Further observations on the production of scrapie in sheep by oral dosing with foetal membranes from scrapie-affected sheep.
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Reciprocal embryo transfers were made between scrapie-inoculated and scrapie-free sheep (Cheviot and Suffolk breeds) to measure scrapie transmission via the embryo (using offspring from embryos of scrapie-inoculated donors and scrapie-free recipients) and via the uterus (using offspring from embryos of scrapie-free donors and scrapie-inoculated recipients taken by cesarean section). Two control groups of offspring, 1 from scrapie-free parents (negative) and 1 from scrapie-inoculated parents (positive), also were included. All sheep were observed for clinical signs of scrapie until death or for a minimum of 60 months. Final diagnosis was made on the basis of histopathologic findings or results of mouse inoculation and/or proteinase-K-resistant protein analysis. Thirty to 61% of the scrapie-inoculated donor/recipient sheep within groups developed scrapie within 8 to 44 months after inoculation. None of the scrapie-free donor/recipients, including those gestating embryos from scrapie-inoculated donors, developed scrapie. Also, none of the offspring observed to > or = 24 months of age from reciprocal cross, via embryo (0/67), or via the uterus (0/25), or from the negative-control group (0/33) developed scrapie. Fifty-six of the offspring via embryo, 19 of these via the uterus, and 31 negative controls survived to > or = 60 months of age. Of the 21 sheep in the positive-control group, 2 (9.5%) developed scrapie, 1 at 31 months of age and 1 at 42 months of age. In the Cheviot offspring, the percentage of sheep carrying the short incubation allele ranged from 24 to 44% and the percentage in the Suffolk offspring ranged from 61 to 83%.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was undertaken in order to examine whether any connection existed between the amounts of iron in forage and the sporadic occurrence of scrapie observed in certain parts of Iceland. As iron and manganese are considered antagonistic in plants, calculation of the Fe/Mn ratios was also included by using results from Mn determination earlier performed in the same samples. Forage samples (n = 170) from the summer harvests of 2001-2003, were collected from 47 farms for iron and manganese analysis. The farms were divided into four categories: 1. Scrapie-free farms in scrapie-free areas (n = 9); 2. Scrapie-free farms in scrapie-afflicted areas (n = 17); 3. Scrapie-prone farms (earlier scrapie-afflicted, restocked farms) (n = 12); 4. Scrapie-afflicted farms (n = 9). Farms in categories 1 and 2 are collectively referred to as scrapie-free farms. The mean iron concentration in forage samples from scrapie-afflicted farms was significantly higher than in forage samples from farms in the other scrapie categories (P = 0.001). The mean Fe/Mn ratio in forage from scrapie-afflicted farms was significantly higher than in forage from scrapie-free and scrapie-prone farms (P < 0.001). The results indicated relative dominance of iron over manganese in forage from scrapie-afflicted farms as compared to farms in the other categories. Thus thorough knowledge of iron, along with manganese, in soil and vegetation on sheep farms could be a pivot in studies on sporadic scrapie.
Mouse peritoneal macrophages were exposed to scrapie (ME7 strain) brain homogenate in vitro for 2 h at 37 degrees. The samples were assayed for infectivity by analysis of scrapie incubation periods and their values compared to those obtained after extended (1-28 days) in vitro incubation. The scrapie incubation periods for scrapie agent-macrophage mixtures which had undergone extended in vitro incubation were longer than for mixtures assayed after a 2-hour exposure to the scrapie agent. The difference in scrapie incubation periods was more dramatic when residual scrapie was eliminated by washing the cells after the 2-hour exposure to brain homogenate. The scrapie incubation period also increased following in vitro incubation of ME7 in the absence of cells; however, the changes were less than those observed for scrapie agent-macrophage mixtures. In a culture in which cells had been destroyed by UV irradiation after exposure to the scrapie agent, there was more scrapie infectivity than in a comparable culture of untreated, scrapie-exposed macrophages. These results show that scrapie infectivity decreases with extended incubation of scrapie-exposed macrophages, and the data suggest that macrophages can inactivate the scrapie agent in vitro.
The aim of this study was to analyze the epidemiology and prion protein (PrP) genetics in scrapie-affected sheep flocks in Germany. For this purpose, 224 German scrapie cases in sheep diagnosed between January 2002 and February 2006 were classified as classical or atypical scrapie and the amino acids at codons 136, 141, 154 and 171 were determined. Likewise, representative numbers of flock mates were genotyped. Significant epidemiological differences were observed between classical and atypical scrapie cases in regard to the numbers of scrapie-affected sheep within a flock, the sizes of flocks with only a single scrapie-positive sheep or more than one scrapie-positive sheep and the age distribution of the scrapie-positive sheep. Sheep with the ARQ/ARQ genotype had by far the highest risk for acquiring classical scrapie, but the risk for atypical scrapie was the highest for sheep carrying phenylalanine (F) at position 141 (AF(141)RQ) and/or the AHQ haplotype. However, atypical scrapie also occurred with a notable frequency in sheep with the PrP haplotypes ARR and/or ARQ in combination with Leucine at position 141 (AL(141)RQ). Furthermore, six atypical scrapie-positive sheep carried the PrP genotype ARR/ARR. The high proportion of sheep flocks affected by atypical scrapie underscores the importance of this scrapie type.
Scrapie is an unconventional neurodegenerative disease in sheep and goats that has been known in Europe for over 260 Years. The scrapie agents affect the brain and are transmissible from animal to animal. Key features of scrapie infections are abnormal behavior and deficits in motor function. These clinical findings can be related to the damage found in the central nervous system. In some scrapie strain-host model systems there are other manifestations of disease that appear to be related to pathological changes found in the peripheral organs, especially in the endocrine organs such as pituitary, adrenal glands, the islet of Langerhans and ovary. In those model systems in which extensive histopathological changes have been seen in peripheral organs, the titers of scrapie infectivity and the levels of the scrapie specific protein, PrPSc, are relatively low in the affected organs. These data suggest but do not prove that changes in peripheral organs are secondary to the scrapie-induced neurodegeneration that is occurring in the brain. In some scrapie strain-host combinations, obesity and aberrant glucose metabolism are seen in the preclinical and clinical phases of the incubation period. There appear to be two pathways that lead to these particular clinical manifestations. In SJL mice infected by the ME7 or 22L strains of mouse-adapted scrapie and in some scrapie-infected sheep, the mechanism is related to changes induced in the hypothalamic-pituitary-adrenal axis. The other pathway is exemplified by hamsters infected with two hamster-adapted scrapie strains, 139H and 22CH; it appears that lesions found in the hypothalamic-islets of Langerhans axis are critical. A number of reviews on the pathological changes in the central nervous system have been published and therefore, in this review article, we focus on the gross and histopathological changes in peripheral organs in several scrapie strain-host combinations. The changes induced in peripheral organs in a number of scrapie strain-host combinations expand the number of diseases in which the unconventional slow infections could serve as a model. Further work in this area could help us to understand the mechanisms and pathways of the pathological changes found in the peripheral organs of the scrapie-infected animals.
Scrapie is a fatal, neurological disease of sheep and goats and belongs to the transmissible spongiform encephalopathies. In 1998, a new type of scrapie, designated scrapie Nor98, was detected in Norway. Scrapie Nor98 differs from classical scrapie in the distribution of pathological changes and of the scrapie prion protein, the Western blot profile of the prion protein, and with isolated cases usually being observed in the case flocks. In 2004, a case-control study was conducted on scrapie Nor98 with 28 cases and 102 randomly selected controls. The questionnaire included questions on demographic data, animal contact between sheep flocks, indirect contact with equipment, use of concentrate feed and supplemental feeds, and use of medicines and vaccines. The data were analysed by using logistic regression with the sheep flock as the statistical unit. In the final model, the detection of scrapie Nor98 was related to the practice of not removing all afterbirths, the use of vitamin and mineral feed supplements, the absence of concentrate feed of swine or poultry on the farm and the presence of dogs on the farm. The results show that the epidemiology of scrapie Nor98 differs from that of classical scrapie in that no risk factors that indicate transmission of scrapie Nor98 between flocks by movement or direct contact between animals were found. Furthermore, the association between scrapie Nor98 and mineral intake shown herein should be explored further. Although the possibility that scrapie Nor98 has a low transmissibility between animals under natural conditions cannot be ruled out, the results would also be in accordance with a spontaneous aetiology.