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      Experimental Oral Transmission of Atypical Scrapie to Sheep

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          Abstract

          Such transmission results in peripheral tissue infectivity that is not detectable by current surveillance screening methods.

          Abstract

          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.

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          Most cited references32

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          Atypical/Nor98 scrapie: properties of the agent, genetics, and epidemiology.

          Atypical/Nor98 scrapie cases in sheep were diagnosed for the first time in Norway in 1998. They are now identified in small ruminants in most European countries and represent an increasingly large proportion of the scrapie cases diagnosed in Europe. Atypical/Nor98 scrapie isolates have shown to be experimentally transmissible into transgenic mice and sheep but the properties of the TSE agent involved, like its biological and biochemical features, are so clearly distinct from the agent involved in classical scrapie that they have provided a challenging diagnostic for many years. No strain diversity has yet been identified among the atypical/Nor98 scrapie sample cases. The genetic predisposition of the sheep affected by atypical/Nor98 scrapie is almost inverted compared to classical scrapie, and the exact origin of this sporadic TSE strain is still speculative, but a spontaneous, non-contagious origin, like sporadic Creutzfeldt-Jakob disease in humans, can not be excluded. Further transmission and epidemiological studies are needed to better address this hypothesis.
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            Polymorphisms at codons 141 and 154 in the ovine prion protein gene are associated with scrapie Nor98 cases.

            Until June 2004, thirty-eight scrapie cases with unusual features, designated Nor98, have been diagnosed in Norway. This study investigated the distribution of PrP genotypes among Nor98 cases, their flock-mates and a random sample of Norwegian slaughtered sheep. The PrP genotype distribution of Nor98 cases differed markedly from that of previous cases of classical scrapie. A leucine/phenylalanine polymorphism at codon 141 with hitherto unknown significance to scrapie was strongly associated with Nor98 cases. Twenty of 38 (52.6 %) cases were either homozygous or heterozygous for phenylalanine at codon 141. In contrast, this allele was present in only 10.5 % of the flock-mates and 4.5 % of the random sample of slaughtered sheep. Moreover, the H(154) allele was represented in 24 of 38 (63.2 %) of Nor98 cases, as opposed to 27.0 % of Nor98 flock-mates and 17.0 % of the slaughtered sheep.
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              Prion diseases are efficiently transmitted by blood transfusion in sheep.

              The emergence of variant Creutzfeld-Jakob disease, following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly high transmission rates by transfusion of 36% for BSE and 43% for scrapie. A proportion of BSE-infected transfusion recipients (3 of 8) survived for up to 7 years without showing clinical signs of disease. The majority of transmissions resulted from blood collected from donors at more than 50% of the estimated incubation period. The high transmission rates and relatively short and consistent incubation periods in clinically positive recipients suggest that infectivity titers in blood were substantial and/or that blood transfusion is an efficient method of transmission. This experiment has established the value of using sheep as a model for studying transmission of variant Creutzfeld-Jakob disease by blood products in humans.
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                Author and article information

                Journal
                Emerg Infect Dis
                Emerging Infect. Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                May 2011
                : 17
                : 5
                : 848-854
                Affiliations
                [1]Author affiliation: Veterinary Laboratories Agency–Weybridge, Addlestone, UK
                Author notes
                Address for correspondence: Marion M. Simmons, Department of Pathology and Host Susceptibility, VLA-Weybridge, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, UK; email: m.m.simmons@ 123456vla.defra.gsi.gov.uk
                Article
                10-1654
                10.3201/eid1705.101654
                3321785
                21529394
                f9ab611c-5d58-4f11-a837-a421e7315871
                History
                Categories
                Research
                Research

                Infectious disease & Microbiology
                atypical,infectivity,sheep,alimentary system,prions and related diseases,scrapie agent,bioassay,research,oral administration

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