Ante mortem diagnosis of paratuberculosis: A review of accuracies of ELISA, interferon-γ assay and faecal culture techniques

Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Veterinary Microbiology (Impact Factor: 2.51). 07/2008; 129(3-4):217-35. DOI: 10.1016/j.vetmic.2007.12.011
Source: PubMed


Infections with Mycobacterium avium subsp. paratuberculosis (MAP) can be latent for years without affecting the animal, but the animal may become infectious or clinical at some point. Diagnosis of paratuberculosis can be a challenge primarily in latent stages of the infection, and different diagnosis interpretations are usually required by the variety of decision makers. The objective of this paper was to provide a critical review of reported accuracies of ELISA tests, interferon-gamma assays (IFN-gamma) and faecal culture (FC) techniques used for diagnosis of three defined target conditions: MAP infected, MAP infectious and MAP affected animals. For each animal species, target condition and diagnostic test-type, sensitivities (Se) and specificities (Sp) were summarised based on a systematic, critical review of information in literature databases. The diagnostic test information often varied substantially for tests of the same type and make, particularly ELISA, which was the most frequently reported test-type. Comparison of the various tests accuracies was generally not possible, but stratification of test-evaluations by target condition improved the interpretation of the test accuracies. Infectious and affected animals can often be detected, but Se for infected animals is generally low. A main conclusion of the review was that the quality of design, implementation and reporting of evaluations of tests for paratuberculosis is generally poor. Particularly, there is a need for better correspondence between the study population and target population, i.e. the subjects chosen for test evaluation should reflect the distribution of animals in the population where the test is intended to be used.

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Available from: Søren Saxmose Nielsen, Aug 14, 2015
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    • "Deciphering host immune responses following exposure to MAP and characterizing responses at different stages of infection remains a complex and a daunting task[16]. It is hypothesized that the variation of the time to shedding and the variable expression of CMI/ AMI responses could be a result of variation in infective doses, temporal variations in pathogenetic events[19], and the complex dynamics of immune responses causing or responding to host transitions through the different stages of infection. Variations can arise from responses that are inherent to an individual host and due to differing virulence of the micro-organisms[20]different groups of sheep[7,14,21]were shown to vary with intensity/dose and type of MAP strain used for infection. "
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    ABSTRACT: Johne's disease (JD) is a chronic disease in ruminants and is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). At late stages of the disease, MAP bacilli are shed via feces excretion and in turn create the potential for oral-fecal transmission. The role of the host immune response in MAP bacteria shedding patterns at different stages of JD is still unclear. We employed mathematical modeling to predict if the variation in MAP shedding could be correlated to the immune response in infected animals. We used a novel inverse modeling approach that assumed biological interactions among the antigen-specific lymphocyte proliferation response (cell-mediated response), antibody/humoral immune responses, and MAP bacteria. The modeling framework was used to predict and test possible biological interactions between the measured variables and returns only the essential interactions that are relevant in explaining the observed cattle MAP experimental infection data. Through confronting the models with data, we predicted observed effects (enhancement or suppression) and extents of interactions among the three variables. This analysis enabled classification of the infected cattle into three different groups that correspond to the unique predicted immune responses that are essential to explain the data from cattle within these groups. Our analysis highlights the strong and weak points of the modeling approach, as well as the key immune mechanisms predicted to be expressed in all animals and those that were different between animals, hence giving insight into how animals exhibit different disease dynamics and bacteria shedding patterns.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "After in utero or fecal-oral infection, cattle go through an extended incubation period that can ultimately result in development of Johne's disease, a noncurable enteritis (Sweeney , 2011). During incubation, infected cattle frequently remain undetected because antibody production and bacterial shedding occur only intermittently (Mortier et al., 2014a,b), and available tests lack accuracy (Nielsen and Toft, 2008), thereby reducing the effectiveness of testing and culling for successful eradication of MAP on cattle farms (Whitlock and Buergelt, 1996; Garry, 2011). As a consequence, most MAP-control programs are not solely based on testing and culling, but encourage implementation of best management practices to prevent MAP introduction and transmission between infectious and susceptible cattle (McKenna et al., 2006). "
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    ABSTRACT: Modern Johne's disease programs aim to control Mycobacterium avium ssp. paratuberculosis (MAP) infection through implementation of management practices that reduce the probability of MAP introduction and within-herd transmission on dairy farms. Success of these programs depends on whether weaknesses in management are corrected through implementation of management improvements. The objectives of this study were, therefore, to (1) assess whether scores in risk-assessment (RA) questions predicted suggestions for management changes for the upcoming year; and (2) determine factors as assessed in an RA that motivated producers to make management improvements and assess whether management improvements were influenced by previously received test results. The RA determining on-farm management related to MAP introduction and transmission were conducted annually by herd veterinarians on 370 dairy farms participating in the Alberta Johne's Disease Initiative. A maximum of 3 management changes that the farmer and the veterinarian agreed upon were recorded in a management plan. The MAP infection status of the herds was assessed through culture of 6 environmental samples. Whereas a management change was proposed for only 4% of questions with scores 1 or 2 (low risk), a change was proposed for 19% of questions with scores >2 [high risk; odds ratio (OR) = 11.4]. Improvement in RA question scores was more likely between the first and second annual RA than between the second and third RA (OR = 1.6). Farms with >3 culture-positive environmental samples collected in the previous year were more likely to improve their management than environmental sample culture-negative farms (OR = 1.3). In conclusion, proposed management changes were oriented toward previously identified weaknesses in management practices, suggesting that the RA was properly used to design targeted management suggestions. Furthermore, improvements in management were not randomly distributed among farms participating in the control program. Instead, knowledge of MAP infection status of a herd, suggestions for management improvements, and duration of participation all influenced implementation of management improvements.
    Full-text · Article · Nov 2015 · Journal of Dairy Science
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    • "paratuberculosis (MAP) (Sweeney, 2011). A MAP infection may be latent for the major part of an animal's life, or infection may develop to infectious and affected disease states (Nielsen and Toft, 2008). The possibility for latent infection makes diagnostic misclassification a general challenge. "
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    ABSTRACT: Paratuberculosis is a chronic infection of economic importance to the dairy industry. The infection may be latent for years, which makes diagnostic misclassification a general challenge. The objective of this study was to identify the spatial pattern in infection prevalence, when results were adjusted for covariate information and diagnostic misclassification. Furthermore, we compared the estimated spatial pattern with the spatial pattern obtained without adjustment for misclassification. The study included 1242 herds in 2009 and 979 herds in 2013. The within-herd prevalence was modelled using a hierarchical logistic regression model and included a spatial component modelled by a continuous Gaussian field. The Stochastic Partial Differential Equation (SPDE) approach and Integrated Nested Laplace Approximation (INLA) were used for Bayesian inference. We found a significant spatial component, and our results suggested that the estimated range of influence and the overall location of areas with increased prevalence are not very sensitive to diagnostic misclassification.
    Full-text · Article · Oct 2015 · Spatial and Spatio-temporal Epidemiology
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