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1

Chastel, Michaël Foucras Gilles. "Épidémiologie de la paratuberculose des ruminants conséquences sur les mesures de contrôle et de prévention /." [S.l.] : [s.n.], 2008. http://oatao.univ-toulouse.fr/2081/1/debouch_2081.pdf.

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2

Marcé, Clara. "Modelling the transmission of and effectiveness of control measures for Mycobacterium avium subsp. Paratuberculosis in dairy herds." Rennes 1, 2010. http://www.theses.fr/2010REN1S047.

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Paratuberculosis is a worldwide incurable disease of ruminants resulting in a decrease in milk production and slaughter value. The aim of this thesis was to evaluate the epidemiological and economic effectiveness of selected control programmes in infected dairy herds. A stochastic simulation model has been developed to represent both the population dynamics within a dairy herd and the transmission of Mycobacterium avium subsp. Paratuberculosis (Map). It has been coupled to an existing bioeconomic model. The spontaneous within-herd progression of Map infection after the introduction of one infected cattle in an initially susceptible herd was studied in the absence of control measure. The effect of within-herd contacts on Map spread in a persistently infected herd was investigated. The cost-effectiveness of test-and-cull strategies to control Map infection in dairy herds was assessed. Simulation outcomes put forward that, even when no control measure is implemented, fadeout can occur if less than two clinically affected animals are present. In persistently infected herds, the two main transmission routes are transmission via the environment of the farm and in utero transmission. Isolating calves from their herd mates during the first weeks of age has no significant impact on Map transmission. Limiting or delaying calf exposure to adult faeces and early culling of clinically affected adults are thus recommended to decrease Map prevalence in infected dairy herds. Systematic test-and-cull appears cost-effective if implemented from the day one infected cattle is introduced. The tool designed here is flexible and enables studying other control options within a dairy herd
La paratuberculose est une maladie incurable des ruminants entraînant une diminution de la production laitière et de la valeur de carcasse des animaux infectés. L'objectif de ma thèse est d'évaluer l'efficacité épidémiologique et économique d'actions de maîtrise en troupeaux bovins laitiers infectés. Un modèle de simulation stochastique représentant la dynamique de population d'un troupeau bovin laitier et la transmission indirecte de Mycobacterium avium subsp. Paratuberculosis (Map) a été, élaboré puis couplé à un simulateur bioéconomique existant. L'évolution spontanée de l'infection après I'introduction d'un animal infecté dans un troupeau initialement sensible est étudiée en l'absence d'action de maîtrise. L'effet de la structure de contact sur la transmission de Map est exploré. La rentabilité de stratégies de maîtrise de l'infection est évaluée. Une extinction de l'infection peut survenir lorsque moins de deux animaux cliniquement infectés sont présents en cinq ans, en l'absence d'action de maîtrise. Dans les troupeaux infectés persistants, la transmission in utero et via l'environnement contaminé sont les deux principales voies de transmission. Empêcher le contact précoce entre veaux n'a pas d'impact sur la transmission de Map. Il est recommandé de limiter ou retarder l'exposition des veaux aux fèces des adultes et de réformer rapidement les animaux cliniquement infectés pour réduire la prévalence de l'infection. L'utilisation de tests suivis de réformes mis en place systématiquement dès l'introduction d'un animal infecté semble rentable. L'outil développé ici est flexible et permettra d'étudier d'autres actions de maîtrise en troupeau laitier
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3

Matado, André Filipe Fernandes. "Seroprevalência de paratuberculose em ovinos e caprinos na região do Baixo Alentejo." Master's thesis, Universidade de Évora, 2011. http://hdl.handle.net/10174/15722.

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No presente trabalho verificámos se existia circulação do agente da paratuberculose nas explorações de pequenos ruminantes no distrito de Beja. Avaliou-se a variação da circulação do agente em função das raças, localização geográfica, coabitação com outras espécies e dimensão das explorações. O estudo consistiu na pesquisa serológica que incidiu em 27 explorações de regime semi-extensivo utilizando um teste ELISA em animais com idade superior a 2 anos. Foram analisadas 25 explorações de ovinos de aptidão carne e duas de caprinos. Foram rastreados no total 187 animais, 172 ovinos e 15 caprinos. A seroprevalência aparente de rebanho encontrada foi 14,8%, com intervalo de confiança 5,9 a 32,5%. Na estimativa da seroprevalência real de rebanho este valor sobe para 41,2%, com intervalo de confiança 16,4 a 90,2%. Apenas o factor coabitação dos rebanhos rastreados com rebanhos de bovinos revelou ter significância, podendo ser considerado factor de risco nos rebanhos de pequenos ruminantes; ABSTRACT: In this study we tested the circulation of Paratuberculosis in small ruminant flocks in the district of Beja. We evaluated the variation of the agent circulation with race, geographic location, cohabitation with other species and flocks size. The study consisted of a serological survey in 27 semi-extensive farms using an ELISA test in animals older than 2 years. We surveyed25 sheep flocks designed for meat production and two goats flocks. We screened a total of 187 animals, 172 sheep and 15 goats. The apparent herd prevalence found was 14.8% with a confidence limit from 5.9 to 32.5%. In estimating the real herd prevalence this figure rises to 41.2% with a confidence limit from 16.4 to 90.2%. Only the cohabitation flocks factor with cattle flocks seems to be significant and can be considered a risk factor in small ruminants.
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4

Beard, Philippa M. "Epidemiology and pathogenesis of paratuberculosis." Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/29893.

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Investigations into three aspects of the epidemiology and pathogenesis of paratuberculosis were undertaken - infection of wildlife with Mycobacterium avium subsp paratuberculosis (M. a. paratuberculosis), the early host immune response mounted against organism, and the influence of host genotype on susceptibility to the disease. The pathology of natural rabbit paratuberculosis was investigated and described, with rabbits exhibiting either mild or severe lesions. The changes noted in the severely affected rabbits included the presence of giant cells containing over 50 nuclei and many acid fast bacteria. M. a. paratuberculosis was cultured from the faeces and urine of the naturally infected rabbits, revealing two possible routes of interspecies transmission of the organism. To investigate the impact of natural rabbit paratuberculosis on the disease in ruminant livestock, young calves were inoculated orally with a strain of M. a. paratuberculosis isolated from a naturally infected rabbit. After an incubation period of six months, the organism was recovered from the intestinal tissues of seven out of eight inoculated calves, with three of these calves also exhibiting pathological changes consistent with chronic paratuberculosis, suggesting that M.a.paratuberculosis from rabbits is capable of causing paratuberculosis in cattle. In a parallel experiment, two groups of rabbits were inoculated with either a bovine or leporine derived strain of M. a. paratuberculosis, but no evidence of infection was noted after a six month incubation period, suggesting that further, as yet unidentified factors, are involved in the pathogenesis of paratuberculosis in rabbits. A large survey in rural Scotland revealed M.a. paratuberculosis infection of 10 species of wildlife - fox, stoat, weasel, crow, rook, jackdaw, rat, wood mouse, hare, and badger. The investigations into wildlife reservoirs of M.a. paratuberculosis, the influence of host genes on susceptibility to the disease, and the role of gd T cells in the initial response to M.a. paratuberculosis infection provide new information on the epidemiology and pathogenesis of this disease, and may have a role to play in creating more effective control measures against paratuberculosis.
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5

Sergeant, Evan Stuart George. "Surveillance and risk assessment for ovine Johne's disease in Australia /." [St. Lucia, Qld.], 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17427.pdf.

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6

Okafor, Chika Chukwunonso. "Detection of Mycobacterium avium subsp. paratuberculosis IgG by a conductometric biosensor an aid in diagnosis of Johne's disease /." Diss., Connect to online resource - MSU authorized users, 2008.

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7

Nyange, John Frederick Charles. "Studies of paratuberculosis of red deer." Thesis, University of Edinburgh, 1991. http://hdl.handle.net/1842/30592.

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The mesenteric lymph nodes of 167 apparently healthy slaughtered red deer (18-24 m.o. old) from a herd in which several cases of paratuberculosis had occurred were examined by histopathology. An infection rate of 38% was found suggesting a high susceptibility of deer to paratuberculosis. Vaccination of all day-old calves with a standard bovine paratuberculosis vaccine stopped the occurrence of disease in yearlings and reduced significantly the rate (64/167 vs 32/201 p < < 0.001) and severity (41/64 vs 4/32 p < < 0.001) of infection as assessed by lymph node pathology of normal slaughter deer. The pathological lesions of paratuberculosis as observed in naturally and experimentally infected red deer, were inconsistent. Nevertheless, the specific lesions were basically similar to those of the disease in other ruminants, especially sheep and goats, where in severe cases, focal necrosis, mineralization and reactive fibrosis accompanied the granulomatous lesions. The clinical and pathological findings of avian tuberculosis in red deer, in a single natural case and in experimentally infected animals, were similar to those of paratuberculosis but they were more severe and widely disseminated into organs other than the intestines and related lymph nodes. The pathogeneses of paratuberculosis and avian tuberculosis in very young deer and very young sheep were shown to be similar by experimental infection. However the two infections progressed more rapidly and severely in deer than in sheep, with avian tuberculosis being more acute and severe than paratuberculosis. Fifty-four isolates of M. paratuberculosis from red deer were shown by cultural characterization to be similar to one another and to isolates of the organisms from a cow and a goat. Analysis of 14 of the isolates by SDS-PAGE and Western blotting did not distinguish them from one another or the bovine and caprine isolates. Despite many similarities in their polypeptide patterns, they were shown to differ from an atypical isolate of mycobacterium (M928), a commercial protoplasmic antigen (PPA-3) and M. avium isolates. Further analysis of six of the isolates by genomic DNA RE digestion with BamHI, PstI and EcoRI and hybridization with 32P-PCR279 (a DNA probe specific for M. ptbc), showed them to be homologous to both the bovine and caprine isolates when using BamHI and PstI, and only to the caprine isolate when using EcoRI. In conclusion, paratuberculosis of deer is basically similar to that of other ruminants, especially sheep and goats. However the short course and severity of disease in young animals is novel, contrasting with cattle, sheep and goats in which older animals become clinically affected.
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8

Pillars, Roxanne Bee. "Control strategies for Johne's disease in dairy cattle." Diss., Connect to online resource - MSU authorized users, 2008.

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Thesis (PH.D.)--Michigan State University. Large Animal Clinical Sciences, 2008.
Title from PDF t.p. (viewed on Aug. 28, 2009) Includes bibliographical references (p. 260-281). Also issued in print.
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9

Bush, Russell David. "The biological and financial impact of Ovine Johne's disease in Australia." Connect to full text, 2005. http://hdl.handle.net/2123/893.

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Thesis (Ph. D.)--University of Sydney, 2006.
Title from title screen (viewed 30 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Veterinary Science. Degree awarded 2006; thesis submitted 2005. Includes bibliographical references. Also available in print form.
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10

Antognoli, Maria Celia. "Screening and diagnosis of paratuberculosis in young and adult dairy cattle." Access citation, abstract and download form; downloadable file 6.78 Mb, 2004. http://wwwlib.umi.com/dissertations/fullcit/3131653.

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11

Lefrançois, Louise. "Etude des adhésines HBHA et LBP impliquées dans l'interaction de Mycobacterium avium ssp. paratuberculosis avec les cellules épithéliales intestinales, cibles privilégiées de la bactérie in vivo." Thesis, Tours, 2012. http://www.theses.fr/2012TOUR4020/document.

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Mycobacterium avium ssp. paratuberculosis (Map), agent étiologique de la paratuberculose, a évolué en deuxtypes dénommés, S pour« Sheep » et C pour « Cattle ». L’intestin grêle est le site primaire de l’infection à Map mais les mécanismes moléculaires impliqués dans l’implantation du bacille restent largement méconnus. L’objectif de mon projet de thèse visait à identifier et caractériser les adhésines exprimées par Map par des approches génétiques et biochimiques. J’ai ainsi purifié la HBHA et la LBP par chromatographie d’affinité puis les ai identifiés en spectrométrie de masse. L’originalité de ce travail repose sur le polymorphisme de ces adhésines observé entre les souches de type C et S. Cette variabilité a été mise en évidence sur le domaine d’interaction avec les sucres sulfatés de la cellule hôte influençant l’affinité des adhésines pour l’héparine. Ce travail de thèse a permis de caractériser pour la première fois ces deux adhésines produites par Map. Le polymorphisme de la HBHA et de la LBP, discriminant les types C et S, ouvre de nombreuses perspectives sur l’évolution de l’espèce M. avium et le rôle de ces adhésines sur le tropisme intestinal, la préférence d’hôte de Map ou encore leur potentiel diagnostic
Mycobacterium avium subsp. paratuberculosis (Map), the etiological agent of paratuberculosis, has evolved into two types called, S for "Sheep" and C for "Cattle." The small intestine is the primary site of Map infection but the molecular mechanisms involved in the establishment of bacilli are still unknown. The aim of my thesis was to identify and characterize the adhesins expressed by Map by genetic and biochemical approaches. I purified HBHA and LBP by affinity chromatography then identified them by mass spectrometry. The originality of this work is based on the polymorphism of these adhesins observed between strains of type C and S. This variability has been demonstrated in the binding domain involved in interaction with sulfated sugars of host cell influences adhesins affinity for heparin. This thesis has characterized for the first time these two adhesins produced by Map. Specific polymorphism highlighted related to the evolution of the species avium, opens large number questions on their role on the pathogenesis of Map including the cellular tropism, host preference or interest of these antigens to improve diagnostic
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12

Gomes, Marcos José Pereira. "Aspectos epidemiológicos da paratuberculose bovina no Rio Grande do Sul." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2002. http://hdl.handle.net/10183/3448.

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Descrevem-se os achados clínicos e patológicos da paratuberculose em uma criação intensiva de bovinos de leite no municí pio de Capela de Santana, RS. Os sinais clínicos foram observados em oito de um total de 345 bovinos, consistindo em diarréia crônica refratária aos tratamentos, emagrecimento progressivo e queda na produção de leite. As principais lesões macroscópicas, observadas nos oito animais necropsiados, incluíam intestino delgado com acentuado espessamento da parede e superfície mucosa de aspecto reticulado, semelhante às circunvoluções cerebrais, lesão essa perceptível, através da serosa. A luz intestinal estava preenchida com conteúdo fluido e de aspecto leitoso. Os vasos linfáticos do mesentério mostravam-se mais evidentes sendo que alguns tinham aspecto varicoso. Os linfonodos mesentéricos estavam aumentados de volume e, ao corte, fluía grande quantidade de líquido leitoso. Focos de mineralização foram observados na íntima das artérias, nas válvulas cardíacas e na serosa do rúmen. As principais lesões macroscópicas incluíam enterite, linfadenite e linfangite granulomatosa caracterizada por infiltrado inflamatório com macrófagos, células gigantes de Langhans que continham grande quantidade de bacilos álcool-ácido-resistentes. As lesões vasculares consistiam em degeneração e mineralização das túnicas í ntimas e média das artérias de grande calibre associada a proliferação de colágeno. Havia calcificação da serosa do rúmen atrofia hepatocelular difusa e hepatite granulomatosa multifocal. O M. avium subsp. paratuberculosis (Map) foi isolado em amostras de intestino e linfonodos de 8 vacas Holandesas (3,5%) com doença de Johne, dentre 229 amostras cultivadas provenientes de um rebanho leiteiro. Amostras inoculadas em HEYM com micobactina produziram colônias identificadas como Map, segundo as caracterí sticas fenotí picas próprias como: crescimento lento, coloração álcool-ácido-resistente (A.A.R.) e dependência a micobactina. O laboratório de Referência da OIE confirmou a amostra isolada. O M. avium subsp. paratuberculosis (Map) foi isolado em amostras de intestino e linfonodos de 8 vacas Holandesas (3,5%) com doença de Johne, dentre 229 amostras cultivadas provenientes de um rebanho leiteiro Amostras inoculadas em HEYM com micobactina produziram colônias identificadas como Map, segundo as caracterí sticas fenotí picas próprias como: crescimento lento, coloração álcool-ácido-resistente (A.A.R.) e dependência a micobactina. O laboratório de Referência da OIE confirmou a amostra isolada. Não houve isolamento do agente em 221 amostras intestinais quando processadas, após 2 anos de sua colheita. O teste de IDGA aplicado como “screening”, detectou 26 vacas (11,4%) positivas, dentre 228 animais testados e sacrificados em matadouro. O teste de ELISA adsorvido, utilizando o antí geno PPA-3 detectou 125 (39,8%) amostras positivas. O ELISA não adsorvido detectou mais 32 (10,1%) reagentes positivos, dentre os 314 bovinos testados. A prevalência da infecção causada pelo Map em 36 rebanhos leiteiros procedentes de 25 municí pios do Rio Grande do Sul foi estimada em 44,6% das 1316 amostras testadas. A infecção foi identificada em 35 (97,2%) dos 36 rebanhos testados e presentes em todos os municí pios incluí dos. A ocorrência da doença de Johne foi enfatizada, tanto a forma clí nica quanto a infecção subclí nica no Rio Grande do Sul, sugerindo a adoção de medidas de controle sejam aplicadas na proteção dos rebanhos leiteiros nacionais.
The clinical and pathological aspects of bovine paratuberculosis in a dairy herd in the county of Capela de Santana, Rio Grande do Sul, southern Brazil are described. Clinical signs in eight cows out 345 cattle included chronic diarrhea refractory to treatment, progressive emaciation and decreased milk production. Necropsy findings included severe and diffuse thickening of the mucosa of the small intestine with exaggerated reticular pattern, reflected in the serosal surface, similar to cerebral gyri. Intestinal loops were filled with whitish watery contents. The lymphatic vessels of the intestinal serosa and of the mesentery were thickened and tortuous. The mesenteric lymph nodes were enlarged and, on cut surface, there were oozing of milky fluid. Plaques of mineralization were evident in the intima of larger arteries, in the endocardium of the heart valves and in the ruminal serosa. There was also edema of abomasal folds and atrophy of caudate lobe of the liver. The main histopathological findings were granulomatous enteritis, lymphadenitis and lymphangitis. The inflammatory infiltrate was composed of macrophages, epithelioid cells and Langhan`s giant cells containing large numbers of acid-fast bacilli. Vascular lesions included degeneration, calcification and collagen proliferation of the intima and media of larger arteries. Other microscopic lesions included calcification of the ruminal serosa, diffuse hepatocellular atrophy and multifocal granulomatous hepatitis. M. avium subsp. paratuberculosis (Map) was isolated from intestines and lymph nodes samples obtained from 8 Holstein cows (3.5%) with Johne’s Disease among 229 inoculated samples from a unique dairy herd in Rio Grande do Sul State, South Brazil. Cultures on HEYM supplemented with mycobactin yielded colonies identified like Map by phenotypic properties: Slow growth, acid-fast stain and mycobactin dependency. OIE Reference Laboratory in Argentine confirmed the strain like Map. The attempts to isolate the agent from 221 intestinal samples processed after 2 years were unsuccessful. The AGIDT applied as a screening test detected 26 positive cows (11.4%) among 228 tested animals at slaughterhouse. The absorbed ELISA test using PPA-3 antigen detected 125 positive animals (39.8%) and 47 (14.9%) suspect samples among 314 animals tested. Nonabsorbed ELISA test detected more 32 (10.1%) positive animals and 18 (5.7%) suspect samples than absorbed ELISA test. The prevalence of infection caused by Map was estimated in 35 bovine dairy herds in Rio Grande do Sul State by absorbed ELISA using PPA-3 commercial antigen. The ELISA test identified 558 positive (44.6%) animals among 1316 samples tested. The infection was detected in 35 dairy herds (97.2%) among 36 tested and was present in all 25 countries performed. The infection by Map was disseminated in dairy herds in Rio Grande do Sul State. It’ s emphasized the occurrence of clinical and subclinical forms of Johne’ s disease in Rio Grande do Sul and should be necessity the adoption of control measures in the protection of National dairy herds.
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13

Bulander, Korinna. "Vergleichende Untersuchungen zum Nachweis von Mycobacterium avium ssp. paratuberculosis in Milchrinderbeständen." Giessen VVB Laufersweiler, 2009. http://d-nb.info/995997667/04.

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14

Dudemaine, Pier-Luc. "Étude de l'état immunitaire des vaches laitière atteintes de la paratuberculose bovine." Mémoire, Université de Sherbrooke, 2013. http://hdl.handle.net/11143/6298.

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La paratuberculose bovine, ou maladie de Johne, est une maladie inflammatoire intestinale chronique provoquant d’importantes pertes économiques chez les producteurs de ruminants du monde entier. Que ce soit chez la vache laitière ou de boucherie, ces pertes sont causées majoritairement par une diminution de la capacité de reproduction, la baisse de production laitière et l’amaigrissement des vaches qui perdent ainsi beaucoup de valeur à l’abattage, en plus d’être sujettes à une réforme précoce. Outre les pertes économiques, le potentiel de transmission à l’humain est un facteur non négligeable en plus d’un risque de contamination de la chaîne alimentaire. Cette maladie est causée par une bactérie intracellulaire obligatoire nommée Mycobacterium avium subspecies paratuberculosis (MAP). II n’existe actuellement aucune stratégie efficace pour combattre l’infection chez les animaux atteints. L’évolution lente de la maladie fait en sorte que les signes cliniques apparaissent tardivement, soit plusieurs années (4 à 7 ans) après l’infection initiale. Au cours de cette progression, les animaux infectés commencent à excréter le pathogène dans leur environnement. Les animaux atteints deviennent infectieux et peuvent contaminer d’autres congénères, ainsi que leur propre veau. Afin de permettre aux producteurs d’éliminer les vaches atteintes avant qu’elles n’atteignent ce stade, il s’avère important d’établir un diagnostic précoce. Actuellement, ce n’est qu’en phase sous-clinique avancée que les tests diagnostiques sont plus sensibles, soit 2 à 3 ans après le début des excrétions fécales chez les animaux infectés. L'incompréhension du manque de sensibilité des tests de dépistage et de l'évolution de cette maladie justifient les efforts de recherche dans ce domaine en vue de mieux comprendre les réponses immunitaires impliquées dans cette maladie. En effet, une meilleure connaissance des processus d’inflammation chronique pourrait aider à développer des outils diagnostiques complémentaires. Nos résultats suggèrent une dérégulation de la réponse immunitaire. Ainsi, en étudiant les composantes et caractéristiques du sang provenant de vaches infectées, il nous a été possible d’observer que les niveaux de cytokines plasmatiques telles l’interleukine 17 et l'ostéopontine se trouvent sécrétées à différents niveaux chez les vaches atteintes de paratuberculose bovine. De plus, l'analyse de la capacité de leur sérum à soutenir efficacement la prolifération des cellules mononucléées du sang périphérique révèle que le sérum de vaches infectées interfère pour atténuer la prolifération cellulaire. II semble qu’un constituant du sérum provoque une diminution de la réponse immunitaire chez les vaches malades. Les résultats offrnt une appréciation des dérèglements immunitaires provoqués par la paratuberculose bovine.
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Cruz, Catarina Lourenço da. "Paratuberculose: associação dos dados clínicos com os dados de rejeição de carcaças de bovino no matadouro por caquexia." Master's thesis, Universidade de Évora, 2015. http://hdl.handle.net/10174/14002.

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O presente relatório refere-se às atividades no estágio curricular do Mestrado Integrado em Medicina Veterinária. Apresentam-se as atividades no âmbito de sanidade animal, clínica de espécies pecuárias e inspeção sanitária. No âmbito da sanidade animal foram acompanhados os procedimentos do plano de erradicação da brucelose nos Açores. Foram ainda acompanhados casos clínicos de várias áreas de intervenção, principalmente em bovinos de leite. A componente de inspeção sanitária foi desenvolvida no Matadouro de São Miguel, onde foram observados e praticados os procedimentos de inspeção sanitária. Como tema de desenvolvimento optou-se pela paratuberculose (PT) bovina que se manifesta pelo emagrecimento progressivo e diarreia crónica. Colheram-se amostras de sangue, junção ileocecal e fezes a 116 bovinos que apresentavam sinais clínicos compatíveis com PT, sendo que 66,38% dos animais tiveram uma das análises (ELISA ou histopatologia) positivas; ABSTRACT: :“Bovine paratuberculosis association between clinical data and rejection data in slaughterhouse for cachexia.” This document describes the activities during the curricular traineeship of the Master Degree in Veterinary Medicine. Activities carried out on animal health, food ani-mal clinic and meat inspection are presented in this report. In relation to animal health the procedures from the plan of eradication of brucel-losis in Azores as well as the clinical cases from several areas of intervention, especially in dairy cattle were followed. The procedures for meat inspection were learned at São Miguel Slaughterhouse. The subject chosen was bovine paratuberculosis (PT). This disease is manifested by progressive weight loss e chronic diarrhea. In the present study 116 cattle samples (blood, ileo-ceacal junction a feces) were collected from animals with clinical signs com-patible with PT. The results show that 66,38% had one of the tests (ELISA or histopathol-ogy) positive. More studies must be carried out to acknowledge the disease behavior in São Mi-guel Isle. Mais estudos devem ser feitos a fim de averiguar o comportamento da doença na ilha de São Miguel
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16

Zanella, Ricardo. "Genetic association of tolerance to Johne's disease." Pullman, Wash. : Washington State University, 2008. http://www.dissertations.wsu.edu/Thesis/Fall2008/r_zanella_120308.pdf.

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Thesis (M.S. in animal sciences)--Washington State University, December 2008.
Title from PDF title page (viewed on Feb. 19, 2009). "Department of Animal Sciences." Includes bibliographical references.
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17

Elze, Julia. "Nachweis von Mycobacterium avium ssp. paratuberculosis bei Schlachtrindern." Hannover Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/1000021831/34.

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18

Smeed, J. "Molecular definition of paratuberculosis pathologies by functional genomics." Thesis, University of Edinburgh, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662050.

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Paratuberculosis (Johne’s disease) is a chronic intestinal disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Three forms have been described in sheep – multibacillary, paucibacillary and asymptomatic. Real-time RT-PCR (qPCR) and microarray analyses were used to compare gene expression in ileal tissue from sheep with the three forms of the disease to try to understand the immune responses underpinning these three defined pathologies. All animals from the infected flocks were IS900 positive by qPCR and therefore infected with MAP. Asymptomatic sheep had no clinical signs of disease, showed no evidence of acid-fast bacteria (ZN-), exhibited normal histology of the terminal ileum and were seronegative. Paucibacillary sheep were ZN- and showed lymphocyte/eosinophil infiltrate into the lamina propria. 2/6 of the paucibacillary animals were seropositive. Multibacillary sheep had high numbers of ZN+ bacteria associated with infiltrating sheets of epithelioid macrophages and were seropositive. Control sheep were IS900 negative and thus uninfected with MAP. qPCR experiments confirmed that pauci- and multibacillary forms are linked to the differential expression of IFNγ and IL-10 respectively. Increased levels of the proinflammatory cytokines IL-1β, IL-8, IL-18, TNFα and TRAF-1, indicative of persistent inflammatory lesions, were observed in clinical tissues. IL-3 was detected at low levels in all infected animals but never in uninfected control samples. IGFBP-6 was upregulated and CXCR4 downregulated in paucibacillary samples compared to multibacillary samples. Microarray experiments discovered 64 differentially expressed genes. Ten genes were found to be differentially expressed in infected tissue compared to uninfected controls, and a further eight in clinical tissues compared to uninfected controls. Fifteen genes were differentially expressed in clinical tissue compared to asymptomatic tissue. Six genes were quantified by qPCR and validated in microarray data well. Pathway analysis of the microarray data identified several immune pathways that are involved in pathogenesis. Infected tissues displayed upregulation of the genes involved in TCR signalling and complement activation, and downregulation of MHC class II genes. In addition, clinical tissues displayed upregulation of genes involved in the JAK-STAT and TLR2 signalling pathways, NK cell cytotoxicity and antibody production. Multibacillary tissues also displayed upregulation of genes involved in leukocyte migration. Overall, these data confirm that multibacillary pathology is linked to type 2 and paucibacillary pathology is linked to type 1 immune responses and identify novel genes and gene pathways for future analyses.
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19

Mathie, Heather. "Early macrophage response to Mycobacterium avium subspecies paratuberculosis." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31378.

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Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic enteritis that has a damaging economic and welfare impact on the livestock industry. Johne's disease in cattle is known to reduce milk yield and carcass value, making it of economic concern to both dairy and beef farmers. In addition, there is cause for concern regarding zoonotic transmission, as there is an unconfirmed but potential relationship between MAP infection and human Crohn's disease, which presents similar clinical symptoms. MAP is most often contracted by neonates through the faecal-oral route, but can also be spread through contact with contaminated milk and colostrum, as well as in utero. Once the host receives an oral dose, the bacteria traverse the gut epithelium and are phagocytosed by gut macrophages residing in the lamina propria and Peyer's patches. MAP are able to evade the macrophage response by resisting intracellular degradation within phagosomes. Infected macrophages respond to the infection by secreting several pro-inflammatory cytokines that drive the downstream immune response and granuloma formation. This work aimed to elucidate key early responses of bovine monocyte derived macrophages (MDM) to MAP infection, and determine the reliability of using the reference strain, K10 (which is likely to have undergone lab adaptation) to model the infection in vitro, by comparing the MDM response to K10 with the response to a recent clinical isolate, C49. At a multiplicity of infection of 5 (MOI 5), there was a significant decrease in K10 intracellular survival (~90%), compared to C49 intracellular survival, over a 24 hour infection time-course. This suggests that K10 may have lost some virulence mechanism through lab adaptation. Understanding the mechanisms of how MDM respond to these two strains could be informative for the design of targeted vaccines When further investigating the MDM response to both strains, it was found that, at MOI 5, MDM infected with K10 secreted higher levels of IL-1β and IL-10, compared to MDM infected with C49. Both cytokines are associated with mycobacterial infection and could perhaps indicate that MDM are more responsive to the K10 strain at early time-points. In addition, MDM infected with K10 produced significantly higher levels of reactive nitrogen species (RNS). RNS are antimicrobial products that can destroy invading pathogens, and have been shown to have bactericidal effects on MAP. The production of RNS could, therefore be a potential mechanism by which MDM are able to kill K10 more efficiently than C49. An additional aim of this project was to understand the importance of the route of phagocytosis in determining the outcome of MAP infection. MDM express several phagocytic receptors, including Fc receptors (FcRs), complement receptors (CR), Ctype lectin receptors and scavenger receptors. This project mainly focused on the role of the mannose receptor (MR) on bacterial uptake and downstream immune responses, as past studies have suggested that other species of mycobacteria such as M. tuberculosis, target the mannose receptor in order to regulate macrophage immune responses. Blocking the MR reduced intracellular survival for both strains of MAP; however, the mechanism by which the MR influences intracellular survival remains poorly understood The effect of opsonisation on MAP prior to uptake by phagocytic cells was also investigated, as presence of opsonins, such a complement proteins and antibody, can change the mechanism by which pathogens are phagocytosed. MAP were incubated in serum from either MAP- negative or MAP- positive cattle, prior to infection and the percentage uptake and survival assessed by performing colony counts. Opsonisation in serum from Johne's negative cattle resulted in marked increase in MAP uptake but not intracellular survival, whereas opsonisation in serum from Johne's positive cattle did not increase uptake but decreased the intracellular survival rate by 24 HPI. This finding highlights a potential protective role of antibody early in the infection process, and could significantly impact how the infection is modelled in future, as anti-MAP antibody may be present in contaminated milk at the point of infection. Taken together, the data presented in this thesis show that bacterial strain has a significant impact on MDM response to MAP infection, which may have important implications for the interpretation of previous studies and the design of future studies investigating host-pathogen interactions in the context of paratuberculosis. Additionally, this work has shown that RNS production and the mechanism of uptake can affect intracellular survival rates, and although this needs further investigation, the findings could have implications for the design of future vaccines.
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Schulze, Martina. "Untersuchungen zur Stammdifferenzierung von Mycobacterium avium subsp. paratuberculosis /." Berlin : Mbv, Mensch-und-Buch-Verl, 2009. http://d-nb.info/995894671/04.

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21

Herthnek, David. "Molecular diagnostic methods for Mycobacterium avium subsp. paratuberculosis : more than a gut feeling /." Uppsala : Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2009. http://epsilon.slu.se/200920.pdf.

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22

Mathevon, Yoann. "Utilisation des analyses en mélanges pour l'évaluation et le suivi du statut sanitaire des troupeaux : application à la paratuberculose des ovins." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30044/document.

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La paratuberculose est une maladie enzootique contagieuse des ruminants due à Mycobacterium avium ssp. paratuberculosis (Map). La longue période d'incubation et les faibles performances diagnostiques des tests limitent l'efficacité des plans de maîtrise. Les grands effectifs des troupeaux ovins limitent l'approche par dépistage individuel exhaustif, et les plans de maîtrise s'orientent vers la vaccination, dont les effets n'ont pas été évalués dans les troupeaux français. Á partir d'échantillons de sérum et de fèces de près de 4000 brebis issues de 30 élevages du Lot, les performances diagnostiques de deux trousses sérologiques ELISA et d'une qPCR sur fèces ont été estimées par des modèles à classes latentes bayésiens et fréquentistes. Nos résultats confirment la faible sensibilité et le défaut de spécificité des sérologies ELISA pour la détection des ovins infectés ; la qPCR présentant de meilleures performances diagnostiques. Par ailleurs nous avons évalué les performances diagnostiques relatives des ELISA et de la qPCR appliquées à des mélanges d'échantillons. Dans les deux cas les animaux forts répondeurs étaient détectés de façon systématique, les animaux faiblement positifs étant détectés de façon moins constante. Sur la base de simulations, nous avons évalué les performances des stratégies de dépistage et de suivi basées sur les analyses de mélanges d'échantillons à l'échelle des troupeaux. Alors que la sérologie ELISA est apparue insuffisamment spécifique, l'analyse de mélange de fèces par qPCR semble être une approche prometteuse, permettant de détecter des faibles prévalences d'infection. Enfin les travaux menés dans les troupeaux vaccinés ont précisé dans quelles mesures leur situation épidémiologique pouvait être approchée par l'emploi d'analyses en mélanges
Paratuberculosis is a contagious enzootic disease in ruminants caused byMycobacteriumavium ssp. paratuberculosis (Map). The long incubation period and the low informative values of antemortem diagnostic tests limit the effectiveness of control plans. In large sheep flocks, exhaustive individual testing is unfeasible and control plansmainly focus on vaccination, the effects of which have not yet been evaluated in French flocks. Using blood and feces samples from nearly 4000 ewes in 30 sheep flocks from the French department of Lot, the diagnostic performances of two serum ELISA and one fecal qPCR kits were estimated using bayesian and frequentist latent class modeling. Our results confirm the low sensitivity and non-perfect specificity of serum ELISA for the detection of subclinically infected animals, while the diagnostic performances of fecal qPCR were better. We also evaluated the relative diagnostic performances of pooled-sample analysis for both tests. Highly qPCR/ELISA positive samples were invariously detected while low positive ones were associated with lower detection rates. The flock-level epidemiological performances of screening strategies based on pooled-sample analysis were evaluated by simulation studies. Pooled serum ELISA appeared lowly specific. Conversely, pooled fecal qPCR appeared promising, allowing the detection of low infection prevalence. Finally, the work carried out in the vaccinated flocks made it possible to better know their epidemiological status and to specify to what extent it could be approached using pooled-sample analysis
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23

Creignou-Mercier, Pascale. "Bases épidémiologiques pour la maîtrise de la paratuberculose caprine." Rennes 1, 2010. http://www.theses.fr/2010REN1S110.

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L’objectif était de produire des connaissances épidémiologiques descriptives pour la conception ultérieure de plans de maîtrise de l’infection des caprins par Mycobacterium avium subspecies paratuberculosis. Une enquête sérologique a permis de confirmer que l’infection par Map était très répandue dans les troupeaux caprins français, avec une prévalence vraie estimée à 63%. La détection des animaux infectés peut être réalisée par un test ELISA, dont la sensibilité et la spécificité ont été estimées à respectivement 53 et 100%. Mais les qualités des tests varient en fonction de l’âge des animaux et les meilleures valeurs ont été obtenues pour les tests ELISA sur des animaux de 2-3 ans. Pour la détection des animaux excréteurs, la PCR est le test le plus précoce (à partir de 8 mois). Comparé à la détection des animaux par PCR, le test de dosage de l’IFNγ a une sensibilité estimée à 49% et le test ELISA a une sensibilité estimée à 29%. Les apports et limites des résultats produits sont discutés dans la perspective de l’élaboration ultérieure d’actions de maîtrise et des perspectives de recherche complémentaires sont avancées
This study aimed at providing descriptive epidemiological knowledge about the infection of goats by Mycobacterium avium subspecies paratuberculosis, in order to design control schemes. A serological study confirmed that Map infection was widespread in goat herds in France (true prevalence estimated to 63%). Detection of infected animals can be made by ELISA, with a sensitivity of 53% and a specificity of 100%. Best values for ELISA tests were obtained for goats aged 2-3 years. For detection of infectious animals, PCR was the earliest test (from 8 months of age). With PCR as reference test, sensitivities for IFNγ test and ELISA test were estimated to 49 and 29%, respectively. Specificities for the 2 tests were estimated to 100%. Lastly, results are discussed in the perspective of the implementation of infection control schemes and further research topics are proposed
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24

Turenne, Christine. "The evolution of the pathogen «Mycobacterium avium» subsp «paratuberculosis»." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32284.

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The genus Mycobacterium is best recognized for its pathogens M. tuberculosis and M. leprae, the etiologic agents of Tuberculosis and Leprosy. Sequencing of their genomes has revealed an evolutionary process of reductive genomics. Another common species, the M. avium complex (MAC), consists of both environmental isolates that can cause opportunistic infection in humans as well as pathogenic isolates that cause disease primarily in birds and livestock. The basis of this variation in disease phenotypes is unknown. Two genome sequences representing a pathogen of cattle, M. avium subsp. paratuberculosis (MAP) and an opportunistic isolate from a human (M. avium subsp. hominissuis) have served as the foundation for the comparative genomics of MAC. This is complicated by a level of genetic variability one log greater than found within the M. tuberculosis complex (MTBC), and by the existence of other MAC subsets beyond the two sequenced strains. In this thesis, I set out to define the phylogenetic relationships of the various members of MAC and explore the evolutionary processes that led to the emergence of the pathogenic species MAP. An identification scheme was developed to unambiguously brand subsets of MAC, a tool lacking in the past thus hampering data interpretation. Expansion to a multilocus sequence analysis (MLSA) system revealed that the MAC consists of a highly variable group with most of the genotypes belonging to what is considered to be the environmental subset. However, both the avian and MAP pathogens manifested as two separate clones that have independently evolved from their larger subset. The distribution and directionality (insertion or deletion) of large se
Le genre Mycobacterium est mieux reconnu pour ses espèces pathogènes M. tuberculosis et M. leprae, les agents étiologiques de la tuberculose et de la lèpre. Le séquençage de leur génome a indiqué un processus évolutionnaire de réduction génomique. Des autres espèces communes, le complexe M. avium (MAC) est composé de souches environnementales qui peuvent causer des infections opportunistes chez l'homme aussi bien que de souches pathogènes qui causent la maladie principalement chez les oiseaux et le bétail. La base de cette variation phénotypique est inconnue. Deux séquences génomiques représentant le pathogène de bétail M. avium subsp. paratuberculosis (MAP) et un isolat opportuniste d'humain (M. avium subsp. hominissuis) ont servi de base pour la génomique comparative du MAC. Ceci est compliqué par un niveau de variabilité génétique d'un ordre logarithmique plus grand que celui qui se trouve dans le complexe de M. tuberculosis (MTBC), et par l'existence d'autres sous-ensembles de MAC au-delà des deux souches séquençées. Dans cette thèse, je cherche à définir les rapports phylogénétiques des divers membres du MAC et à explorer les processus évolutionnaires qui ont mené à l'apparition de l'espèce pathogène MAP. Une technique d'identification a été développée pour déterminer clairement les sous-ensembles de MAC, un outil dont l'absence par le passé limitait l'analyse des données. La possibilité d'utiliser un système d'analyse par séquençage multi-locus (MLSA) a révélé que le MAC est composé d'un groupe hautement variable avec la plus grande partie des génotypes appartenant à ce que l'on considère comme étant le$
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25

Rumsey, John. "SURVIVAL OF MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS IN THE POL." Master's thesis, University of Central Florida, 2004. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3554.

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Mycobacterium avium subspecies paratuberculosis (map) is an intracellular pathogen that is known to parasitize macrophages and monocytes. Map infiltrates gastrointestinal tract host tissue where it is the known etiological agent of johne's disease in ruminants and implicated in the etiology of crohn's disease in humans. Map's ability to survive within macrophages enables it to disseminate throughout the rest of the host, possibly infecting other circulating blood leukocytes. In this study, the survival and fate of map strain atcc 43015 (human isolate) following phagocytosis was determined using in vitro murine macrophage cell line j774a.1 and polymorphonuclear cells (pmnc's) from five crohn's disease patients. Pmnc's from three healthy individuals and two ulcerative colitis patients, as well as escherichia coli (atcc 11303) and mycobacterium tuberculosis strain h37ra (atcc 25177), were included as controls (moi 10:1). Maturation of the phagosome was determined by evaluating the presence of stage specific markers on the surface of the phagosomal membrane. The endosomal protein, transferrin receptor, and the lysosomal marker, lamp-1, were then immunostained with cy-5 conjugated secondary antibodies, and colocalization of bacteria with each marker was evaluated separately using confocal scanning laser microscopy (cslm). In both tissue models, colocalization of viable map and m. Tuberculosis with the early endosomal marker, transferrin receptor occurred with an estimated five fold higher frequency than did association with the late lysosomal marker, lamp-1, as compared to live e. Coli, and all dead bacterial species. Using differential live/dead staining and fluorescent microscopy, survival of m. Tuberculosis and map was estimated at 85% and 79%, respectively compared to only 14% for e. Coli. The outcome was similar for both tissue culture and pmncs from all patients tested, suggesting that map and m. Tuberculosis can survive readily in both cell types, and regardless of the disease state of the host or the killing power of the cell. Map's survival appears to mimic m. Tuberculosis', suggesting the ability to resist phagolysosome fusion, by maintaining association with the early endosomes. Overall, the data confirms map virulence in host human blood leukocytes.
M.S.
Department of Molecular Biology and Microbiology
Burnett College of Biomedical Sciences
Molecular Biology and Microbiology
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26

Sánchez, Rosales Lilian Giovanna. "Paratuberculosis bovina: diagnóstico, prevención y control en hatos lecheros." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2019. https://hdl.handle.net/20.500.12672/11299.

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La paratuberculosis bovina es una enfermedad infecciosa presente en nuestro país, que se caracteriza por una enteritis crónica debilitante en bovinos adultos. Causa grandes pérdidas económicas para los ganaderos debido al descarte prematuro de los animales afectados y la disminución en la producción de carne y leche. Actualmente, sólo 22 países cuentan con un programa formal de control y eliminación de la enfermedad, la mayoría de Europa. En sur y Centroamérica, el 76% de los países no cuentan con programas oficiales de control de esta enfermedad. El diagnóstico de paratuberculosis es complicado debido a las características del agente patógeno, el largo período de incubación y el cambio en la respuesta inmune. La ausencia de una técnica de diagnóstico con alta sensibilidad y especificidad en las diferentes fases de la enfermedad es uno de los principales problemas para la determinación de la prevalencia, para el control y eliminación de la paratuberculosis bovina en los establos lecheros. Por ahora, la prueba de ELISA es el método de diagnóstico más económico y práctico de realizar en campo, pero debe complementarse con otra prueba adicional tal como PCR, y se debe establecer un protocolo que aplique ambas técnicas de forma rutinaria, recomendablemente cada seis meses, para detectar los animales positivos a la enfermedad. Los bovinos con enfermedad clínica y los que salgan positivos a ELISA en tres veces consecutivas o a PCR en cualquier momento deben ser eliminados del hato. Como medida de control, la formación de un hato paralelo puede ser una buena alternativa para originar un hato libre de la enfermedad a partir de un hato infectado. El ternero recién nacido debe ser separado inmediatamente después de nacer y alimentado con calostro y leche de vacas negativas a paratuberculosis. Estos animales del nuevo hato, negativos a la enfermedad, deben ser sometidos a estrictas medidas de manejo y bioseguridad.
Trabajo de suficiencia profesional
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27

Bush, Russell David. "The Biological And Financial Impact Of Ovine Johne’s Disease In Australia." University of Sydney, 2006. http://hdl.handle.net/2123/893.

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Doctor of Philosophy(PhD)
This study was conducted to provide accurate information about the impact of OJD on sheep mortality and financial status on infected farms in Australia. Industry considered this research to be important because little credible information was available regarding the magnitude of the OJD problem and the responses required to control and manage OJD in southern Australia. This 3-year study, conducted on 12 OJD-infected farms in southern NSW, commenced with a 12-month observational study in 2002. During this year OJD mortality estimates were derived from farm records (livestock inventories) and quarterly farm visits (necropsy inspections). Questionnaires, climatic records and pasture samples enabled a detailed description of each farm to be made and a single collection of blood and faecal samples provided OJD prevalence information for specific age cohorts of sheep in each flock. The financial impact of OJD was established using two approaches, a gross margin analysis and the provision of a financial value on the mortalities inspected during the necropsy inspection periods. For a further 2 years, inventory and management information was collected from each of the twelve farms to provide 2003 and 2004 estimates for OJD mortality and financial loss due to OJD based on gross margin analyses. A more detailed gross margin model was developed that has the capacity to compare three disease status scenarios (uninfected, infected and vaccinated) for a number of different sheep production enterprises. These enterprises include fine, medium and strong wool Merino ewes and wethers as well as 1st and 2nd cross lamb production. From the four 5-day necropsy inspections conducted in 2002, a most likely cause of death was determined for 362 necropsied sheep on the basis of findings related to the environment, clinical signs, gross pathology and histopathology. Of these, OJD was most likely to have contributed to the death of 250 sheep, OJD was unlikely to have contributed to the death of 1 sheep and OJD did not contribute to death of 111 sheep. During 2002, across the 12 farms, there were a total of 52,718 wethers and 47,374 ewes at-risk of becoming infected with OJD. The distribution of mortalities in each sex group translates to an OJD mortality rate of 4.3% among wethers and 4.9% among ewes. Distribution across inspection periods showed a trend among OJD-related necropsies and total necropsies with the majority occurring in winter (31%) and spring (35%) and fewer in autumn (18%) and summer (16%). Across the 12 farms, the annual OJD mortality rate ranged from 1.8% to 17.5% during the 3-year study with mean annual figures of 6.2% in 2002, 7.8% in 2003 and 6.4% in 2004. Of concern is the fact that these mean OJD mortality figures were all above the accepted annual mortality rate from all causes for adult sheep of 4-6% (McGregor et al., 2003) for Australian flocks. Gross margins were calculated for each of the 12 farms assuming each farm was free of OJD and then these were compared with the actual farm gross margin. The mean percentage decrease in gross margin due to a farm being infected with OJD was 6.4% in 2002, 8.5% in 2003 and 7.4% in 2004. This equates to a mean reduction in annual income of $15,000 per farm in 2002, $12,154 in 2003 and $13,991 in 2004. Using the necropsy inspection information the mean estimated cost of OJD losses on the 12 farms over 2002 was $60,500 (range $10,978 to $150,836). The estimated cost of OJD losses accounted on average for 69.4% (range 19.4% to 100%) of the estimated total loss related to sheep deaths over the 12-month period. The OJD prevalence in 2-year old sheep in 2002 based on pooled faecal culture (PFC) ranged from 0.7% to > 23% on the 12 farms and was found to be associated with OJD mortality rate (P = 0.02). In contrast, no significant relationship was found between faecal excretion rate of MAP in two-year old sheep based on PFC and OJD mortality rate, or between age-related OJD seroprevalence and OJD mortality rate. The association between various environment, management and disease factors and quarterly OJD mortality rate was analysed and several factors (including flock size, stocking rate, area of improved pasture and weaning age) were identified as being important for further investigation. Definite conclusions based on statistical analysis could not be made due to the small number of farms and use of whole flock data. However, the results provide strong support for an additional study, involving a large number of farms and focusing on a specific sheep cohort, to identify the major risk factors for OJD. The necropsy study in 2002 established 31% of deaths were due to causes other than OJD and could have been prevented in most cases. More than half (63%) of the non-OJD deaths were attributed to malnutrition, with 57% of these deaths occurring on one farm where pregnancy toxaemia resulted from sheep receiving inadequate nutrition in late pregnancy. Many of these deaths could have been prevented with earlier feeding. The occurrence of grain poisoning on some farms reinforces the need for improved strategies when supplementary feeding. Under more favourable seasonal conditions these nutritional syndromes are unlikely to occur. Sporadic drought conditions throughout the 3-year study period, for each of the four study regions, were likely to have a minimal effect on measuring the impact of OJD on the 12 farms. At the end of 2002, following the realisation the drought would likely persist into 2003, the 12 farms on average selectively reduced flock numbers by 25%. However, this reduction is unlikely to have had an adverse effect on establishing the proportion of OJD mortalities as stock reductions occurred mainly towards the end of 2002 and the sheep most likely to be sampled at each necropsy inspection period were unlikely to be sold, as they displayed low body condition score and showed signs of weakness. A gross margin model was developed to provide an estimate of the on-farm cost of OJD. Non-infected, infected (status quo) and infected (vaccination) disease scenario examples were run for 1000 head Merino ewe and wether enterprises as well as first and second cross prime lamb enterprises. The total cost of OJD (relative to an uninfected status) and an avoidable cost of OJD (using GudairTM vaccination) were reported at four investment horizons to illustrate the cost of an OJD infection on a flock as well as the potential cost saving if a control strategy involving vaccination is implemented. Although vaccination reduces OJD mortalities, there is still an unavoidable cost incurred by the producer when compared to an uninfected flock. Results are presented as cumulative gross margin per dry sheep equivalent expressed in net present value terms (GM (NPV)/DSE) at 5, 10, 15 and 20-year intervals to enable a comparison between enterprises. The model suggests a vaccination breakeven point is achieved in two to three years for breeding enterprises if the level of OJD is high. If the level of OJD is low a vaccination breakeven point is achieved in three years for either a 1st cross or 2nd cross enterprise and seven years for a Merino ewe enterprise. The Merino ewe enterprises take the longest time to reach a vaccination breakeven point as more young sheep are retained annually for breeding in addition to the cost involved with vaccinating lambs, which is borne by all three breeding enterprises. The returns to vaccination are greatest for the 1st and 2nd cross lamb enterprises due to the value and number of lambs sold annually. With Merino wethers a vaccination breakeven point is reached in year one for all disease categories due to vaccinated replacement hoggets being introduced to provide an immediate response in reducing OJD mortalities, however as no breeding occurs the ability to increase income is limited. In the absence of OJD mortalities with the at-risk disease category, a vaccination breakeven point is not reached within the model’s 20-year time frame for any of the enterprises. This study provided the first objective data on the true impact of OJD on 12 farms, and the findings are generally applicable to sheep flocks in southern Australia. Industry groups claiming that OJD does not present a threat on-farm can now be provided with accurate figures on direct losses attributable to OJD within the endemic area of NSW. There was a wide range of impacts, with some very high mortality rates. The data can be used to justify vaccination programs, other control options and the general concept of disease control and prevention. The challenge now for industry is the design and implementation of an education and extension package that can incorporate these findings and the gross margin model along with other recent research findings to address issues of misinformation about OJD and inform producer decisions regarding on-farm disease control.
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28

Spangler, Elizabeth. "The diagnosis and epidemiology of paratuberculosis in dairy cattle in Central Ohio /." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu14873257407207.

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29

Dalto, André Gustavo Cabrera. "Achados clínicos e patológicos de paratuberculose em búfalos (Bubalus bubalis) no Rio Grande do Sul - Brasil." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/32134.

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Descrevem-se os aspectos epidemiológicos e clínico-patológicos da paratuberculose em um rebanho de búfalos no Município de Guaíba no Rio Grande do Sul. A propriedade possuía cento e noventa e quatro búfalos principalmente da raça mediterrâneo e destinava-se a produção de leite e carne. No período de abril de 2009 a setembro de 2010 seis búfalos apresentaram diarreia crônica intermitente, perda de peso e apetite normal. Na neccropsia observaram-se vasos linfáticos proeminentes no mesentério e na mucosa do intestino. Os linfonodos mesentéricos estavam moderadamente aumentados, com áreas escuras entremeadas com focos multinodulares brancacentos, principalmente na região cortical. A mucosa do intestino se encontrava espessa e cerebriforme. Ao exame histológico, desde o duodeno até o intestino grosso havia infiltrado composto principalmente por macrófagos epitelióides e, em menor escala, linfócitos, plasmócitos e células gigantes tipo Langhans. Outros achados observados foram dilatação dos vasos linfáticos, linfangite granulomatosa e linfangiectasia. Nos linfonodos mesentéricos verificaram-se lesões histológicas semelhantes. A coloração de Ziehl-Neelsen e a imuno-histoquimica revelaram bacilos álcool-ácido resistentes no interior de macrófagos, de células gigantes de Langhans e livres na mucosa e submucosa do intestino e dos linfonodos mesentéricos. Mycobacterium avium subsp. paratuberculosis foi isolado em cultivo bacteriano de amostras de fezes, raspado de mucosa intestinal e de linfonodos mesentéricos. A identificação do agente foi realizada pela técnica de PCR IS900. Foi realizado, também, levantamento sorológico de 136 búfalos da propriedade através da técnica de ELISA, na qual foram observados 15,45 % reagentes. O diagnóstico da paratuberculose foi baseado nos dados clínicopatológicos, sorologia, isolamento e identificação do agente.
It´s described the epidemiologic, clinical and pathologic aspects of paratuberculosis in a bubaline herd in Guaiba city, southern Brazil. The property had one hundred and ninety animals for milk and meet production. Six adults Mediterranean breed bubalines showed chronic intermittent diarrhea, lost of weight and normal appetite. At necropsy, the lymphatic vessels were prominent in the serosa, the mesenteric lymphnodes were slightly enlarged with dark areas interwoven by multinodular white spots mainly in the cortical region. The intestine mucosa were thickened and of corrugated aspect. The microscopic exam revealed severe diffuse granulomatous inflammation, marked dilatation of the lymphatic vessels, granulomatous lymphangitis and lymphangioectasia from the duodenum to the large bowl. The mesenteric lymphnodes showed similar histological lesions. Acid-fast bacilli in macrophages, in Langhans giant cells and freely in the mucosa and submucosa of the small intestine and lymphnodes were shown at Ziehl-Neelsen staining and immunohistochemistry. Mycobacterium avium subsp. paratuberculosis was isolated through bacterial cultivation of samples taken from feces, intestinal mucosa, mesenteric lymphnodes, and identified through IS900 PCR. In addition, a serologic survey was performed in the property by ELISA test. 15.45 percent of the animals reacted positive to the test. The diagnosis of paratuberculosis was based on clinical, pathological and epidemiological data, serology exam, bacterial isolation and identification of the agent.
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30

Gutiérrez, Duprat Ximena Alejandra. "Detección de Mycobacterium avium subsp. paratuberculosis en caprinos de la Región Metropolitana." Tesis, Universidad de Chile, 2005. http://repositorio.uchile.cl/handle/2250/130864.

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Memoria para optar al Título Profesional de Médico Veterinario
La Paratuberculosis es una enfermedad infecto contagiosa crónica con un largo período de incubación causada por Mycobacterium avium subsp. paratuberculosis (MAP), que afecta principalmente a los rumiantes, generando diarrea en algunas especies, caquexia y debilitamiento progresivo y como consecuencia, perdidas económicas en los rebaños. También infecta a animales silvestres que actuarían como posibles reservorios y se le asocia un posible potencial zoonótico, habiendo sido aislada la bacteria en algunos pacientes con la Enfermedad de Crohn, siendo el posible vehículo de infección la leche, ya que esta bacteria resistiría la pasteurización. En este estudio se trata de detectar la presencia de Mycobacterium paratuberculosis desde heces de caprinos de la región Metropolitana. Se realizaron cultivos bacteriológicos para M. paratuberculosis según recomendaciones del Australian Standard Diagnostic Techniques (ASDT) y con las modificaciones que permiten una mejor eficiencia en la recuperación de la bacteria. El medio de cultivo para aislamiento primario es el medio de Herrold con yema de huevo (HEYM) más mycobactina J. Se tuvo acceso a 10 rebaños donde se seleccionaron el número de animales en múltiplos de cinco, tratando de abarcar el 25% de la población de cada rebaño. Se recolectaron muestras directamente desde el recto, tomando 1 a 2 heces de cada caprino, que se depositaron en bolsas de plástico estéril agrupándose en “pools” de cinco animales. Para tener una mayor probabilidad de detectar rebaños caprinos infectados con MAP, se consideraron hembras mayores de un año, y en lo posible animales que hayan presentado signos de diarrea, debilitamiento, pérdida de peso progresiva, disminución de la producción láctea, etc. Se comprobó la presencia de MAP desde heces de caprinos de la Región Metropolitana en 3 rebaños de los 10 muestreados, encontrándose un 18% de los “pools” positivos a MAP. El medio HEYM más la adición de mycobactina J demostró claramente ser muy efectiva para el aislamiento del MAP a partir de muestras de heces de animales que ya estaban diseminando el microorganismo
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31

CHARLES, JEAN-DOMINIQUE. "Mycobacterium paratuberculosis et maladie de crohn : a propos d'une observation." Lyon 1, 1990. http://www.theses.fr/1990LYO1M245.

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32

ALBUQUERQUE, Pedro Paulo Feitosa de. "Detecção do Mycobacterium avium subespécie paratuberculosis em amostras de leite de bovinos na microrregião de Garanhuns, Pernambuco." Universidade Federal Rural de Pernambuco, 2014. http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/5062.

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Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
The aim of the present study was to detect the IS900 region of MAP in bovine milk samples using the Real Time Polymerase Chain Reaction (qPCR) and conventional PCR, as well as to study the agreement between the tests used. In total, 121 bovine milk samples were collected from properties considered as a focus of MAP in the micro-region of Garanhuns, Pernambuco, Brazil. Of the 121 milk samples analyzed, it was possible to detect the DNA of MAP in 20 samples (16.52%) using conventional PCR and in 34 samples (28.09%) using qPCR. The DNA of the agent was detected on all of the six properties studied, ranging from 10.00% to 23.81% in the conventional PCR and from 10.00% to 36.84% in the qPCR. The agreement between qPCR and conventional PCR was moderate (Kappa =0.53; χ2 = 38.08; p<0.000). The sensitivity and specificity of conventional PCR in relation to qPCR was 50% and 96.6%, respectively. Based on these results, it was possible to conclude that the IS900 region of MAP is present in bovine milk in the micro-region of Garanhuns, Pernambuco. It was also possible to conclude that the qPCR technique used in the present study was more sensitive than conventional PCR in terms of detecting these bacteria in milk samples.
Objetivou-se com este estudo detectar a região IS900 do MAP em amostras de leite bovino utilizando-se as técnicas de Reação em Cadeia da Polimerase em Tempo Real (qPCR) e a PCR convencional, e realizar um estudo de concordância entre os testes utilizados. Foram coletadas 121 amostras de leite bovino de propriedades consideradas foco para o MAP pertencentes à microrregião de Garanhuns, Pernambuco, Brasil. Das 121 amostras de leite analisadas foi possível detectar o DNA do MAP em 20 (16,52%) amostras na PCR convencional e em 34 (28,09%) na qPCR. O DNA do agente foi detectado em todas as seis propriedades estudadas, variando de 10,00% a 23,81% na PCR convencional e de 10,00% a 36,84% na qPCR. A concordância entre a qPCR e PCR foi moderada (Kappa =0,53; χ2 = 38,08; p<0,000) e a sensibilidade e especificidade da PCR convencional com relação a qPCR foi de 50% e 96,6%, respectivamente. Conclui-se que o DNA da região IS900 do MAP está presente no leite bovino na região estudada e que a qPCR é uma técnica sensível e rápida para detecção desse agente em amostras de leite.
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33

Begg, Douglas, and n/a. "Immune profiles in sheep following experimental infection with Mycobacterium paratuberculosis." University of Otago. Department of Microbiology & Immunology, 2005. http://adt.otago.ac.nz./public/adt-NZDU20070427.142318.

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Johne�s disease in ruminants is caused by the pathogenic bacterium Mycobacterium avium subspecies paratuberculosis. An experimental infection model in sheep was developed as a prelude to the testing of new vaccines and the development of improved diagnostic assays for Johne�s disease. The final challenge model developed used four doses of 10⁹ viable organisms given at two to three day intervals. Gross and microscopic lesions were found in a high proportion of sheep (80%) at ten months post challenge. There was considerable variation in immune responses from animals challenged with different strains of M. paratuberculosis. Sheep challenged with a low passage laboratory culture of strain (W) M. paratuberculosis, produced strong lymphocyte transformation responses and Interferon gamma (IFN-γ) production at two months post challenge. Subsequent necropsy and culture from intestinal tissues showed only a low level of infection (25%). In comparison a primary tissue isolate of M. paratuberculosis (JD3) resulted in higher (60-90%) infection rates in orally challenged animals. The immune profile from these animals showed very little reactivity for the first three months post challenge, after which IFN-γ production could be detected. Antibody production and lymphocyte transformation response could not be measured until at least seven months post challenge. Sheep challenged with the primary tissue isolate instilled directly into the tonsil resulted in equivalent levels of Johne�s disease to those obtained with oral challenge. However, intratonsillar challenge resulted in higher levels of immune reactivity than oral challenge. The proprietary Johne�s vaccines; NeoparsecTM and GudairTM and an Aqueous vaccine were tested in sheep. The immunological reactions of the sheep to these vaccines showed some variations between the two separate studies, with the NeoparasecTM and GudairTM vaccines evoking high levels of CMI and humoral reactivity within two months of vaccination. Detailed immunological examination of gut associated lymphoid tissues were carried out on subgroups of animals that were either vaccinated or non-vaccinated and went on to develop disease or were immune to experimental challenge. The results showed that the diseased animals examined had multibacillary lesions and strong CMI and humoral responses. There were decreased proportions of CD4⁺, CD8⁺ and CD25⁺ T cells in peripheral blood and gut associated lymphatics of diseased animals compared with the immune or unchallenged subgroups. Profiles from the immune subgroups showed a stronger lymphocyte transformation response than case matched diseased animals. Tissues from immune animals showed increased proportions of B cells above those seen in diseased or unchallenged animals. This study has resulted in the development of a robust experimental sheep model in which Johne�s disease occurs in a high proportion of challenged animals. Critical time points for the establishment of infection or disease have been determined. It can be used in the future to evaluate protective efficacy of vaccines or to critically chart immunological profiles that are associated with infection, disease or protective immunity. Considerable research is needed to develop improved diagnostic tests to identify patterns of immunity during the early stages of infection or while the animal has subclinical disease.
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34

Lei, Liying. "Role of dendritic cells in Mycobacterium avium subspecies paratuberculosis infection." [Ames, Iowa : Iowa State University], 2007.

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35

Elze, Julia [Verfasser]. "Nachweis von Mycobacterium avium ssp. paratuberculosis bei Schlachtrindern / Julia Elze." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/1000021831/34.

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36

Schulze, Martina [Verfasser]. "Untersuchungen zur Stammdifferenzierung von Mycobacterium avium subsp. paratuberculosis / Martina Schulze." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/102370840X/34.

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37

Lalande, Jean-Daniel. "NOD2 mediates innate and adaptive immunity to «Mycobacterium avium paratuberculosis»." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106471.

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Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic granulomatous enteritis of ruminants. MAP has been specifically and significantly associated with Crohn's disease (CD), a human enteritis with similarities to paratuberculosis. While these observations do not attest to causality of disease, they have potentiated efforts to investigate whether CD-susceptibility genes play a role in MAP infection. Specifically, our interests lie in the gene NOD2. NOD2 is part of the NOD-like receptor family and is involved in innate recognition of muramyl dipeptide (MDP), a component of bacterial peptidoglycan. Interestingly, CD-associated polymorphisms abrogate this response. In addition, NOD2 appears to be especially sensitive to mycobacterial MDP; thus we hypothesized that NOD2 would play a role in control of MAP infection. Using Nod2-/- mice as models of human NOD2 deficiency, we tested ex vivo and in vivo bacteriological, immunological and pathological phenotypes in response to MAP infection. Stimulation of peritoneal Nod2-/- macrophages revealed impaired innate recognition of MAP, a phenotype not seen when using Escherichia coli. Furthermore, we consistently observed higher burdens of MAP (~0.3 log) in Nod2-/- macrophages cell culture at 5 days post-infection; E. coli intracellular growth was NOD2-independent. Four weeks following intraperitoneal MAP infection, NOD2 disruption led to weakened adaptive immune responses towards infection as evidenced by diminished MAP-specific IFN-γ producing cells. Moreover, Nod2-/- splenocytes provided no anti-mycobacterial benefit in MAP-infected macrophage co-culture, as opposed to Nod2+/+ splenocytes which were directly responsible for a ~0.5 log reduction in MAP burden. During long-term investigations, we observed mesenteric adenitis, but no gut pathology following a 1 year MAP-infection in Nod2+/+ and Nod2-/- and a 6 month infection in Cybb-/- mice, despite isolation of organisms from mesenteric lymph nodes. In contrast, Irf-1-/- mice showed impaired elimination of MAP. Taken together, NOD2 is involved in control of intracellular growth of MAP and disruption leads to impaired innate and adaptive immune responses towards MAP infection. The subtle nature of this pathogen indicates that Nod2-/- and Cybb-/- are unlikely to serve as tractable murine models of paratuberculosis. However, Irf-1 disruption did lead to enhanced persistence of MAP.
Mycobactérium avium paratuberculosis (MAP) est l'agent causal de la paratuberculose, une entérite granulomateuse chronique chez les ruminants. MAP a été spécifiquement et significativement associé à la maladie de Crohn, une entérite chez les humains qui est semblable à la paratuberculose. Alors que ces observations ne prouvent pas une causalité entre la bactérie MAP et la maladie de Crohn, elles ont potentialisé des investigations dans le but de déterminer si les gènes reliés à la maladie de Crohn jouent un rôle lors d'une infection à MAP. Spécifiquement, nous sommes intéressés au gène NOD2. NOD2 fait partie de la famille des récepteurs NOD-like et est impliqué dans la reconnaissance innée de muramyl dipeptide (MDP), un composant de la peptidoglycane bactérienne. Il est intéressant de noter que les mutations au gène NOD2 qui sont associées à la maladie de Crohn abolissent cette réponse. De plus, il a été démontré que NOD2 est extrêmement sensible au MDP mycobactérien; ainsi nous avons fait l'hypothèse que NOD2 joue un rôle dans le contrôle d'une infection à MAP. En utilisant une souche de souris Nod2-/- comme modèle pour la déficience de NOD2 chez les humains, nous avons évalué les phénotypes bactériens, immunologiques et pathologiques ex vivo et in vivo, par rapport aux infections à MAP. La stimulation de macrophages péritonéales provenant de souris Nod2-/- a révélé une déficience dans la reconnaissance innée de MAP, un phénotype qui n'était pas présent lors de stimulation avec Escherichia coli. En plus, nous avons constamment observé un taux de MAP plus élevé (~0.3 log) dans les cultures de macrophages Nod2-/- 5 jours après l'infection; la croissance intracellulaire de E. coli était indépendant de NOD2. Quatre semaines suivant une infection intrapéritonéale de MAP, la perturbation de NOD2 a affaibli les réponses immunitaires adaptatives envers l'infection de MAP. Ceci était caractérisé par une réduction de cellules spécifique à MAP produisant de l'IFN-γ. Aussi, les splénocytes de génotype Nod2-/- n'ont fourni aucun avantage anti-mycobactérienne lors de co-culture avec des macrophages infectés avec MAP. Au contraire, les splénocytes Nod2+/+ étaient directement responsable d'une réduction de ~0.5 log de MAP. Ces observations nous ont mené à poursuivre des investigations de pathologie d'infection de MAP à long-terme. Malheureusement, nous n'avons pas observé de pathologie touchant les intestins de souris infectés chroniquement à MAP pendant 1 ans, malgré l'isolation d'organismes dans les ganglions mésentériques. De façons similaires, les souris Cybb-/- ont développé une adénite mésentérique chronique, avec pathologie intestinale mineure, lors d'une infection de 6 mois de MAP. Par contre, l'infection de souris Irf-1-/- a révélé une déficience dans le contrôle d'infection à MAP. Pris dans leur ensemble, NOD2 est impliqué dans le contrôle de la croissance intracellulaire de MAP et sa perturbation mène à la déficience de réponses innées et adaptatives envers MAP. La nature subtile de ce pathogène nous a révélé que les souris Nod2-/-et Cybb-/- ont peu de chance de servir de modèle utile de la paratuberculose chez les souris, mais la perturbation de Irf-1 à causé une augmentation dans la persistance de MAP.
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38

Kreitmann, Louis. "Investigations of Irgm1 during experimental infections with «Mycobacterium avium paratuberculosis»." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121520.

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Introduction: Mycobacterium avium paratuberculosis (MAP) is the causative agent of a chronic granulomatous enteritis of ruminants called Johne's disease (JD). Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology affecting humans. Due to histological similarities between the two conditions, it has been suggested that MAP could be responsible for a subset of cases of CD. Irgm1 (murine ortholog of IRGM, a CD susceptibility gene) has been linked to host defence against mycobacteria. Methods: In the first part of this work, we have attempted to study the immune response of the Irgm1-/- mouse to systemic infection with MAP. In the second part, we have attempted to use the Irgm1-/- mouse as a host susceptible to lead to significant pathology after intra-intestinal infection with MAP (a murine model of JD) and documented its response to therapeutics used in the care of patients with CD. Results: First, we have shown that mice deleted for Irgm1 have a major susceptibility to systemic MAP infection, with accelerated rate of death and uncontrolled bacterial replication. To explain this, we have identified a defect of Irgm1-/- macrophages in controlling the intracellular growth of MAP. We have also identified severe haematological abnormalities leading to their death. Second, we have devised a protocol for the surgical inoculation of ~ 109 MAP colony forming units (CFUs) in the jejunum of Irgm1-/- mice. After 1 and 2 months of infection, we have observed significant intestinal histopathological lesions resembling those seen in Johne's disease, including focal and transmural lympho-histiocytic infiltrates and mesenteric lymphadenopathy. Mice infected according to this protocol were submitted to: 1) a systemic treatment with methylprednisolone, which did not lead to increased mortality; and 2) a treatment with an anti-tumor necrosis factor-alpha (TNF-α) antibody, which did not lead to uncontrolled MAP replication in the host.Conclusion: Irgm1-/- mice are markedly susceptible to systemic MAP infection. When inoculated with ~ 109 MAP CFUs in the lumen of the jejunum, they develop stable histological lesions resembling those of JD. Interestingly, treatments used in the cure of patients with CD did not have a deleterious effect.
Titre du mémoire : Etude du rôle d'Irgm1 au cours d'infections expérimentales par Mycobacterium avium paratuberculosis Introduction : Mycobacterium avium paratuberculosis (MAP) est responsable d'une entérite chronique granulomateuse chez les ruminants, la maladie de Johne (ou paratuberculose). La maladie de Crohn est une maladie inflammatoire chronique du tube digestif d'étiologie indéterminée qui affecte les humains. Du fait de similarités histologiques entre les deux conditions, il a été suggéré que MAP pouvait être responsable de certains cas de maladie de Crohn. Irgm1 (orthologue murin de IRGM, un gène de susceptibilité à la maladie de Crohn), a été impliqué dans la réponse immunitaire contre les mycobactéries. Méthodes : Dans la première partie de ce travail, nous avons étudié la réponse immunitaire de la souris Irgm1-/- au cours d'une infection systémique par MAP. Dans la second partie, nous avons cherché à utiliser la souris Irgm1-/- pour induire des lésions histologiques après infection intra-intestinale par MAP (réalisant un modèle murin de maladie de Johne), et avons documenté la réponse de ce modèle à des traitements utilisés chez les patients atteints de maladie de Crohn. Résultats : Nous avons montré que la souris Irgm1-/- présente une susceptibilité majeure à une infection systémique par MAP, avec mortalité accélérée et réplication bactérienne incontrôlée. Nous avons identifié un défaut des macrophages Irgm1-/- à contrôler la croissance intra-cellulaire de MAP. Nous avons aussi identifié des anomalies hématologiques expliquant leur mortalité accélérée. Dans un second temps, nous avons conçu un protocole consistant en l'injection par voie chirurgicale de ~ 109 unités formant colonies (UFC) de MAP au sein de la lumière du jéjunum de souris Irgm1-/-. Nous avons observé qu'à 1 et 2 mois post-infection, nous avions induit des lésions histologiques ressemblant à celles rencontrées dans la maladie de Johne, notamment des infiltrats lympho-histiocytiques focaux et transmuraux et une lymphadénopathie mésenterique. Des souries infectées selon ce protocole ont été soumises à: 1) un traitement systémique par methylprednilosone, qui n'a pas entrainé une augmentation de la mortalité; et 2) un traitement par anticorps anti-tumor necrosis factor-alpha (TNF-α), qui n'a pas provoqué une réplication bactérienne incontrôlée. Conclusion : Les souris Irgm1-/- sont susceptibles à une infection systémique par MAP. Après inoculation par voie chirurgicale de ~ 109 UFC de MAP, elles développent des lésions histologiques stables analogues à celles de la maladie de Johne. Des traitements utilisés pour traiter la maladie de Crohn n'ont pas entrainé d'effet délétère. Des travaux supplémentaires sont nécessaires pour évaluer l'utilité de ce modèle dans les recherches sur la maladie de Johne et sur la maladie de Crohn.
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39

Safavi-Khasraghi, Mitra. "EXPRESSION AND CHARACTERIZATION OF MYCOBACTERIUM PARATUBERCULOSIS 19KDA WITH POSTTRANSLATIONAL MODIFICATION." Master's thesis, University of Central Florida, 2006. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3080.

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Despite the fact that E. coli supports limited posttranslational modification, this bacterium has been universally used as the expression system of choice. Expression of modified proteins in E. coli may lead to expression of recombinant proteins that lack essential immunomodulatory or catalytic components essentials for infectious processes. Previously in our laboratory, pMptb#28 plasmid containing a 4.8 kb insert from M. paratuberculosis has been identified which expressed 16 kDa recombinant protein in E. coli and 19 kDa recombinant protein in Mycobacterium smegmatis. The objective of this study is to identify the ORF sequence, investigate possible posttranslational modification and characterize the protein forms in the two hosts. Earlier in the study, the genome sequence for M. paratuberculosis was not available and therefore sequencing both the 5' and 3' ends of the 4.8 kb insert did not help in the identification of the ORF. However, unidirectional Exonuclease deletion resulted in identification of subclones containing possible ORF sequence. Later on, the publication of the M. paratuberculosis genome sequence along with BLAST analysis of sequences from the subclones resulted in the identification of 486 bp ORF with significant identity to that from M. tuberculosis and M. leprae. Cloning of the 486 ORF coding sequence in E. coli resulted in the expression of 16 kDa protein similar to the calculated predicted size of translated peptide. Cloning of the 486 bp ORF coding sequence in M. smegmatis resulted in the expression of 19 kDa protein similar to that from M. paratuberculosis. The 16/19 kDa forms of the same protein were verified using rabbit anti-M. paratuberculosis antibodies adsorbed in E. coli and M. smegmatis lysates. The size of the 19 kDa proteins was not reduced following treatment with deglycosylation enzymes in absence of any enzyme inhibitors. The 19 kDa product was confirmed not be a glycoprotein when failed to react with ConA stain. The 16/19 kDa forms of the protein were evaluated against T-lymphocytes from Crohn's disease patients and normal controls. T- proliferation assay included controls such as PHA and PPD from M. paratuberculosis. There was not a significant difference between the two forms of the protein (16/19 kDa) against T-cell response from both populations. Overall, the study identified the ORF of the 19 kDa non-glycoprotein from M. paratuberculosis. Moreover, this is the first study which reports that the zoonotic M. paratuberculosis supports posttranslational modification similar to M. tuberculosis and M. leprae pathogens. Although the posttranslational modification component in this 19 kDa nonglycoprotein did not affect T- cell response, the finding is significant toward glycoproteins from M. paratuberculosis and their role in the pathogenesis of this bacterial infection in animals and humans.
M.S.
Department of Molecular Biology and Microbiology
Burnett College of Biomedical Sciences
Molecular Biology and Microbiology
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40

Millar, Douglas Spencer. "Mycobacterium paratuberculosis, mycobacteria and chronic enteritis in humans and animals." Thesis, St George's, University of London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308932.

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41

Martinho, António Pedro Alegre. "Rastreio de mycobacterium avium subsp. paratuberculosis na doença de Crohn." Master's thesis, [s.n.], 2012. http://hdl.handle.net/10284/3571.

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Trabalho apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
O possível envolvimento de Mycobacterium avium subsp. paratuberculosis (MAP) na etiologia da doença de Crohn tem gerado muita controvérsia ao longo dos anos. A utilização de métodos de identificação por PCR reportou a detecção de MAP em pacientes com doença de Crohn, mas também em indivíduos sem doença. Outros estudos reportam resultados negativos para ambos os grupos. O objectivo deste trabalho foi verificar se na população de doentes estudada se encontrava uma associação entre presença de MAP e DC. Efectuou-se detecção de MAP em 29 amostras de sangue periférico: 11 amostras de pacientes com doença de Crohn e 18 amostras de indivíduos controlos. As amostras foram analisadas por desagregação das células e extracção do DNA tendo sido, de seguida, utilizada a técnica de PCR-nested para amplificação de parte da sequência de inserção IS900, específica do MAP e presente em elevado número de cópias. A análise dos produtos amplificados foi efectuada por electroforese em gel de agarose. DNA de MAP foi detectado em 9 dos 11 pacientes (82%) e 4 dos 18 controlos (22%), o que sugere uma associação entre MAP e DC na população estudada.
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42

Little, David. "The pathology and immunology of paratuberculosis in sheep and goats." Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/29852.

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Mycobacterium avium subspecies paratuberculosis (Map) infects macrophages and causes severe lesions of chronic granulomatous enteritis in sheep and other ruminants (Johne's disease). In this study, ovine paratuberculosis cases were examined histologically, and the presence of two distinct forms of intestinal pathology confirmed, characterised by either multibacillary lesions which exhibited a positive correlation with the presence of a marked macrophage infiltrate (lepromatous cases), or paucibacillary lesions which showed correlation with a cellular infiltrate which was lymphocytic in nature (tuberculoid cases). The presence of acid-fast bacteria was also found to correlate with evidence of serum antibody. Genomic DNA was extracted from the ileum of infected sheep and polymerase chain reaction (PCR) performed using IS900 primers to confirm Map infection. Immunoperoxidase staining of ileum demonstrated that the lymphocyte populations differed in density and relative percentages between both histological groups. The tuberculoid group had higher densities of CD4+, CD8+ and γδTCR+ subsets, and the lepromatous group lower densities of CD4+ and CD8+ subsets, when compared with control animals. Tuberculoid cases were associated with an increase in the relative percentage of CD4+ lymphocytes, whereas lepromatous cases had an increased relative percentage of γδTCR+ cells. Flow cytometry of lamina propria lymphocytes (LPL) isolated from the ileum of infected and control animals confirmed increased percentages of γδTCR+ cells in lepromatous cases than in controls, and higher percentages of CD8+ and γδTCR+ cells than in tuberculoid cases, which had correspondingly higher percentages of CD4+ cells. Higher percentages of γδTCR+ cells were also noted in mesenteric lymph node lymphocytes (MLNL) from lepromatous cases compared with control animals. Peripheral blood lymphocytes (PBL) of infected animals had increased percentages of B cells, and an associated increase in the percentage of MHC Class II positive cells compared with normal controls. The findings of this study suggest that ovine paratuberculosis is a disease with an immunological spectrum broadly comparable with that described for leprosy, with an apparent Thl like response in the tuberculoid form and a Th2 like response in the lepromatous form.
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43

Ghadiali, Alifiya H. "Studies on Mycobacterium avium subsp. paratuberculosis genotypic and phenotypic variations /." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1110229469.

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Thesis (Ph. D.)--Ohio State University, 2005.
Document formatted into pages; contains xxi, 216 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 March 9.
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44

Braga, Isis de Freitas Espeschit. "Mycobacterium avium ssp. paratuberculosis (MAP): Identificação água e fatores de risco para a presença em amostras de biópsias intestinais." Universidade Federal de Viçosa, 2015. http://www.locus.ufv.br/handle/123456789/6739.

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Mycobacterium avium ssp. paratuberculosis (MAP) é o agente etiológico da doença de Johne ou paratuberculose, enterite granulomatosa crônica caracterizada por diarreia persistente e perda de peso progressiva que acomete ruminantes. Pode também ser isolado a partir de amostras intestinais de pacientes humanos, com doenças intestinais, principalmente portadores da doença de Crohn. Essa é uma doença de etiologia desconhecida, que se caracteriza por inflamação crônica, focal, assimétrica transmural e ocasionalmente granuloma- tosa, que pode acometer qualquer segmento do tubo digestivo. O isolamento de MAP e as semelhanças entre os processos clínicos e histopatológicos da paratuberculose e da doença de Crohn são algumas das razões pelas quais se investiga o potencial zoonótico da bactéria. As principais vias de eliminação do agente são através do leite e das fezes que contaminam os pastos e, direta ou indiretamente os cursos d’agua podendo dessa forma infectar humanos pela ingestão de água contendo o micro-organismo viável. MAP é uma bactéria resistente e responsável por grandes prejuízos econômicos e produtivos, sendo demonstrada sua sobrevivência no ambiente por longos períodos, além da resistência a pasteurização e à agentes de desinfecção aplicados ao tratamento da água para consumo humano. Diante disso, o estudo teve como objetivos: - identificar fatores de risco envolvidos com a presença de MAP em amostras de intestino humano, através da aplicação de questionário, em conjunto com da- dos prévios sobre a presença da bactéria em amostras de biópsias intestinais de pacientes portadores de Doença de Crohn, retocolite ulcerativa e portadores de doenças intestinais não inflamatórias, -verificar a presença do agente na água para consumo humano e animal através de PCR convencional e do cultivo microbiológico de amostras coletados em 10 propriedades de caprinocultura leiteira da Zona da Mata Mineira e realizar uma revisão bibliográfica dos estudos sobre a paratuberculose na América Latina. Quanto às amostras de água, MAP foi identificado viável em quatro (40%) das amostras de consumo animal, e identificado por PCR em três (30%) das de consumo humano além de uma quinta amostra de consumo animal (10%). Esse resultado demonstra o papel da água como reservatório do agente, mantendo o ciclo de infecção ativo e servindo de amostra confiável para o diagnóstico da presença do agente no rebanho já que, aparentemente não está condicionada a eliminação intermitente, como ocorre com as fezes desses animais. Nesse estudo também puderam ser identificados fatores de risco para a ocorrência do agente na água e em biópsias intestinais humanas, como o consumo de leite e derivados informais, assim como histórico familiar de agravos intestinais. Na América Latina MAP foi pesquisado em 10 países e identificado em nove, infectando, bovinos, caprinos e animais silvestres. Os resultados desse estudo contribuem para a identificação de fatores de risco envolvidos na transmissão de MAP para humanos, permitindo a sugestão de medidas que previnam ou reduzam a exposição ao agente. Esses fatores de risco identificados também demonstram a importância do leite na veiculação do agente por leite e produtos lácteos, com destaque para aqueles que não passaram pela pasteurização. Além disso, os estudos sobre água auxiliaram a elucidação do papel da ingestão da água na transmissão do agente, que não é pesquisado na rotina de tratamento, indicando exposição ao agente para humanos pode ser dar através do consumo de água contaminada por fezes de animais com paratuberculose. Esse estudo foi o primeiro sobre o agente na água no Brasil, e um dos poucos no mundo.
Mycobacterium avium ssp. paratuberculosis (MAP) is the etiologic agent of Johne's disease or paratuberculosis, a chronic granulomatous enteritis characterized by persistent diarrhea and progressive weight loss that may affects ruminants. MAP is also be isolated from intestinal samples from human patients with intestinal diseases, particularly Crohn's disease patients. This is a disease of unknown etiology that is characterized by chronic inflammation, focal, transmural asymmetric and occasionally granulomatous lesions, which can affect any segment of the digestive tract. The isolation of MAP and the similarities between the clinical and pathologic processes of paratuberculosis and Crohn's disease are some of the reasons for investigating the zoonotic potential of bacteria. The main agent’s disposal routes are through feces and milk that contaminate pastures and directly or indirectly the watercourses and can thus infect humans by drinking water containing viable microorganism. MAP is a resistant bacteria and responsible for significant economic and productive loss, and demonstrated its survival in the environment for long periods, in addition to the resistance to pasteurization and disinfection agents applied to water treatment for human consumption. Thus, the study aimed to: - identify risk factors involved with the presence of MAP in human gut samples, through the questionnaire, together with previous data on the presence of bacteria in samples of intestinal biopsies of patients Crohn's disease, ulcerative colitis and patients with non- inflammatory intestinal diseases, -check the agent's presence in the water for human and animal consumption by conventional PCR and microbiological culture samples collected in 10 properties of dairy goat of the Zona da Mata Mineira and,- conduct a literature review of the studies on paratuberculosis in Latin America. As for the water samples, MAP was identified feasible in four (40%) of the samples of animal feed, and identified by PCR in three (30%) of human consumption as well as a fifth sample of animal consumption (10%). This result demonstrates the role of water as an agent of the reservoir, keeping the active infection cycle and serving as a reliable sample for the diagnosis of the agent's presence in the herd since apparently is not subject to intermittent shedding, as with the feces of these animals. In this study could also be identified risk factors for the occurrence of the agent in in human intestinal biopsies, as the consumption of unpasteurized milk and informal derivatives as well as family history of bowel diseases. In Latin America MAP was investigated in 10 countries and identified in nine, infecting, cattle, goats and wild animals. The results of this study contribute to the identification of risk factors involved in the MAP transmission to humans, allowing the suggestion of measures to prevent or reduce exposure. These identified risk factors also demonstrate the importance of milk in placement agent for milk and milk products, especially those who have not gone through the pasteurization. Furthermore, studies on water helped to elucidate the role of water ingestion in the transmission of the agent, which is not searched in routine treatment, indicating exposure to the agent for humans can occur through the consumption of water contaminated by faeces of animals carrying paratuberculosis. This study was the first about the agent in water in Brazil, and one of the few in the world.
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45

Heaslip, Darragh G. "Studies on a 34kDa protein of M. avium subsp. paratuberculosis, a putative virulence factor." Thesis, University of Surrey, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247997.

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46

Herthnek, David. "Detection and confirmation of Mycobacterium avium subsp. paratuberculosis in clinical samples /." Uppsala : Dept. of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/10210535.pdf.

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47

Thanigachalam, Saisathya. "Dubious role of Mycobacterium paratuberculosis in pathogenesis of Type I diabetes." Master's thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5528.

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INTRODUCTION: Type 1 Diabetes Mellitus (T1DM) is a chronic disorder with unknown etiology and associated with insulin deficiency. Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of paratuberculosis in cattle, has been implicated in many autoimmune diseases including Crohn's disease, TIDM and others. We hypothesize that the molecular mimicry including epitope homology between MAP-Hsp65 and pancreatic Glutamic Acid Decarboxylase65 (GAD65) may play a role in the auto destruction of pancreatic beta cells leading to insufficient insulin production and the development of TIDM, following exposure to MAP. METHODOLOGY: Peptide sequences of MAP-Hsp65 and GAD65 were analyzed using BLAST and PyMOL bioinformatics tools. Cross reactivity between the two proteins were evaluated using immunoblot and ELISA. Furthermore, coded EDTA blood samples were collected from 18 subjects (12 DM and 6 controls) and investigated for the presence or exposure to MAP. Peripheral leukocytes were investigated for harboring viable MAP using long-term culture followed by nested PCR. Clinical plasma samples were used for measurement of anti-MAP IgG titer as well as glucose and Insulin concentrations. Moreover, coded bovine sera from 100 cattle (50 MAP infected and 50 healthy) were investigated for possible correlation between MAP infection and plasma levels of glucose and insulin. RESULT: Peptide BLAST analysis revealed a 44% identity between MAP Hsp65 and GAD65 proteins with 75% positive identities in a 16 amino acid region. PyMOL 3-D structural analyses identified a shared epitope region within the 16 amino acid motif which is known to be an antigenic site on GAD65 antigen. MAP DNA and anti-MAP IgG were detected in the blood of TD8, a TIDM subject. Strong cross reactivity was observed between plasma from TD8 and MAP Hsp65 in proteins samples from M. tuberculosis, and E. coli recombinant clone expressing MAP Hsp65. A weak cross reactivity was also observed between rat pancreatic tissue homogenate and rabbit anti-MAP IgG. Long term culture of leukocytes from 18 blood samples resulted in the detection of MAP in 3/10 (30%) TIDM and 4/8 (50%) control subjects whereas anti-MAP IgG were detected in 5/10 (50%) TIDM samples compared to 3/8 (37.5 %) controls. In MAP infected cattle, insulin level ranged from below 0.1ng/ml to 2.456 ng/ml with an average of 0.36 +/- 0.57ng/ml compared to 0.1ng/ml to 13.47ng/ml with an average of 2.86 +/- 3.00ng/ml in healthy cattle (P<0.0001). CONCLUSION: We identified and confirmed a shared epitope region between MAP Hsp65 and human pancreatic GAD65. The shared epitope is a known antigenic binding site. Although MAP DNA was detected in both TIDM and control subjects, a strong correlation was found between anti-MAP IgG titer and MAP-positive culture in clinical samples, regardless of diagnosis. The correlation between MAP infection and insulin level in cattle is significant. Overall the result is intriguing and requires further investigation of MAP in well-characterized clinical samples.
M.S.
Masters
Molecular Biology and Microbiology
Medicine
Molecular and Microbiology
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48

Judge, Johanna. "Rabbits (Oryctolagus cuniculus) as a host of Mycobacterium avium subspecies Paratuberculosis." Thesis, University of York, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438079.

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Nicol, Louise Maureen Marie. "Investigating differential T cell polarization in the two pathological forms of sheep paratuberculosis." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22855.

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Paratuberculosis is a chronic enteropathy of ruminants that presents as two distinct disease forms in sheep; paucibacillary (or tuberculoid) and multibacillary (or lepromatous) disease. The immunopathology of paucibacillary and multibacillary sheep paratuberculosis has been linked to inflammatory Th1/Th17 cell and Th2/macrophage responses respectively. IL23 and IL25 are key to the development of these responses by interaction with their complex receptors, IL23R/IL12RB1 and IL17RA/IL17RB. Furthermore, the polarization of T cells and the development of appropriate immune responses is controlled by the master regulator transcription factor; T-bet, GATA3, RORγt and RORα. In humans, variations in the structure, sequence and/or expression of the genes encoding these proteins have been implicated in the different pathological forms of tuberculosis and leprosy, and gastrointestinal inflammatory disorders such as Crohn’s disease. In the current study, sequencing has identified multiple transcript variants of sheep IL23R, IL12RB1 and IL17RB and a single IL17RA transcript. RT-qPCR assays were developed for the cytokine receptor variants identified in this study and known transcript variants of the transcription factor genes. Expression levels were compared in the ileo cecal lymph node of paucibacillary or multibacillary paratuberculosis diseased sheep. Of the cytokine receptors; the IL12RB1v3 variant, which lacks the receptor activation motif, was differentially expressed and was significantly increased in multibacillary disease; this may contribute to high Th2 responses. Full length IL17RB was differentially expressed and was significantly increased in multibacillary pathology, which may also contribute to Th2 polarization. IL17RA was significantly increased in paucibacillary disease. The contrast between the IL17RA and IL17RB results may indicate that, in addition to Th1 cells, Th17 T cells are also involved in paucibacillary pathology. Of the transcription factor transcripts; full length TBX21 (T-bet) was differentially expressed and was significantly increased in paucibacillary disease; this may explain increased Th1 responses in these sheep. Full length GATA3 was significantly increased in paucibacillary compared to multibacillary sheep, suggesting a loss of Th2 responses in late-stage multibacillary pathology. RORAv1 variant was differentially expressed and was significantly increased in paucibacillary pathology, indicating a role of Th17 T cells in paucibacillary pathology.
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Füllgrabe, Regina A. R. "Untersuchungen zum kulturellen und molekularbiologischen Nachweis von Mycobacterium avium ssp. paratuberculosis (MAP) aus humanen Darmbioptaten." Giessen VVB Lauferweiler, 2008. http://d-nb.info/993780016/34.

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