Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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scrapie evidence, likely to contain BSE infectivity. In

fact, subsequent transmission studies from natural

cases of BSE have only detected infectivity in the

central nervous system. Other tissues, including

blood, milk, and muscle meat, show no detectable

infectivity. Subsequently it was shown that the agent

causing BSE in cattle was indistinguishable biologic-

ally from the vCJD agent, i.e., the strain type was the

same. Furthermore, the strain-type characteristics

were different from the agents causing conventional

forms of sporadic CJD and scrapie. Molecular analy-

sis of the prion protein (PrP) from some of these

species has also shown distinct similarities between

them. In particular, that from vCJD cases has a

unique molecular signature that distinguishes it

from conventional sporadic and other forms of CJD.

0003 The following is a brief account of the BSE epi-

demic in cattle, where it exists, how it is being elimin-

ated, and how both public health and animal health

are being protected.

The Cause of BSE

0004 BSE is caused by the BSE agent. TSE agents can be

biologically strain-typed in inbred strains of mice, a

process that usually takes years. The BSE agent exists

as a single major strain and is different from the

agents that cause scrapie, TME, CWD and all forms

of human TSE except vCJD.

The Nature of TSE Agents and Diagnostic

Methods

0005 The nature of TSE agents is disputed. They have been

variously described as prions, virinos, and unconven-

tional viruses. They are unlike bacteria and conven-

tional viruses as they provoke no conventional

immune response in infected hosts. Therefore there

is no immunological test that can be used to identify

an infected individual before the onset of clinical

signs. TSE agents are the nearest things to indestruct-

ible forms of life. They can resist boiling, conven-

tional autoclaving, dry heat to over 300



C (and

perhaps more) for an hour, ionizing and ultraviolet

radiation, burial for up to 3 years, formaldehyde, and

a range of chemicals that are effective against conven-

tional bacteria and viruses. Nevertheless, several of

these treatments do reduce the titer of infectivity,

often substantially. Specified autoclave conditions

and incineration, sodium hypochlorite, and sodium

hydroxide are either effective or useful in practice.

The Prion Hypothesis and PrP Detection

0006 The prion hypothesis, in its purest form, proposes

that the agent is an infectious protein, an altered

form of a host protein known as PrP. This protein is

coded for by the PrP gene that exists in all cells of an

individual. The gene is highly preserved in mammals

and some other orders of animals. PrP is found in

several tissues of mammals but is most abundant

in nervous tissue and particularly nerve cells, where

it is regarded as a neuronal membrane protein. The

function of this protein is unknown though it may

control programmed cell death. Mice appear to live

successfully if the PrP gene is deleted (PrP knockout

mice), though some models have shown altered circa-

dian rhythm and others deficits in synaptic function.

0007The protein found in normal individuals is called

PrP

. In disease there is a post-translational confor-

mational change that results in the formation of

PrP

. This involves a change in shape from mainly

a helix to mainly b sheet. PrP

is denatured by prote-

ases such as proteinase K. PrP

, on the other hand, is

insoluble and partially protease-resistant. It is then

known as PrP-res. These features have been exploited

to develop diagnostic methods to identify the protein

in infected tissues. Such methods include immuno-

blotting (Western blotting), dot blotting, and

immunohistochemistry (the detection of PrP in tissue

sections). Disease-associated PrP tends to aggregate in

tissues. Diagnostic use is made of this phenomenon by

detection of disease-specific fibrils (scrapie-associated

fibrils or SAF) by electron microscopy. This is done on

detergent extracts of brain or spinal cord, treated

with proteinase K, and followed by electron-dense

staining. More recently Rapid diagnostic tests have

been developed for use in cattle and sheep to aid

surveillance for the disease (active surveillance). All

Rapid tests are based on the detection of PrP

central nervous tissue collected after death.

The Virino Hypothesis

0008There is no doubt that infectivity and PrP are closely

associated and difficult to separate. However, doubt

has been cast on the validity of the prion hypothesis.

This is because some features of the transmissibility

and dynamism of TSE agents, such as mutation and

agent strain differences, for which there is abundant

evidence, are not well explained by the basic ‘protein-

only’ hypothesis. These observations have been made

following transmission experiments between species.

This has meant that various modifications to the

prion hypothesis have been proposed over the years

to explain the observations. One of these modifica-

tions is the proposition that ‘protein X’, an unidenti-

fied protein, is required for infectivity. This may act as

a molecular chaperone. A second is that in some prion

disease neurodegeneration occurs in the absence of

PrP

. Instead, it may be caused by a transmembrane

form of PrP, called

Ctm

PrP.

BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) 575

0009 Although the biological features of agents isolated

from cattle with BSE and several other species with

recently discovered, natural, or experimental TSE,

including three human patients with vCJD, are indis-

tinguishable (the biological strain type is the same),

the primary PrP amino acid sequence from each is

different. This feature, mutation, and strain variation

in general can be more readily explained by conven-

tional molecular theory, namely that the agent has a

genome that is, perhaps, a small nucleic acid. The

agent therefore is hypothesized to be a hybrid mixture

of PrP and the agent genome. However, the weakness

in the hypothesis is that this genome has remained

undiscovered.

Unconventional Virus Hypothesis

0010 There are generally fewer supporters of this hypo-

thesis but most of them claim it has not been dispro-

ved. An infection-specific nucleic acid has not been

identified.

0011 Whatever is the structure of the causal agent it is

clear that the PrP plays a central role and this must be

accommodated in any hypothesis. Claims that BSE is

an autoimmune disease or alternatively that organo-

phosphorus compounds are a prime cause are not

viable theories.

Epidemiology of BSE

Origin of BSE

0012 The UK epidemic of BSE had an extended common

source. The features were consistent either with an

origin from sheep affected with a scrapie-like agent or

from a cattle-adapted scrapie-like agent. They were

not consistent with exposure to a mutant form of

scrapie. The source of infection has been identified

as concentrate feed and the vehicle is ruminant-

derived protein in the form of meat-and-bone-meal

(MBM). Bovine blood, fetal calf blood, components

of blood, and bovine milk have shown no detectable

infectivity following bioassay. Positive epidemiolo-

gical evidence for transmission of BSE via milk is

also absent. All authorities, including the World

Health Organization (WHO), Office International

des Epizooties (OIE), European Commission (EC),

Food and Drug Administration (FDA), and Spongi-

form Encephalopathy Advisory Committee (SEAC),

having reviewed the evidence conclude that bovine

milk is a safe product in regard to TSE, for all pur-

poses. This means that suckled cattle, not the off-

spring of a BSE case, reared entirely on milk and

subsequently on grassland have a negligible risk of

developing BSE. It also follows that unadulterated

bovine blood and milk products can safely be used

in pharmaceuticals, biologicals, and cosmetics. How-

ever, in the case of bovine blood an additional safe-

guard against contamination is to source the material

from countries that are classified in the highest

category of safety.

0013The genetic component in BSE is small. Thus, the

disease can be considered as an infectious disease

transmitted mainly via feed.

0014There is a possibility that maternal transmission

may play a minor role in the transmission of BSE in

the UK but, even if it does, it will not itself prevent the

elimination of the disease.

0015It has not been possible to transmit BSE via

embryos derived from clinical cases of BSE either to

the offspring so derived, or to recipient dams after a

7-year period. Male or female reproductive tissue,

including embryos, fluids used for flushing embryos

from the uterus, placenta, and milk, have not revealed

detectable infectivity following bioassay. Neverthe-

less a cohort study, confounded by accidentally feed-

ing MBM to both cases and controls, provided some

evidence that there was a risk of maternal transmis-

sion at a level around 10% in the study. The risk was

highest for calves born whilst the dam was clinically

affected but there was also a significant risk for calves

born in the 6 months prior to onset of clinical signs in

the dam. Subsequent experience of BSE in the UK as

the epidemic declines and following detailed epidemi-

ological study of a few BSE cases born after 1 August

1996, when the second feed ban was considered

complete, has not supported such a high incidence

of maternal transmission. Furthermore, no BSE has

been reported in any offspring of dams with BSE in

any other country, even though over 3000 cases or

positive animals have occurred. In summary, mater-

nal transmission cannot be entirely ruled out but

evidence for it is meager and no plausible method

has been proposed for its occurrence.

0016A recent review reports that, during the period

1970–88 (a ruminant feed ban was introduced in

July 1988 in GB) feed manufacturers introduced

MBM into rations for calves from the first or second

week of age. Accordingly, in the UK, a high propor-

tion of dairy cows and cross-bred suckler cows de-

rived from dairy cows will have been fed MBM as

calves. This was an important risk factor for BSE and

accounted for most cases of BSE being in dairy cows

or cows derived from the dairy herd.

0017Commercially and safety-stimulated changes in the

processing of animal waste around 1980 in the UK

apparently permitted an increase of BSE agent infec-

tivity to enter the MBM, sufficient to cause detectable

disease by 1985–86. Disease resulted after the mean

60-month incubation period was complete. Recycling

BSE infection from cattle via MBM exacerbated the

576 BOVINE SPONGIFORM ENCEPHALOPATHY (BSE)

epidemic, whether its origin was from sheep or cattle.

Recycling commenced from infected tissues of incu-

bating cattle, before BSE was even discovered, and

resulted in a marked increase in incidence from mid-

1989. MBM was probably also the source of infec-

tion for a small number of captive wild Bovidae

that developed TSE during the late 1980s and early

1990s in the UK. The origin of TSE in captive wild

Felidae was consumption of uncooked carcass mater-

ial from fallen stock (animals that die on the farm or

in transit) that contained central nervous system

(CNS) tissue. It is these tissues that contain the

highest levels of infectivity in clinically affected

animals. The precise origin of feline spongiform en-

cephalopathy (FSE) in domestic cats is less certain but

was via feed.

0018 The Scientific Steering Committee (SSC) of the EC

has frequently been confronted with unresolved

issues relating to the origin of BSE and with alterna-

tive hypotheses for the transmission of this disease

other than via animal proteins and maternal transmis-

sion. They reviewed the evidence in 2001 provided in

reports by the TSE/BSE ad hoc group and gave an

opinion. They concluded that:

0019 Epidemiological studies, rendering studies, and the

effect of feed bans in all countries with BSE very

clearly support the hypothesis of infected mamma-

lian protein in the form of MBM being the major

vehicle for BSE transmission in cattle. It can enter

the feed deliberately or accidentally by cross-

contamination that can occur readily during feed

preparation in feed mills, during transportation, or

on the farm.

0020 Maternal transmission is theoretically a possible

route of transmission, although it has not yet been

demonstrated.

0021 Other infected materials, such as gelatin and/or fat,

incorporated in feed represent another possibility

of transmission.

0022 The PrP theory remains central to BSE and other

TSE.

0023 It is wise at present to maintain an open mind on

the nature of the BSE agent(s).

0024 A number of other hypotheses have been proposed

on the nature of the responsible agent(s) of BSE

(e.g., a toxin, a bacterium, alkaloidal glycosidase

inhibitors, autoantibodies, and a single-stranded

DNA), but for none of them is sufficient scientific

evidence available and some are clearly implausible

or very difficult to investigate.

0025 The origin of the BSE prion is not known. Many

hypotheses have been suggested, including, for

example, an origin from mammalian species other

than cattle (a mutant form of scrapie agent, a

natural TSE in Bovidae or Felidae or other wild

animals whose carcasses were rendered into

MBM, the existence of a form of sporadic TSE-

like sporadic CJD of humans, a spontaneous muta-

tion of normal bovine PrP into an infectious and

protease-resistant TSE prion, etc.). For none of

these hypotheses are there enough data either to

substantiate or to reject it.

0026In regard to routes of transmission other than those

mentioned above (the so-called third route), not

one of the many possibilities considered has been

substantiated by scientific evidence so far.

0027Factors that have been suggested as having a po-

tential for affecting susceptibility of cattle to BSE

include some metal ions (e.g., copper and manga-

nese), organophosphorus compounds, and anti-

oxidants. However, supporting data for all these

hypotheses are very limited and do not allow any

conclusions to be drawn.

Geographical Distribution of BSE and Related

Diseases

0028Imported cases

In cattle BSE has occurred in a small number of cattle

exported from countries with BSE (mostly the UK) to

other countries. These countries are as far afield as

Canada, the Falkland Islands, the Sultanate of Oman,

and some European countries. In these countries, so

long as cases occur only in imported animals, the sur-

veillance for disease is sound, affected cattle are com-

pletely destroyed, infected cattle and their offspring are

quarantined, and no infected organs are permitted to

enter any food or feed chain, any residual risk is likely

to be extremely small.

0029In other species FSE has been reported in a small

number of cheetahs exported from the UK and

imported into captivity in the Republic of Ireland,

France, and Australia.

0030Cases in native-born animals

In cattle Up until June 2002, countries with BSE in

native-born cattle, mostly dairy cattle, are (cumula-

tive numbers of confirmed cases including cases

found by active surveillance using ‘rapid’ tests): Aus-

tria (1), Belgium (81), Czech Republic (2), Denmark

(8), Finland (1), France (567), Germany (163), Greece

(1), Italy (54), Israel (1), Japan (3) Liechtenstein (2),

Luxembourg (1), Netherlands (35), Northern Ireland

(1977), Poland (1), Portugal (631), Republic of

Ireland (953), Slovakia (5), Slovenia (1), Spain (137),

Switzerland (416), UK (179 488) and other British

Isles (1287). (Data courtesy of DEFRA and DARDNI

for the UK and OIE/EC for other countries).

BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) 577

0031 In other animal species A total of 37 cases of SE

in captive wild Bovidae and Felidae and 90 cases of

FSE in domestic cats have been confirmed in the UK

to June 2002. One case each of FSE in domestic cats

has been reported in Norway, Liechtenstein, and

Switzerland. (Data courtesy of DEFRA, UK).

0032 In humans Up until June 2002, there has been a

total of 113 definite and probable cases of vCJD in

the UK, four cases in France, and one each in the

Republic of Ireland and Italy. Each of these countries

has had BSE in native-born cattle. By contrast, in

2001 the total number of all forms of definite and

probable CJD in the UK was 77 (sporadic 50, iatro-

genic 3, familial 2, GSS 2 (all these completely separ-

ate from vCJD), and vCJD 20: data courtesy of

Department of Health). Two or three further cases

of vCJD have been confirmed in countries with-

out BSE, but these are included in the UK total be-

cause the epidemiological evidence points to them

having been exposed in the UK during residence

there.

0033 The SSC of the EC has classified a range of

countries wishing to trade in bovine products with

member states of the European Union (EU) and in-

cluding all member states into one of four categories

on the basis of an analysis of submitted dossiers con-

taining relevant data. This analysis is called the Geo-

graphical BSE Risk (GBR) risk assessment. Although

the list is dynamic, at the present time the UK and

Portugal are in the highest risk category and countries

like Argentina, Australia, and New Zealand that have

reported no BSE and have good surveillance for the

disease are in the lowest risk category. The OIE has

defined five categories dependent upon the occur-

rence and incidence of BSE but has categorized no

individual country. The two apparently different ap-

proaches are in fact very closely aligned and it is

anticipated that eventually they will coincide. The

EC is currently re-evaluating the GBR for over 80

countries to reflect the current situation more accur-

ately and since BSE has been reported in widely

separated regions of the world.

Processing of Waste Animal Tissues – Rendering

0034 Epidemiological studies In the UK, MBM had been

fed to cattle for decades before the first case of BSE

was discovered in 1986, without any knowledge of a

problem and despite the fact that scrapie-infected

sheep tissues were in the starting material. At this

time and until it was stopped many years later by

EC decision, the starting material had included cer-

tain bovine TSE-risk byproducts from abattoirs. Also

included were condemned materials and fallen stock.

During the 1970s and early 1980s commercially

motivated changes were occurring in the UK

rendering industry.

0035First, there was a change from batch processing to

continuous processing. But this did not result in an

equivalent change in the processing parameters (such

as processing at lower temperatures or for shorter

times) that might reasonably have been associated

with a reduced inactivation of a scrapie-like agent.

0036Second, there was a phasing-out of the hydrocar-

bon solvent extraction of tallow, particularly in the

period of the putative first exposures to the BSE

agent. This was believed to be critical. This change

appears to have permitted an increased amount of

TSE agent infectivity to escape inactivation, and this

was sufficient to produce disease at a detectable inci-

dence. However, subsequent laboratory inactivation

studies using hydrocarbon solvents previously used to

extract tallow, and the additional heat process used to

recover the solvent, showed that these had little effect

on TSE agent inactivation, though possibly just suffi-

cient to restrict an effective oral dose being delivered.

Nevertheless, some doubt was cast on the ‘rendering’

hypothesis, but no plausible alternative explanation

has been proposed for the timing of the first effective

exposures.

0037Experimental studies Experimental studies on

animal waste processing, as conducted throughout

the EU, showed that viable scrapie and BSE agents

could survive some processes that were used in the

countries where BSE occurred, thus supporting the

notion that MBM was the vehicle of transmission.

As a result of all these studies, the procedures adopted

in the EU for processing mammalian waste now re-

quire the following parameters: a maximum particle

size of 50 mm in the raw material, followed by pro-

cessing (pressure cooking) at a minimum temperature

of 133



C at 3 bar pressure, for 20 min. However,

laboratory studies suggest that no rendering process,

including pressure-cooking, can guarantee complete

inactivation of TSE agents.

0038A new European regulation to control animal

waste is likely to become law by 2003 and covers all

member states of the EU. Amongst other things, this

determines that waste is divided into three categories

of risk, each of which has a predetermined disposal

method applied to it. The highest risk material would

be incinerated and the lowest could only come from

animals passed fit for human consumption and then

be treated in approved ways before being permitted

into animal feed or for other purposes. A major step

forward was the earlier introduction, consolidated

into the new regulation, of the rule whereby animal

feed derived from animal byproducts can only use

starting materials passed fit for human consumption

578 BOVINE SPONGIFORM ENCEPHALOPATHY (BSE)

and processed by approved methods. Furthermore,

within-species recycling of animal protein (other

than milk and a few other exceptions) will not be

permitted. Of course ruminants would not be permit-

ted to receive protein from any animal species. In

addition, there is a temporary ban on feeding animal

protein to any food animal species, mainly to combat

the problem of cross-contamination of ruminant feed

and the occurrence of cases of BSE born after the feed

ban was put in place.

Gelatin, Skull, and Vertebral Column

0039 Gelatin is a product with a wide range of uses, includ-

ing in food, confectionery, and medicines. The raw

materials are animal bones or skin from pigs and

cattle. The only starting material with which there is

concern is bovine bone, not because of any inherent

infectivity in it in clinically healthy animals, but

rather because of the possible contamination with

specified risk materials (SRM), particularly brain,

spinal cord, and associated ganglia. Thus the bones

most likely to be a risk are ruminant skull bones (that

are SRM throughout the EU) and vertebral column,

excluding the tail vertebrae. These, respectively, could

easily retain residual brain and spinal cord and the

vertebral column would certainly retain dorsal root

ganglia in which TSE infectivity has been found in

experimental BSE. Depending on the GBR category

to which a country has been allocated by the EC, the

risk bones are designated SRM and cannot be used for

gelatin manufacture. In addition, the processing par-

ameters must follow prescribed rules that have been

shown experimentally to reduce the titer of spiked

BSE material by substantial amounts. If this is done

the residual TSE risk in gelatin is negligible.

0040 Because of the same TSE concerns with the starting

material (bovine skull and vertebral column) it is now

prohibited to use ruminant bones in the EU to manu-

facture mechanically recovered meat that has been

widely used in human food in the past and was

thought by some to be a possible source of vCJD

infection from cattle. All ruminant bones are now

proscribed because it would be impossible otherwise

to police the ban.

The Source of BSE Infection and Effect of the

Removal of the Source

0041 The coordinated epidemiological studies on BSE

commenced in mid-1987 when there were fewer

than 10 confirmed cases of the disease. By the end

of the year, there had been almost 200 cases, sufficient

to enable a working hypothesis for the origin to be

drafted. Thus, the MBM hypothesis was established.

The results from this study led to the introduction, in

July 1988, of a major measure to control the disease,

the ban on feeding ruminant protein to ruminant

animals, with certain exceptions like milk protein.

0042Withdrawal of mammalian MBM from the rations

of cattle and other Bovidae in 1988 effected a marked

reduction in incidence of BSE and feed/BSE-related

ruminant TSE in the UK, and strongly supports the

hypothesis of an origin from TSE-infected raw mater-

ial that somehow survived processing. The decline in

incidence became clear from 1992–93 onwards; the

delay was due to the mean 5 years’ incubation period

for BSE.

Descriptive Epidemiology

0043All breeds of cattle and both sexes appear to be

equally susceptible; however, the disease affects

mostly breeding dairy cows due to the methods of

feeding the calves of these animals. Unlike beef

breed calves that are suckled, dairy calves are re-

moved from the dam after sucking colostrum. They

are then fed artificial milk and later concentrates that,

until 1988 in the UK, often contained MBM.

Amongst dairy cattle in the UK, the incidence of

disease between breeds is similar, but the number of

confirmed cases by breed is directly proportional to

the numerical size of the breed. Thus, most cases

occur in Holstein-Friesian cattle and crosses with

this breed, because they are the most abundant. Be-

cause of the widespread use of artificial insemination,

bulls are much less numerous than cows and this

largely explains why so few bulls (just under 500 in

GB) have been affected by BSE compared with cows.

0044The risk of BSE occurrence in a herd increases with

increase in herd size. This is attributed to the greater

risk attached to purchasing an infected ration because

in large herds more batches of feed would be bought.

Of herds affected by BSE in the UK, nearly 35% have

had only one case and over 80% have had seven or

less. The mean within-herd incidence has remained

more or less constant at less than 3% in any 6-month

period, though it is now falling as the epidemic de-

clines. Collectively these data and the results of a

case-control study do not support contagion being

important in BSE. Instead, it seems that infection

and disease result from a random low-dose exposure

to a common source of infection in MBM that is in

‘packets’ rather than being evenly distributed within

feed, though this hypothesis is disputed by some

workers.

Control and Elimination Measures

Animal Health Control Measures

0045The objective of member states of the EU and

Switzerland is elimination of BSE from the territory.

BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) 579

A new regulation of the European Parliament and of

the Council (EC no. 999/2001 of 22 May 2001)

details the rules for the prevention, control, and eradi-

cation of TSE. Eradication (elimination of BSE from

all countries in the world) is the eventual objective,

but with several countries reporting BSE for the first

time in the period 1999–2002, this task will not be

achieved in the immediate future.

0046 The main measures to protect ruminants from BSE

are a ban on the inclusion of ruminant protein (sub-

sequently mammalian MBM) in ruminant diets and

the authorization only of the most effective rendering

processes (pressure-cooking or methods giving equal

or better inactivation of BSE and scrapie agents)

where this is permitted for processing mammalian

waste. Legislation to achieve the former has been

adopted in the major cattle-rearing countries of

Europe, North and South America, Australasia, and

some other countries. Rendering process controls are

in place throughout the EU.

0047 In the UK a ban on the use of certain specified

bovine offals (SBO) thought most likely to contain

BSE infectivity in cattle incubating BSE, originally

introduced to protect public health in 1989, was

extended in 1990 to protect all species of animal

and bird. More recently, the SRM ban was introduced

in the UK to protect public and animal health. SRM

include some tissues from sheep and goats. An EU-

wide SRM ban was introduced in June 2000 and has

subsequently been modified to improve its scope.

SRM must be destroyed completely by approved

processes.

0048 The feed ban, introduced in its initial form in 1988

in the UK, has a sound scientific basis but was not

completely effective in reducing exposure from feed

sources, so that cases of BSE have occurred in animals

born after the ban was introduced. Indeed, over

43 500 such ‘born after the ban’ or BAB cases have

been reported in GB and most current cases of BSE in

Europe have occurred in animals born after the date

of feed bans applied in individual countries. In the

UK, new exposures from feed in cattle born since

1 August 1996 should in theory be entirely prevented

as a result of banning the use of mammalian MBM in

the feed for any food animal species, including horses

and fish. An even more extensive ban now applies

throughout the EU and essentially prohibits the feed-

ing of any animal protein, except milk protein, to

food animals. The major stimulus to introduce

these extended and strict bans is because cross-

contamination of ruminant diets with MBM or diets

for pigs and poultry containing MBM (nonruminant

diets legitimately could, prior to the regulation, in-

clude MBM as a constituent) could not be prevented

in feed mills, during transport, or on-farm. Research

has shown that very small amounts (< 1 g) of brain

material can carry a lethal infective oral dose for a

cow.

0049The epidemics of BSE in the UK and Portugal are

now declining towards elimination. It is hoped that

Switzerland and all EU member states will follow as

the extended bans become completely effective.

0050The OIE (World Organization for Animal Health)

has produced an International Animal Health Code

chapter on BSE that determines the requirements to

facilitate safe trading in cattle and cattle products in

regard to BSE throughout the world.

Public Health Control Measures

0051In addition to the SRM ban mentioned above, all

cattle suspected of having BSE are compulsorily

slaughtered and totally destroyed (since 1988 in the

UK and 1990 in the EU) so they can enter no food or

feed chain. This is now practiced in all countries and

is endorsed by WHO that has also recommended

global surveillance and diagnosis of all forms of

CJD. The WHO collaborates with the OIE in recom-

mending surveillance and monitoring for animal TSE,

including BSE in all countries.

The UK BSE Situation Contrasted with that in other

European Countries

0052It is clear that the total number of cases of BSE and

the incidence of BSE in GB (> 179 000 to date)

exceeds, by far, the number of cases and the incidence

in other countries (collectively > 3000 to date). How-

ever, the annual number of suspect cases reported and

confirmed in the UK has declined since 1992 and is

still declining toward extinction and in line with pre-

dictions. As a result of passive surveillance, at the

peak of the epidemic in GB in 1992 > 36 000 cases

of BSE were confirmed. In 2001 only 781 were con-

firmed. There is greater than a 40% reduction in cases

by year, though the epidemic is expected to have a

long ‘tail’. Furthermore, the residual risk to humans

and animals is probably lower in the UK than any-

where else, because of the extensive interlocking

measures applied and enforced to protect animal

and human health. A significant measure applied

after March 1996 in the UK is the scheme that

prohibits the use for any purpose of products from

cattle over 30 months (OTM) of age. A conditional

exclusion is permitted for hides. This OTM scheme

exists in no other country. However, cattle from herds

in the UK beef assurance scheme may be slaughtered

for human consumption up to 42 months of age.

Because cattle in these closed herds are mainly grass-

fed and have not received MBM in their diet, they

present a low risk from BSE.

580 BOVINE SPONGIFORM ENCEPHALOPATHY (BSE)

0053 Some British and continental veterinarians have

formally expressed in 1997 concern that there could

be more cases of BSE occurring outside the UK than

were being officially reported. Indeed, there have

been studies into the expected incidence of BSE in

cattle exported from the UK to other member states.

It was concluded that it was likely that BSE cases had

occurred in cattle in member states that had been

imported from the UK. The (average) number of po-

tential cases in animals imported between 1985 and

1989 was estimated to be 1642, a much higher

number than had been officially reported to the

EC or OIE. BSE cases in imported cattle could also

have been the source of secondary cases of BSE. Such

cases could have resulted from the recycling of

infected cattle tissues through the rendering system

(depending on the efficacy of the processing in the

country in question) and then back to cattle via con-

taminated feed. These predictions have come true.

0054 Following the announcement of 10 cases of vCJD

in March 1996, several countries reported an increase

in the number of BSE cases. For example, all three

Benelux countries reported their first BSE cases in

1997 and Denmark, Germany, and Spain their first

native-born case in 2000, and several other European

countries followed suit during 2001 and 2002. BSE

has now been reported in Japan and Israel. The

number of confirmed cases currently being reported

in these countries is small and less than the number

currently being reported in the UK. However,

the epidemics in most countries, as judged by the

numbers of cases reported in successive years and

identified by both passive and active surveillance,

are increasing, whereas those in the UK and Portugal

are declining. The occurrence of clinical cases refers

back to exposures 5 years previously, so it is quite

possible that new infections in most European coun-

tries are currently very low and will be reflected as a

declining incidence in the coming years.

Feed Bans in other European Countries

0055 It is only since 1994 that a uniform MBM feed ban

(for ruminants) and rendering control has been deter-

mined by EC legislation. Switzerland (who alone

adopted an SBO ban like the UK in 1990), Denmark,

France, Ireland, the Netherlands and some other

countries imposed a national ruminant feed ban

from 1990. In at least one country, the ban was

applied to cattle feed only, and not to other ruminant

feed, thus potentially exposing sheep and other

ruminants to infected MBM via feed until the law

was changed some years later. All other member

states with BSE in native-born cattle have had, like

the UK, cases in animals born after the respective

dates of the feed ban in their own country. Most

agree that these probably result from cross-contamin-

ation of ruminant feed with infected MBM intended

for monogastric species (mainly pigs and poultry).

Mammalian MBM, including ruminant MBM, was

permitted until 1 January 2001 for feeding to non-

ruminant farm animals in all member states except

the UK and Portugal.

Offal Bans in other European Countries

0056In 2000, uniform SRM controls in the EU were intro-

duced, though several countries with BSE in native-

born animals had some form of ban prior to this.

However, some member states with no BSE in

native-born animals until recently had no SRM ban

at all, despite the known risks. This meant that it was

possible that consumers of permitted but dangerous

offals (SRM) in those countries had risked exposure

to BSE if the offals were derived from incubating

animals. Nowhere were the various offals/materials

bans so extensive as in the UK. However, before 1996

in the UK, compliance with and enforcement of the

ban were incomplete. There was leakage of some

infected material, largely into waste destined for ren-

dering, which was recycled to pigs and poultry via

MBM. This contributed to an extension of the cattle

epidemic because of accidental cross-contamination

of ruminant diets with MBM intended only for non-

ruminants. There is no clear indication that such

bans, where they existed, were as rigorously enforced

as they are now in the UK. The EU-wide SRM ban in

place since 2000 will only be effective if it is com-

pletely and continuously enforced. However, Rapid

tests applied to cattle over 24 or 30 months old in EU

abattoirs and destruction of the whole carcasse of

those that fail the test are added consumer safeguards.

Passive Surveillance

0057For the most part, the surveillance for BSE in all

member states is passive, relying on the clinical iden-

tification of suspect animals by farmers and veterin-

arians. This is followed by compulsory slaughter and

by microscopic examination of brains to confirm or

deny a diagnosis of SE, according to standard criteria

set down by the EC and the OIE. Such surveillance

relies for its success on the vigilance of the observers

and awareness of the clinical signs of the illness. Such

surveillance is likely to underestimate the real number

of cases and cannot detect preclinical cases (or, if they

exist, subclinical cases) of BSE.

Active Surveillance

0058As a result of research into methods of detecting PrP

in the brain or spinal cord of BSE-affected cattle, a

number of confirmatory tests have been developed

BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) 581

and evaluated by the EC. Using one of these tests,

in January 1999, the Swiss State Veterinary Service

initiated a targeted, active surveillance system for

three categories of cattle. These are fallen stock, cattle

slaughtered in emergency, and a proportion of

healthy cattle slaughtered for human consumption.

Twelve out of 4868 tested fallen stock were positive

and four out of 2274 tested emergency slaughter

animals were positive. Two out of 4847 healthy

slaughter animals were positive, probably because

they were in the last few months of incubation.

Thus, 18 additional cases of BSE that otherwise

would not have been detected have been identified

by this method before the end of 1999. This was

about the same low number of cases detected by

conventional passive surveillance in that period. The

underreporting of BSE in 1999 in Switzerland was

thus estimated to be about 50%.

Future Outlook

0059 A successful EC-funded comparative evaluation of

four Rapid tests for PrP using brain or spinal cord

tissue for the postmortem confirmation of BSE in

clinically affected cattle has been reported. The ap-

proved tests are now being used throughout the EU on

fallen stock and cattle sent for emergency slaughter

over 24 months of age and on all cattle for slaughter

for human consumption over 30 months of age. Some

countries test all animals for human consumption

over 24 months of age. Any animals that fail the test

must be completely destroyed. Application of several

million tests has already identified several hundred

additional animals with BSE infection that would

otherwise have escaped detection. Results of tests

must be regularly reported to the EC and are pub-

lished. The true incidence of disease and the extent of

underreporting are thus being revealed.

0060 Though not currently validated for use in clinically

healthy cattle, studies are in progress to determine

how effective some of these tests are for detecting

preclinical cases of BSE. This will be done by using

CNS tissue derived from a study of the pathogenesis

of experimental BSE in cattle. In contrast to the situ-

ation in scrapie-infected sheep, the distribution of

infectivity in cattle with naturally occurring BSE is

restricted to inaccessible tissues even in the clinical

phase of disease, namely the brain spinal cord and the

retina. In the experimental disease, infectivity has

been detected in the distal ileum in the preclinical

phase of disease, and in central ganglia and possibly

in bone marrow during the clinical phase. Because

none of these tissues is easily accessible, the prospect

of a reliable and practical test being soon available to

detect preclinical BSE in live cattle is remote.

Conclusions

0061The epidemic of BSE in the UK is clearly under

control and heading for elimination, as predicted. It

is probably similarly heading for elimination in

Portugal. All products permitted for sale from cattle

slaughtered in the UK in 2002 are as safe, if not safer

in regard to the BSE risk, as those are from any other

country with BSE. The situation in other countries is

less certain but, provided all those countries at risk

adopt the lessons learned in the UK, Portugal, and

Switzerland, the future prospects for the elimination

of BSE are also good. The critical issue is to insure

that ruminant feed is not contaminated with infected

MBM. This is a difficult task and interlocking

and enforced measures are essential to success. Also

essential is to conduct surveillance of targeted popu-

lations of cattle using the most sensitive and specific

tests available.

0062Surveillance for all forms of CJD in humans is

also vital. Of current concern is the future size and

duration of the vCJD epidemics and of the possible

occurrence of scrapie in sheep caused by the BSE

agent. There is no evidence for the latter. In regard

to the former, predictions are not possible due to

several uncertainties, including the length of the incu-

bation period, the number of humans exposed, and

the precise source of infection. Concerns have been

expressed about the possible transmission of vCJD

from human to human, particularly via blood trans-

fusion or surgical instruments. Currently, there is no

evidence for transmission of vCJD by any means

between humans, but nevertheless, strict risk manage-

ment procedures have been put in place to reduce any

possible risk.