National Scrapie Plan: Atypical Cases of Scrapie
Classical Scrapie
Transmissible Spongiform Encephalopathies (TSEs) are a family of fatal diseases of the brain and include scrapie and BSE. In Great Britain scrapie has been known to be present in sheep for more than 200 years and over the years it has been clearly shown that there is a genetic influence that appears to determine whether an animal will succumb if exposed to infection. This genetic effect is linked to the PrP gene and sheep carrying the VRQ allele appear to be the most susceptible to clinical scrapie with ARR carrying sheep being the most resistant. More information on alleles and genotyping is available.
However, recently, across Europe, including Great Britain, following the introduction of more rigorous surveillance with new, sensitive, diagnostic tests, there have been reports of what appears to be a previously undetected form of scrapie, termed atypical scrapie. There are some clear differences between the newly identified atypical scrapie and the classical strains of scrapie that are well documented in the UK.
Atypical Scrapie - Active (Targeted) Surveillance
In GB these atypical scrapie cases were first detected through the active surveillance programme where brain samples from sheep and goats sent for slaughter and from fallen stock are tested for the presence of a TSE. This EU-wide active surveillance programme was launched in 2002 with the aim of establishing the prevalence of TSEs in Europe. During the first year of testing the Veterinary Laboratories Agency (VLA) reported that there were a number of samples from sheep that were giving unusual results and required further investigations.
These further investigations revealed that the samples give very distinct
results that are different from both classical scrapie and experimental
BSE in sheep, using the current diagnostic methods. What is also striking
about these atypical cases of scrapie are the genotypes in which these
cases occur. As stated above, for classical scrapie the VRQ allele appears
to confer most susceptibility with the ARR allele conferring the most
resistance. However the atypical cases of scrapie tend to occur in sheep
carrying the alleles considered to be more resistant to scrapie, including
the ARR allele. Table 1 shows the number of atypical and classical scrapie
cases detected by active surveillance since 2002 up to December 2006 against
the genotypes of the affected sheep. (Note: the samples from the abattoir
are taken from older animals so the survey is likely to underestimate
the number of classical scrapie cases in the VRQ/VRQ genotype as they
will have already succumbed to the disease at a younger age).
| PrP Genotype |
NSP Type |
Number of Classical Scrapie |
Number of Atypical Scrapie |
| ARR/ARR |
1 |
0 |
16 |
| ARR/AHQ |
2 |
0 |
40 |
| ARR/ARH |
0 |
1 |
|
| ARR/ARQ |
1 |
18 |
|
| AHQ/AHQ |
3 |
1 |
19 |
| AHQ/ARH |
0 |
3 |
|
| AHQ/ARQ |
4 |
31 |
|
| ARH/ARH |
0 |
0 |
|
| ARH/ARQ |
2 |
1 |
|
| ARQ/ARQ |
27 |
19 |
|
| ARR/VRQ |
4 |
40 |
0 |
| VRQ/AHQ |
5 |
0 |
0 |
| VRQ/ARH |
15 |
0 |
|
| VRQ/ARQ |
91 |
1 |
|
| VRQ/VRQ |
15 |
0 |
Table 1: Genotype profile of classical and atypical cases of scrapie detected from testing 205,677 active surveillance samples (as of December 2006).
The discovery of these cases through the EU wide surveillance programme has prompted much scientific discussion and research, both within Great Britain and across Europe. However there still remains much uncertainty as to the significance of these cases and what they represent, although there are some points that there appears to be agreement on:
-
Results for atypical cases are not consistent with the results obtained from experimental BSE in sheep;
-
The atypical cases of scrapie are now being detected because developments and improvements to diagnostic methods have made them more sensitive.
Atypical Scrapie - Passive (Scanning) Surveillance
The more sensitive diagnostic methods are now being applied to animals that are being reported through the passive surveillance programme. Passive surveillance is where animals showing clinical signs suggestive of the disease are reported, as required by law, to Animal Health. Samples of brain material are then tested by the VLA for the presence of a TSE. The new diagnostic methods allow the VLA to define a TSE positive sample as having:
- Classical Scrapie;
- BSE or
-
Atypical Scrapie.
By testing the samples submitted through passive surveillance the VLA has detected a number of animals with clinical signs that have atypical scrapie. Small numbers have also been detected in other European countries. It should, however, be noted that no country has yet reported an atypical case of scrapie with clinical signs in an ARR/ARR animal.
Since July 2004 up to December 2006, the VLA has detected 6 cases of atypical scrapie through the passive surveillance with 3 cases in AHQ/ARQ sheep, 2 in ARR/AHQ sheep and 1 AHQ/AHQ sheep.
In this country atypical scrapie has so far only been detected in sheep. However within the rest of Europe there have been a small number of reports of atypical scrapie occurring in goats.
Application of EU Control Measures to Atypical Scrapie
Atypical cases of scrapie are assumed to be true TSEs, so flocks where these sheep are considered to have been infected should theoretically be subject to the measures under the Compulsory Scrapie Flocks Scheme (CSFS). Under this Scheme flocks are either genotyped and the susceptible genotypes culled or the whole flock culled. However, the Department’s view is that this action does not appear to be appropriate for flocks with atypical cases of scrapie for a number of reasons, including:
-
The cases tend to occur in animals with genotypes considered to be more resistant to classical scrapie;
-
In Europe where whole flock culls have taken place and the culled animals TSE tested, they do not find more than two or three additional animals that have atypical scrapie. In fact in most flocks they do not find any other positive atypical cases of scrapie. It therefore remains to be confirmed that atypical scrapie transmits naturally from sheep to sheep.
For these reasons, at present flocks where atypical scrapie occurs are not subject to the CSFS controls. However, if a case of atypical scrapie is recorded on a holding this does mean that under the current rules of Regulation 999/2001 (EC) as amended, breeding sheep and goats from that holding are not eligible for intra-community trade for a period of three years from the date that the last case occurred, except for animals of the ARR/ARR genotype.
Also an epidemiological study has been launched to try and establish whether or not atypical scrapie behaves similarly to classical scrapie.
Q&A
1, What do atypical scrapie cases mean for the National Scrapie Plan?
The atypical cases of scrapie were discussed in January 2006 by the
Spongiform Encephalopathy Advisory Committee
(SEAC) Sheep Subgroup. The Subgroup’s Position
Statement 
(80 KB) concluded that: “The new data, and identification of the
atypical cases of scrapie, while of concern, are insufficient to justify
immediate changes to the NSP. Nevertheless, the subgroup strongly recommends
that the NSP should be kept under continuous review as new findings emerge.”
2. Did the Sheep Subgroup reach any other conclusions?
Yes - the subgroup made a number of recommendations for research that they feel should be implemented. They also discussed if there was any potential impact for human health and concluded that “there is no evidence of a risk to human health, but a theoretical risk cannot be excluded."
3. What does the Food Standards Agency say about atypical scrapie?
In December 2006 the Food Standards Agency launched a new website detailing their current position on atypical scrapie.
4. If an animal from my flock is confirmed as having atypical scrapie, what will happen?
Currently if a case of atypical scrapie is recorded on your holding, restrictions will not be imposed. However it is possible that new EU rules may require restrictions to be imposed if cases occur in the future.
However, if a case of atypical scrapie is recorded on a holding this does mean that under the current rules of Regulation 999/2001 (EC) as amended, breeding sheep and goats from that holding are not eligible for intra-community trade for a period of three years from the date that the last case occurred, except for animals of the ARR/ARR genotype.
5. Is atypical scrapie caused by BSE in sheep?
No - using the current diagnostic methods and the knowledge that has been gained through transmitting BSE experimentally to sheep, atypical scrapie appears to be very different and distinct from BSE (and from classical scrapie).
6. Are all atypical scrapie cases the same?
There appears to be very subtle differences between some of the cases and it is possible that the atypical scrapies represent more than one type of scrapie. However it is not yet possible to precisely subdivide cases into specific types.
7. How does an animal get atypical scrapie?
In classical scrapie it is known that most animals are infected through exposure to scrapie infected sheep and their environment, especially during lambing. However at present it is unclear if this is the case for atypical scrapie. At this time it is not known whether atypical scrapie can transmit naturally between sheep.
8. Do atypical cases of scrapie really belong to the Transmissible Spongiform Encephalopathy family?
Yes - atypical scrapie does appear to be a true TSE. Research has shown that atypical scrapie cases can be transmitted to genetically altered mice (these are called transgenic mice and in this case they had been altered to carry the sheep VRQ allele) demonstrating that atypical scrapie is truly transmissible. More recently atypical scrapie has also been transmitted experimentally to sheep.
9. In November 2006 Defra reported that atypical scrapie had occurred in a flock believed to be free of TSEs. What does this mean?
- Information bulletin - November 2006
The VLA maintains a flock of sheep imported from New Zealand, a country considered to be free of TSEs, for research purposes. A sheep from that flock, which was born to New Zealand parents, has tested positive for atypical scrapie. Defra has informed colleagues in New Zealand of this finding and initiated an independent audit of the finding. This audit has now been completed and has been published in a report (152 KB). For a brief summary of this report, please see this Information Bulletin. The VLA's observations (211 KB) on this report are also available. This report will be discussed by SEAC at their meeting on 10th May 2007.
10. What is the European Commission doing about atypical cases of scrapie?
In the Commission’s TSE
Roadmap
(117 KB) published in July 2005, which sets out future proposals for the
control of TSEs in Europe, the Commission acknowledged that the current
control measures might not be appropriate in cases with atypical scrapie
and discussions on changes to these control measures are currently on-going.
11. Have the European Food Safety Authority (EFSA) made any comments about atypical scrapie?
EFSA’s BIOHAZ Panel has issued two opinions relating to atypical scrapie. The first opinion relates to the classification of atypical Transmissible Spongiform Encephalopathy (TSE) cases in small ruminants. The second relates to the breeding programme for TSE resistance in sheep, which includes the impact that atypical scrapie might have on these programmes. The opinion concludes ‘that on the general risks associated with current breeding strategy up to date no adverse effects have been stated’.
12. Is there a research programme under way in Great Britain to investigate what the atypical cases of scrapie are?
Yes - several research projects have been initiated. However, because
of the long incubation period of TSEs, it will take a number of years
before some of the results of this work are available. An overview of the current research into atypical scrapie is available.
Page last
modified:
19 March, 2008
Page last reviewed:
19 March, 2008