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The role of the pre-implantation embryo in the vertical transmission of natural scrapie

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Abstract of Summary of a project undertaken by the Scottish Agricultural College, Edinburgh.

In recent years diseases that are termed "transmissible spongiform encephalopathies" (TSEs) have caused widespread public attention. These diseases include BSE of cattle which was first seen in the 1980s, CJD in humans and scrapie in sheep. Scrapie has been known for centuries, it is common and untreatable and results in brain degeneration and death.

Recently our understanding of scrapie infection has improved but there is still some uncertainty as to how lambs become infected, so it is unclear how to prevent the spread of infection. A common method to ensure that infections are not spread is to introduce new animals into groups by embryo transfer (ET) by collecting from donor animals their fertilised eggs (embryos) that are uninfected by diseases and to put these into surrogate mothers in new flocks or groups. Though generally used as a means of disease control and with international standards for embryo handling published by the International Embryo Transfer Society (IETS) it is not clear if scrapie can be spread through ET. In part, this is because TSE infections do not belong to the conventional type of diseases, like virus or bacterial infections, but also because of conflicting views and reports. Findings from the USA had not shown the spread of scrapie from experimentally infected donor sheep to their lambs.

The objective of the study was to see if embryos collected from sheep that subsequently died of scrapie could be transferred into a new group of animals without the transmission of scrapie. To avoid the potential for other sources of scrapie infection the study was carried out on quarantined premises and also included sheep that were highly susceptible to scrapie but imported from New Zealand to ensure freedom from the disease. The study is important in establishing the potential for spread of scrapie by the embryo and has major implications for control of infection through the use of embryo transfer technology.

- 57 lambs were produced from embryos collected from ewes that died of scrapie in an infected flock

- 50 of the lambs were confirmed as being susceptible to scrapie. These animals were born and kept in an isolation facility with other animals and with lambs that were bred from New Zealand imported sheep using the same ET methods.

- Lambs were kept to 5 years of age and 41 of the study animals survived to the end point of the work

- Post-mortem examinations were carried out on all animals in the study, including those of New Zealand origin, and in none was any evidence of scrapie found

- In the original flock of sheep there was 56% mortality in scrapie susceptible animals between 1989 and 1994 with 76 individuals dying of scrapie between 19 and 64 months with the mean age for the first signs of scrapie infection being considerably shorter than the 5 years for which the study animals were kept without evidence of scrapie

The work shows no evidence for the spread of scrapie through the embryos collected from embryo infected sheep. However, the size of the experiment does not exclude the possibility that scrapie transmission may occur at a low level and below the limit of detection for the study. To examine this further, information from the flock of origin can be used for statistical comparison and this allows us to be 95% confident that if scrapie is transmitted via transferred embryos then it must occur at a rate of less than 7 in 100. This work reinforces earlier published evidence from the USA that concluded that spread of scrapie can be avoided by embryo transfer procedures. The conclusions are scientifically robust and are of major relevance to policy makers and to the international trade in livestock.

For the full report and references see: http://randd.defra.gov.uk/Document.aspx?Document=SE1834_6974_FRP.doc

[01/02/2008]