NR ASAE
AU anonym
TI BSE - BOVINE SPONGIFORM ENCEPHALOPATHY ("MAD COW DISEASE")
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The Institute of Food Science & Technology, through its Public Affairs and Technical & Legislative Committees, has authorised the following Position Statement, dated 6 February 1996, updating the previous Statement of 25 January 1996, and replacing any previous version [see appended Editorial Note on the change from the 25 January Statement] :-
Summary
BSE is an extremely serious disease of cattle, the eradication of which is of primary importance to safeguard herds, and hence future supply of dairy and bovine meat products for the human and pet food chains, together with important bovine by-products.
For there to be any risk to humans consuming beef, two conditions would both have to be fulfilled: that BSE could be transmitted from cows to humans; and that parts of the animal capable of carrying the infective agent could enter the human food chain. As to the first, there is no scientifically valid evidence that BSE can be transmitted from cows to humans, and some research evidence suggesting that it cannot. As to the second, muscle meat and milk have been shown to be incapable of carrying the infective agent, and measures have been taken, and strengthened, to exclude from the food chain certain parts of the animal, including all those parts shown to be capable of carrying the infective agent.
As regards animal health, successful measures have been taken, and strengthened, to reduce the incidence of BSE in cows and these are expected to lead to the virtual elimination of the disease.
While that sums up the present state of knowledge, scientists always have to keep open minds. They have to act on existing knowledge while recognising that further research will bring new information and knowledge, which may in turn lead to revised conclusions.
Background
Bovine spongiform encephalopathy (BSE) is a fatal brain disease of cattle which has only come to light in recent years, having been first recognised in the UK in 1986. The disease is caused by an unconventional infectious agent, originally described as a 'slow virus', a 'self-replicating protein' and more recently as a 'prion', an abberant conformation of normal protein (PrP). Research is increasingly supporting Prusiner's hypothesis, whereby a prion molecule contacts a normal PrP molecule in the membrane protein of the brain, and induces it to refold into the abberant conformation, and molecules so formed go on to do the same to other normal PrP molecules, thus creating further replicas from normal protein.
Scrapie in sheep, BSE in cattle and Creutzfeldt-Jakob Disease (CJD), a rare brain disease in humans, are all neurodegenerative disorders thought to be transmitted by such proteinaceous infective agents. These infective agents have many similar common characteristics.
The incubation period in cattle is very long, commonly 3-5 years (but the range can be considerably wider), and there were fears that meat and milk from cattle which were infected with the agent (but not yet showing clinical signs of the disease) could enter the human food supply chain and transmit the disease to man. Such fears were exacerbated by alarmist publicity in the media, by news of bans on UK beef applied from overseas and by a dearth of easily assimilated and verified information.
Independent and UK Government experts considering the problem, from 1988 to the present, have judged that the chance of man becoming infected in some way through meat or milk from BSE infected cattle were extremely remote, this view being endorsed by the House of Commons Agriculture Committee in their 1990 report and by the Southwood Committee set up in 1988 specifically to consider the BSE problem. Other experts and perceived experts were not so convinced and expressed varying degrees of concern. Since 1986, more than 150,000 cases of BSE in cattle have been identified in the UK, and the disease has been confirmed in Eire, and in some other overseas locations.
The disease
Infected cattle appear nervous (there is no conventional madness), lose weight and have difficulty in walking; milk yields decline, but as yet confirmation of disease is only possible following post-mortem examination of brain tissue and there is no test confirmed as being able to detect the disease in live animals. Incubation in cattle is 2 to 8 years or longer. Scrapie is a fatal brain disease of sheep and goats endemic in many countries and recorded in the UK for well over 200 years. It is apparently naturally transmitted between sheep and has an incubation period of 2 and 4 years. There is no good evidence that scrapie can be transmitted to man either occupationally or by eating sheep meat. While scrapie is common in sheep, CJD is very rare in humans.
The causative agents of these diseases are thought to have very similar characteristics. Such agents are very heat resistant, and while some loss of infectivity occurs at temperatures above 100 deg C, more than 120 deg C is needed for inactivation in regimes proposed by UK and USA health authorities. Resistance to sterilants is very high, as is resistance to extremes of pH.
Transmission
Epidemiological evidence indicated that the primary cause was likely to have been the use of commercial cattle feed concentrates which contained meat and bone meal derived from sheep (and possibly cattle) presumed to have been infected and not having been processed at such high temperature as in earlier times. It appears that the species barrier between animals can be crossed in created extremes such as where infected material is injected into the brain of another animal. Placental transmission has been identified as a likely route in sheep. Development of infection appears to be related to size of inoculum.
There is at present no evidence of maternal transmission in cattle, and epidemiological evidence [Hoinville et al, Veterinary Record(1995) 136, 312] strongly suggestive of non-occurrence.
The only long-term experimental trials are those started in 1989. They are due to run until November 1996, when the youngest animal reaches seven years of age, at which time all will be slaughtered and their brains examined histologically. The analysis and results will be available in early 1997.
Research recently published in Nature (Collinge et al, "Unaltered susceptibility to BSE in transgenic mice expressing human prion protein", Nature (1995), 378, 21/28 December), is suggestive of the inability of bovine aberrant PrP to affect normal human PrP. Professor J Collinge and his colleagues at Imperial College School of Medicine studied mice genetically-engineered so that they produced human prion protein as well as normal mouse prion protein. They injected the mice with CJD, and the mice fell victim to the disease, demonstrating that with human protein, the human disease CJD was transmitted. They then exposed similar mice to BSE. Abnormal _mouse_ prion protein was formed, but no abnormal human prion protein. An encouraging first stage, but they are now repeating the experiments with genetically-modified mice that express only human protein and no mouse protein. These remain well at 264 days after inoculation (60 days longer than for CJD to develop in mice of this genotype) but this study may need to go on for 600 -700 days if these mice die of old age rather than succumbing to BSE. Thereafter, it is considered important to repeat the studies with mice expressing human protein of genotypes other than the one originally chosen (which was the one considered to be most susceptible to human prion diseases). Even if successful, as Prof Collinge has pointed out, safety can never be proved with certainty. But then that is true of safety in any aspect of life.
Animal Health Aspects
The control measures in the UK for control of the epidemic in cattle were:
to destroy animals diagnosed on the farm;
to prohibit the feeding of material containing animal protein derived
from ruminants to cattle and other ruminants;
to destroy carcases of cattle affected with BSE;
The banning of ruminant material from animal feedstuffs from July 1988 has led, after a time lag (due in part to farmers using up their stocks of cattle feed after July 1988, but due mainly to the incubation period) to a dramatic decline in new cases (30% drop from 1993 to 1994, and an estimated 47% drop from 1994 to 1995). This may be seen as confirming the feedstuff hypothesis. It also lends support to the view that cattle will prove to be a "dead end host" for BSE, and that, if the control measures are strictly adhered to, the disease will eventually become virtually extinct.
The human aspect
If BSE were transmitted to man, the clinical disorder would probably resemble CJD and the incubation period could range from, say, one year to several decades. Theoretically, the greatest risk to man could be by direct infection, e.g. through medicinal products derived from bovine brain or lymphoid tissue acting as a vector.
In a number of published research papers, all kinds of tissues and secretions from confirmed BSE cattle have been injected into or fed to mice, and, with the exception of brain and spinal cord, and more recently the retina, all have failed to transmit the disease. In particular, milk and beef muscle meat proved not to carry the infective agent.
The control measures to prevent potentially infective materials entering the food chain were:
to extend the list of specified bovine offals (SBOs) banned for use in the food chain to cover a wider range of potentially infective materials (these are required to be stained with Brilliant Blue V (E131), while unfit meat is stained with Black PN dye (E151) prior to any movement).
to extend slaughterhouse requirements in order to tighten controls; and, to destroy milk from cattle suspected of having BSE.
Where subsequent research has shown that milk and certain of the SBOs do not carry the infective agent, these controls have nevertheless been retained as an extra precaution.
Where experience has shown that some of the original controls did not fully live up to expectations, more stringent controls have been introduced - although not always as rapidly as might have been wished, with the benefit of hindsight.
Monetary compensation to farmers for BSE infected animals has increased steadily since the problem first arose. In response to further advice from SEAC, after a meeting on 23 November 1995, expressing concern about instances of failure to achieve complete removal of the spinal cord, measures were introduced to prevent the use of spinal column (excluding the tail) being used in the mechanical recovery of meat. In retrospect, this control could have been effected much earlier had action been taken at the time on the forewarning of exactly this difficulty by the House of Commons Agriculture Committee in its 5th Report on BSE in 1990.
In a statement of 13 November 1995, the UK Ministry of Agriculture, Fisheries and Food (MAFF) stated that the measures taken were recognised as being sufficient by the World Health Organisation, the International Veterinary Organisation (the OIE) and the EC Scientific Veterinary Committee. The independent Spongiform Encephalopathy Advisory Committee (SEAC) which advises the UK Government on all aspects of BSE and CJD also endorsed the measures and continued to state that in its view there was no evidence of a link between BSE and CJD. An open letter from the Chairman and Vice-Chairman of SEAC on 13 December 1995 stated that if there ever were any risk to human health from BSE, and there may be none, it was very much less in December 1995 than it had ever been.
On 11 January 1996, Independent Television News, reporting on the work of the CJD Surveillance Unit at Edinburgh, included an interview with Dr Robert Will, the Director of the Unit and Deputy Chairman of SEAC, in which it was stated that deaths from CJD were not thought to relate to BSE. World-wide, CJD occurred naturally at a more-or-less constant rate regardless of whether BSE occurred at all. Comparing in-brain development characteristics of BSE with those of CJD did not indicate any link. Work on lesion profiles in mouse brain was being carried out on both BSE and CJD, and if these were the same it might indicate a link. The difficulty of proving a negative was emphasised.
General comment
The whole BSE/spongiform encephalopathy scenario is extremely complicated and difficult to understand. There can be no _definitive_ scientific opinion until all the work currently being carried out (and probably a lot that has not even been started or thought of yet) has been completed and the results assessed. There may well be public confusion because of an expectation that a condition undetectable in animals during the incubation period should be removed from the system by the powers that be. It is not always recognised that the precautions applied are so applied with the expectation that, even if the infection could be passed to humans (and there is no evidence that it can), and even if an undetected infection is present in an animal passed as fit for human consumption, there is no risk attached to the consumption of those parts of the carcase that go into the food chain.
Some experts still have reservations about the animal feed hypothesis, and it seems quite possible that encephalopathies arise as a result of a number of coincidental factors coming into play in a combined circumstance. Nevertheless, the prohibition of the ruminant material from the animal feed, and the dramatic reductions in new cases over the past two years seem to demonstrate that the animal feed was the key factor.
IFST continues to support the need for continuing research in this whole area, and particularly that aimed at developing a rapid and easily used diagnostic test for such conditions.
Further information
Reports and articles on BSE and other encephalopathies have appeared widely in the scientific literature. Information on the MAFF control programme is available from the MAFF Veterinary Division, Tolworth, Surrey, UK.
Outlines of ongoing research projects on BSE at the Institute of Animal Health may be found at its World Wide Web address http://www.iah.bbsrc.ac.uk/Institut/public/3wtse.htm
Editorial Note re changes from the previous version dated 25 January 1996
It is regretted that the Statement dated 25 January 1996 (and its predecessor of 7 December 1995) included two factual errors relating to possible vertical transmission in cattle. It was stated, under the heading Transmission, that "In trial circumstances maternal transmission can occur" and that "further long-term vertical transmission trials are likely to be completed in February". Having checked all the related published and ongoing research, it has become evident that both statements were incorrect, and we apologise to any who may have been confused or misled by them.
The former erroneous phrase was carried forward, in good faith, from an unpublished 1992 draft, and the source of the phrase cannot currently be traced.
The only long-term experimental trials are those started in 1989. They are due to run until November 1996, when the youngest animal reaches seven years of age, at which time all will be slaughtered and their brains examined histologically. The analysis and results will be available in early 1997. Meanwhile, the results of an extensive epidemiological study, published in April 1995, showed that there was no statistical difference in the incidence of BSE between the offspring, of subsequently affected and non-affected cattle born after the feed ban, thus suggesting the absence of evidence of vertical transmission.
That part of the Position Statement has been amended accordingly.
References
The Specified Bovine Offal Order 1995. HMSO.
The Specified Bovine Offal (Amendment) Order 1995. HMSO.
The Bovine Offal (Prohibition) Regulations 1989 as amended. HMSO.
Barlow, R M et al, (1990,) Veterinary Record, 126, 111.
Frazer, H et al, (1992), Journal of General Virology, 73, 1891.
The Animal By-Products (Identification) Regulations 1995. HMSO.
Taylor, D M et al, (1994), Archives of Virology, 139, 313.
Prusiner, S B. The Prion Diseases. Scientific American, 1995, 272 (1).
Smith, P E M et al, "CJD in a Dairy Farmer", (1995), The Lancet, 346, 30 September, 898.
Delasnerie-Laupretre, N et al, "CJD in Europe", (1995), The Lancet, 346, 30 September, 898.
Hoinville, L et al (1995), Veterinary Record, 136, 312.
Taylor, D M et al, (1995), Veterinary Record, 136, 592.
Simon Jenkins. "Give me a diet of reason". The Times, 6 December 1995.
Collinge et al, (1995), Nature, 37821-28 December, 779.
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