Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is a fatal neurodegenerative disease (encephalopathy) in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of four to five years, all breeds being equally susceptible.[1] In the United Kingdom, the country worst affected, more than 180,000 cattle have been infected and 4.4 million slaughtered during the eradication program.[2]
The disease may be most easily transmitted to human beings by eating food contaminated with the brain, spinal cord or digestive tract of infected carcasses.[3] However, it should also be noted that the infectious agent, although most highly concentrated in nervous tissue, can be found in virtually all tissues throughout the body, including blood.[4] In humans, it is known as new variant Creutzfeldt–Jakob disease (vCJD or nvCJD), and by October 2009, it had killed 166 people in the United Kingdom, and 44 elsewhere.[5] Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989.[6]
A British inquiry into BSE concluded the epizootic was caused by cattle, which are normally herbivores, being fed the remains of other cattle in the form of meat and bone meal (MBM), which caused the infectious agent to spread.[7][8] The cause of BSE may be from the contamination of MBM from sheep with scrapie that were processed in the same slaughterhouse. The epidemic was probably accelerated by the recycling of infected bovine tissues prior to the recognition of BSE.[9] The origin of the disease itself remains unknown. The infectious agent is distinctive for the high temperatures at which it remains viable; this contributed to the spread of the disease in the United Kingdom, which had reduced the temperatures used during its rendering process.[7] Another contributory factor was the feeding of infected protein supplements to very young calves.[7][10]
The first reported case in North America was in December 1993 from Alberta, Canada.[11][12]
A new case of BSE disease was recently found in a dairy cow on April 23, 2012 in California during a planned Agriculture Department surveillance program.
CJD is a degenerative neurological disorder (brain disease) that is incurable and invariably fatal.[2] CJD is at times called a human form of mad cow disease (bovine spongiform encephalopathy or BSE)
Signs and symptoms
The first symptom of CJD is rapidly progressive dementia, leading to memory loss, personality changes and hallucinations. This is accompanied by physical problems such as speech impairment, jerky movements (myoclonus), balance and coordination dysfunction (ataxia), changes in gait, rigid posture, and seizures. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks (Johnson, 1998). In some people, the symptoms can continue for years. In most patients, these symptoms are followed by involuntary movements and the appearance of an atypical diagnostic electroencephalogram tracing. Most victims die six months after initial symptoms appear, often of pneumonia due to impaired coughing reflexes. About 15% of patients survive two or more years.[10]
The symptoms of CJD are caused by the progressive death of the brain's nerve cells, which is associated with the build-up of abnormal prion proteins forming amyloids. When brain tissue from a CJD patient is examined under a microscope, many tiny holes can be seen where whole areas of nerve cells have died. The word "spongiform" in "transmissible spongiform encephalopathies" refers to the sponge-like appearance of the brain tissue.
Cause
Transmissible spongiform encephalopathy diseases are caused by prions. The diseases are thus sometimes called prion diseases.
The prion that is believed to cause Creutzfeldt–Jakob exhibits at least two stable conformations. One, the native state, is water-soluble and present in
The CJD prion is dangerous because it promotes refolding of native proteins into the diseased state[13] The number of misfolded protein molecules will increase exponentially and the process leads to a large quantity of insoluble protein in affected cells. This mass of misfolded proteins disrupts cell function and causes cell death. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop.
Stanley B. Prusiner of the University of California, San Francisco (UCSF) was awarded the Nobel Prize in physiology or medicine in 1997 for his discovery of prions. For more than a decade, Yale University neuropathologist Laura Manuelidis has been challenging this explanation for the disease. In January 2007, she and her colleagues published an article in the Proceedings of the National Academy of Science and reported that they have found a virus-like particle (but without finding nucleic acids so far) in less than 10% of the cells a scrapie-infected cell line and in a mouse cell line infected by a human CJD agent.[14]
Transmission
The defective protein can be transmitted by contaminated harvested human brain products,[15] Immunoglobulins (IVIG), corneal grafts, dural grafts or electrode implants (acquired or iatrogenic form: iCJD);
It is thought[citation needed] that humans can contract the disease by consuming material from animals infected with the bovine form of the disease. The only suspected cases to arise thus far have been vCJD, although there are fears—based on animal studies[17]—that consuming beef or beef products containing prion particles can also cause the development of classic CJD. When BSE material infects humans, the resulting disease is known as (new) variant CJD (nvCJD).[12]
The diagnosis of CJD is suspected when there are typical clinical symptoms and signs such as rapidly progressing dementia with myoclonus. Further investigation can then be performed to support the diagnosis including
Electroencephalography — often has characteristic triphasic spikes
Cerebrospinal fluid analysis for 14-3-3 protein
MRI of the brain — often shows high signal intensity in the caudate nucleus and putamen bilaterally on T2-weighted images.
Diffusion Weighted Imaging (DWI) images are the most sensitive. In about 24% of cases DWI shows only cortical hyperintensity; in 68%, cortical and subcortical abnormalities; and in 5%, only subcortical anomalies.[34] The involvement of the thalamus can be found in sCJD, is even stronger and constant in vCJD.[35]
The classic histologic appearance is spongiform change in the gray matter: the presence of many round vacuoles from one to 50 micrometres in the neuropil, in all six cortical layers in the cerebral cortex or with diffuse involvement of the cerebellar molecular layer. These vacuoles appear glassy or eosinophilic and may coalesce. Neuronal loss and gliosis are also seen.[41] Plaques of amyloid-like material can be seen in the neocortex in new-variant CJD.
