in Crohn's disease in humans (18). M. avium subsp. avium and M. avium subsp. silvaticum are limited almost exclusively to avian species (53), in which they cause tuberculosis. M. avium subsp. hominissuis is a recent designation and was added to reflect the distinction of human and porcine isolates from bird-type strains when genotypic methods showed that M. avium isolates from humans in particular but also pigs rarely shared the genetic profiles of organisms found in birds (38,53). M. avium subsp. hominissuis and M. intracellulare are ubiquitous, saprophytic mycobacteria commonly found in so...

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Specificity of two tests for the early diagnosis of bovine paratuberculosis based on cell-mediated immunity: the Johnin skin test and the gamma interferon assay

Cited by 63 publications

References 17 publications

Sensitivity and specificity of the agar-gel-immunodiffusion test, ELISA and the skin test for detection of paratuberculosis in United States Midwest sheep populations

Sensitivity and specificity of the agar-gel-immunodiffusion test, ELISA and the skin test for detection of paratuberculosis in United States Midwest sheep populations

Evaluation of the Gamma Interferon ELISA in Sheep Subclinically Infected withMycobacterium AviumSubspeciesParatuberculosisUsing a Whole-Cell Sonicate or a Johnin Purified-Protein Derivative

Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex

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