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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: 2.73). 07/2008; 129(3-4):217-35. DOI: 10.1016/j.vetmic.2007.12.011
Source: PubMed

ABSTRACT 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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    • "To be able to estimate transmission parameters and to gauge the predictive value of simulation models, obtaining precise data from commercial dairy farms is important. Particularly for MAP, field data are not easily obtained as the progress of infections is slow and the diagnosis of the correct infection state in both young and adult animals is often imprecise (Nielsen and Toft, 2008). Hence, long term longitudinal data are essential. "
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    ABSTRACT: Mathematical models for infectious disease are often used to improve our understanding of infection biology or to evaluate the potential efficacy of intervention programs. Here, we develop a mathematical model that aims to describe infection dynamics of Mycobacterium avium subspecies paratuberculosis (MAP). The model was developed using current knowledge of infection biology and also includes some components of MAP infection dynamics that are currently still hypothetical. The objective was to show methods for parameter estimation of state transition models and to connect simulation models with detailed real life data. Thereby making model predictions and results of simulations more reflective and predictive of real world situations. Longitudinal field data from a large observational study are used to estimate parameter values. It is shown that precise data, including molecular diagnostics on the obtained MAP strains, results in more precise and realistic parameter estimates. It is argued that modeling of infection disease dynamics is of great value to understand the patho-biology, epidemiology and control of infectious diseases. The quality of conclusions drawn from model studies depend on two key issues; first, the quality of biology that has gone in the process of developing the model structure; second the quality of the data that go into the estimation of the parameters and the quality and quantity of the data that go into model validation. The more real world data that are used in the model building process, the more likely that modeling studies will provide novel, innovative and valid results.
    Preventive Veterinary Medicine 12/2014; 118(2-3). DOI:10.1016/j.prevetmed.2014.12.009 · 2.51 Impact Factor
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    • "From a diagnostic point of view, difficulties for invivo detection of latent form cases compared to patent form cases have been repeatedly reported, and are the main cause of failure of some radical testing and culling eradication programs (Jungersen et al., 2012). As expected, the sensitivity of serological PTB diagnosis strongly varied between both profiles (Nielsen & Toft, 2008; Jungersen et al., 2012). "
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    ABSTRACT: Paratuberculosis is a chronic mycobacterial infection causing granulomatous enteritis in ruminants, whose pathogenesis and epidemiology poses numerous challenges, including latency and reactivation. The most recent and complete classification of paratuberculosis immunopathological types in cattle recognized five categories. In this study, 1031 slaughtered Friesian cattle were submitted to serological, microbiological and pathological examinations with the aim of maximizing the rate of case detection. In most cases, infected animals had minimal lesions and almost no other proof of infection (38.9%), while the more characteristic types with the whole constellation of microbiological and immunological evidences accounted for a lower proportion (7.7%). As these findings in cattle suggest similarities with the epidemiology of tuberculosis in humans, we propose to re-group the original immunopathological types into two broader paratuberculosis epidemio-pathogenic forms or states: latent and patent. The former term would define infections with focal lesions and might constitute an apparent resilience status representing a difficult to detect reservoir of infection whose role could become critical if later immune-compromising factors lead to re-activation. The latter would group those cases with multifocal and diffuse inflammatory lesions with higher mycobacterial load and viability suggestive of a more immediate epidemiological risk. Interestingly, the relative frequency of presentation of each profile varied with age. The proportion of latent forms remained relatively constant between 33.8% and 54.3% through adulthood from 3 years of age, while patent forms were more frequent during the first years of age and tended to decrease among the oldest individuals.
    SPANISH JOURNAL OF AGRICULTURAL RESEARCH 10/2014; 12(4):1049-1060. DOI:10.5424/sjar/2014124-5978 · 0.51 Impact Factor
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    • "To achieve this purpose, the recent approach to classifying MAP infection forms into " latent " and " patent " could prove to be very useful, since its hallmark is based on the relationship between the histopathological findings, the presence of specific antibodies against MAP, and the presence of viable forms or DNA of MAP in tissues [25]. This pathological criterion is what precisely marks the difference with other PTB classifications which are mainly based on microbiological variables and especially with MAP fecal shedding, such as those proposed by Nielsen and Toft [26] and Zanella et al. [21]. Hence, according to our simplified model, " latent " infections, corresponding to the focal immunopathological form of Pérez et al. [27] and González et al. [22] and defined by delimited granulomatous lesions and scarce humoral response or MAP presence, might represent forms of resistance that could prevent animals from developing more severe forms. "
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    ABSTRACT: A genetic susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infections in ruminants has been longtime suspected to exist. Recently, natural infections in cattle have been reclassified into latent and patent forms based on histopathological findings and their associations with immunological and microbiological variables. This study aims to explore whether these newly defined phenotypes are associated with twenty-four single-nucleotide polymorphisms (SNPs) in six bovine candidate genes: nucleotide-binding oligomerization domain 2 (NOD2), solute carrier family 11 member A1 (SLC11A1), nuclear body protein SP110 (SP110), toll-like receptors (TLRs) 2 and 4, and CD209 (also known as DC-SIGN, dendritic cell-specific ICAM3-grabbing nonintegrin). SNPs were genotyped for 772 Holstein-Friesian animals (52.6% apparently free; 38.1% latent; 9.3% patent) by TaqMan OpenArray technology. Genotypic-phenotypic associations were assessed by logistic regression analysis adjusted for age at slaughter, under five models (codominant, dominant, recessive, overdominant, and log-additive), and corrected for multiple testing. The rs208222804 C allele (CD209 gene) was found to be associated with latent paratuberculosis (log-additive model: P < 0.0034 after permutation procedure; OR = 0.64, 95% CI = 0.48-0.86). No significant association was detected between any SNP and the patent phenotype. Consequently, CD209 gene may play a key role in the pathogenesis of bovine paratuberculosis.
    05/2014; 2014(3):321327. DOI:10.1155/2014/321327
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