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Genetic variation for infection status as determined by a specific antibody response against Mycobacterium avium subspecies paratuberculosis in milk of Dutch dairy goats
Hulzen, K.J.E. van; Koets, A.P. ; Nielen, M. ; Hoeboer, J. ; Arendonk, J.A.M. van - \ 2012
Journal of Dairy Science 95 (2012)10. - ISSN 0022-0302 - p. 6145 - 6151.
johnes-disease - holstein cows - fecal culture - heritability - susceptibility - elisa
Classical control strategies based on management restrictions to reduce transmission, culling of infected goats, and vaccination have not been able to eradicate Johne’s disease from infected herds. Selective breeding for less susceptibility to disease may be a useful additional tool to contribute to control of the disease. The aim of this study was to estimate genetic variation and heritability for infection status as determined by a specific antibody response against Mycobacterium avium subspecies paratuberculosis in milk of Dutch dairy goats. Milk samples from 950 goats were tested for antibodies specific to Johne’s disease by ELISA on 5 consecutive test days, with a time interval of around 3 mo. Test results were coded as infected or not infected according to the instructions of the manufacturer. Heritability of infection status was estimated for 3 data sets to determine the effect of repeated sampling: only test results obtained on the first test day (first-test); the maximum test result of each animal obtained on 1 of the 5 test days (max-test); and all test results per animal, with a maximum of 5 consecutive samplings (all-test). Data sets first-test and max-test were analyzed with a sire model with fixed effects for year of birth and stage of lactation, and random effects for sire and error. For data set all-test, an additional permanent environment effect was included in the model. The estimated heritability on the underlying scale ranged from 0.12 in data set first-test, to 0.09 in data set max-test, to 0.07 in data set all-test.
Genome-wide association study to identify chromosomal regions associated with antibody response to Mycobacterium avium subspecies paratuberculosis in milk of Dutch Holstein-Friesians
Hulzen, K.J.E. van; Schopen, G.C.B. ; Arendonk, J.A.M. van; Nielen, M. ; Koets, A.P. ; Schrooten, C. ; Heuven, H.C.M. - \ 2012
Journal of Dairy Science 95 (2012)5. - ISSN 0022-0302 - p. 2740 - 2748.
single nucleotide polymorphisms - estimated breeding values - quantitative trait loci - genetic-variation - johnes-disease - linkage disequilibrium - short-communication - us holsteins - infection - cattle
Heritability of susceptibility to Johne's disease in cattle has been shown to vary from 0.041 to 0.159. Although the presence of genetic variation involved in susceptibility to Johne's disease has been demonstrated, the understanding of genes contributing to the genetic variance is far from complete. The objective of this study was to contribute to further understanding of genetic variation involved in susceptibility to Johne's disease by identifying associated chromosomal regions using a genome-wide association approach. Log-transformed ELISA test results of 265,290 individual Holstein-Friesian cows from 3,927 herds from the Netherlands were analyzed to obtain sire estimated breeding values for Mycobacterium avium subspecies paratuberculosis (MAP)-specific antibody response in milk using a sire-maternal grandsire model with fixed effects for parity, year of birth, lactation stage, and herd; a covariate for milk yield on test day; and random effects for sire, maternal grandsire, and error. For 192 sires with estimated breeding values with a minimum reliability of 70%, single nucleotide polymorphism (SNP) typing was conducted by a multiple SNP analysis with a random polygenic effect fitting 37,869 SNP simultaneously. Five SNP associated with MAP-specific antibody response in milk were identified distributed over 4 chromosomal regions (chromosome 4, 15, 18, and 28). Thirteen putative SNP associated with MAP-specific antibody response in milk were identified distributed over 10 chromosomes (chromosome 4, 14, 16, 18, 19, 20, 21, 26, 27, and 29). This knowledge contributes to the current understanding of genetic variation involved in Johne's disease susceptibility and facilitates control of Johne's disease and improvement of health status by breeding.
Consensus based reporting standards for diagnostic test accuracy studies for paratuberculosis in ruminants.
Gardner, I.A. ; Nielsen, S.S. ; Whittington, R.J. ; Collins, M.T. ; Bakker, D. ; Harris, B. ; Sreevatsan, S. ; Lombard, J.E. ; Sweeney, R. ; Smith, D.R. ; Gavalchin, J. ; Eda, S. - \ 2011
Preventive Veterinary Medicine 101 (2011)1-2. - ISSN 0167-5877 - p. 18 - 34.
avium subsp-paratuberculosis - linked-immunosorbent-assay - pooled fecal culture - real-time pcr - mycobacterium-avium - johnes-disease - dairy-cattle - ovine paratuberculosis - bovine-paratuberculosis - serological tests
The Standards for Reporting of Diagnostic Accuracy (STARD) statement (www.stard-statement.org) was developed to encourage complete and transparent reporting of key elements of test accuracy studies in human medicine. The statement was motivated by widespread evidence of bias in test accuracy studies and the finding that incomplete or absent reporting of items in the STARD checklist was associated with overly optimistic estimates of test performance characteristics. Although STARD principles apply broadly, specific guidelines do not exist to account for unique considerations in livestock studies such as herd tests, potential use of experimental challenge studies, a more diverse group of testing purposes and sampling designs, and the widespread lack of an ante-mortem reference standard with high sensitivity and specificity. The objective of the present study was to develop a modified version of STARD relevant to paratuberculosis (Johne's disease) in ruminants. Examples and elaborations for each of the 25 items were developed by a panel of experts using a consensus-based approach to explain the items and underlying concepts. The new guidelines, termed STRADAS-paraTB (Standards for Reporting of Animal Diagnostic Accuracy Studies for paratuberculosis), should facilitate improved quality of reporting of the design, conduct and results of paratuberculosis test accuracy studies which were identified as "poor" in a review published in 2008 in Veterinary Microbiology
Age at which dairy cattle become Mycobacterium avium subsp. paratuberculosis faecal culture positive
Weber, M.F. ; Kogut, J. ; Bree, J. de; Schaik, G. van; Nielen, M. van - \ 2010
Preventive Veterinary Medicine 97 (2010)1. - ISSN 0167-5877 - p. 29 - 36.
genetic-variation - johnes-disease - ssp-paratuberculosis - antibody-response - immune-responses - diagnostic-tests - infection - calves - susceptibility - polymorphisms
Age at which cattle become faecal culture positive for Mycobacterium avium subsp. paratuberculosis (Map) can be used as a proxy parameter for age at onset of faecal shedding, which is an important parameter in the control of Map in cattle herds. To investigate the age at becoming faecal culture positive, survival analysis methods were applied. The analyses were carried out on asynchronous interval censored data of faecal culture results of samples collected from 18,979 female Holstein-Frisian cattle in 353 Dutch herds between 1996 and 2002. The data were analysed with a Weibull proportional hazards model. The results indicate that the distribution of age at onset of faecal shedding in Holstein-Frisian dairy cattle in infected herds is associated with the within-herd prevalence. In higher classes of apparent prevalence, cattle started to shed Map at younger age on average. In herds with an apparent prevalence = 0.2, the proportion (95% CI) of cattle with onset of faecal shedding before 2 years of age was estimated at 1% (0.5%; 2%), 4% (3%; 5%), 8% (5%; 10%) and 20% (11%; 32%), respectively. This study indicates that a considerable proportion of young stock is shedding Map, especially in high prevalence herds. Therefore, infectious young stock should be a major concern in the control of paratuberculosis
Efficacy of novel lipid-formulated whole bacterial cell vaccines against Mycobacterium avium subsp paratuberculosis in sheep
Griffin, J.F.T. ; Hughes, A.D. ; Liggett, S. ; Farquhar, P.A. ; Mackintosh, C.G. ; Bakker, D. - \ 2009
Vaccine 27 (2009)6. - ISSN 0264-410X - p. 911 - 918.
johnes-disease - oral vaccination - bovis bcg - ovine paratuberculosis - pulmonary tuberculosis - brushtail possums - calmette-guerin - resistance - infection - protection
Mycobacterium avium subsp. paratuberculosis [MAP], the Causative agent of enteric Johne's disease, incurs significant economic losses to the livestock industry. Prophylactic vaccination can be employed as a control means, however mineral oil-based vaccines Currently in practice have limited efficacy, produce strong antibody responses that confound serological diagnostic testing, and cause severe injection site reactions. In the present study, the safety and efficacy of a commercial mineral oil-adjuvanted vaccine (Gudair (TM)) was compared with novel parenteral-route vaccines in sheep: these comprised live or heat-killed (HK) whole cell preparations of MAP strain 316F, formulated into a food-grade lipid vaccine delivery matrix. Subcutaneous administration of lipid-formulated live or I HK 316F-induced significantly fewer adverse injection site reactions than Gudair (TM); adverse injection site reactions were eliminated altogether by intraperitoneal (i.p.) injection of lipid-formulated live 316F Injections of lipid-formulated 316F-induced significant peripheral blood cell-mediated immune (CMI) responses in the absence of antibody, while Gudair (TM)-induced strong antibody and CMI reactivity. Vaccinated and non-vaccinated control sheep were challenged via oral inoculation of a virulent MAP isolate, and disease progress was monitored for 16 months, followed by necropsy. All vaccine regimes reduced the overall pathological grading of biopsied intestinal tract (IT) tissues; among these, only Gudair (TM) promoted a significant reduction in the incidence of histopathological IT lesions, while only i.p. injection of lipid-formulated live 316F significantly reduced the incidence of gross IT lesions. All lipid-formulated vaccines (but not Gudair (TM)) significantly reduced the incidence of bacteriological culture-confirmed MAP infection. This study identifies a new vaccination strategy against Johne's disease in sheep using conventional MAP vaccine strains formulated in a metabolisable lipid delivery matrix. (C) 2008 Published by Elsevier Ltd.
Paratuberculosis sero-status and milk production, SCC and calving interval in Irish dairy herds
Hoogendam, K. ; Richardson, E. ; Mee, J.F. - \ 2009
Irish Veterinary Journal 62 (2009)4. - ISSN 0368-0762 - p. 265 - 271.
bovine viral diarrhea - mycobacterium-paratuberculosis - johnes-disease - infection - cattle - cows - usa - association - parameters - michigan
The objective of this study was to investigate the impact of paratuberculosis sero-status on milk yield, fat, protein, somatic cell count and calving interval in Irish dairy herds. Serum from all animals over 12 months of age (n=2,602) in 34 dairy herds was tested for antibodies to Mycobacterium avium subsp. paratuberculosis using an ELISA. Herds were categorised by sero-status into positive, non-negative and negative, where a positive herd contained two or more positive cows, a non¿negative herd contained only one positive cow and a negative herd contained no positive cows. Data at animal, parity and herd-level were analysed by multiple regression using general linear models. Positive herds (mean herd size=129 cows) and non-negative herds (81 cows) were larger than negative herds (72 cows) (P
Sensitive detection of Myobacterium avium subsp paratuberculosis in bovine semen by real-time PCR
Herthnek, D. ; Englund, S. ; Willemsen, P.T.J. ; Bolske, G. - \ 2006
Journal of Applied Microbiology 100 (2006)5. - ISSN 1364-5072 - p. 1095 - 1102.
polymerase-chain-reaction - mycobacterium-paratuberculosis - crohns-disease - johnes-disease - diagnosis - organs - is900 - milk - dna - herpesvirus
Aims: To develop a fast and sensitive protocol for detection of Mycobacterium avium subsp. paratuberculosis (MAP) in bovine semen and to make a critical evaluation of the analytical sensitivity. Methods and Results: Processed semen was spiked with known amounts of MAP. Semen from different bulls as well as semen of different dilutions was tested. The samples were treated with lysing agents and beadbeating and the DNA was extracted with phenol and chloroform. Real-time PCR with a fluorescent probe targeting the insertion element IS900 detected as few as 10 organisms per sample of 100 ¿l semen. PCR-inhibition was monitored by inclusion of an internal control. Pre-treatment with immunomagnetic separation was also evaluated, but was not shown to improve the overall sensitivity. Conclusions: Real-time PCR is a sensitive method for detection of MAP in bovine semen. Lysis by mechanical disruption followed by phenol and chloroform extraction efficiently isolated DNA and removed PCR-inhibitors. Significance and Impact of the Study: The high sensitivity of the applied method allows reliable testing of bovine semen used for artificial insemination to prevent the spread of Johne's disease, caused by MAP.
Immunological and molecular characterization of susceptibility in relationship to bacterial strain differences in Mycobacterium avium subsp paratuberculosis infection in the red deer (Cervus elaphus)
O'Brien, R. ; Mackintosh, C.G. ; Bakker, D. ; Kopecna, M. ; Pavlik, I. ; Griffin, J.F.T. - \ 2006
Infection and Immunity 74 (2006)6. - ISSN 0019-9567 - p. 3530 - 3537.
fragment-length-polymorphism - johnes-disease - protective efficacy - immune-responses - new-zealand - wild ruminants - farmed deer - tuberculosis - sheep - is900
Johne's disease (JD) infection, caused by Mycobacterium avium subsp. paratuberculosis, represents a major disease problem in farmed ruminants. Although JD has been well characterized in cattle and sheep, little is known of the infection dynamics or immunological response in deer. In this study, typing of M. avium subsp. paratuberculosis isolates from intestinal lymphatic tissues from 74 JD-infected animals showed that clinical isolates of M. avium subsp. paratuberculosis from New Zealand farmed red deer were exclusively of the bovine strain genotype. The susceptibility of deer to M. avium subsp. paratuberculosis was further investigated by experimental oral-route infection studies using defined isolates of virulent bovine and ovine M. avium subsp. paratuberculosis strains. Oral inoculation with high (109 CFU/animal) or medium (107 CFU/animal) doses of the bovine strain of M. avium subsp. paratuberculosis established 100% infection rates, compared to 69% infection following inoculation with a medium dose of the ovine strain. The high susceptibility of deer to the bovine strain of M. avium subsp. paratuberculosis was confirmed by a 50% infection rate following experimental inoculation with a low dose of bacteria (103 CFU/animal). This study is the first to report experimental M. avium subsp. paratuberculosis infection in red deer, and it outlines the strong infectivity of bovine-strain M. avium subsp. paratuberculosis isolates for cervines.
Secreted antigens of Mycobacterium avium subspecies paratuberculosis as prominent immune targets
Willemsen, P.T.J. ; Harders-Westerveen, S.F. ; Dinkla, A. ; Bakker, D. ; Zijderveld, F.G. van; Thole, J.E.R. - \ 2006
Veterinary Microbiology 114 (2006)3-4. - ISSN 0378-1135 - p. 337 - 344.
heat-shock protein - nucleotide-sequence - molecular-cloning - johnes-disease - tuberculosis - gene - expression - reactivity - identification - antibodies
We here describe the identification and characterization of three novel secreted Mycobacterium avium subsp. paratuberculosis antigens of 9, 15 and 34 kDa (Map2609, Map2942c and Map0210c, respectively) by screening a genomic expression library with a serum of a naturally infected clinical cow. The 9, 15 and 34 kDa antigens display strong homology to previously described M. tuberculosis antigens, TB8.4, MPT53 and Erp, respectively. Furthermore, these antigens were shown to be recognized by antibodies from infected cattle, when tested with a limited number of sera from subclinical (n = 7) and clinical (n = 3) infected cattle.
Progressive bovine paratuberculosis is associated with local loss of CD4(+) T cells, increased frequency of gamma delta T cells, and related changes in T-cell function
Koets, A. ; Rutten, V. ; Hoek, A. van; Mil, F. van; Muller, K. ; Bakker, D. ; Gruys, E. ; Eden, W. van - \ 2002
Infection and Immunity 70 (2002)7. - ISSN 0019-9567 - p. 3856 - 3864.
blood mononuclear-cells - lymphoblast proliferative capacity - johnes-disease - monoclonal-antibodies - mycobacterium-paratuberculosis - para-tuberculosis - lymphocytes-t - ovine paratuberculosis - lymph-node - alpha-beta
Bovine paratuberculosis is caused by the infection of young calves with Mycobacterium avium subsp. paratuberculosis, resulting in a chronic granulomatous infection of predominantly the ileum. After an incubation period of 2 to 5 years, the disease becomes progressive in some of the chronically infected, but asymptomatic cows. This results in a protein-losing enteropathy that will ultimately be fatal. A loss of cell-mediated immune responses in symptomatic animals has been described, but no information is available concerning immune reactivity in the intestine. We sought to investigate putative disease status-associated lymphocyte subset distributions and antigen-specific functional characteristics of mononuclear cells isolated from blood, gut-associated lymphoid tissue, and the intestinal walls of 22 cows in different stages of disease and in control animals. The results demonstrated a significant decrease in CD4+ T-cell frequency and a significant increase in TcR1-N12+ T-cell frequency in ileum lamina propria lymphocytes of symptomatic animals compared to the asymptomatic shedders. Immunohistology revealed that there was also an absolute decrease in the number of CD4+ T cells in sections of the lesional ileum. Our findings also indicated that both peripheral and intestinal cell-mediated responses are decreased in symptomatic animals compared to asymptomatic animals. We conclude that the decrease in cell-mediated responses is likely related to a loss of antigen-specific CD4+ T cells, which is most prominent in the lesional ileum from symptomatic animals, thus contributing to the progressive nature of bovine paratuberculosis