Statement

- 10th July 1996

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A. The experimental transmission of BSE to sheep

Studies have shown that the "negative" line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE). Five of the six sheep inoculated intracerebrally developed disease between 440 and 2353 days after inoculation. The short incubation periods were found in animals homozygous for alanine at codon 136 and for glutamine at codon 171 of the PrP gene. One of the six sheep challenged orally developed disease with an incubation period of 734 days. It too was homozygous for alanine at codon 136 and for glutamine at codon 171.

Brain and spleen tissue from the orally infected sheep and the intracerebrally infected sheep with an incubation period of 440 days were inoculated into the panel of mouse strains used for strain typing. The incidence of spongiform encephalopathy in all strains of mice was high (excluding intercurrent deaths) and similar for both tissues from both sheep. The pattern of incubation periods and lesion profiles of the transmissions from the four sheep tissues was very similar to that seen with BSE from cattle and clearly different from natural scrapie in a Greyface sheep tested concurrently. These data indicate that:

the infectivity recovered from sheep is BSE-like on strain typing but in terms of one biological characteristic, recovery of significant infectivity from the spleen, BSE in sheep is scrapie-like, raising the possibility that the BSE agent might behave like scrapie and become endemic in a flock;

polymorphisms at codon 136 and 171 of the PrP gene may have an important effect on the susceptibility of sheep to BSE and the incubation period.

B. The risk of exposure of sheep to BSE through feed

Production of sheep concentrates increased steadily between 1980 (131,000 tonnes) and 1994 (567,000 tonnes). This increase is greater than the rise in the sheep population. In 1980 1 tonne of concentrate per 230 sheep was produced, in 1984 1 per 125, in 1988 1 per 90 and in 1992 1 tonne per 80 sheep. This compares with 1 tonne of cattle concentrate per 3 cows in 1988 but takes no account of more targeted use of concentrates in the national flock (or herd).

Government statistics do not record the inclusion rates of raw materials in sheep rations. Enquiries of member companies of UKASTA indicate that meat and bone meal was not used by some companies because of concerns about palatability for sheep, but it was used by others, some regularly and some irregularly depending on price. Overall the range of incorporation of meat and bone meal would have been 1-5% but it has been illegal to use meat and bone meal in sheep rations since July 1988. However exposure due to accidental contamination in feed mills might have occurred.

Two thirds of the sheep concentrates produced are for breeding ewes. Moreover hill flocks receive far less concentrates than lowland flocks. The other extreme is the early lambing flock which is smaller than hill flocks, requires winter housing and considerable supplementary feeding. Lambs born in early winter with a target of being sold as fat lambs for Easter require large quantities of supplementary feed. Regimens of intermediate intensity will apply to lowland and upland early/spring lambing flocks depending on early access to grass and the breed. Some flocks act as sources of replacement breeding stock for later cross-breeding and thus do not need to rely on supplementary feeding prior to sale. If an early lambing flock was infected with BSE the risk to other flocks is low because most lambs are fed and slaughtered within the first few months of life and culled ewes are almost always slaughtered rather than sold for breeding. This information indicates that:

a search for the BSE agent in sheep should concentrate on early lambing flocks, where both lambs and ewes are likely to have been fed meat and bone meal in the past, taking genotype into account (see Section A);

a search should include young animals to help distinguish endemic infection from that induced by contaminated feed.

C. The incidence of scrapie in the national flock

Historically scrapie cases were recorded as those which were confirmed at a Veterinary Investigation Centre, often from flocks which had not previously experienced the disease. The figures are an underestimate as many farmers would recognise the disease without submission to post-mortem examination. Nevertheless the figures for sheep scrapie cases (top line) and BSE in cattle (bottom line) by year of diagnosis are:

The scrapie figures are distorted because payments were offered between October 1990 and August 1992 for cases when brain pools were being assembled for rendering experiments. A total of 2867 brains was collected many of which were recorded in the data base. The figures are further distorted by the requirements to notify scrapie from 1993 onwards. The effect of this is that during a given two-year period only the first case in a flock is recorded and, therefore, since 1993 the statistics denote affected flocks rather than individual cases. The data indicate that:

it is impossible to say whether or not there has been any change in incidence of sheep scrapie coincident with BSE in cattle in the UK.

D. The survey of sheep scrapie strains since 1986

To date nine UK isolates of scrapie contemporary with the outbreak of BSE have been strain typed. None has proved to be BSE-like and all seven that have been transmitted to mice have strain typing characteristics within the range expected of classical scrapie. In project SE 1919 at the Central Veterinary Laboratory, brains from sheep with scrapie born after January 1 991 in flocks already known to have confirmed scrapie are being collected. Payment is offered to owners as an incentive to notify cases. Brains will be pooled according to sheep genotype at codons 136 and 171 to increase the opportunity of isolating a BSE-like strain. The project is still in the collection phase. A later collection phase is planned to include pools of LRS tissues as well as of brains.

A similar project (SE 1423) at NPU will attempt isolation from single sheep again selected according to genotype. The avoidance of pooling should increase the sensitivity of isolation but the extent of the project will not provide a nationwide screen. At a meeting on 1 February 1996, SEAC recommended that high priority should be given to a study to infect, by the oral route, scrapie-free sheep (preferably from New Zealand) of a PrP genotype known to be susceptible to BSE, and then investigate whether or not BSE was transmitted naturally to subsequent generations.

From the above date we conclude that:

results of a sufficiently representative survey of the strain characteristics of the infectious agent of scrapie in the national flock since the start of the BSE epidemic are not yet available.

E. Sheep slaughter practices

Information on the age of scrapie cases in the UK is limited but analysis of the data from scrapie cases confirmed between 1980 and 1990 for which the age is known shows the following:

The scrapie agent is present at high titre in the brain and spinal cord during the clinical phase. In a study of natural scrapie in Suffolk sheep this occured at 34-57 months. In these sheep the agent was detectable at low to medium titre in the intestines, lymph nodes, spleen and tonsils, at 10-14 months and at low titre in the brain at about 25 months when the a nimals were in the preclinical phase of the infection.

Approximately half the national flock is slaughtered each year. Of these approximately 80% are lambs and 20% rams and ewes. Intestines are processed for human consumption but not brains or spleens except to minority groups. Four Halal sheep slaughterhouses were visited in April 1996 by the SVS. At one of the premises, brains were being removed for supply to retail outlets, another was supplying whole skinned heads and a third had supplied brains until a few months previously. The fourth treated all heads as waste. A few spleens were said to be supplied to retail outlets from one of the premises. From the foregoing we conclude that

if BSE is capable of infecting man by the oral route and if BSE is present in the sheep population then brain could pose a potential risk to human health if eaten. Spinal cord could also present a risk if consumed. The agent will be present in lower titre in these tissues in animals the preclinical phase of infection.

if BSE has passed to sheep and behaves like scrapie

it would also be present in the lymph nodes, spleen and parts of the intestine in medium titres in animals in the preclinical phase.

F. Discussion

There is not the same accurate picture of the incidence of scrapie in the UK as there is of BSE in cattle and CJD in humans. It is thus impossible to tell whether the incidence has changed in the past 10 years. It is important that accurate data are gathered in case BSE is linked to human disease and in case the causative agent has been transmitted to the national sheep flock in which it might become naturally sustained. Scrapie could be quite common. If there was 10-fold under reporting in the year of highest recorded incidence (1991) up to 1 in 500 rams and ewes going to slaughter could be affected. We therefore advise

the immediate initiation of a research programme to establish the prevalence of scrapie. This could include microscopic examination of the brain or tonsil after suitable staining and/or immunoblotting of CNS or peripheral tissues such as spleen and lymph nodes.

Sheep in the UK have been given less concentrates than cattle and some of the concentrates fed to sheep would not have contained meat and bone meal. Nevertheless, it is possible that feed-borne infection of some sheep with the BSE agent has occurred. The key questions are (a) the extent of feed-borne infection, if it has occurred, and (b) whether or not this could have led to sufficient natural transmission of the BSE agent for it to become established as an endemic infection of sheep. For these reasons it is essential to extend our knowledge of the characteristics of the scrapie strains currently present in the national flock. Projects SE 1919 and SE 1423 are critical to this and we therefore advise that:

the resources devoted to these projects (and the other project that was highly recommended at the meeting of SEAC 24) be reviewed to decide whether it would be possible to minimise the time taken to accumulate the data.

If these studies provide evidence that the BSE agent is endemic in at least part of the national flock, the potential risks to humans from sheep could no longer be regarded as being as low as in the past and measures to protect public health would certainly have to be considered. It is also possible that a mutant scrapie strain, quite unrelated to BSE, could arise at any time in the sheep population and, depending on the PrP genotype, might then be selected to become a major new scrapie strain. There could be a potential risk to man from such a strain, particularly from exposure to large amounts of agent. In young infected animals, the spleen and lymph nodes contain more infectious agent than the central nervous system but this changes during the second half of the incubation period and, eventually, the CNS contains far more agent than any other tissue.

In view of an inherent degree of uncertainty about the continuing low risk to man from scrapie, SEAC considers that a high prevalence of endemic scrapie in the United Kingdom's large sheep population will not be acceptable in the long term. Therefore, we recommend that:

Ministers should consider supporting a strategic programme of research, which fully exploits the major technical and other recent advances in the field, with the objective of controlling scrapie and, ultimately, of eradicating it from the United Kingdom.

G. Conclusion

BSE has been experimentally transmitted to sheep by the oral route. It is quite likely that some sheep in the national flock have been exposed to an infectious dose through being fed contaminated concentrates. Whether or not BSE is being sustained in any part of the national flock is completely unknown. Extreme prudence in protecting public health might dictate the introduction of a sheep offal ban. All members of SEAC recognise that this might have a very damaging effect on the sheep industry. There are simply insufficient data from which to draw a logical conclusion and a judgement must be made. Some members of SEAC judge a sheep offal ban to be completely unnecessary. Most feel that, at the very least, brains from older sheep should not be consumed. At the end of our discussion we were unable to come to a unanimous view about the balance between an unquantifiable risk which might have significant public health implications and the economic, social and indirect public health consequences of recommending action. We advise that the Government: