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.

Zugl.: Giessen, Univ., Diss., 2009

Paratuberculosis (Johne's disease) imposes a significant problem to the world dairy and beef industries and today is considered a potential zoonosis. The disease is caused by Mycobacterium avium subsp. paratuberculosis and is characterized by progressive weight loss and profuse diarrhoea. Susceptibility to infection is suspected to have a genetic component, and moderated values for heritability of infection have been reported. Interferon gamma is an inducible cytokine with a crucial role in the innate host response to intracellular bacteria. Toll-like receptors are trans-membrane structures responsible for coordination of innate and adaptive immune responses. The solute carrier family 11 member 1 (SLC11A1, formerly NRAMP1) gene plays an important role in innate immunity, preventing bacterial growth in macrophages during the initial stages of infection. The objective of this candidate gene case-control study was to characterize the distribution of polymorphisms in three candidate genes related to the immune function; interferon gamma (BoIFNG), toll-like receptor 4 (TLR4), and SLC11A1 genes and to test their role as potential risk factors for paratuberculosis infection in cattle. The statistical analysis demonstrated significant differences in allelic frequencies between cases and controls for BoIFNG-SNP12781 and SLC11A1 microsatellites, indicating a significant association between infection and variant alleles. In the analysis of genotypes, a significant association was also found between infection status and BoIFNG-SNP12781 and SLC11A1-275-279-281 microsatellites. However, when variables such as breed and age were included in the multivariate logistic regression analysis, a tendency toward statistical significance for the effect of polymorphisms in the odds of infection was only found for alleles SLC11A1-275 and 279.

No description available.

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

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2009. / Härtill 5 uppsatser.

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.

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.

Zugl.: Oldenburg, Universiẗat, Diss., 2009.

Zugl.: Giessen, Univ., Diss., 2008