Bovine Spongiform Encephalopathy (Mad Cow Disease)

Bovine Spongiform Encephalopathy, also known as Mad Cow Disease, is a progressive neurological disorder of cattle that can affect other species through ingestion of infected meat.

History

The first signs of BSE were in Britain in 1986.[11] People Started to notice the cattle suffering from a condition similar to scrapie in sheep. The disease was nicknamed "mad cow disease" due to the "mad" behavior of the infected cow. The cause was unknown, although some people suspected the cause was the feeding of scrapie infected sheep to the cattle. By 1988, 421 cattle in Britain were diagnosed with BSE. [11] In 1989 Britain banned human consumption of certain organ meats; including the brain and spinal cord. The United States, concerned about the spreading of Mad Cow Disease to the states, prohibited import of live cattle, sheep, bison, and goats from any countries known to have cases of BSE in cattle. [11] In the early 1990's, British government insisted the disease could not affect humans. At the same time, domestic cats were dying from beef products in their food. [11] The same year, five types of antelope that had been fed cattle food died in British zoos from TSE's. [11] By 1993, 120,000 cattle were diagnosed with BSE in Britain. In the mid-1990's, Britain banned feeding of meat and bone meal to animals and the use of meat and bone meal as farm fertilizer. [11] In an effort to eliminate the spread of the disease, the British government began tracking individual animals and testing any cow over 30 months old intended for human consumption.[11] In 1995, 19 year old Steven churchill becomame the first victim of a new version of creutzfeldt-Jakob disease (CJD). [11] Two others died from CJD the same year. In 1996, British government admitted BSE could be transmitted to humans. [11] They also confirmed that BSE is transmitted from cow to calf genetically. Out of fear, 4.5 million cattle were destroyed. [11] The same year, a British coronor rules the death of 20 year old vegetarian was from eating beef burgers as a child. This verdict was the first to link human death to mad cow disease. [11] Some estimate three farmers per week killed themselves. In 1997, there were 21 known CJD victims in Britain. In 1999 the export ban on British beef was lifted after 3 1/2 years. Japan had it's first outbreak of BSE in 2001. [11] In 2002, a 22 year old British woman in Florida was the first case of CJD was found in America. [11] The same year, a Canadian man died from contracting CJD while in Britain. [11] The first case of BSE in Canada was in 2003. [11] In 2004, the FDA banned feeding cow blood, chicken waste, and restaurant scraps to cows, in an attempt to control the disease. [11] The same year, 143 people were diagnosed with variant CJD and 180,000 cattle were known to have BSE. [11] In an attempt to eliminate BSE, the USDA announced it would test at least 268,000 cattle a year. [11]

Symptoms and Diagnosis

Symptoms of an Infected Cow

A cow infected with BSE would exhibit the following symptoms:

• Weight loss-even under a normal diet [13]
• Reduced milk production [13]
• Increased agression/nervousness [13]
• Poor coordination [13]
• Abnormal posture [13]

The disease can lay dormant from two to eight years, but once the symptoms have occurred the cow's health will deteriorate until death which will last from two weeks to six months. [13]

Symptoms of Creutzfeldt-Jakob Disease in a Human

A human infected with BSE, or Creutzfeldt-Jakob Disease, would exhibit similar symptoms to an infected cow [4]. The symptoms observed in an infected human are:

• emotional and personality changes (ie forgetfulness and depression)[4]
• strange physical sensations [4]
• loss of eyesight [4]
• dementia [4]
• jerking muscles [4]
• phsychosis [4]

Death occurs 4-6 months after first signs of infection. [4]

Mechanism

Even though humans cannot technically get BSE since they are not cows, the disease can be tansferred in a variant form of Creutzfeldt-Jakob disease, also known as vCJD, which has essentially the same physiological effects on the human body as BSE has on the body of an infected cow. Both BSE and vCJD are caused by prions. These prions occur naturally and are transmissable. Humans, cows, or any other animal that consumes these particular prions do not automatically take effect.

Prions are proteins that cause diseases. As said earlier the prions occur naturally, and in humans the prion that causes CJD appears in one out of a million people. Since the prions are naturally occuring proteins the immune system does not mark them as foreign. Prions can also alter other proteins into causing the disease as well. These two factors, the immune system not being stimulated and the increase in number of disease causing proteins, makes the family of transmissable spongiform encephalopathies lethal.

The protein on the left in the diagram shows the normal folding pattern of the prion that causes vCJD. [13]
When the protein alters its folding pattern from an alpha helical to a beta plate as seen in the prion on the right,

the altered protein begins to affect the body and cause the vCJD.

The altered protein targets the cellular proteins within the brain deteriating the proteins into the infectious form. This then leads to a drastic cascade as more proteins are infected which become the harmful and infectious prions that can infect other proteins. These prions will then accumulate to form dense plaques that will eventually appear as the holes in the brain. The plaques are caused by the "clumping together" of water insoluble prions that have altered their original shape in which they were water soluble.

The following link shows a video clip of how BSE works. [1]

Current Treatment

There is currently no treatment for BSE or CJD, but it's currently being researched.

Current Research

Process developed by researchers to filter
disease causing protein from scrapie infected animal
blood, preventing diseases such as "madcow" [5]

Of the current research topics one of the most prevelent topics is finding a treatment or cure for humans. Currently there are no known treatments or cures for this disease. In Priola et al. 2003 they discuss a cyclic tetrapyrrole phthalocyanine tetrasulfonate (PcTS) which is a drug used to treat the disease. During this study they infected mice with BSE and then treated them with PcTS. In their results they noted that treatments of this disease with this drug notibly slowed the progression of the disease within the mouse hosts. The paper also noted that PcTS stopped the infection even if treatment was conducted several weeks after the initial infection. PcTS completely inactivated low levels of infectivity. This was noted when incubation occured with the infectious inoculum. Thus, PcTS has a broad range of anti-TSE activities. These findings suggest that cyclic tetrapyrroles may be used both prophylactically and therapeutically against TSE diseases in vivo. There are also useful for the inactivation of TSE infectivity when suspended in solution.

Another area of research deals with the human variation of the disease known as Creutzfeldt-Jakob disease (vCJD) and the dangers associated with blood transfusions. Sachse et al. 2003 the exposure of humans to orally ingested BSE agent in contaminated meat products ,presumably led to the emergence of vCJD. In vCJD, prions can be detected immunohistochemically not only in neuronal tissue but also in lymphoreticular tissue. vCJD is of significance in transfusion medicine because of the hypothetical transmission of prions by blood products. In this paper they look at the infectious isoform PrP^Sc and use several techniques designed to isolate and locate them in the human host. They were able to locate accumulations of these prions within human lymphoreticular tissue,the cerebrum, and the cerebellum of sCJD patients. They also found accumulations in the lymph nodes, tonsils, and spleen of vCJD patients using immunohistochemistry.

In 2000 there was a funded project to develop a blood test for the prion protein, the major cause for the Mad Cow disease. Research has continued under a grant from the Department of Defense through 2004. The project that had been currently under grant was focused on developing a blood-screening test for animals or humans, which will allow for the detection of prion disease as early as before the beginning symptoms. Before this project began the only way to diagnose the disease was to have a brain biopsy of the animal or human that has contracted it. Other than a biopsy there are no other ways to test for the disease before symptoms occur. It appears that the prion protein is present in the blood from the evidence that is shown from the spread of the disease after the blood transfusion from an infected sheep to a healthy sheep. Earlier techniques allow for the detection of the protein in the brain; however they are not strong enough to test for it in the blood. The newly developed test utilizes a combination of two very sensitive techniques so that it is able to detect protein levels several thousand fold or more lower than the current method.

References

[1]http://www.lifespan.org/services/infectious/diseases/mad_cow.htm
"Mad Cow Cartoon" [[2]]
[2]http://www.umm.edu/features/madcow.htm
[3]http://www.nature.com/news/2004/040729/full/news040726-11.html
[4]http://www.helpguide.org/elder/creutzfeldt_jakob.htm
[5]http://www.healthnews-stat.com/?id=291&keys=blood-sc
[6]http://www.pamrotella.com/health/bovinebacteria.html
[7]http://www.pamrotella.com/health/MadCow.pdf
[8]http://chemistry.about.com/cs/howthingswork/a/aa122703a.htm
[9]http://journals.ohiolink.edu/ejc/pdf.cgi/Tse_Yiuman.pdf?issn=02707314&issue=v26i0004&article=315_hmcfoacs
[10]http://journals.ohiolink.edu/ejc/pdf.cgi/Hofman_A.pdf?issn=03922990&issue=v07i0005&article=466_rocdireacsie
[11]http://www.centerforfoodsafety.org/pubs/MadCowTimeline.pdf
[12]http://www.umm.edu/features/madcow.htm
[13]http://www.millerandlevine.com/news/bse/
[14]Winston, Mark. Travels in the Genetically Modified Zone. Harvard University Press: Massachusetts. 2002
[15]Charles, Daniel. Lords of the Harvest. Perseus Publishing: Massachusetts. 2001
[16]http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=8875786&site=ehost-live
[17]http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=10672593&site=ehost-live