Chapter 8

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8. Prevention

8. Prevention

8.1 Restrictions on trade in live cattle
8.2 Restrictions on trade in meat and bone meal
8.3 Sterilization of meat and bone meal
8.4 Restricted use of meat and bone meal
8.5 Minimizing exposure of the human population
8.6 Minimizing the exposure of other species

It scarcely needs stating that, at present, vaccination is not an appropriate way of preventing any of the diseases in the scrapie family; there is no known protective immune response to infection for a vaccine to enhance. However, BSE is obviously not a highly contagious disease and it can be prevented by other simple means because the epidemiology is relatively simple.

As stated previously, the single known source of infection is concentrated feedstuffs containing contaminated meat and bone meal. The only major uncertainty is whether there are any natural routes of infection between cattle. By analogy with scrapie, the most likely possibility is transmission of infection from cow to calf. A major experiment has been set up in the United Kingdom to investigate this (see The possibility of endemic infection, p. 55). There are two ways in which countries without BSE might acquire it: first, by the importation of live animals and contaminated feedstuffs from countries with BSE; and second, by allowing endemic scrapie to infect cattle (see Sterilization of meat and bone meal, p. 47, and Restricted use of meat and bone meal, p. 49). Both are easily prevented.

8.1 Restrictions on trade in live cattle

There is obviously a chance that some breeding animals imported from the United Kingdom for example, might be infected with BSE. Unless large numbers of animals are imported, the statistical probability is quite small. The occurrences of BSE in Oman (Carolan, Wells and Wilesmith, 1990) and the Falkland Islands are the only definite instances of this to date. The long incubation period of BSE means that quarantine is of limited practical value except in special circumstances when the need to import animals outweighs the difficulties and expense of a quarantine period lasting several years.

If there are no natural routes for the spread of infection from cattle to cattle, the only risk from imported livestock would be after slaughter, when infected material might enter the animal feed chain. The chances of this infecting other cattle would be quite small because of extensive dilution with uninfected material. The risk should be zero from animals born in the United Kingdom after the ruminant protein ban came into effect in July 1988.

Nevertheless, natural transmission of BSE infection in cattle is still a possibility (Anon., 1991b). Because of this, the CEC limited the importation of live cattle from the United Kingdom to animals born after July 1988, provided that they were not born to suspect or confirmed BSE cows (CEC, 1989).

A later amendment (CEC, 1990a) further restricted imports of live cattle from the United Kingdom to young calves which have to be slaughtered by six months of age in the importing country. This amendment solves the problem of the importing countries having to remove and dispose of the specified bovine offals in line with United Kingdom legislation. The specified offals ban was introduced as a precautionary public health measure but it does not apply to young calves (of six months or less) because no part of these animals is considered to be a significant risk even if they are infected (see Minimizing exposure of the human population, p. 50).

An increasing number of cattle in the United Kingdom have never been fed ruminant protein. Trade in live animals born there after the ruminant protein ban would thus not be a risk to importing countries unless there is cattle-to-cattle transmission of infection. The OIE has recommended specific conditions for the trade in live cattle embryos from countries with high or low incidences of BSE (OIE, 1992).

8.2 Restrictions on trade in meat and bone meal

The United Kingdom has introduced two restrictions on the use of meat and bone meal in ruminant feeds. The first is a complete ban on the feeding of ruminant-derived protein to ruminants, which was introduced to control BSE by preventing new infections from contaminated feeds (HMSO. 1988a).

The second restriction came in later, initially for public health reasons (see Minimizing exposure of the human population, p. 50) and latterly for animal health reasons (see Minimizing the exposure of other species, p. 53). This bans the use of certain specified bovine offals in human food and animal feedstuffs. The banned offals are those likely to contain the highest amounts of BSE agent in infected cattle. The second restriction also prevents the export to other EEC Member States of specified offals from all bovine animals over the age of six months, and any food products derived from them (HMSO, 1990b).

However, there are no United Kingdom restrictions on the export of meat and bone meal derived from the non-specified bovine wastes (which would have very little infectivity) or material derived from sheep (which would have a significant amount of infectivity). Nor has the EEC imposed any restrictions on trade in meat and bone meal (although several member countries have banned imports from the United Kingdom).

Since the feeding of material of ovine origin to cattle is believed to have been the origin of the BSE epidemic in the United Kingdom, countries wishing to import British meat and bone meal from this country would be well advised not to feed it to ruminants. The feeding of meat and bone meal from other countries with scrapie is considered below.

8.3 Sterilization of meat and bone meal

The epidemiology studies described in Chapter 4 show that the potential for BSE to occur in the United Kingdom existed for a long time before the epidemic actually started. One of the lessons of BSE is that a similar potential may exist in other countries.

The occurrence of BSE depends on the simultaneous presence of three factors (Wilesmith and Wells, 1991):

• a large sheep population (in relation to that of cattle) with a sufficient level of endemic scrapie;
• the use of substantial quantities of meat and bone meal derived from sheep, in cattle feed;
• conditions of rendering that allow the survival of significant amounts of infectivity (which will depend on the extent of the initial contamination).

The very low average level of exposure of cattle in the United Kingdom illustrates how nearly the epidemic might have been avoided if any one of these factors had been limiting. The need for all three factors is the reason why few if any other countries in the world are likely to experience BSE on the scale of the United Kingdom epidemic. But there is a real danger of B SE occurring regionally whenever a local combination of these factors leads to the infection of cattle from sheep. Although the reasons for the recent cases of BSE in Switzerland and France are not known, these are the kind of occasional outbreaks to be expected. The United States Department of Agriculture (USDA) has made a detailed analysis of the BSE factors at both national and regional levels (USDA, 1991a; 1991b).

BSE can be prevented by removing any one of the above three factors. In practice, neither the eradication of endemic scrapie nor the depopulation of sheep is a realistic option except in countries which are already close to being in one or other of these positions. Australia and New Zealand are the two major sheep-rearing countries which are generally regarded as scrapie-free. But several others have witnessed little or no scrapie in recent years.

This leaves two major approaches for the prevention of BSE from sheep scrapie. The first is to ensure that meat and bone meal is produced under conditions that achieve total disinfection of the most heat-resistant strains of infectious agent (see below). The second is to avoid the use of meat and bone meal in feedstuffs (see Restricted use of meat and bone meal, p. 49).

For economic reasons, few modern processes still use solvent extraction, which, as previously mentioned, was an important factor in limiting the exposure of cattle in the United Kingdom before 1981/82. With most processes, disinfection of scrapie relies on heating. In common with several other microbial agents, the heat sensitivity of scrapie is greatest in the presence of water. Since most rendering plants operate at atmospheric pressure, the wetheating stage will take place at temperatures up to about 100C, to which the scrapie agent is substantially resistant.

Higher temperatures will be achieved once most of the water has been removed. Wilesmith Ryan and Atkinson (1991) found that the mean temperature achieved in different United Kingdom plants was 124 C and the maximum was about 150 C. Undoubtedly, these temperatures would produce some inactivation. The absence of data, however, makes it difficult to ascertain how much infectivity would be lost under different heating conditions (Taylor, 1989a).

In theory, a simple way to inactivate the scrapie/BSE agent is to employ the standard conditions currently used for the disinfection of the CJD agent in United Kingdom hospitals, namely autoclaving at 134-138C for 18 minutes (DHSS, 1984). This standard is based on the most heat-stable strain of scrapie (Kimberlin et al., 1983). However, there is a big difference between the porous load sterilization of surgical instruments in hospitals and the steam sterilization of large amounts of either untreated abattoir waste or meat and bone meal (Taylor, 1989a). The practicalities and the effectiveness of such treatments need careful investigation. These studies are in progress but they will take a few years to complete.

8.4 Restricted use of meat and bone meal

By far the simplest way to prevent BSE is to avoid the use of meat and bone meals and any other sources of ruminant protein, in cattle feed. This approach can take more than one form.

Material from sheep can be rendered separately from that of other species and specifically excluded from cattle feed. But this would not prevent the recycling of infection that was already present in cattle. This is why the United Kingdom ruminant protein ban applied to material derived from all ruminants, including cattle (HMSO, 1488a).

The ban also applied to the feeding of ruminant protein to sheep (as well as to cattle and deer) to prevent the recycling of scrapie infection in the sheep population which, in the past, may have contributed to endemic scrapie.

The most effective approach is a complete ban on the feeding of all ruminant protein to ruminants, as originally introduced and maintained in the United Kingdom (HMSO, 1988a; 1988e; 1989a; 1990b). This would prevent the feedborne spread of infection to cattle from both native flocks and imported sheep. It would also prevent the recycling of infection from imported adult United Kingdom cattle which may have been infected, but were too young to show clinical signs of BSE at the time of slaughter.

Such a measure would also take account of the formal possibility that BSE infection may already exist in other countries, quite independently of the United Kingdom and the Republic of Ireland. However unlikely this possibility may seem, the recycling of in apparent infection in cattle could create just the conditions for the selection of more highly neurovirulent strains that could lead to a disease problem.

Several countries, including the United States and members of the EEC, have initiated surveillance programmes to detect evidence of BSE in their national herds. The EEC has made BSE a notifiable disease with effect from I April 1990 (CEC, 1990a). The surveillance programmes are based on the histological examination of brain sections from older cattle showing neurological signs. An obvious source of material is suspect cases of rabies. But, until such studies provide evidence to the contrary, it would be prudent to prevent the feed-borne spread of inapparent BSE infection between cattle.

8.5 Minimizing exposure of the human population

A great deal of concern, much of it avoidable, has been expressed over the possible public health consequences of BSE. This is understandable given that the scrapie family of diseases includes some that affect human beings. But the very existence of human scrapie-like diseases long before BSE was discovered means that the possible epidemiological relationships between the animal and human diseases have already been the subject of intensive study. As a result, the circumstances in which BSE might pose a risk to public health can be defined quite precisely, and simple measures have been devised to preempt this risk. This issue was considered in the "Southwood report," (DoH and MAFF, 1989) and it has been discussed at length elsewhere (Kimberlin, 1990b; 1990c; Taylor, 1989b). The salient features of the problem and its solution are described below.

The problem

If scrapie or BSE were to cause disease in human beings, it would probably be recognizable as CJD. Although the epidemiology of CJD is not understood in detail, the possibility that it is caused by scrapie infection of human has been studied and the evidence is firmly against such a causal link. Plausible hypotheses for CJD are discussed elsewhere (Kimberlin, 1990a).

It is highly improbable that the absence of an aetiological link between CJD and scrapie is because human beings have never been exposed to scrapie. On the contrary, their exposure to scrapie infection must have been considerable in several countries for very long periods of time. But, as the epidemiological evidence shows, such exposure has not been high enough to overcome the species barrier which limits the interspecies transmission of these diseases.

In the absence of a demonstrable public health risk from scrapie, the same could well apply to BSE. The only circumstance which could alter this assessment is if the transmission of scrapie to cattle has considerably increased the effective exposure of human beings to infection. The greatest uncertainty would be if cattle had selected scrapie strains which differ from those preexisting in sheep. That such a possibility exists is demonstrated by laboratory studies of single (cloned) strains of scrapie in mice showing that crossing the species barrier (into hamsters) can permit the selection of mutants with different biological properties from the original strains (Kimberlin, Cole and Walker, 1987; Kimberlin, Walker and Fraser, 1989).

As shown previously, the recycling of BSE infection in the cattle population would have favoured the selection of cattle-adapted strains. Rendering processes may also have had a selective effect by favouring heat-stable strains of agent. However, strain selection per se would not necessarily create a problem because the selected strains could be even less likely than scrapie to cross the species barrier to human beings. The only concern is if they happened to be more able to infect the human population. Unfortunately, there is no easy way of testing this possibility.

It is important to emphasize that any primary human exposure would still be across a species barrier and there would be no recycling of food-borne infection in the human population, as happened with kuru and with BSE in cattle. Nevertheless, there is a theoretical risk to human beings from a disadvantageous selection of BSE strains. The logical way to address this risk is to make sure that exposure to BSE is kept low.

The solution

Attention in the United Kingdom was initially focused on clinically affected cattle which were excluded from the human food chain from August 1988 (HMSO, 1988b). Soon afterwards, the destruction of milk from suspect cases was enforced (HMSO, 1988d; 1988e).

As the number of BSE cases continued to increase, however, there was concern that some animals, at a very early stage of the clinical disease, might escape detection. Even more worrying was the possibility that infected animals were being slaughtered for meat before the age at which clinical signs appear (two years and over). If cattle are dead-end hosts for infection, the number of subclinically infected animals would decrease progressively since the introduction of the meat and bone meal ban in July 1988. But efficient maternal transmission of infection, if it occurred, could change this situation.

This possibility was countered by banning certain specified types of bovine offal from entering the human food chain. The ban came into effect in England and Wales in November 1989 (HMSO,1989b), and in Scotland and Northern Ireland in January 1990.

The basis of the specified offals ban is that agents in the scrapie family only multiply to an appreciable extent in a small number of tissues (Hadlow, Kennedy and Race, 1982). Indeed, limitations on multiplication and on the cell-to-cell spread of infection are the underlying reason for the long incubation periods of all these diseases (Kimberlin, 1990a).

Most tissues, including milk and muscle, have little or no detectable infectivity by parenteral injection, and effectively none at all by alimentary exposure (because of major differences between routes in the relative efficiency of infection). This is borne out by feeding large quantities of various bovine tissues from BSE cases to mice. Only those mice which were fed brain became infected (Barlow and Middleton, 1990a; 1990b).

There are few bovine tissues used in human food which also have the potential to support significant multiplication of the agent. The most important, quantitatively, are brain, spinal cord, tonsil, spleen, thymus and intestine (the last because of the presence of Peyer's patches). These are the specified offals that are excluded by the ban (HMSO, 1989b).

To be effective, the specified offals ban has had to be applied to all cattle regardless of whether they are infected. The only exception is calves of under six months of age which are exempted on the grounds that none would have been fed ruminant-derived meat and bone meal and, even if there is maternal transmission of infection, little or no detectable infectivity would be expected (from studies of scrapie) in any tissues.

A major feature of the offals ban is that it safeguards public health even if BSE develops into an endemic infection of cattle (see The possibility of endemic infection, p. 55). In other words, it separates the animal health and the public health aspects of BSE.

Logically, the ban should also be applied to the large lymphnodes. In the United Kingdom, these are removed as a matter of course, along with other waste tissue (including large nerves), either in the abattoir or when individual cuts of meat are prepared. In 1990 these steps were given added force by EEC decisions taken to facilitate trade in United Kingdom beef.

For boneless beef, there is a requirement to remove obvious nervous and lymphatic tissue during the cutting process before export (CEC, 1990b). These trimmings are excluded from use in human food. For bone-in beef, the animals must not come from a holding in which BSE has been confirmed in the previous two years (CEC, 1990b). The scientific basis for this second measure is dubious but it was expedient for political reasons.

The OIE initially endorsed these conditions for the trade in meat and meat products for human consumption from countries with a high incidence of BSE (OIE, 1990). Subsequently, the organization recommended that the conditions for trade in bone-in beef should be the same as for boneless beef (OIE, 1992). The OIE has also recommended that there are no grounds for restrictions in trade in milk or milk products because of BSE (OIE, 1990; 1992).

8.6 Minimizing the exposure of other species

During the time that cattle were exposed to contaminated meat and bone meal, which led to BSE, pigs were also exposed with no ill effects. Indeed, the exposure of pigs would have been higher than cattle because of the greater inclusion rates of meat and bone meal in commercial pig feeds.

If the effective exposure had been the same for both species, about 1 000 cases of spongiform encephalopathy would have been seen by now in the population of breeding sows in the United Kingdom. The clinical appearance of porcine spongiform encephalopathy is known from studies of the experimental disease (Dawson, Wells, Parker and Scott, 1990), and it is improbable that a naturally occurring disease in pigs would have been undetected. It must be concluded that an effective exposure to produce the disease in cattle was insufficient in pigs.

The ruminant protein ban, introduced in 1988 to control BSE, did not apply to pigs, which have continued to be exposed along with some other species. Two events in 1990 led to a reappraisal of the risks to pigs and other species.

First, the scale of the recycling of infection within the cattle population and its effect on the BSE epidemic became clear. As shown in Chapter 4, the consequences of recycling include changes not only in the amount of infectivity but, possibly, in the strains of agent. In other words, it could not be assumed that the effective exposure of pigs would stay constant.

The second event was the occurrence of several cases of spongiform encephalopathy in domestic cats (Wyatt et a/., 1990; Leggett, Dukes and Pirie, 1990). It is too early to know the reasons for the feline cases, but it may be significant that they have occurred relatively late in the BSE epidemic. One possibility is that feline spongiform encephalopathy may have been a consequence of changes in the character (strain and effective dose) of BSE infection of cattle.

For these two reasons, it was desirable on animal health grounds to reduce the exposure of all animal species to BSE. The introduction of the specified offals ban in 1989 made this easy to achieve without a complete ban on the use of all meat and bone meal in feeds. Because the specified offals include the major tissues likely to contain high BSE infectivity, all that was needed was to extend the specified offals ban. Since September 1990 these bovine offals may not be fed in any form to any species of' mammal or bird (HMSO, 1990b).

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