Bovine Spongiform Encephalopathy

Mad Cow Disease, BSE
Last Modified: May 2, 2012

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease, caused by a prion, that mainly affects cattle. Other ruminant species, cats, non-human primates and humans are occasionally affected; this disease is called feline spongiform encephalopathy (FSE) in cats, and variant Creutzfeldt–Jakob disease (vCJD) in people. BSE is a relatively new disease that was first reported in the United Kingdom in the 1980s. It is spread by ingestion; animals or humans become infected when they eat prion-containing tissues from an infected animal. Cooking and standard disinfection procedures do not destroy this agent. Infected animals or people do not become ill for years; however, the disease is always progressive and fatal once the symptoms develop. The origins of BSE are unknown; however, the recycling of ruminant proteins in ruminant feed amplified this prion and caused an explosive epidemic in the U.K in the 1980s and 1990s. This epidemic peaked in 1992, with almost 1,000 new cases diagnosed each week. Although cases continue to be detected, control measures have greatly decreased their prevalence; fewer than 15 bovine cases were reported annually in the U.K. during 2009-2011. BSE also spread to many European countries, North America, parts of Asia, and possibly other areas of the world. The presence of BSE in a country can result in trade sanctions, as well as increased public concern about meat safety. Many nations, including the U.S., conduct control and surveillance programs. Many countries have also passed new regulations to prevent BSE-containing tissues from entering human or animal food supplies. As a result of increased surveillance, BSE prions that differ from the prion causing ‘classical’ BSE have been identified at very low levels in cattle populations. Currently, it is thought that these “atypical” prions may represent a spontaneous form of prion disease. Some experiments suggest that an atypical prion might have given rise to the BSE epizootic when it was amplified in cattle feed.

BSE is a member of the transmissible spongiform encephalopathies (TSEs), a group of neurodegenerative disorders caused by unconventional disease agents. These agents are resistant to the treatments that ordinarily destroy bacteria, spores, viruses, and fungi. They are generally thought to be prions, although a minority opinion suggests that TSEs may be caused by virinos or retroviruses. Prions are infectious proteins that appear to replicate by converting a normal cellular protein into copies of the prion. The cellular protein, which is called PrP c, is found on the surface of neurons. Pathogenic isoforms of PrP c are designated PrPres; PrPSc or PrPTSE are other names for this protein. Prions that cause different diseases (e.g. BSE or scrapie) are considered to be different strains of PrP res. In addition to the ‘classical’ BSE prion, at least two atypical BSE prions can be found in cattle. One has higher molecular mass fragments than classical BSE and is called ‘H-type’ BSE or H-BSE; the other has a lower molecular mass and is called ‘Ltype’ BSE or L-BSE. Some authors call the disease caused by the latter organism ‘bovine amyloidotic spongiform encephalopathy (BASE).’ Atypical BSE prions are thought to represent additional strains of BSE. Currently, the most likely hypothesis is that these prions arise spontaneously in cattle, similarly to some prion diseases in other species (e.g., spontaneous Creutzfeldt–Jakob disease in humans). Atypical LBSE has been reported to change to a classical BSE phenotype on transmission to inbred mice or to some transgenic mice. Similarly, H-BSE developed features of classical BSE in some wild type mice. This has led to the suggestion that one of these prions may have originally given rise to the BSE epidemic after amplification through the food chain.

Geographic Distribution
Cases of BSE have been reported in indigenous cattle in most European countries, Canada, the U.S., Israel, and Japan. This disease was seen in imported cattle in the Falkland Islands and Oman. Some countries including Iceland, Australia, and New Zealand appear to be free of BSE. The presence or absence of this disease cannot be determined in countries without adequate surveillance programs.
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however. Transmission to humans and iatrogenic spread In humans. In a recently published study. Bloodborne transmission has been demonstrated in this species. They are also likely to exist in other countries.. some studies report that the tissue distribution of atypical L-BSE and H-BSE seems to resemble that of classical BSE. the thymus. distal ileum (particularly in the Peyer’s patches). transmission studies suggest that BSE is not transmitted in milk.) H-BSE and L-BSE have also been found in peripheral nerves and sensory receptors (muscle spindles) and the trigeminal ganglion in some studies. Transmission from two ewes to their lambs occurred in an experimental flock. Very little is known about the potential for vertical transmission. In naturally infected cattle. ileocecal junction.. and additional routes of transmission may occur. However. For example. vertical transmission seems to be rare. Using a very sensitive system (transgenic mouse bioassay). as the result of surveillance programs for BSE. Some tissues may contain prions only in the late stages of the disease. The risks of transmission from various tissues are still incompletely understood. Canada. (There are. trigeminal ganglion. the accumulation of these agents in the peripheral nerves and adrenal gland seems to coincide with or follow prion accumulation in the CNS. lymph nodes. however. the quantity of prions may be low or the incidence rare. but more sensitive techniques have recently detected this agent in the dorsal root ganglia. In sheep inoculated orally. meat could become contaminated with CNS tissues during slaughter or processing. and gut-associated lymphoid tissue (GALT). infectivity was recently detected in the tongue and nasal mucosa of cattle in the terminal stages of the disease. very weak immunostaining was also detected in the renal tubular epithelial cells. however. If it occurs. BSE prions are readily found in many lymphoid tissues including the spleen. PrP res was reported to occur in the muscles of L-BSE infected cattle by immunostaining. In one study. tonsils. it has been reported from the CNS. For this reason. peripheral nerves (including the optic. colon. although no prions could be found by immunoblotting or the protein misfolding cyclic amplification (PMCA) method. spinal cord.e. or embryos. and the risk of transmission is uncertain. retina. some peripheral nerves. Young animals may be particularly susceptible to infection. and L-BSE was detected in the adrenal gland. the confidence interval included zero. dorsal root ganglia. but the prions are more widely disseminated in the body. jejunum. Probable person-to-person spread was reported in several patients who received blood transfusions from asymptomatically infected individuals. and the islets of Langerhans. the U. and adrenal glands. These observations have led to speculation that vertical transmission might be possible. Atypical BSE In cattle. adrenal glands. immunostaining detected prions in the macrophages of the subiliac lymph nodes but not other lymph nodes tested. and the route is unknown. In this animal. One calf born to a cow in the late stages of infection with L-BSE did not have any evidence of infection. The prions are thought to replicate initially in the Peyer’s patches of the ileum. cecum. There is also potential for transmission by routes such as transplantation or the use of prion-contaminated Transmission BSE is usually transmitted when an animal or human ingests tissues containing the BSE prion. Epidemiological evidence and Last Updated: April 2012 © 2012 CFSPH page 2 of 13 . In one animal. however. except in one sample tested by mouse bioassay. semen. Based on studies in humanized transgenic mice. Unpublished data suggested that BSE prions might occur in the lymphoid tissues of nictitating membranes. and infectivity was found in muscle homogenates using a transgenic mouse bioassay. Classical BSE has not been found in muscle.Bovine Spongiform Encephalopathy Atypical BSE prions have been reported in Europe. and distal ileum. and Japan. variant Creutzfeldt-Jakob disease usually results from the ingestion of BSE prions. as well as in the CNS. nearer to the onset of clinical signs). One model suggested that the cumulative risk of BSE transmission from dam to offspring is about 2%. facial and sciatic nerves). high-risk slaughter and processing techniques have been banned in many nations (see ‘Prevention’). then are transported via the peripheral nerves to the central nervous system (CNS). There is no evidence that BSE is transmitted horizontally between cattle. but no evidence to confirm this has been published.S. BSE transmission in experimentally infected sheep resembles transmission in cattle. prions can accumulate in the brain as early as 24 months after infection. BSE prions have been found mainly in the brain. In some tissues. some differences in the pattern of distribution within the brain. where infectivity was thought to be associated with the endings of the sciatic nerve. it is not known whether this event took place in utero or soon after birth. there is an unexplained increase in the risk of BSE among the offspring of infected animals. thoracic ganglia. In cattle. with prions detected mainly in the CNS. some studies suggest that most cattle become infected with BSE during the first six months of life. In experimentally infected cattle. some authors have suggested that BSE isolates from sheep and goats might be more readily transmitted to humans than isolates from cattle. the highest prion concentration occurs in the CNS and ileum. Iatrogenic transmission has also been seen. and bone marrow. the risk that a calf would develop BSE appeared to be higher when the dam was in the later stages of infection (i. myenteric plexus of the intestines.

Origins of the BSE epidemic The origins of BSE are not well understood. In experiments. and one study found that BSE prions from cattle were more resistant than prions from human spontaneous CJD. optic nerves. a stainless-steel wire remained infectious after cleaning with sodium hydroxide and autoclaving. however. Theoretical possibilities include inadequate heating of bone meal or tallow used in concentrates and milk replacers. Few effective decontamination techniques have been published. hamster-adapted scrapie prions have been shown to survive in the soil for at least three years. New commercial decontaminants have been developed for prions. Prions have been found in the appendix as early as two years before the onset of clinical disease. retina. MBM is a rendered concentrate derived from animal offal and carcasses. but cases have been reported in cattle born after these regulations came into effect (“born-after-the-ban” cases). but residual infectivity has been demonstrated in some studies. Surfaces should be treated for more than 1 hour at 20°C (68°F). A 1-2 N sodium hydroxide solution. and an enzymatic cleaner combined with vaporized hydrogen peroxide were shown to inactivate scrapie prions. Prions bound to metal seem to be highly resistant to decontamination. without losing infectivity. trigeminal ganglia. Although prions are particularly common in the spleen. A combination of chemical and physical decontamination can be more effective than either procedure alone. an alkaline cleaner (KOH with detergents). chemical disinfection should be carried out first. particularly when they are protected in organic material or preserved with aldehyde fixatives. and lymphoid tissues of humans with vCJD. and environments is difficult. Banning ruminant tissues from ruminant feed has significantly reduced the number of new cases of BSE. Current diagnostic techniques are not sensitive enough to detect very low levels of prions. milder treatments including a phenolic disinfectant. One of these solutions was prepared in an 2 M NaOH alkali carrier. Anecdotal evidence suggests that decontamination of contaminated facilities is very difficult. Even the harshest combination of chemical and physical disinfection is not guaranteed to destroy all prions. which may have contributed to its effectiveness. it was amplified by recycling tissues from infected cattle into ruminant feed supplements. tonsils. Surgical instruments that have undergone repeated cycles of cleaning and disinfection have transmitted the sporadic (genetic) form of CJD iatrogenically. appendix and other gut-associated lymphoid tissues (GALT). and there is little information on prion survival in the environment. Disinfection Prions can differ in their resistance to inactivation. horizontal transmission. Decontamination of prion-contaminated tissues. were those that contained proteolytic agents. or when the prion titer is high. These agents are highly resistant to most disinfectants (including formalin). spinal cord. These cases might be caused by the use of imported feed components produced under inadequate quality controls. dorsal root ganglia. surfaces. Other sources suggest that BSE might have originated from a wildlife population or a human TSE agent. but it was probably present in cattle since the 1970s or earlier. or hamster prions. but the epidemic may have been facilitated by changes in rendering practices that allowed more prions to survive. including stainless steel and plastic. or crosscontamination of cattle feed with swine or poultry feed. In one experiment.Bovine Spongiform Encephalopathy equipment during surgeries. Autoclaving items in water is more effective than autoclaving without immersion. They have not been demonstrated in human blood. disposable equipment and instruments may be recommended instead of disinfection during some medical procedures. Cleaning before disinfection removes organic material that may protect prions. Physical inactivation of prions can be carried out by porous load autoclaving at 134-138°C (273-280°F) for 18 minutes at 30 lb/in2. ultraviolet radiation. or a sodium hypochlorite solution containing 2% available chlorine. For this reason. they can also be found in lymph nodes throughout the body. the most effective commercial reagents. The two most popular hypotheses are that BSE originated as a spontaneous PrPc mutation in cattle. This disease was first reported in the 1980s. heat. Prions can bind tightly to some surfaces. illegal feeding of ruminant proteins. In experiments. or environmental reservoirs. Last Updated: April 2012 © 2012 CFSPH page 3 of 13 . Once the BSE agent entered cattle populations. mouse-passaged BSE prions. but this may be due to the insensitivity of the assays used to detect these agents. Overnight disinfection is recommended for equipment. using a rodent prion on stainless steel wires. then the items should be rinsed and autoclaved. or that it came from a mutated scrapie prion that contaminated ruminant feed. mainly as meat-andbone meal (MBM). and ionizing radiation. hamster-adapted scrapie prions can survive dry heat at temperatures as high as 360°C (680°F) for an hour. has traditionally been recommended for equipment and surfaces. Prions can be found in the brain. Person-to-person transmission of vCJD does not occur during casual contact. The alkaline cleaner and phenolic disinfectant were also effective against BSE and vCJD prions. A commercial alkali/detergent reagent was unable to completely decontaminate the wires. Dry heat is less effective. Rendering cannot completely inactivate prions.

Some nations conduct active surveillance of cattle at slaughter (using rapid tests) to detect cases of BSE. Other iatrogenic routes of transmission may be possible. In humans. however. slurring of speech. the incubation period was 6 to 8. Some countries with a low incidence of disease.5 years. memory loss. entire intestines.. The median age of onset is 26 years (range 12 to 74 years). usually at necropsy. dystonia. of prion protein can be found around the plaques by immunohistochemistry. and the spinal column in cattle over 30 months of age. Slaughter and processing techniques that have a high risk of contaminating muscle tissues with CNS have been prohibited in many countries. Active surveillance for BSE has been conducted in the E. however. and mesentery are not allowed from any cattle. Communicability Person-to-person transmission of vCJD does not occur during casual contact. Because prions can be found in the tonsils.S. Cognitive function gradually deteriorates. In three cases transmitted in blood transfusions. spinal cord. depression. and most of the vertebrae from cattle 30 months of age and older.Bovine Spongiform Encephalopathy Infections in Humans Incubation Period The incubation period for vCJD is difficult to establish with certainty. Chorea. incoordination. Probable human-to-human spread has been reported in several patients who received blood transfusions from asymptomatically infected individuals. including transmission in transplants or by contaminated equipment during surgeries. dorsal root ganglia. myoclonus. trigeminal ganglia.. and incubation periods up to 16 years have been reported. and/or persistent painful sensory symptoms.U. These animals cannot be used in human food. and dementia typically develop late in the course of disease. but have been reported up to 40 years after exposure. in countries with a significant risk Clinical Signs The symptoms of vCJD are broadly similar to the sporadic (genetic) form of CJD. including the U. the Japanese government required all slaughtered cattle to be tested for BSE. and sheep are also susceptible to experimental infection. other than supportive care.U. The tonsils. and the carcass is held until testing is complete. and cortical atrophy on magnetic resonance imaging (MRI) of the brain. Since 2005. Diagnostic Tests A tentative diagnosis can be made before death by the history. the diagnosis is made by microscopic examination of brain tissue. such as anxiety. Prevention Variant Creutzfeldt-Jakob disease can usually be avoided by not eating tissues from BSE-infected cattle.S. member states and some other areas. Lower age limits apply to cattle from a few E. In the E. In other cases. frank neurological signs such as gait disturbances. Numerous amyloid plaques surrounded by vacuoles are found in vCJD. test only a percentage of cattle at slaughter. Large amounts Last Updated: April 2012 © 2012 CFSPH page 4 of 13 . eyes. some other human prion diseases have similar median incubation periods. Treatment No treatment is available. prions can be found in the CNS and many lymphoid tissues including the tonsils. when this disease is suspected. The first signs are usually psychiatric symptoms. but later develops characteristic abnormalities. some authors also suggest that disposable equipment always be used during tonsillectomies. In the U. such plaques are seen in only 5-10% of cases of sporadic (genetic) CJD.U. neurological signs coincide with or precede psychiatric symptoms in a minority of patients. undergo emergency slaughter. For comparison.. the age limits have increased since the programs began.. Tissues that have a high risk of transmitting BSE have been banned from human food in many countries. since 2001. however.S.S. social withdrawal. however. skull. Because BSE has been detected in goats. the average incubation period is estimated to be 11 to 12 years. The tonsils and distal ileum from all cattle are also banned. it has required only cattle that are 21 months of age or older to be tested.U. or display certain abnormalities at antemortem inspection. and local authorities have continued to test all slaughtered cattle regardless of age. some countries may also conduct BSE surveillance in small ruminants. member states must test cattle over the age of 48 months that die. Prions have been found in the appendix as early as two years before the onset of clinical disease. prohibited tissues include the brain. Japan conducts unusually rigorous testing. In the U. A definitive diagnosis can be made if the abnormal prion protein is found in tonsil biopsies by immunoblot (Western blot) or immunohistochemistry. including the U. there has been public resistance to relaxing the testing requirements. Most patients die in six months to two years. most E. surveillance is targeted particularly at high risk cattle such as nonambulatory animals and those with neurological disease. and tremor appear a few months later. ataxia. The electroencephalogram (EEG) is sometimes normal during the early stages of disease. In most patients. but usually appear in younger patients. Healthy cattle over the age of 72 months and intended for human consumption must also be tested. are killed for reasons other than human consumption. banned tissues include the skull (including the brain and eyes but not the mandible) and spinal cord in cattle over 12 months of age. As of 2011. visual disturbances. Person-to-person transmission of vCJD can be reduced by the use of disposable surgical instruments in high risk surgeries. clinical signs. At one time. insomnia.

scimitar-horned oryx (Oryx dammah). however. all cases of vCJD in the U. Prion filters have been developed to reduce infectivity in plasma. BSL-3 is the recommended level of protection. but it is possible that children and adolescents are more susceptible to infection than adults. 176 cases of vCJD had been reported in the U. Transmission in blood cannot be completely prevented with current techniques. ocelots (Felis pardalis). All clinical cases have occurred in people with this genotype.K. Saudi Arabia. (See the feline spongiform encephalopathy factsheet for details on infections in felids.000 population. but these prions are also likely to be of zoonotic concern. patients born after 1996 in the U. tigers (Panthera tigris). the BSE agent has been experimentally transmitted to mink. In addition.K. and Taiwan have each reported one case. however. As of April 2012. intravenous.) Two lemurs at a French zoo were apparently infected in contaminated feed. Morbidity and Mortality The prevalence of vCJD is unknown. The number of people who are infected but asymptomatic is unknown. no human infections have been reported with atypical BSE prions. gemsbok (Oryx gazella). Variant Creutzfeldt–Jakob disease is usually seen in young patients. There is currently no evidence that this is the case for H-BSE. Japan. many countries do not allow people who have spent time in the U. and/or other European countries to be blood donors. Between 2006 and 2011. and experimental infections have been reported in both sheep and goats.. for vCJD (range 12 to 74 years). it is 65 years (range 15 to 94 years) in the sporadic (genetic) form of Creutzfeldt–Jakob disease. As of April 2012. Pigs could be infected by the intracranial.S. Disposable instruments and work clothing can also be used. BSE prions have also caused disease in various felids including housecats. People who are homozygous for methionine at codon 129 in the PrPC protein have an increased risk of developing vCJD.K. pumas (Felis concolor). Although laboratory or abattoir-related cases have not been reported. as well as to intracerebral inoculation. mice. and intraperitoneal routes. One infection was reported in a person who was heterozygous for methionine/valine at this codon. and bison (Bison bison). 25 cases had been reported from France. three each from the United States and the Netherlands. Disposable plastic-coated paper sheets can be used to protect tables and other surfaces. but are still being evaluated and are not in wide use. this disease is always fatal. some sources suggest that.K.K. however. Some countries import fresh frozen plasma from low-risk countries for patients without dietary exposure to BSE (e. estimated a prevalence of 1 case per 10. as well as four from the Republic of Ireland. No vaccine is available.K. suggested a prevalence of 237 cases per million population. Another study. Most cases have been seen in people who lived in either the U. The median age of onset is 26 years Last Updated: April 2012 © 2012 CFSPH page 5 of 13 . with a shorter incubation period and more rapid progression. Portugal. five from Spain. Based on the pattern of infection in the U. but the host range of this prion is unusually broad compared to most prions. kudu (Tragelaphus strepsiceros). It is not known whether people with resistant genotypes (valine/valine or methionine/ valine) are completely resistant to the development of disease. To date. such as universal leucodepletion of blood. A negative pressure laminar flow hood should be used for tissue manipulations whenever possible. and Asian golden cats (Catopuma temminckii). based on samples from tonsils. affected species include nyala (Tragelaphus angasi). two to five cases were reported each year. Infections in Animals Species Affected BSE mainly occurs in cattle. in contrast. eland (Taurotragus oryx). Some countries have taken other measures. Arabian oryx (Oryx leucoryx). to reduce the risk of vCJD. and two from Canada. but short-term feeding trials did not cause disease. and ingestion.g. and develop neurological signs. This person became infected in a blood transfusion and died of unrelated causes after five years. cheetahs (Acinonyx jubatus). marmosets. contamination of abraded skin. but did not develop vCJD symptoms. The incidence peaked in 2000. In particular.Bovine Spongiform Encephalopathy of this disease. at most. and Italy. L-BSE seems to be more virulent than classical BSE in intracerebrally inoculated macaques and humanized transgenic mice. when 28 cases were diagnosed. Rare field cases have been documented in goats. BSE has been reported from exotic ruminants in zoos.). Once the symptoms of vCJD develop. surveillance conducted on appendectomy samples in the U. squirrel monkeys (Saimiri sciureus) and cynomolgus macaques (Macaca fascicularis). One study reported that sea bream (Sparus aurata) might be susceptible to infection. 70 additional cases can be expected. The reason is unknown. European red deer (Cervus elaphus elaphus) are susceptible to oral exposure at a high dose. H-BSE (like L-BSE) is capable of changing to resemble classical BSE in transgenic mice. ankole cattle. As of 2012. precautions should be taken to avoid contamination of surfaces and equipment. seem to have been acquired in other countries. and gradually fell to five cases per year in 2005. veterinarians and laboratory workers should always take precautions when conducting necropsies on BSE suspects or handling tissues. Standard precautions include the use of protective clothing and the avoidance of penetrating injuries. although they did not develop clinical signs. with 95% confidence intervals of 49-692. Because prions may be able to survive in the environment for years and are difficult to disinfect. or simply have a longer incubation period. or France during the peak of the BSE epidemic.

and death. similarly to cattle with classical BSE. coma. hyperresponsiveness to stimuli. but some animals may lick or rub persistently. but not to light or sound. Both “dull” and “nervous” forms of the illness were reported in this study. other animals did not develop ataxia or difficulty rising. in Holstein–Friesian cattle inoculated with German isolates of H-BSE and LBSE. a modified gait in which the legs move in lateral pairs. the symptoms appear. although the initial signs appear to be more nonspecific and subtle in atypical BSE. In Friesian and Alpine brown cattle. Another experiment used Danish Holstein/ Aberdeen Angus crosses inoculated with an Italian L-BSE strain and an H-BSE strain. The animals in this study were reported to be hyperresponsive to tactile facial stimuli. and muscle atrophy. In genetically resistant (ARR/ARR) sheep. tremors. However. low carriage of the head. BSE is always progressive and fatal. The final stages are characterized by recumbency. Another group reported that. hyperreactivity to stimuli. and may be suggestive of this disease. The symptoms of BSE usually worsen gradually over a few weeks to six months. however. Most atypical strains have been found in asymptomatic cattle during routine surveillance. occurred in 25% of the cattle with BSE in one study. changes in temperament. nervousness or apprehension. acute onset neurological disease seems to be particularly common in exotic ruminants in zoos. sudden falls were seen. It has also been transmitted to lemurs by the oral route. The combination of behavioral changes. H-BSE associated with neurological signs was reported in a 19-year-old zebu bull (Bos indicus) at a zoo. and behavioral changes such as aggression. The early clinical signs included muscle fasciculations. this is based on comparisons in intracerebrally inoculated cattle and bovinized transgenic mice. and mild kyphosis. In experimentally infected macaques inoculated orally. Nonspecific signs include loss of condition. One European red deer challenged by the oral route developed clinical signs after approximately 4 years. 9 months. teeth grinding (possibly due to visceral pain or neurological disease). The peak incidence of disease occurs in four to five year old animals. Some research suggests that the incubation period might be shorter for atypical L-BSE than classical BSE. Once Last Updated: April 2012 © 2012 CFSPH page 6 of 13 . L-BSE and H-BSE can infect mice by intracerebral inoculation. Low head carriage and separation from the herd did not occur consistently. and decreased milk production. and altered heart rhythms have also been reported. and motor signs were all seen. However. the same breeds inoculated with classical BSE prions developed behavioral changes including aggressiveness. Animals tended to separate from the herd and carried their head low. these cattle were hyperresponsive to acoustic and visual stimuli as well as tactile facial stimuli. or at emergency slaughter. and gait abnormalities is highly suggestive of BSE. decreased alertness. with relative sparing of forelimb muscles. with some researchers concluding that L-BSE can be distinguished clinically from classical BSE. Intense pruritus is not usually seen in cattle. weight loss. and 18 to 24 months in lambs inoculated orally at two weeks of age. the differences are not sufficient to unambiguously distinguish these forms from classical BSE. Clinical Signs Cattle with classical BSE Bovine spongiform encephalopathy is a neurological disease that usually has an insidious onset in cattle. but some animals exhibit only one category of neurological signs. In genetically susceptible sheep. the first signs were weight loss and loss of condition. which began in the gluteal region and progressed to involve other areas. mental dullness. The incubation period in experimentally infected sheep varies with the animal’s age and genetic susceptibility. In this experiment. while four other deer were still healthy more than 5 years after challenge. Rapid. with the development of neurological signs. the incubation period was 3. in fallen stock (‘downer’ cattle). but rare cases can develop acutely and progress rapidly. These signs progressed to muscle atrophy. as well as postural abnormalities and hyperresponsiveness to stimuli. Behavioral. and cattle infected with HBSE and L-BSE had similar clinical signs. bradycardia. The symptoms may include gait abnormalities (particularly hindlimb ataxia). However. and the route of exposure and dose. sensory. Experiments (all using intracerebrally inoculated cattle) have reported varying clinical signs. and most of the animals had no signs of Incubation Period The incubation period for classical BSE is estimated to be 2 to 8 years in cattle. the incubation period was 21 to 38 months for animals inoculated orally at six months of age. These researchers concluded that. bellowing and head shaking. and others reporting that the spectrum of clinical signs overlaps to a greater or lesser extent between all forms of BSE. Decreased rumination.6 to 5 years.Bovine Spongiform Encephalopathy L-BSE can infect cynomolgus macaques by intracerebral inoculation. Atypical BSE is usually detected in cattle that are at least eight years of age. Pacing. a dull coat. Cattle with atypical BSE The features of atypical BSE in cattle are still incompletely understood. Although a “downer” cow was reported in this study. the incubation period was approximately 3 to 5 years. and even frenzy. one group of researchers reported that an Italian isolate of L-BSE mainly causes a form characterized by inactivity. which could be distinguished from classical BSE. Ataxia and difficulty rising were also reported in this experiment.

but none progressed to permanent recumbency (unlike animals with classical BSE that develop ataxia). This disease is usually diagnosed by detecting prions (PrP res) in the CNS. In one study. with the exception of nonspecific signs. and these signs became more pronounced with Last Updated: April 2012 time. ataxia. automated immunoblotting (Western blotting) and lateral flow devices (LFD) are available. hyperresponsiveness to stimuli. and reported that the clinical signs were similar in all animals. Accumulations of prions can be found in unfixed brain extracts by immunoblotting. In indigenous French breeds. Positive samples in rapid tests are traditionally confirmed with more specific assays such as immunohistochemistry or immunoblotting. Ataxia was not seen in orally inoculated goats. Diagnostic Tests There is no live animal test for BSE. A diagnosis of BSE may also be confirmed by finding characteristic prion fibrils called scrapie-associated fibrils (SAF) with electron microscopy in brain extracts. Other signs in some animals included behavioral changes. Sheep with classical BSE Various neurological signs have been reported in experimentally infected sheep. but also included a few individuals of other breeds. a negative result on the confirmatory test is not adequate to rule out BSE. the OIE now states that confirmation of positive results with a second rapid test is acceptable under some circumstances. early in the course of the disease. the cattle tended to develop dysmetria and have difficulty in rising. the route is unknown. many animals became hyperreactive to external stimuli including tactile and facial stimuli. hypperresponsiveness to auditory stimuli or decreased menace response in a few animals. No cattle developed tremors. tremors. the signs in orally inoculated goats were mainly lethargy and weight loss. In this study. The course of the illness lasted 16 to 20 weeks before animals were culled due to the progression of neurological signs. including rapid tests. Techniques used diagnostically to detect prions are relatively insensitive compared to assays for other types of pathogens. Cheviot sheep mainly developed ataxia with minimal pruritus. in animals infected with H-BSE or © 2012 CFSPH page 7 of 13 . The histopathologic lesions are confined to the CNS. which progressed to recumbency over three weeks. and progressed rapidly in intracerebrally inoculated goats. teeth grinding. intracerebrally inoculated Saanen goats developed abnormalities in movement (e. and weight loss and loss of body condition. or kicking. Post Mortem Lesions Click to view images Gross lesions are not found in BSE. In addition. Neuronal vacuolation and non-inflammatory spongiform changes in the gray matter are characteristic of the disease in cattle. In another study. and weight loss. Neurological signs have been reported in experimentally infected animals. and should be investigated with other assays. and especially hypermetria) and hyperresponsiveness to stimuli. If vertical transmission is possible. several rapid diagnostic tests based on enzyme-linked immunosorbent assays (ELISAs). the disease was characterized by ataxia and tremors. Similar spongiform changes occur in experimentally infected sheep and macaques. Altered behavior combined with ataxia and pruritus was detected in 40% of these sheep. including head tossing or shaking. Communicability There is no evidence that the BSE agent is transmitted horizontally between cattle. but are associated with L-BSE prions.Bovine Spongiform Encephalopathy dullness. the symptoms included ataxia and intense pruritus with loss of fleece. Over the course of the experiment. Preferred test combinations. postural deficits.. however. an absent menace response. Goats with classical BSE The few BSE cases that have been reported in naturally infected goats were discovered during routine surveillance at slaughter. Atypical prions can be detected with the same tests. ataxia mainly of the hindlegs. are listed on the OIE website. difficulty rising. One goat carried its head low when undisturbed and was inappetent. Two rapid tests can only be used to confirm a BSE case. and in fixed brains by immunohistochemistry. Rapid tests allow large numbers of samples to be screened. movement abnormalities including tremor and ataxia. the offspring of infected animals have an increased risk of developing this disease. and neither intracerebrally nor orally inoculated goats had signs of pruritus. These animals deteriorated slowly and died in approximately three months. teeth grinding. and are often used in surveillance and slaughter testing. sniffing and nibbling of the animal handlers and instruments changed to aversive behavior. These lesions are usually but not always bilaterally symmetrical.g. which are not in danger of producing false positives by the use of shared reagents. and died in a few days to a week. it should be noted that this sign was also reported in 29% of the sheep that did not have evidence of BSE at slaughter). One goat was reported to be a scrapie suspect. Pruritus was detected in all clinically affected sheep in this study (however. however. prions cannot usually be detected in the brain until 3 to 6 months before the onset of disease. A study that used a Japanese L-BSE isolate in Holstein cattle reported decreased activity. Instead. Some of these tests can be used on frozen or autolyzed brains. and little aggression. However. Amyloid plaques are not typical of classical BSE or infection with H-BSE. A third study mainly used ARQ homozygous Suffolk and Romney sheep. In one study. such as emaciation or wasting. Other signs in some animals included pruritus.

the affected herd is quarantined. with certain exceptions such as milk and blood. since 2001. as well as from each other. L-BSE has a lower molecular mass than classical BSE prions. In addition. In the U. The latter measures can help prevent cross-contamination and accidental exposure of cattle to BSE prions. the annual incidence in affected herds was approximately 2- © 2012 CFSPH page 8 of 13 . These carcasses cannot be used as food and must be destroyed. In some countries. as cooking or rendering cannot completely inactivate prions. test only a percentage of cattle at slaughter. there has been public resistance to relaxing testing requirements. In the U.. epidemic peaked in 1992. and mesentery are not allowed from any cattle. Many nations have now banned the use of either ruminant or mammalian proteins. BSE suspects are usually euthanized for testing. they are usually traced and euthanized. however.Bovine Spongiform Encephalopathy L-BSE. but some animals in early stages of infection have few or no spongiform changes. entire intestine. In the U. are killed for reasons other than human consumption. and the carcass is held until testing is complete. all three prions can be detected in the obex. due to the long incubation period. Prevention BSE can be prevented by not feeding ruminant tissues that may contain prions to susceptible species. countries may place trade bans on the importation of live cattle and certain ruminant proteins from affected countries. prohibited tissues include the brain. The distribution patterns of HBSE and L-BSE in the brain differ somewhat from that of classical BSE.U. Surveillance can help prevent infected animals from being used in food. Healthy cattle over the age of 72 months and intended for human consumption must also be tested. in livestock feed. Slaughter and processing techniques that have a high risk of contaminating muscle tissues with CNS have been prohibited in many countries. Last Updated: April 2012 Morbidity and Mortality Classical BSE is seen most often in four to five year old cattle. BSE carcasses are rendered at 133°C (3 bar pressure) for at least 20 minutes.S. Its glycosylation pattern differs from classical BSE. BSE epidemics were reported in several European countries. cattle that must be tested (with rapid tests) in most E. only cattle that are 21 months of age or older must be tested.S.. including the U. In the E. At one time. When an infected animal is identified. H-BSE has higher molecular mass fragments than classical BSE. the Japan government required all cattle to be tested for BSE.U.S. These animals cannot be used in human food.. however. spinal cord. Treatment There is no treatment for BSE. Some countries may also conduct BSE surveillance in small ruminants. including the U. Complete avoidance is generally necessary. and most of the vertebrae from cattle 30 months of age and older. and the spinal column in cattle over 30 months of age. the estimated prevalence in various countries ranged from more than 100 cases per million cattle to fewer than two cases per million. surveillance is targeted particularly at high risk cattle such as nonambulatory animals and those with neurological disease. The first outbreak occurred in the U. This disease is always fatal once the symptoms appear. A complete evaluation of the rapid tests has not been done for these prions. Histological examination of the brain can be very helpful in diagnosis. member states include animals over the age of 48 months that die. and it has an unusual deposition pattern characterized by amyloid plaques. undergo emergency slaughter. Tissues that have a high risk of transmitting BSE have been banned from human food in many countries.. skull. where more than 180. As of 2011. Serology is not useful for diagnosis. the age limits have increased since the programs began. Suspect animals are usually euthanized for testing. The U.000 new cases confirmed each week. and local authorities have continued to test all slaughtered cattle regardless of age. Some nations conduct active surveillance of cattle at slaughter (using rapid tests) to detect cases of BSE. BSE can be detected by transmission studies in mice. Some countries with a low incidence of disease. or even to fertilizer. The prevalence of BSE varies widely. Japan has unusually strict requirements.K. Since 2005. however. The latter are defined as World Organization for Animal Health (OIE) ‘minimal risk’ countries for BSE. Atypical prions can be differentiated from classical BSE prions by their biochemical properties. and protein sources prohibited. trigeminal ganglia. Active surveillance for BSE has been conducted in the E. for example by immunoblotting.S. with nearly 1.K. an incubation period of several months makes this technique impractical for routine diagnosis. The tonsils. dorsal root ganglia. The U. vary with the country.S. At one time. The tonsils and distal ileum from all cattle are also banned. however. Control measures have greatly decreased the prevalence in the most severely affected nations since that time. The specific bans. also conducts passive surveillance for BSE. particularly dairy animals.. or display certain abnormalities at ante-mortem inspection. eyes.. Lower age limits apply to cattle from some other areas. At the time. Preventing prions from re-entering the ruminant food chain can interrupt transmission and control BSE epidemics. as antibodies are not made against the BSE agent.U. however. banned tissues include the skull (including the brain and eyes but not the mandible) and spinal cord in cattle over 12 months of age. Due to the increased risk of BSE in the offspring of infected cattle. and the source of the infection is investigated.K. It also reacts with a monoclonal antibody to an N-terminal epitope that is not found in classical BSE after proteinase K cleavage. In addition. bans also apply to other animal feeds. the number of BSE cases may not decline for some time.000 cases have been confirmed since the 1980s.

Department for Environment Food and Rural Affairs.inspection. Mathey J. if it occurs at all.cjd. with the exception of an L-BSE prion reported from a 23-month old steer in Japan. This number continued to drop. United Kingdom. Sarradin P. Bovine Spongiform Encephalopathy http://animalhealth.htm World Health Organization.europa.92(Pt 2):467-76. Estimation of the age-dependent risk of infection to BSE of dairy cattle in Great Britain. Miele G. Berthon P. Groschup OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals http://www. http://www.usda. One case occurred in an animal imported from Canada. Costes P. Bovine Spongiform Encephalopathy http://www. Bovine spongiform encephalopathy agent in spleen from an ARR/ARR orally exposed sheep. The National Animal Health Information System (NAHIS). Estimates of the maximum proportion of sheep TSE cases that could be BSE range from 0. Kaatz en. Heikenwalder M. Prev Vet but the specific form has not yet been As of 2012. with the annual incidence decreasing to 99 confirmed cases in ndex. Balkema-Buschmann A. Balkema-Buschmann A. Infections have not been seen in sheep or deer other than experimentally infected animals. Morel N. Espinosa JC. but are not immune to infection or disease.S. Cases of BSE are very rarely reported in goats.html Last Updated: April 2012 © 2012 CFSPH page 9 of 13 . 35 cases in 2008.htm The National Creutzfeldt-Jakob Disease Surveillance Unit. Torres JM. Barc C.htm United Kingdom.oie. Bernardet P.102(2):112-7.114:153-160.ed.7% to As a result of control measures (particularly feed bans). 2006. and 7 to 11 cases each year between 2009 and 2011. Animal and Plant Health Inspection Service. In the U. Available at: http://www. J Gen Virol. BSE infectivity in the absence of detectable PrP(Sc) accumulation in the tongue and nasal mucosa of terminally diseased cattle.html United States Food and Drug–bin/aphb/ahsq?dislist=alpha.shtml USDA Foreign Agricultural Service. Eiden M. Keller M. J Gen Virol. and therapeutics of prion diseases.htm The Merck Veterinary Manual http://www. diagnostics. Bovine Spongiform Encephalopathy http://www. Schelcher World Organization for Animal Health (OIE) http://www.defra. Three additional cases have been reported in indigenous cattle.fda.fas. Arnold ME. Surveillance conducted in Europe suggests that the prevalence of BSE is very low in sheep. Bovine Spongiform Encephalopathy http://www. The incidence of atypical BSE appears to be much lower than classical BSE. Its prevalence among cattle in France and Germany may be as low as 1 case per 3 million adult cattle. Bovine spongiform encephalopathy [online]. McIntyre L. Ziegler U. 2011.Bovine Spongiform Encephalopathy nceenforcement/complianceenforcement/bovinespongi formencephalopathy/default.htm European Commission.gc. Animal Health Australia.The peak of the epidemic curve occurred later in countries where feed bans were established more recently. TSE/BSE http://ec. the incidence declined to approximately 5-10 new cases per week in 2004. one was caused by the Hform of atypical BSE. Corbière only four cases of BSE have been reported. Tabouret G. Andréoletti O.oie.66:35-47. Ziegler U. J Clin Invest. Grassi J. 2004. Keller M. United States Department of Agriculture (USDA). Wilesmith JW. approximately 60 cases of L-BSE or HBSE have been identified worldwide as a result of surveillance for classical BSE. Hoffmann C. Nearly all LBSE and H-BSE prions have been detected in cattle over the age of 8 years. Internet Resources Canadian Food Inspection Agency http://www. Bovine Spongiform Encephalopathy http://www.* Accessed 7 Nov 2001. Prev Vet Med. Pathogenesis of classical and atypical BSE in cattle. Lantier References Aguzzi Kaatz M.jsp?cfile =htm/bi/ Hills B. OIE Terrestrial Animal Health Code http://www.aphis. Eiden M.usda. Experimentally infected sheep that are genetically resistant to scrapie seem to have some resistance to BSE. Lacroux 323991912972 Centers for Disease Control and Prevention http://www.cdc. Rouillon V. Groschup MH.. 2011.oie. The most recent case (April 2012) was infected by an L-BSE prion.who. Progress and problems in the biology. Lugan S. Fast C.

Dehen C. Jackman R. Kirkwood JK. 2004. Last Updated: April 2012 © 2012 CFSPH page 10 of 13 . Bovine spongiform encephalopathy infectivity in greater kudu (Tragelaphus strepsiceros). Reid HW. Iwamaru Y. Steele P. 2005. 2007. Okada H. Vet Rec. Reine F. Deslys JP.155:420-422. Rogers M. Green RB. Natural transmission of BSE between sheep within an experimental flock. Dexter G.70(3):511-8. Everest SJ. Lakhdar L. Hamilton S. Spencer YI. 2007 Jul. Groschup MH.12:1816-1821. Castilla J. Biacabe AG. J Neurosci. Baron T. Dawson M. Thorne LT. Hauri S. Salès N.europa. Espinosa JC. Vet Rec. Castilla J. Sisó S. Doherr MG. Herzog L. European Food Safety Authority [EFSA]. Andréoletti O. Editorial team. Gonzalez L. J Gen Virol. Torres JM. Euro Brandner S.efsa. 2006. Seoanes R. McBride PA. Fontaine JJ. Hammersley C. Kasai K. Peretz D. Eloit M. Emergence of classical BSE strain properties during serial passages of H-BSE in wild-type mice. Simmons MM. 2011. FEBS J. Comoy E. 2008 Aug 20. 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Experimental challenge of cattle with German atypical bovine spongiform encephalopathy (BSE) isolates. Hawthorn JA. Zanusso G. Giles K. Shimizu Y. Baron T. J Gen Virol. Progression of prion infectivity in asymptomatic cattle after oral bovine spongiform encephalopathy challenge. Masujin K.12:E070118.4:17. Experimental transmission of bovine spongiform encephalopathy to European red deer (Cervus elaphus elaphus). 2005. McDonnell G. Hawkins SA. Kilpatrick J. Laude H. Le Dur A. Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice. Vaccine. Caramelli M. Duval C. Biacabe AG. Glidden DV. Enhanced animal health protection from BSE. Deslys JP. No abnormal prion protein detected in the milk of cattle infected with the bovine spongiform encephalopathy agent. EFSA opinion on the likelihood of BSE infectivity in specified risk material. Vaccine. Matsuura Y. Abee CR. Vilotte JL. Lantier F. Beckwith R. Biacabe AG. Sayers R. 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