Bovine spongiform encephalopathy (BSE) is a progressive, fatal, infectious, neurologic disease of cattle that resembles scrapie of sheep and goats (see Scrapie). It was first diagnosed in the UK in 1986. Approximately 200,000 cases of BSE have been diagnosed in cattle, with 97% reported from the UK. In 1992, at the peak of the UK outbreak, 37,280 cases were reported in a single year. Lower incidences were found in cattle native to most European countries and to Israel, Japan, USA, Canada, and Brazil. The economic consequences of the BSE epidemic are important. Countries with BSE cases experienced a dramatic drop of consumer confidence in beef products and trade restrictions of cattle commodities. Since effective control measures have been implemented, BSE incidence has decreased to single cases in 2013.
In the 1990s, there was intensive debate on the nature of the BSE pathogen. To date, the most widely accepted hypothesis is that a proteinaceous infectious particle (prion) causes the disease. Prions are misfolded conformational isoforms of host-encoded proteins that induce protein misfolding, protein aggregation, and disease upon transmission to other organisms. This hypothesis is supported by the agent’s apparent resistance to heat, freezing, ultraviolet light, and chemical disinfectant procedures effective against bacteria and viruses. Prions are also responsible for scrapie of sheep and goats (see Scrapie); chronic wasting disease of cervidae (see Chronic Wasting Disease); transmissible mink encephalopathy (see Transmissible Mink Encephalopathy); and kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, and similar disorders of people. All these conditions are also termed prion diseases, and the related protein is the prion protein (PrPd, in which d stands for "disease associated"). Based on the anticipated mechanisms that trigger initial PrPd misfolding, prion diseases are classified as infectious, sporadic, or genetic. The classic type of BSE is caused by infectious prions; however, in the past decade, rare, so-called atypical BSE cases have been described. There is epidemiologic and experimental evidence that classic and atypical BSE differ in their etiology.
Classic BSE develops as a result of foodborne exposure to prions via contaminated animal-source proteins (meat and bone meal [MBM]) in cattle rations. Horizontal transmission is not a significant source of new BSE infections. Calves born to infected cows are at greater risk of 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. BSE is not transmitted horizontally by contact or aerosols. 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. Most cases are diagnosed in cattle 3–6 yr old. The incubation period after 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. Atypical BSE cases have been described from countries with no apparent classic BSE epidemic. Moreover, animals affected with atypical BSE are relatively old, and the incidence rates do not follow the trends observed for classic BSE. Together, these findings led to the hypothesis that atypical BSE results from spontaneous prion protein misfolding and is not related to ingestion of prion-contaminated feed. However, the mechanisms that induce the spontaneous prion formation remain obscure. It has been postulated that atypical BSE was at the origin of the BSE epidemic in the UK.
BSE has been transmitted experimentally to many animal species by intracerebral inoculation. During the epidemic of BSE in the UK and continental Europe, a few cases were seen in several species of captive-bred wild ungulates and in domestic companion cats as well as in big cats in zoologic gardens. BSE has also been confirmed in two goats, one from France and another from Scotland, but there is no evidence that BSE infected the small ruminant population on a broader scale.
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. Yet, in a large portion of affected animals, clinical signs may be nonspecific, and involvement of the nervous system is not obvious in every case.
Clinical examinations do not provide a definitive diagnosis. In case of a clinical suspicion of BSE, the animal should be euthanized and the brain subjected to neuropathologic examination. In most countries, BSE is a notifiable disease, and a suspect case must be reported to the veterinary authorities. The OIE has nominated OIE Reference Laboratories to assist national authorities of OIE member states in the diagnosis of BSE. Confirmatory diagnostic methods include PrPd immunohistochemistry and Western immunoblot in brain tissue. The identification of characteristic vacuolar changes by histopathology in specific target structures of the CNS alone is no longer the method of choice for BSE confirmation. In most countries with a BSE case history, active surveillance programs have been established. Approximately a dozen commercial BSE screening tests are available for active disease surveillance: ELISA , Western immunoblot, and immunochromatographic test formats. All these tests are based on the immunologic detection of PrPd in medulla oblongata samples.
Differential diagnoses include nervous ketosis, hypomagnesemia, polioencephalomalacia, lead poisoning, ingestion of plant or fungal tremoragens, rabies, listeriosis, and other viral and bacterial neuroinfectious diseases. In contrast to these 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 national veterinary authorities and ensure that definitive postmortem diagnostic tests are performed.
There is no effective treatment or vaccine 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 MBM to cattle. MBM supplements for cattle have been banned in many countries as a consequence of the BSE epidemic. Because of the risk of cross-contamination in feed mills, control has been effected in the UK and other European countries by similar statutory prohibitions of the use of MBM in all farm animal diets.
With the drastic decline of classic BSE cases over the past years, there is an ongoing discussion on possible alleviations of the complete MBM ban from feed of animals other then cattle, ie, of pigs and poultry. In this regard, it is important to remember that any reemergence of BSE will remain unrecognized for years because of the extraordinarily long incubation period of the disease. Moreover, with atypical BSE persisting in the cattle population, there is a constant risk of reintroduction of BSE in the population. This highlights the need to maintain a high level of disease awareness as well as effective surveillance and control measures.
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 also been seen outside the UK. A proportion of the affected individuals had been living in the UK, but cases have been seen in Italy and France among people who had not visited the UK. 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 people 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.