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Experimental oral transmission of atypical scrapie to sheep

by Vets-net.com May 27 2011
Experimental oral transmission of atypical scrapie to sheep To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals' peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain. Since the discovery of atypical scrapie and its subsequent identification, mostly through active surveillance, in several countries (some with no previous history of transmissible spongiform encephalopathies [TSEs]) such as New Zealand and Australia, scientists have debated whether this form of TSE is in fact spontaneous or acquired rather than contagious. The epidemiologic studies that have been undertaken suggest that atypical scrapie does not appear be transmitted between animals in the field situation. Although the routes by which natural transmission occurs have never been fully established for TSEs, it is widely accepted that ingestion of infective material, i.e., the oral route, is a key component in some TSEs, e.g., kuru, variant Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, and transmissible mink encephalopathy. Within the sheep population, susceptibility to particular strains of TSE has been shown to be heavily affected by polymorphisms of the prion protein gene of the sheep. The successful transmission of atypical scrapie to sheep after intracerebral inoculation has been previously reported for sheep of 1 genotype (A136H154Q171/A136H154Q171), and challenges in other homologous and heterologous genotype combinations are ongoing. However, successful intracerebral transmission of a particular TSE agent in a particular species does not necessarily indicate susceptibility by the oral route. The tissue distribution of infectivity or disease-specific prion protein (PrPSc) in bovine spongiform encephalopathy in sheep has led to extensive public health control measures based on the known pathogenesis and distribution of PrPSc in edible tissues, and their removal from carcasses of animals over a certain age. Classic scrapie may also show the widespread accumulation of PrPSc in peripheral tissues. Although early studies of atypical scrapie did not show PrPSc or infectivity outside the brain, recent data indicate that peripheral tissues from naturally infected animals can harbor infectivity either in the presence or absence of PrPSc. However, whether this infectivity is established before or after the agent has propagated in the central nervous system is unknown. The first aim of the current study was to examine the distribution of infectivity in peripheral tissues in animals at and beyond the cutoff point for the current meat hygiene regulations of the European Commission (i.e., 12 months of age). The second aim was to investigate the potential for oral transmission of atypical scrapie. Emerging Infectious Diseases May 17, 2011
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