Bovine spongiform encephalopathy (BSE) is a progressive, fatal, neurologic disease of cattle that resembles scrapie of sheep and goats (see Scrapie). It was first diagnosed in Britain in 1986. Approximately 200,000 cases of BSE have been diagnosed in cattle, with 97% reported from the UK. At the peak of the UK outbreak, 37,280 cases were reported in a single year. Lower incidences have been reported in cattle native to several European countries, and isolated cases have been diagnosed in the Middle East, Japan, USA, and Canada.

Etiology

The most widely accepted hypothesis regarding the causative agent, a prion, is that the infectious principal is an altered form of a protein normally present in the host. The abnormal protein induces a structural change in normal host proteins that confers protease resistance. Thereafter, altered proteins, which are now infectious, accumulate in host tissues. This hypothesis is supported by the agent's apparent resistance to heat, freezing, ultraviolet light, and chemical disinfectant procedures that are effective against bacteria and viruses. Similar agents appear to be responsible for scrapie of sheep and goats (see Scrapie); chronic wasting disease of cervidae (see Chronic Wasting Disease); transmissible mink encephalopathy (see Mink: Transmissible Mink Encephalopathy); and kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, and similar disorders of humans.

Transmission, Epidemiology, and Pathogenesis

BSE develops as a result of foodborne exposure to infectious proteins via contaminated animal-source proteins in cattle rations. Horizontal transmission is not a significant source of new BSE infections. Calves born to infected cows are at greater risk for acquiring BSE than calves born to noninfected cows; however, this mode of transmission is of minor importance relative to infections acquired through contaminated feed sources. There is no sex or breed predisposition. In the UK, clinical disease was more common in dairy cows, probably because they were more likely to be fed animal-source protein supplements. The majority of cases are diagnosed in cattle 3–6 yr old. The incubation period following exposure is ~2–8 yr, and animals as young as 22 mo have been diagnosed with BSE. The details of pathogenesis are unknown, but studies indicate that after oral exposure the agent replicates in the Peyer's patches of the ileum followed by migration, via peripheral nerves, to the CNS. Recent reports suggest that in some instances, spontaneous cases of BSE may occur in cattle not exposed to the infectious agent. Mutations in the cattle genome may alter sequences of the normal host prion protein.

BSE has been transmitted experimentally to mice, pigs, sheep, goats, cattle, mink, macaques, and marmosets. During the epidemic of BSE in the UK, a few cases were seen in several species of captive-bred wild ungulates and in cats. A low incidence has been seen in domestic cats in the British Isles, with one isolated case in Norway.

Clinical Findings

Initial clinical signs are subtle and behavioral in nature. The spectrum increases and progresses over weeks to months, with most animals reaching a terminal state by 3 mo after clinical onset. Commonly observed clinical signs include hyperesthesia, nervousness, difficulty negotiating obstacles, reluctance to be milked, aggression toward either farm personnel or other animals, low head carriage, hypermetria, ataxia, and tremors. Weight loss and decreased milk production are common.

Diagnosis

Clinical examinations do not provide a definitive diagnosis. Confirmatory diagnostic methods include histopathology, immunohistochemistry, and electron microscopy, after detergent extraction, for scrapie-associated fibrils to detect abnormal prion protein. The last 2 methods can be used on autolyzed brain tissue, and immunohistochemistry positivity precedes morphologic, vacuolar changes. Histologic changes are confined to the CNS and include bilateral, symmetric vacuolation of gray matter neuropil (spongiosis) and neurons and the accumulation of protein fibrils characteristic of prion-associated diseases. Two specific ELISA methods and a Western immunoblot method are available for active surveillance of cattle populations.

Differential diagnoses include nervous ketosis, hypomagnesemia, polioencephalomalacia, lead poisoning, rabies, and ingestion of plant or fungal tremoragens. In contrast to these other differential diagnoses BSE typically has a slow onset of clinical signs, with an extended and progressive clinical course. Veterinarians considering BSE as a likely differential diagnosis should contact regulatory personnel and ensure that definitive post-mortem diagnostic tests are performed.

Treatment and Control

There is no effective treatment for BSE. Euthanasia is advisable as soon as there is some certainty of the clinical diagnosis because animals become unmanageable and their welfare is at risk.

The most effective control measure is prohibition of the feeding of mammalian-derived protein sources to cattle. Most mammalian-source protein supplements for cattle have been banned in the USA since 1997. Control has been effected in Britain and other European countries by similar statutory prohibitions of the use of mammalian-derived protein in all farm animal diets.

The occasional isolated diagnoses of BSE in the USA and Canada raise questions that deserve serious consideration. Perhaps the ban on feeding animal-source proteins to cattle is less stringent or effective than desired. In some instances, cattle may have ingested animal-source protein prior to the ban in 1997. Finally, some background rate of spongiform encephalopathy resulting from spontaneous host mutations is likely in most mammalian species. Recent reports have suggested that spontaneous BSE is likely. Ongoing rigorous application of feed bans should prevent transmission to other cattle.

Zoonotic Risk

A novel variant of Creutzfeldt-Jakob disease (vCJD) in the human population in Great Britain, initially seen in 1996, has been associated with the emergence of the BSE agent. Cases of vCJD have been seen outside Britain. A proportion of the affected individuals had been living in Britain, but cases have been seen in Italy and France among people who had not visited Britain. The single person diagnosed with vCJD in the USA was a recent immigrant from the UK, and it is presumed that this person was exposed and infected while residing in the UK. Infection of humans is thought to result from eating infected bovine tissues. As a result, many countries have introduced the statutory removal of high-risk bovine tissues from the human food chain and/or banned human consumption of cattle >24 mo old. No cases of vCJD have been seen in laboratory workers, but appropriate safety precautions for handling the BSE agent and conducting necropsies of cattle suspected of being infected are recommended. Safety precautions should primarily be aimed at avoiding accidental exposures.

Last full review/revision July 2011 by Jeffrey W. Tyler, DVM, MPVM, PhD,Deceased