SEAC

Position Statement

Food standards agency atypical scrapie contingency plan

Issue

1. In June 2006 the Food Standards Agency (FSA) Board considered current precautionary risk management measures for small ruminants. The Board agreed that current precautionary measures were sufficient. However, they wished to develop a contingency plan in case SEAC’s understanding of the risk of atypical scrapie for human health changed. To inform this contingency plan the FSA requested SEAC advice on potential outcomes of research on atypical scrapie, or surveillance results, that may lead to a change in SEAC’s estimate of the risk to human health.

Background

2. In February 2006 the SEAC sheep subgroup published a position statement on atypical scrapie1 which concluded that atypical scrapie should be considered a distinct transmissible spongiform encephalopathy (TSE) of small ruminants and not simply a variant of classical scrapie. While there was no evidence that atypical scrapie could infect humans, a theoretical risk could not be excluded. SEAC concluded, however, that there were insufficient data available to adequately assess the potential risks to human health. The subgroup recommended that an adequate assessment of the potential risk to human health of atypical scrapie might come from studies on the prevalence, transmission in animal models, tissue distribution and human health surveillance.

3. SEAC considered the potential significance of the outcomes of these areas of research for the human health risk from atypical scrapie, based on scenarios put forward by the FSA2.

Prevalence

4. The SEAC sheep subgroup statement concludes that there could be around 82,000 sheep in the UK infected with atypical scrapie. Future surveillance and epidemiological studies along with the analysis of sheep brain tissue samples dating back to 1964 may confirm the historical presence of the disease, changes in prevalence over time, and whether or not atypical scrapie may occur in countries previously thought to be free from classical and atypical scrapie. SEAC considered that the identification of historical cases, new cases in scrapie-free countries, and changes in prevalence of atypical scrapie would be significant from a public health perspective. If such data indicate that atypical scrapie has been present for many years, and is not increasing in prevalence then, by analogy with classical scrapie the human health risk would be considered low. However, if atypical scrapie were found to be spreading rapidly, this would imply it is a new disease and any human health risk would be more uncertain. It is therefore important to continue to assess the historic prevalence of atypical scrapie, and for archived sheep samples be analysed for the presence of the disease.

5. A human health risk would only be confirmed by concomitant changes in the prevalence of new types of Creutzfeldt-Jakob Disease (CJD). Because of the long incubation periods of prion diseases, such data may not become apparent for many years, although atypical scrapie has been identified in a UK sheep from 1989, implying that humans may have been exposed to atypical scrapie via the dietary route for a number of years. In the absence of data suggesting a link to a new type of CJD SEAC would be unlikely to change its current assessment of the human health risk.

Transmission studies

6. Results from transmission studies using non-human primates, particularly via the oral route, would strongly inform the understanding of human health risk. The immune and lymphoreticular systems of non-human primates are closely related to those of humans and the peripheral pathogenesis of TSEs in non-human primates mimics that in humans. However, non-human primates only provide data relating to one genotype, MM, which comprises about 37% of the UK population3. Assessment of the level of risk would require comparison with transmissions of other TSEs in the same models, in particular BSE, some of which are already available.

7. Humanised mice can provide data on all three human prion protein genotypes. It is important to be aware of the possibility that such mice may not show any clinical sign of infection after primary transmission of atypical scrapie, yet a secondary transmission from these animals to others may result in clinical disease due to loss of the interspecies transmission barrier. Although humanised mice are a good model for human disease, it will be critical to compare the behaviour of atypical scrapie with other TSEs, especially classical scrapie and BSE, in several mouse models after secondary transmission in order to obtain the most reliable risk assessments.

8. The barrier to transmission of atypical scrapie between animal and human can be tested in vitro by cell free conversion assays. However, care is needed in interpreting the significance of such experiments as ex vivo data do not always correlate well with in vivo studies. Nevertheless, they could provide data on whether conversion of the normal prion protein in humans to the abnormal form by the atypical scrapie prion is or is not possible.

Tissue Distribution

9. Little is known about the tissue distribution of abnormal prion protein (PrPsc) and infectivity in sheep with atypical scrapie. If atypical scrapie is found to be a health risk to humans, data from studies to assess the tissue distribution of PrPsc and infectivity are essential to allow an assessment of the risk under specific control measures.

Human Health

10. Establishing a definitive link between an animal and a human TSE is extremely difficult. Animal model data will only be indicative, and not definitive, although if carried out appropriately could be strongly indicative of a human health risk. The emergence of a new type of CJD which shows the same transmission characteristics as atypical scrapie in non-human primates and humanised mice would provide a strong indication that transmission had occurred through the consumption of infected material. Thus, ongoing human surveillance is critical.

11. It is difficult to conclude that atypical scrapie is not a human health risk from negative experimental or surveillance results. However, negative results from current and retrospective surveillance and transmission studies, over a significant period of time to allow for possibly long incubation periods, would imply a negligible human health risk.

Conclusion

12. It is not possible to assess the human health risk from atypical scrapie, or changes in risk, in the absence of hard scientific data. No single data set is likely to be definitive and it would be essential to consider all the information available, rather than data from single studies in isolation. Studies comparing the properties of atypical scrapie and other TSE agents using the same animal model, especially humanised mice or non-human primates, would be most informative in the short term. Surveillance data to assess any association between forms of CJD and atypical scrapie prevalence would be most persuasive but are unlikely to become available in the short term. SEAC would have to review experimental methods and results, should they emerge, before any conclusion of a change to the risk to human health from atypical scrapie could be made.

 

1 http://www.seac.gov.uk/pdf/positionstatement-sheep-subgroup.pdf (97 KB)
2 http://www.seac.gov.uk/papers/97-3.pdf (110 KB)
3 Palmer and Collinge (1993) Mutations and polymorphisms in the prion protein gene. Hum. Mutat. 2, 168-173.

Page updated: 6 September, 2007