Memoria para optar al Título Profesional de Médico Veterinario / La Brucelosis bovina es una enfermedad que ha llevado a los distintos países a establecer estrategias de control y prevención de la enfermedad. En Chile las estrategias establecidas por el Servicio Agrícola y Ganadero (SAG) son vigilancia, saneamiento y prevención en el ganado bovino. Esta última medida consiste en la vacunación con B. abortus cepa RB51. La ventaja de esta cepa es que no produce interferencia diagnóstica con pruebas que utilizan el lipopolisacárido liso (s-LPS) como antígeno. El presente estudio caracterizó la respuesta inmune humoral y celular generada en el ganado bovino vacunado con esta cepa. Para esto se contó con un grupo de 25 terneras las cuales fueron vacunadas con 1- 3 x 1010 UFC de B. abortus RB51, entre la edad de 4 y 8 meses. Estas fueron mantenidas y manejadas en su rebaño durante el período de estudio en el cual se realizaron cuatro muestreos los días 0, 30, 180 y 360 post vacunación, recolectando dos muestras de sangre de cada animal una con y otra sin anticoagulante (heparina de sodio). Las muestras obtenidas fueron procesadas en cinco pruebas diagnósticas distintas y éstas son: rosa de bengala, ELISA indirecto, ELISA competencia las cuales detectan la respuesta inmune humoral al s-LPS de Brucella. También se usaron la prueba de ELISA citosol de RB51 que detecta la respuesta inmune humoral frente a proteínas del citosol de RB51 y finalmente la prueba de IFN bovino, que detecta la respuesta inmune celular frente a RB51. Los resultados obtenidos, demostraron que la cepa RB51 no induce anticuerpos contra el s-LPS de Brucella tal como era esperado, pero sí induce anticuerpos frente a proteínas citosólicas de cepa RB51. Durante el período de estudio, sólo una vaquilla arrojó resultados positivos a estas pruebas y esto se debió probablemente al resultado de una infección natural como consecuencia de la presencia de brucelosis en el rebaño. Los resultados obtenidos frente a la prueba de IFN bovino demostraron que cepa RB51 induce respuesta inmune celular, detectable mediante la presencia de esta citoquina que fue liberada al plasma bovino por los linfocitos estimulados con el citosol de RB51. La evolución del porcentaje de animales negativos a las pruebas que usan s-LPS como antígeno fue estable ya que, exceptuando la vaquilla positiva antes mencionada, todos los animales permanecieron negativos a los cuatro muestreos. La prueba de ELISA citosol de RB51muestra un evidente aumento en el porcentaje de animales positivos entre el primer y segundo muestreo, para luego permanecer constante en los muestreos siguientes, esto debido a los anticuerpos generados como respuesta post vacunatoria a las proteínas de RB51, que decaen con el tiempo. Finalmente la prueba de IFN bovino muestra un aumento del porcentaje de animales positivos entre el primero y segundo muestreo y luego decrece en forma constante, hasta el último muestreo / Financiamiento: IFS B/1800-2

Vaccines are a highly effective means of preventing infectious disease. However, for many diseases of livestock the available vaccines are ineffective or sub-optimal. This is partly due to challenges surrounding the specific targeting of antigen presenting cells (APCs). In order to improve the delivery of protective antigens to host APCs, a novel lentiviral vector derived from visna / maedi virus (VMV) has been developed. Initial characterisation using an enhanced green fluorescent protein (eGFP) reporter transgene found that the novel VMV vector efficiently transduced a wide range of cell lines including cells of ovine, human, murine, bovine and caprine origin. In addition, the VMV vector was found to elicit sustained transgene expression for at least 4 weeks in rapidly dividing cell lines. One of the most important factors for acceptable vaccines is their safety. Therefore, in order to increase the bio-safety of the VMV vector, integration-defective and self-inactivating forms were produced. Integration-defective VMV lentiviral vectors (IDLVs) were found to produce 1-LTR circular episomes favourably over integrated provirus following the transduction of target feline and ovine cell lines. This led to a decrease in transgene expression over time in dividing cells. In contrast, in non-dividing cells transgene expression was maintained at a similar level to integration-competent VMV vectors. Self-inactivating (SIN) VMV vectors were constructed and found to have a significant decrease in LTR activity. Transgene expression was maintained by the insertion of an internal promoter derived from human cytomegalovirus (CMV) acting directly on the transgene. When self-inactivating and integration-defective modifications were incorporated into the same vector particle, a 4-fold decrease in transduction relative to the parent vector was observed. Ovine monocyte-derived dendritic cells (MDDCs) and macrophages (MDMs) were found to be efficiently transduced by the VMV vector, whereas lentiviral vectors derived from HIV-1 poorly transduced both of these primary cell populations. Following this work, the ability to deliver pathogen genes into APCs was studied using the Chlamydia abortus (C. abortus) major outer membrane protein (MOMP) as the transgene. C. abortus is the most common infectious cause of ovine abortion worldwide and MOMP has previously been shown to stimulate strong antibody responses after vaccination. Unexpectedly, the VMV vector encoding either eGFP or MOMP was found to induce apoptosis in MDDCs and MDMs using Annexin V staining. Apoptotic cells were detectable as early as 6 hours post-transduction of cells. Furthermore, release of the pro-inflammatory cytokine IL-1β was associated with the formation of late apoptotic cells. Apoptotic bodies produced post-transduction were able to be phagocytosed by immature MDDCs and the transgene efficiently cross-presented to T-cells. The ability of the novel VMV vector to induce a suitable recall immune responses was investigated using an in vitro model. Here, an autologous population of MDDCs were cultured with the apoptotic bodies produced post-transduction before the addition of autologous PBMC. Proteins from the apoptotic bodies were presented by the MDDCs to PBMC leading to a strong, antigen specific recall immune response against C. abortus MOMP. This was proven by the detection of cytokines IFNγ and IL-10 in the co-culture supernatant from PBMC activated by the MOMP transgene cross-presented by MDDCs. No release of IL-4 or IL-17A could be detected. These data presented in this thesis show the potential for improving delivery of antigens in livestock vaccines by the use of lentiviral vectors. In addition, this vector system provides a strong base for the study of other potential protective antigens in vitro.

Un brote de bovinos de raza Hereford fueron inoculados a repetición con Brucella abortus cepa 19 durante un período de doce meses. Elaboraron anticuerpos correspondientes a la clase Ig M e Ig G, siendo los últimos los que predominaron y persistieron hasta el final del experimento. Los anticuerpos de la clase Ig G correspondieron a poblaciones de anticuerpos diferentes: aglutinantes y no aglutinantes o bloqueantes, estos detectados por reacción de Coombs. Ambos tipos de anticuerpos fueron separados mediante inmunoadsorciones seriadas y purificadas por cromatografía de intercambio iónico. Se les caracterizó como pertenecientes aa calse Ig G1, siendo estudiadas sus propiedades inmunoquímicas y biológicas. Los anticuerpos aglutinantes fueron capaces de aglutinar el antígeno, fijar complemento y facilitar la depuración sanguínea de Brucella abortus cepa 19 marcada con 131 I en ratones e inhibieron la multiplicación de Brucella abortus en el bazo de ratones inoculados con estas bacterias. Por el contrario los anticuerpos coaglutinantes, fueron incapaces de facilitar la depuración sanguínea de bacterias y facilitaron su multiplicación en bazo. A la luz de estos resultados postulamos la hipótesis de que estos anticuerpos intervendrían en el facilitamiento de la permanencia y multiplicación de las brucelas en el huésped, siendo éste, uno de los mecanismos responsables de la iniciación y/o mantenimiento de la cronicidad en la brucelosis bovina. / Hereford cattles were repeatedely inoculated with Brucella abortus strain 19 for twelve months. Antibodies elaborated belonging to classes Ig M and Ig G, thelatter being the ones that predominated and persisted till the end of the experiment. Ig G antibodies were related to two different types of antibodies: agglutinating and non-agglutinating antibodies, were specifically purified by immunoadsortion and latter purified by ionic exchange chromatography. They were characterised as Ig G1, and its inmunochemical and biological properties were studied. Agglutinating antibodies were able to agglutinate the antigen, fix the complement and increased blood clearance of Brucella abortus strain 19 marked with 131 I in mice and inhibited the multiplication of Brucella in mice spleen inoculated with these bacteria. On the other hand, the co-agglutinating antibodies unable to facilate the bacterial blood clearence and enhaced its multiplication in spleen. Owing to these results we postulate that these antibodies would facilitate the permanence and multiplication of bacteria in the guest. This mechanism would be responsible for the beginning and maintainans of chronic cattle brucellosis.

Chlamydia abortus is the most common known infectious cause of ovine abortion worldwide but is rarely linked with bovine abortion. The reasons for this differential pathogenesis are unknown but may involve differences in innate immune recognition and immune responsiveness. This is supported by the observation that chlamydial abortion in sheep is associated with an inflammatory cytokine/chemokine cascade that is not commonly observed in cattle. Studies with other Chlamydia species have demonstrated that innate inflammatory pathways including inflammasome activation contribute to both pathogen clearance and pathology. Pattern recognition receptors (PRRs) activate these innate immune signalling pathways but are relatively poorly characterized in ruminants. We hypothesize that the ruminant hosts differ in their ability to innately sense C. abortus infection and activate the inflammasome. The main aims of this project were to: analyse PRR expression in innate immune cells; assess cytokine production from innate immune cells in response to C. abortus; investigate the role of PRRs in the induction of innate immune responses to C. abortus; and, conduct RNA-seq analysis on macrophages following infection with C. abortus to identify important immune signalling pathways. Ruminant oro-nasal turbinate cells, monocyte derived dendritic cells (MDDCs) and monocyte derived macrophages (MDMs) express the cell-surface PRRs TLR2 and TLR4 and also the intracellular PRRs NOD 1 and NLRP3. Oro-nasal turbinate cells produce CXCL8 late into the chlamydial developmental cycle independent of IL-1β. In contrast, ruminant MDMs and MDDCs secrete early IL-1β in response to C. abortus infection. In MDMs and MDDCs, live and UV-inactivated C. abortus induced TNF-α and CXCL8 but live infection was required for IL-1β secretion. Therefore, intracellular C. abortus multiplication is necessary to stimulate the IL-1β processing pathway within these cells. In order to determine PRR function, NOD1 and NLRP3 were knocked down in ruminant MDMs using siRNA. In both ovine and bovine MDMs, NOD1 was identified as a factor in C. abortus mediated IL-1β production. NLRP3 knockdown in bovine but not ovine MDMs also reduced IL-1β production, indicating species-specific differences in C. abortus recognition. The RNA-seq analysis of ruminant MDMs identified novel pathways of immune activation by C. abortus and potentially important species-specific differences. An improved understanding of the innate immune pathways activated in susceptible and resistant hosts following C. abortus infection will inform on disease pathogenesis and could contribute to novel chlamydial vaccine design.

A mortalidade fetal é uma causa importante de perdas reprodutivas em animais domésticos e tem impacto significativo na rentabilidade de um sistema de produção animal. No Brasil, poucas informações são disponíveis sobre as principais causa de aborto em bovinos. O presente estudo resultou em cinco artigos. O primeiro artigo descreve as principais causas de aborto bovino diagnosticadas no Setor de Patologia Veterinária da Universidade Federal do Rio Grande do Sul no período 2003-2011. Neste período um total de 490 fetos bovinos foi analisado. Causas específicas de aborto foram encontradas em 46,7 % dos casos. Infecções por protozoários, em especial Neospora caninum acometeram 33 % dos casos (162/490). Bactérias em 6,3 % (31/490), seguidas por fungos 0,8% (4/490) foram causas adicionais de abortos. Em dois fetos (0,4 %), coinfecções por dois agentes foram identificadas. Causas não infecciosas foram observadas em 3 % dos abortos e malformações congênitas a 2,6%. No segundo artigo estima-se a ocorrência de abortos por Brucella abortus em bovinos na região sul, caracterizando os achados macroscópicos, histopatológicos, bacteriológicos, imuno-histoquímicos e de PCR desta enfermidade. No terceiro artigo relata-se a infecção por Geotrichum candidum em feto bovino abortado associado a lesões de pele e pulmonares. A ocorrência de malformações congênitas múltiplas em um feto bovino abortado é relatada no quarto artigo e casos de condrodisplasia tipo Dexter em fetos bovinos abortados são descritos no quinto. / The fetal mortality is an important cause of reproductive failure in domestic animals and has a significant impact on the profitability of a livestock production system. In Brazil, little information is available on the main cause of abortion in cattle. This study resulted in five articles. The first article describes the main causes of abortion in cattle diagnosed in the period January 2003 to december 2011. A total of 490 fetuses, from several Brazilian states, were evaluated. Specific causes of abortion were found in 46,7 % of cases. Protozoan abortions especially Neospora caninum were detected in 33 % (162/490) of the cases. Bacterial abortions corresponded to 6,3 % (31/490), followed by fungal 0,8 % (4/490). In two aborted fetuses (0,4 %), a co-infection with two agents could be identified. Noninfectious diseases could be associated with 3 % of the abortions and congenital malformations with 2,6%. In the second article estimated the incidence of abortion by Brucella abortus in cattle in the southern region, characterizing the macroscopic findings, histological, bacteriological, immunohistochemical and molecular aspects of this disease. The third article relates a Geotrichum candidum infection in aborted bovine fetus associated with skin and lung lesions. The occurrence of multiple congenital malformations in an aborted bovine fetus is reported in the fourth article and cases of Dexter chondrodysplasia type of aborted fetuses are described in the fifth.

Submitted by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2017-07-07T19:08:23Z No. of bitstreams: 1 texto completo.pdf: 867144 bytes, checksum: b1dfb9c08a4b085feda6d150ced1327c (MD5) / Made available in DSpace on 2017-07-07T19:08:23Z (GMT). No. of bitstreams: 1 texto completo.pdf: 867144 bytes, checksum: b1dfb9c08a4b085feda6d150ced1327c (MD5) Previous issue date: 2017-03-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Mycobacterium bovis e Brucella abortus são os agentes etiológicos da tuberculose e da brucelose bovinas, doenças infectocontagiosas de ocorrência mundial que geram grandes prejuízos econômicos e podem ser transmitidas aos humanos principalmente através do contato direto com animais contaminados e da ingestão de leite cru e derivados. No Brasil existe o Programa Nacional de Controle e Erradicação da Brucelose e Tuberculose, criado pelo Ministério da Agricultura, Pecuária e Abastecimento, que estabelece a realização do diagnóstico e normatiza as medidas de controle dessas zoonoses. Os métodos oficiais para diagnóstico de brucelose e tuberculose no animal vivo possuem sensibilidade e especificidade variáveis, são laboriosos e demandam tempo. Para aumentar a eficácia do controle destas doenças são necessários métodos rápidos e acurados, que atuem como ferramenta auxiliar no diagnóstico in vivo dessas enfermidades sem a necessidade de procedimentos invasivos. Para garantir a credibilidade e confiabilidade de novos métodos de diagnóstico é necessário que os mesmos sejam validados. No presente estudo foram realizados ensaios para a validação de uma reação em cadeia da polimerase em tempo real (qPCR) para a detecção do DNA de M. bovis e B. abortus em amostras de leite cru artificialmente contaminados, usando como critério o desempenho analítico (sensibilidade e especificidade analítica), repetibilidade, reprodutibilidade interna e robustez. Inicialmente cinco metodologias de extração de DNA foram testadas e as que apresentaram melhores resultados foram os kits comerciais DNeasy mericon Food Kit – Qiagen e Maxwell® 16 Tissue DNA Purification Kit – Promega. Os limites de detecção obtidos na qPCR validada nesse estudo foram de 2,3 pg de DNA de M. bovis e 20,7 fg de DNA de B. abortus. As repetibilidades eviii reprodutibilidades aliadas à robustez apresentadas nesse trabalho indicam que os métodos avaliados podem ser utilizados de forma auxiliar ao diagnóstico in vivo oficial de tuberculose e brucelose bovinas, após ser testada em animais naturalmente infectados. / Mycobacterium bovis and Brucella abortus are the etiological agents of bovine tuberculosis and brucellosis, infectious diseases globally disseminated that cause substantial economic losses and can be transmitted to humans mainly through direct contact with contaminated animals and the intake of raw milk and milk products. In Brazil there is the National Program for the Control and Eradication of Brucellosis and Tuberculosis, created by the Ministry of Agriculture, Livestock and Supply, which establishes the diagnosis and regulates the control measures of these zoonosis. The official methods for diagnosis of brucellosis and tuberculosis in the living animal have variable sensitivity and specificity, are laborious and time consuming. In order to increase the efficacy of brucellosis and tuberculosis control, rapid and accurate methods are necessary to act as an auxiliary tool in the in vivo diagnosis of these diseases without the need of invasive procedures. To ensure the credibility and reliability of new diagnostic methods, they must be validated. In the present study, the validation of a real-time polymerase chain reaction (qPCR) for the detection of M. bovis and B. abortus in artificially contaminated raw milk samples was performed using analytical performance (analytical sensitivity and specificity), repeatability, internal reproducibility and robustness. Initially five DNA extraction methodologies were tested and the ones that presented the best results were the commercial kits “DNeasy Mericon Food Kit – Qiagen” and “Maxwell® 16 Tissue DNA Purification Kit – Promega”. The limits of detection obtained in the qPCR validated in this study were 2.3 pg of M. bovis DNA and 20.7 fg of B. abortus DNA. The repeatability and reproducibility associated with the robustness presented in this study indicate that the evaluated methods can be used as an auxiliaryx tool to the in vivo official diagnosis of bovine tuberculosis and brucellosis, after being tested in naturally infected animals. / Nos dois impressos faltaram as últimas 12 páginas com referência bibliográfica.

Made available in DSpace on 2014-06-11T19:27:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-07-27Bitstream added on 2014-06-13T20:35:27Z : No. of bitstreams: 1 blankenheim_tm_me_jabo.pdf: 1604167 bytes, checksum: 4a1bd2c15849129ba10ee344bb637ad3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O trabalho teve como objetivo analisar a resposta sorológica induzida pela vacinação com a dose padrão de 60-120x109 organismos da amostra B19 de Brucella abortus em bezerras da raça Tabapuã, com idade entre 3 e 8 meses, pelos testes sorológicos preconizados pelo Programa Nacional de Controle e Erradicação da Brucelose e Tuberculose (PNCEBT) para diagnóstico da brucelose bovina. Foram examinadas amostras de soro sanguíneo de 72 animais em quatro provas sorológicas: antígeno acidificado tamponado (AAT), teste de soroaglutinação lenta juntamente com o teste de 2-mercaptoetanoll (2-ME), reação de fixação de complemento (RFC) e teste de polarização fluorescente (TPF), o qual foi interpretado de duas formas: ponto de corte variável e ponto de corte fixo. As amostras de soro sanguíneo foram colhidas imediatamente antes da vacinação, e após 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 e 360 dias. Foi calculada a especificidade dos testes, e os resultados foram comparados pelo indicador kappa e pelo teste ² de McNemar. O TPF apresentou especificidade mais elevada do que os outros testes nas amostras colhidas dos 30 aos 90 dias após a vacinação, mas com o passar do tempo a diferença entre a especificidade do TPF e a dos outros testes diminuiu. Aos 270 dias de vacinação, observou-se especificidade de 93,74% no AAT, no 2-ME e na RFC. No TPF com ponto de corte variável a especificidade foi 87,5%, e com ponto de corte fixo foi 100,0%. Foi possível concluir que o TPF apresentou maior capacidade de discriminação dos títulos de anticorpos vacinais logo após a vacinação, quando comparado com os outros testes preconizados pelo PNCEBT, apresentando-se, portanto, como uma ferramenta útil para o diagnóstico da brucelose bovina, além de ser de execução fácil e rápida / The study aimed to analyze the antibody response induced by vaccination with the standard dose of 60-120x109 organisms of Brucella abortus strain 19 in Tabapuã heifers, aged between 3 and 8 months, by serological tests recommended by the National Program for Brucellosis and Tuberculosis Control and Eradication (PNCEBT) for the diagnosis of bovine brucellosis. Serum samples of 72 animals were examined by four serological tests: rose Bengal test (RBT), standard agglutination test with the 2-mercaptoetanol (2-ME) test, complement fixation test (CFT) and fluorescence polarization assay (FPA), which was interpreted in two ways: variable cutoff and fixed cutoff. Heifers were bled immediately prior to vaccination, and after 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 days. Specificity of the tests were calculated, and the results were compared using the kappa statistic and the McNemar's ² test. The FPA had a higher specificity than the other tests on the samples collected from 30 to 90 days after vaccination, but over time this difference decreased. At 270 days of vaccination, the specificity of RBT, 2-ME and RFC was 93.74%. The specificity of the FPA with variable cutoff was 87.5%, and with fixed cutoff was 100.0%. It was concluded that FPA had a higher discrimination ability for vaccination antibody titers shortly after vaccination, when compared with other tests recommended by the PNCEBT, and is a useful tool for the diagnosis of bovine brucellosis, besides being easy and quick to perform

Orientador: Luis Antonio Mathias / Coorientador: Raphaella Barbosa Meirelles Bartoli / Banca: Samir Issa Samara / Banca: Anna Monteiro Correia Lima Ribeiro / Resumo: O trabalho teve como objetivo analisar a resposta sorológica induzida pela vacinação com a dose padrão de 60-120x109 organismos da amostra B19 de Brucella abortus em bezerras da raça Tabapuã, com idade entre 3 e 8 meses, pelos testes sorológicos preconizados pelo Programa Nacional de Controle e Erradicação da Brucelose e Tuberculose (PNCEBT) para diagnóstico da brucelose bovina. Foram examinadas amostras de soro sanguíneo de 72 animais em quatro provas sorológicas: antígeno acidificado tamponado (AAT), teste de soroaglutinação lenta juntamente com o teste de 2-mercaptoetanoll (2-ME), reação de fixação de complemento (RFC) e teste de polarização fluorescente (TPF), o qual foi interpretado de duas formas: ponto de corte variável e ponto de corte fixo. As amostras de soro sanguíneo foram colhidas imediatamente antes da vacinação, e após 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 e 360 dias. Foi calculada a especificidade dos testes, e os resultados foram comparados pelo indicador kappa e pelo teste ² de McNemar. O TPF apresentou especificidade mais elevada do que os outros testes nas amostras colhidas dos 30 aos 90 dias após a vacinação, mas com o passar do tempo a diferença entre a especificidade do TPF e a dos outros testes diminuiu. Aos 270 dias de vacinação, observou-se especificidade de 93,74% no AAT, no 2-ME e na RFC. No TPF com ponto de corte variável a especificidade foi 87,5%, e com ponto de corte fixo foi 100,0%. Foi possível concluir que o TPF apresentou maior capacidade de discriminação dos títulos de anticorpos vacinais logo após a vacinação, quando comparado com os outros testes preconizados pelo PNCEBT, apresentando-se, portanto, como uma ferramenta útil para o diagnóstico da brucelose bovina, além de ser de execução fácil e rápida / Abstract: The study aimed to analyze the antibody response induced by vaccination with the standard dose of 60-120x109 organisms of Brucella abortus strain 19 in Tabapuã heifers, aged between 3 and 8 months, by serological tests recommended by the National Program for Brucellosis and Tuberculosis Control and Eradication (PNCEBT) for the diagnosis of bovine brucellosis. Serum samples of 72 animals were examined by four serological tests: rose Bengal test (RBT), standard agglutination test with the 2-mercaptoetanol (2-ME) test, complement fixation test (CFT) and fluorescence polarization assay (FPA), which was interpreted in two ways: variable cutoff and fixed cutoff. Heifers were bled immediately prior to vaccination, and after 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 days. Specificity of the tests were calculated, and the results were compared using the kappa statistic and the McNemar's ² test. The FPA had a higher specificity than the other tests on the samples collected from 30 to 90 days after vaccination, but over time this difference decreased. At 270 days of vaccination, the specificity of RBT, 2-ME and RFC was 93.74%. The specificity of the FPA with variable cutoff was 87.5%, and with fixed cutoff was 100.0%. It was concluded that FPA had a higher discrimination ability for vaccination antibody titers shortly after vaccination, when compared with other tests recommended by the PNCEBT, and is a useful tool for the diagnosis of bovine brucellosis, besides being easy and quick to perform / Mestre

A mortalidade fetal é uma causa importante de perdas reprodutivas em animais domésticos e tem impacto significativo na rentabilidade de um sistema de produção animal. No Brasil, poucas informações são disponíveis sobre as principais causa de aborto em bovinos. O presente estudo resultou em cinco artigos. O primeiro artigo descreve as principais causas de aborto bovino diagnosticadas no Setor de Patologia Veterinária da Universidade Federal do Rio Grande do Sul no período 2003-2011. Neste período um total de 490 fetos bovinos foi analisado. Causas específicas de aborto foram encontradas em 46,7 % dos casos. Infecções por protozoários, em especial Neospora caninum acometeram 33 % dos casos (162/490). Bactérias em 6,3 % (31/490), seguidas por fungos 0,8% (4/490) foram causas adicionais de abortos. Em dois fetos (0,4 %), coinfecções por dois agentes foram identificadas. Causas não infecciosas foram observadas em 3 % dos abortos e malformações congênitas a 2,6%. No segundo artigo estima-se a ocorrência de abortos por Brucella abortus em bovinos na região sul, caracterizando os achados macroscópicos, histopatológicos, bacteriológicos, imuno-histoquímicos e de PCR desta enfermidade. No terceiro artigo relata-se a infecção por Geotrichum candidum em feto bovino abortado associado a lesões de pele e pulmonares. A ocorrência de malformações congênitas múltiplas em um feto bovino abortado é relatada no quarto artigo e casos de condrodisplasia tipo Dexter em fetos bovinos abortados são descritos no quinto. / The fetal mortality is an important cause of reproductive failure in domestic animals and has a significant impact on the profitability of a livestock production system. In Brazil, little information is available on the main cause of abortion in cattle. This study resulted in five articles. The first article describes the main causes of abortion in cattle diagnosed in the period January 2003 to december 2011. A total of 490 fetuses, from several Brazilian states, were evaluated. Specific causes of abortion were found in 46,7 % of cases. Protozoan abortions especially Neospora caninum were detected in 33 % (162/490) of the cases. Bacterial abortions corresponded to 6,3 % (31/490), followed by fungal 0,8 % (4/490). In two aborted fetuses (0,4 %), a co-infection with two agents could be identified. Noninfectious diseases could be associated with 3 % of the abortions and congenital malformations with 2,6%. In the second article estimated the incidence of abortion by Brucella abortus in cattle in the southern region, characterizing the macroscopic findings, histological, bacteriological, immunohistochemical and molecular aspects of this disease. The third article relates a Geotrichum candidum infection in aborted bovine fetus associated with skin and lung lesions. The occurrence of multiple congenital malformations in an aborted bovine fetus is reported in the fourth article and cases of Dexter chondrodysplasia type of aborted fetuses are described in the fifth.

A mortalidade fetal é uma causa importante de perdas reprodutivas em animais domésticos e tem impacto significativo na rentabilidade de um sistema de produção animal. No Brasil, poucas informações são disponíveis sobre as principais causa de aborto em bovinos. O presente estudo resultou em cinco artigos. O primeiro artigo descreve as principais causas de aborto bovino diagnosticadas no Setor de Patologia Veterinária da Universidade Federal do Rio Grande do Sul no período 2003-2011. Neste período um total de 490 fetos bovinos foi analisado. Causas específicas de aborto foram encontradas em 46,7 % dos casos. Infecções por protozoários, em especial Neospora caninum acometeram 33 % dos casos (162/490). Bactérias em 6,3 % (31/490), seguidas por fungos 0,8% (4/490) foram causas adicionais de abortos. Em dois fetos (0,4 %), coinfecções por dois agentes foram identificadas. Causas não infecciosas foram observadas em 3 % dos abortos e malformações congênitas a 2,6%. No segundo artigo estima-se a ocorrência de abortos por Brucella abortus em bovinos na região sul, caracterizando os achados macroscópicos, histopatológicos, bacteriológicos, imuno-histoquímicos e de PCR desta enfermidade. No terceiro artigo relata-se a infecção por Geotrichum candidum em feto bovino abortado associado a lesões de pele e pulmonares. A ocorrência de malformações congênitas múltiplas em um feto bovino abortado é relatada no quarto artigo e casos de condrodisplasia tipo Dexter em fetos bovinos abortados são descritos no quinto. / The fetal mortality is an important cause of reproductive failure in domestic animals and has a significant impact on the profitability of a livestock production system. In Brazil, little information is available on the main cause of abortion in cattle. This study resulted in five articles. The first article describes the main causes of abortion in cattle diagnosed in the period January 2003 to december 2011. A total of 490 fetuses, from several Brazilian states, were evaluated. Specific causes of abortion were found in 46,7 % of cases. Protozoan abortions especially Neospora caninum were detected in 33 % (162/490) of the cases. Bacterial abortions corresponded to 6,3 % (31/490), followed by fungal 0,8 % (4/490). In two aborted fetuses (0,4 %), a co-infection with two agents could be identified. Noninfectious diseases could be associated with 3 % of the abortions and congenital malformations with 2,6%. In the second article estimated the incidence of abortion by Brucella abortus in cattle in the southern region, characterizing the macroscopic findings, histological, bacteriological, immunohistochemical and molecular aspects of this disease. The third article relates a Geotrichum candidum infection in aborted bovine fetus associated with skin and lung lesions. The occurrence of multiple congenital malformations in an aborted bovine fetus is reported in the fourth article and cases of Dexter chondrodysplasia type of aborted fetuses are described in the fifth.