SEAC : Public summary of the meeting on 9th November 1998

Public summary of the meeting on
9th November 1998

The Spongiform Encephalopathy Advisory Committee (SEAC) met at the offices of the Ministry of Agriculture, Fisheries and Food, Tolworth, on 9 November 1998. The Committee conducted its regular review of research findings and epidemiological information on BSE and vCJD.

The number of cases of BSE continues to decline in line with predictions about the decay of the epidemic.

The Committee noted that at that time the total number of vCJD cases in the UK was 30*. The Committee reviewed the latest experimental results on infectivity in bone marrow and dorsal root ganglia of BSE-affected cattle. The report of the latest scientific assessment has been provided to Ministers and a copy is attached.

The Committee considered preliminary results of research on methods of slaughter and the possible association with neural emboli (small, possibly even microscopic, pieces of tissue dislodged and carried into the bloodstream during the slaughter process) in the blood. The Committee noted that the research confirmed previous findings that high pressure pneumatic stunners that had not been used in the UK resulted, in some cases, in the presence of emboli in the blood in the large veins draining the head. They concluded that the study of the stunning and pithing methods used in the UK should be extended to evaluate whether the trauma caused by these methods had historically represented any risk of contamination of bovine blood with BSE. The Committee noted that the number of infected cattle that might have infectivity in their brain when slaughtered for human consumption at the present time was very low. Thus the results of this research would not give rise to concern about the risk of transmitting BSE by current practice.

The Committee identified criteria whereby the controls on beef over thirty months of age could be reviewed in the future and hoped to begin to address this at the meeting planned for March 1999. The Committee recognised that this would require careful study and would almost certainly need to be considered over several meetings.

The Committee further considered the practice of spreading rendering condensate on to fields. They noted the procedures associated with the processing of fallen stock. They further noted the difficulty of establishing the origin of any protein found in condensate. They therefore concluded that the spreading of rendering condensate on fields where cattle might graze should be prohibited. The Committee's concerns were related to the risk from BSE to animal rather than human health.

SEAC considered a draft report from its sub-group which had been looking at research and surveillance for TSEs in sheep. It was agreed that a further draft should be prepared incorporating the views of SEAC and those members of the sub-group who had not yet had a chance to comment. It is expected that the final report will indicate the priority of recommendations for further work.

The Committee reviewed the use of human splenic extract in the Kveim test, (a diagnostic skin test used in sarcoidosis). They recommended that where human spleen was used as the raw material for preparations which may be administered to humans, the spleens used should be low risk material, preferably originating from a BSE-free country and screened by immunocytochemistry prior to use.

The Committee agreed to hold a press briefing after each meeting in future, once the public summary of business had been agreed and was ready for publication.

* A further 2 cases of nvCJD were confirmed on 12 and 16 November 1998

SEAC
November 1998

Spongiform Encephalopathy Advisory Committee
- Report to Ministers

A review of infectivity in bone marrow and Dorsal Root Ganglia in cattle infected with BSE

In December 1997 SEAC provided advice to Ministers on the risk to public health from infectivity in dorsal root ganglia and provisional results on infectivity in bone marrow. This report updates that advice taking account of further experimental and epidemiological evidence.

Bone Marrow

Interim results from the BSE pathogenesis experiment in cattle were reported to Ministers in December last year and published in the scientific press in January this year1. Further experiments on the infectivity in bone marrow have now been concluded and the results were considered at the SEAC meeting on 9 November. In the experiment conducted by MAFF, groups of cattle were exposed orally to infection with BSE and were then killed sequentially from two to 40 months later. Tissues, including the bone marrow, from the cattle in each group were tested for infectivity by inoculation into mice. The tests for infectivity of the bone marrow were only positive in the group killed at 38 months after infection with BSE, when clinical disease was evident in the cattle, and not at any earlier (2 to 36 months) or later (40 months) time after exposure to BSE2.

We agree this positive bone marrow result can be interpreted in three ways:

a) infectivity may occur occasionally in the bone marrow of clinically affected animals;

b) the test is only able to detect infectivity above a certain level and, for BSE infectivity in the bone marrow of cattle, it is operating on the borderline of its sensitivity;

c) in the case of the group of cattle killed at 38 months after exposure to BSE, the pooled tissue sample was accidentally contaminated at some point during post mortem procedures.

Current evidence does not allow us to determine which of these interpretations is correct. Consequently, our conclusion is that the positive result at 38 months cannot be discounted and may indicate that infectivity in bone marrow occurs occasionally, when clinical signs are apparent and there are already very high levels of infectivity in the central nervous system (brain and spinal cord).

Although BSE and scrapie are not directly comparable (e.g. detectable levels of infectivity in peripheral tissues is a usual occurrence in scrapie but not in BSE in cattle), we have noted that research on scrapie in sheep conducted some years ago demonstrated infectivity in bone marrow of a clinically affected sheep but it was reported as a rare occurrence 3 .

Infectivity has not been detected in bone marrow before cattle reach the clinical stage of the disease. All clinically affected cattle are removed from the food chain. So too are the majority of infected cattle that are at an advanced stage of incubation and close to developing clinical disease, when they are slaughtered and destroyed as part of the Over Thirty Months Scheme (OTMS). Consequently the risk to public health from infectivity in the bone marrow of cattle killed for human consumption is likely to be very small and does not have the same significance as infectivity in dorsal root ganglia.

Dorsal Root Ganglia

Infectivity was consistently demonstrated in dorsal root ganglia of cattle in the pathogenesis experiment in the groups of infected cattle killed 32, 36, 38 and 40 months after oral exposure to BSE. At 32 months the animals did not show any clinical signs of disease; these were first seen at 35 months. In some of the dorsal root ganglia transmissions the number of mice infected is very similar to that found with the brain of the same infected cattle, suggesting that high levels of infectivity may be present in the dorsal root ganglia.

Any continuing risk to public health must be evaluated in light of the number of animals likely to be carrying infectivity, their age, how far the disease may have progressed when they are slaughtered, and how the carcass is processed for distribution and consumption. Infected animals may have one of three fates; they may be slaughtered for human consumption before the age of 30 months, they may be slaughtered and destroyed as part of the OTMS, or, if they have developed clinical signs, they will be slaughtered and destroyed as a suspect case of BSE. The BSE epidemic in cattle continues to decline. As a result the number of infected animals which are slaughtered for human consumption also continues to decline.

In our advice of December 1997 we referred to the risk from the dorsal root ganglia of animals which, had they lived, would have developed clinical BSE before the age of 38 months. Based on mathematical modelling of the BSE epidemic, we now have estimates4 of the number of animals under the age of 30 months that will be slaughtered for human consumption during 1999 but would have developed clinical disease within 12 months if they had not been slaughtered. The predictions indicate that in 1999 there will be only 1 or 2 (95% PI* : 0, 5) such infected cattle which will be slaughtered for human consumption. The comparable figure for 1998 was 3 or 4 (95% PI: 0, 8) and for 1997, 5 or 6 (95% PI: 1, 11).

It is possible that small amounts of infectivity might be present in the dorsal root ganglia of animals slaughtered more than 12 months before they would have developed clinical disease had they lived. Current estimates are that in total there will be 43 (95% PI: 25, 66) infected animals which will be slaughtered for human consumption in 1999. The comparable figure for 1998 was 99 (95% PI: 68, 136) and for 1997, 184 (95% PI: 145, 228). We think that infectivity in dorsal root ganglia is likely to increase through the incubation period, so the levels of infectivity will be highest in those animals close to clinical onset. Of the 43 infected animals estimated to be slaughtered in 1999, it is estimated that only 9 or 10 (95% PI: 3, 18) would have developed clinical signs of disease within 2 years if they had not been slaughtered and 22 (95% PI: 11, 37) within 3 years. For comparison we note that the estimated number of infected animals which entered the food chain between 1974 and the introduction of the specified bovine offal ban in 1989 was almost 480,000 (95% PI: 474,000, 819,000), with a further 292,000 (95% PI: 284,000, 303,000) to the end of 1995. In the peak single year 1989 there would have been of the order of 200,000 infected animals slaughtered for human consumption.

Conclusions

It is still not known how many humans have become infected with vCJD as a result of exposure to the BSE agent, nor how much BSE infectivity is needed to cause disease. Consequently it is still not possible to predict with any degree of precision the risks to public health from dorsal root ganglia or bone marrow.

However with the continuing decline in the numbers of infected cattle which are slaughtered for human consumption each year any risk from dorsal root ganglia and bone marrow is now less than it was 12 months ago. The pattern of results obtained with bone marrow leads us to conclude that the risk, if any, from this tissue is likely to be very small. With the OTMS in place, we think it likely that the risk from dorsal root ganglia is also very small and negligible in comparison to the possible risk earlier in the epidemic.

It is clearly important that the public are kept informed of these issues and we therefore recommend that the experimental data we have considered and our assessment of its implications are made public.

** 95 % prediction intervals, calculated allowing for model fit uncertainty and Poisson variation.

Refs

1. Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy(BSE): an update. GAH Wells et al. Veterinary Record (1998) 142, 103-106.

2. Personal communication. GAH Wells.

3. Natural infection of Suffolk sheep with scrapie virus. WJ Hadlow et al. Journal of Infectious Diseases (1982) 146, 657-664.

4. C. Donnelly & N. Ferguson, Personal Communication: Data drawn from the best fitting model described in ' The epidemiology of BSE in cattle herds in Great Britain. II. Model construction and analysis of transmission dynamics' Ferguson N.M. et al 1997 Phil.Trans. R. Soc. Lond. B 352, 803-838.