Bovine Spongiform Encephalopathy: Introduction

Etiology

Transmission, Epidemiology, and Pathogenesis

Clinical Findings

Lesions

Diagnosis

Treatment and Control

Zoonotic Risk

Bovine spongiform encephalopathy (BSE) is a progressive, fatal, neurologic disease of adult domestic cattle that resembles scrapie of sheep and goats ( Scrapie: Introduction). It was first diagnosed in Britain in 1986.

BSE has been transmitted experimentally to mice, pigs, sheep, goats, cattle, mink, Macaque monkeys, and marmosets. During the epidemic of BSE in Great Britain, small numbers of cases of spongiform encephalopathy were seen in several species of captive bred ungulates (nyala, gemsbok, eland, arabian oryx, kudu, scimitar oryx, ankole cow, and bison) and in 5 species of felids (puma, cheetah, ocelot, lion, and tiger) either kept in or originating from British zoologic collections. A low incidence has been seen in domestic cats in the British Isles, with one isolated case in Norway. The ungulates were infected from the same foodborne source as cattle (see below), and all species of felids were most likely infected by consuming infected bovine tissues.

Only the UK has experienced a significant epidemic that, at its peak at the end of 1992, represented an annual incidence of ~1% of adult cattle. Lower incidences have been seen in indigenous cattle in Ireland, France, Switzerland, the Netherlands, Portugal, Germany, Denmark, Italy, Spain, Austria, Belgium, the Czech Republic, Finland, Greece, Israel, Japan, Liechtenstein, Luxembourg, Poland, Canada, Slovakia, and Slovenia. BSE has been detected in the majority of these countries as a result of active surveillance (see below). Cases in animals exported from Great Britain have been seen in Canada, the Falkland Islands, and the Sultanate of Oman. Cattle populations in other countries may have become infected as a result of the importation of cattle and/or ruminant-derived meat and bone meal from countries with the disease.

Etiology:

The molecular nature of the agent causing BSE is uncertain. The disease is associated with an abnormal form of a membrane protein, PrP (prion protein). This has led to the prion hypothesis for which this abnormal protein is assumed to be the infectious agent. These agents, in addition to causing scrapie in sheep, cause transmissible mink encephalopathy ( Viral Diseases), chronic wasting disease of deer and elk ( Chronic Wasting Disease: Introduction), and kuru and Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia in humans.

Transmission, Epidemiology, and Pathogenesis:

BSE develops as a result of foodborne exposure to a scrapie-like agent via contaminated meat and bone meal included in cattle rations. There is no evidence that transmission occurs naturally between cattle; however, there is some evidence suggesting a maternally-associated risk for calves born to affected cows.

There is no sex or breed predisposition, and no genotypic variation in susceptibility as there is in sheep to the scrapie agent. The modal age at onset is 5 yr, with a range from 2 yr to the extent of the commercial lifespan of cattle. The incidence within affected herds is generally low; in the peak year of the epidemic in Britain, an average of 2% of cattle developed clinical disease in affected herds.

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.

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. With repeated examinations, a reduced time spent ruminating can be detected by an experienced clinician; an increased frequency of nose licking, sneezing or snorting, nose wrinkling, head rubbing and tossing, and tooth grinding are all indicative of a disturbance of the trigeminal sensory nerve. Restrained animals exhibit exaggerated responses to the menace reflex, the corneal reflex, and sensation of nasal mucosae; frenzy, head shyness, and kicking also occur. Unrestrained animals in familiar environments demonstrate an increased startle response to unexpected visual, auditory, or tactile stimuli. If undisturbed, animals with advanced disease appear to have general hypokinesis, with long periods spent standing or idling with a low head carriage and a fixed, staring facial expression. Locomotory signs of gait ataxia, hypermetria, falling, and generalized paresis eventually become dominant. Weight loss and decreased milk production are common. Tremors and muscle fasciculations occur, but intense pruritus of the trunk, as seen in sheep scrapie, is rare. Euthanasia is advisable as soon as there is some certainty of the clinical diagnosis because animals become unmanageable and their welfare is at risk.

Lesions:

Lesions are confined to histologic changes in the CNS and comprise bilateral, usually symmetric, vacuolation of gray matter neuropil (spongiosis) and neurons, similar to the lesions seen in scrapie. Gross pathologic changes associated with falling and recumbency may be present.

Diagnosis:

Repeated clinical examinations do not provide a definitive diagnosis. The accepted international confirmatory diagnostic methods on the hindbrain are histopathology, immunohistochemistry (IHC), and electron microscopy, after detergent extraction, for scrapie-associated fibrils to detect abnormal PrP. The last 2 methods can be used on autolyzed brain tissue and IHC positivity precedes morphologic, vacuolar changes. Two specific ELISA methods and a Western immunoblot method are available for active surveillance of cattle populations.

The furious form of rabies ( Rabies: Introduction) has clinical similarities, but the clinical course of BSE is more protracted. Other differential diagnoses include encephalitic listeriosis ( Listeriosis: Introduction), hypomagnesemia ( Hypermagnesemia), lead poisoning ( Lead Poisoning: Introduction), downer cow syndrome ( Problematic Bovine Recumbency: Introduction), nervous ketosis, intracranial abscess or tumors, lesions in the CNS, and trauma to the spinal column. The protracted clinical course of the disease is helpful in differentiation, but in a small proportion of cases the clinical duration is short (days or weeks), and the extent that animals have been observed needs to be considered.

Treatment and Control:

Treatment is ineffective. Control has been effected in Britain and other European countries by the statutory prohibition of the use of mammalian-derived protein in the rations for all farm animal species. The USA has also banned the use of such proteins as a preventive measure.

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. Infection of humans is presumed to result from eating infected bovine tissues. As a result, BSE-affected countries have introduced the statutory removal of high-risk bovine tissues from the human food chain. 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 ocular or oronasal exposures.