Presented by Presented by

hadah al- khaldihadah al- khaldi

History of Mad Cow Disease: History of Mad Cow Disease:

BSE, or bovine spongiform encephalopathyBSE, or bovine spongiform encephalopathy, was first noticed in , was first noticed in the United Kingdom in 1986. Cattle became infected with this the United Kingdom in 1986. Cattle became infected with this disease as a result of being fed ground up sheep parts, which were disease as a result of being fed ground up sheep parts, which were contaminated with contaminated with scrapiescrapie, a common disease among sheep. As a , a common disease among sheep. As a result of the public's demand for cheap food, the meat industry has result of the public's demand for cheap food, the meat industry has been forced to increase their milk and meat yield in a way which been forced to increase their milk and meat yield in a way which does not cost a lot for the industry or the consumer. This involved does not cost a lot for the industry or the consumer. This involved giving the cattle, who are normally herbivores, a protein-based feed giving the cattle, who are normally herbivores, a protein-based feed made from animal offal (innards). The disease was able to survive in made from animal offal (innards). The disease was able to survive in the sheep offal, even after being subjected to extreme temperatures the sheep offal, even after being subjected to extreme temperatures during processing procedures of the feed. Therefore, this disease during processing procedures of the feed. Therefore, this disease was able to transmit from the sheep population to cattle. was able to transmit from the sheep population to cattle.

Transmission:Transmission:

it can be it can be transmitted from one animal species to transmitted from one animal species to anotheranother. Scrapie and BSE come from the same type . Scrapie and BSE come from the same type of disorder, spongiform encephalopathy, but are found of disorder, spongiform encephalopathy, but are found in two different species. Further experimentation has in two different species. Further experimentation has shown that it can be transmitted to other animals, such shown that it can be transmitted to other animals, such as mice, monkeys, pigs, and felines as well. For many as mice, monkeys, pigs, and felines as well. For many years zoo animals were fed protein supplements years zoo animals were fed protein supplements made from the offal of British cattle. made from the offal of British cattle.

Even though the use of British beef for food supplements was banned in 1996, Even though the use of British beef for food supplements was banned in 1996, effects are still being seen. As recently as March 1999, monkeys and lemurs in effects are still being seen. As recently as March 1999, monkeys and lemurs in French zoos have been identified as infected with a form of spongiform French zoos have been identified as infected with a form of spongiform encephalopathy. These animals had not been fed offal from British cattle for three encephalopathy. These animals had not been fed offal from British cattle for three years, but as a result of the long years, but as a result of the long incubation periodincubation period of this type of disorder, from of this type of disorder, from 2 to 8 years, these animals, who previously appeared healthy, are now showing 2 to 8 years, these animals, who previously appeared healthy, are now showing symptoms similar to BSE. This evidence illustrates how easily the disease can be symptoms similar to BSE. This evidence illustrates how easily the disease can be transmitted from one animal species to another, but BSE becomes a greater transmitted from one animal species to another, but BSE becomes a greater problem when it poses a threat to humans.problem when it poses a threat to humans.

Human Risks: Human Risks: What is the risk that BSE will infect humans? What is the risk that BSE will infect humans? It appears the risk of infection is dependent on:It appears the risk of infection is dependent on: Susceptibility to infective agent. Susceptibility Susceptibility to infective agent. Susceptibility

depends on depends on bothboth species differences and within species differences and within species protein sequence variations. species protein sequence variations.

Dose of infective agent. Dose of infective agent.

Infectivity of bovine tissues and body fluidsInfectivity of bovine tissues and body fluids Highest infectivityHighest infectivity brain brain spinal cord spinal cord eye eye Medium infectivityMedium infectivity spleen spleen tonsil tonsil lymph node lymph node ileum ileum proximal and distal colon proximal and distal colon pituitary gland pituitary gland adrenal gland adrenal gland cerebrospinal fluid cerebrospinal fluid placenta placenta pineal gland pineal gland

Low infectivityLow infectivity peripheral nerve peripheral nerve liver liver lung lung pancreas pancreas bone marrow bone marrow thymus thymus nasal mucosa nasal mucosa No infectivityNo infectivity skeletal muscle (meat) skeletal muscle (meat) heart heart mammary gland - milk, colostrum mammary gland - milk, colostrum blood - blood clot, serum or plasma blood - blood clot, serum or plasma kidney kidney thyroid gland thyroid gland salivary gland salivary gland ovary ovary uterus uterus testis testis seminal vesicle seminal vesicle fetal tissues fetal tissues hair hair skin skin bone bone cartilaginous tissue cartilaginous tissue connective tissue connective tissue bile bile saliva saliva urine urine feces feces

What is Mad Cow Disease?What is Mad Cow Disease? Mad cow diseaseMad cow disease, or , or bovine spongiform bovine spongiform

encephalopathyencephalopathy (BSE), is a fatal brain (BSE), is a fatal brain disorder that occurs in cattle and is caused by disorder that occurs in cattle and is caused by some unknown agent. In BSE, the unknown some unknown agent. In BSE, the unknown agent causes the cow's brain cells to die, agent causes the cow's brain cells to die, forming sponge-like holes in the brain. The forming sponge-like holes in the brain. The cow behaves strangely and eventually dies. cow behaves strangely and eventually dies. The connection between BSE and humans The connection between BSE and humans was uncovered in Great Britain in the 1990s was uncovered in Great Britain in the 1990s when several young people died of a human when several young people died of a human brain disorder, brain disorder,

The Disease Causing AgentThe Disease Causing Agent The disease appears to be caused by an The disease appears to be caused by an

unconventional infectious agent, originally unconventional infectious agent, originally believed to be a "slow virus," a "self-replicating believed to be a "slow virus," a "self-replicating protein. protein.

Recently the causitive agent was found to be an Recently the causitive agent was found to be an abnormal conformation form (abnormal conformation form (PrPsc) PrPsc) of a of a normally occurring protien (normally occurring protien (PrPPrP). ). PrPPrP is the is the abbreviation used to identify the normal "prion" abbreviation used to identify the normal "prion" protein. This agent is extremely resistant to heat protein. This agent is extremely resistant to heat and to normal sterilization processes. and to normal sterilization processes. PrPscPrPsc does not evoke a detectable immune response does not evoke a detectable immune response or inflammatory reaction in host animals. or inflammatory reaction in host animals.

Why is the manifest late?Why is the manifest late? Takes time to switch to infectious PrP.Takes time to switch to infectious PrP. Takes time to infect other normal PrP.Takes time to infect other normal PrP. Takes time to cause brain damage Takes time to cause brain damage What is the PrP?What is the PrP? The prion protein, The prion protein, PrPPrP, is a normal cell , is a normal cell

protein present on nerve cell membranes. protein present on nerve cell membranes. The gene for PrP is present in most The gene for PrP is present in most mammals. However, PrP's normal function mammals. However, PrP's normal function is unclear; mice without the protein appear is unclear; mice without the protein appear to be fine. to be fine.

PrPPrP's amino acid sequences are 's amino acid sequences are highly conserved across species highly conserved across species (>85% identity between human, (>85% identity between human, mouse, sheep and cattle). This mouse, sheep and cattle). This similarity permits similarity permits PrPPrP from one from one species to interact with species to interact with PrPPrP from from another species (a requirement another species (a requirement for infectivity) for infectivity)

Resistance of Resistance of PrPscPrPsc . Some loss of infectivity . Some loss of infectivity

occurs at temperatures above occurs at temperatures above 100°C100°C

Electron Microscopy of a PrionElectron Microscopy of a Prion

PrPPrP PrPscPrPsc

Structure high in alpha-Structure high in alpha-helix.helix.

Structure high in beta-Structure high in beta-structure.structure.

Protease susceptible.Protease susceptible. Core residues are Core residues are protease resistant.protease resistant.

Monomeric species.Monomeric species. Forms multimeric Forms multimeric aggregates.aggregates.

We don't know the agent that causes We don't know the agent that causes BSE, but we do know the following BSE, but we do know the following

The agent's size must be as small or smaller The agent's size must be as small or smaller than a than a virusvirus. .

You can't kill it by cooking or freezingYou can't kill it by cooking or freezing Disinfectants don't workDisinfectants don't work It does not appear to have genetic It does not appear to have genetic

informationinformation

Pathology:Pathology: Movement of PrP following oral exposureMovement of PrP following oral exposure 1)1) PrPsc PrPsc enters the body when foods are consumed enters the body when foods are consumed - MBM for BSE.- MBM for BSE. 2) 2) PrPscPrPsc pass through the pass through the - Esophagus into- Esophagus into - Acidity of the stomach - Acidity of the stomach - And the destructive enzymes of the small intestine - And the destructive enzymes of the small intestine EnoughEnough PrPsc PrPsc may remain intact to be absorbed and cause infection. may remain intact to be absorbed and cause infection. PrPscPrPsc traverse the intestine going into lymph nodules ( Peyer’s patches ) traverse the intestine going into lymph nodules ( Peyer’s patches )

of of the distal intestine (ileum).the distal intestine (ileum). PrPscPrPsc may replicate in follicular dendritic cell of the Peye’s patches. may replicate in follicular dendritic cell of the Peye’s patches. Most of the other proteins consumed are converted to small polypeptides orMost of the other proteins consumed are converted to small polypeptides or into fee amino acids before being absorbed and entering the blood or lymph into fee amino acids before being absorbed and entering the blood or lymph

systems.systems. ..

3) 3) PrPscPrPsc are transferred to the spleen and are found on the surface of are transferred to the spleen and are found on the surface of - T lymphocytes.- T lymphocytes. - B lymphocytes.- B lymphocytes. - Follicular dendritic cells.- Follicular dendritic cells. PrPscPrPsc probably proliferate here before infecting the nervous system.probably proliferate here before infecting the nervous system. Without involvement of the lymphoreticular system or during Without involvement of the lymphoreticular system or during Immunodepression, infection is possible but impaired.Immunodepression, infection is possible but impaired. Stimulation of B and cells or immune system enhances infectionStimulation of B and cells or immune system enhances infection

4) 4) Despite the presence of B and T lymphocytes in the circulation, neither Despite the presence of B and T lymphocytes in the circulation, neither blood nor most peripheral tissues containing and continuously exposed blood nor most peripheral tissues containing and continuously exposed

to blood are infectious.to blood are infectious. 5) 5) PrPscPrPsc eventually establish and multiply within the brain and spinal cord eventually establish and multiply within the brain and spinal cord forming plaques, killing nervous and disrupting brain function.forming plaques, killing nervous and disrupting brain function.

The main sites affected are:The main sites affected are:

1) 1) Thalamus.Thalamus. 2) 2) Cerebllum.Cerebllum. Clinical signs of BSE include:Clinical signs of BSE include: abnormally stilted gait abnormally stilted gait high stepping high stepping heightened sensory perception heightened sensory perception itching itching anorexia anorexia excessive licking excessive licking death. death.

Diseases caused by infected prion Diseases caused by infected prion protein:protein:

Prion diseases are often called Prion diseases are often called spongiform spongiform encephalopathiesencephalopathies because of the post mortem because of the post mortem appearance of the brain with large vacuoles in the appearance of the brain with large vacuoles in the cortex and cerebellum. Probably most mammalian cortex and cerebellum. Probably most mammalian species develop these diseases. Specific species develop these diseases. Specific examples include: examples include:

ScrapieScrapie: sheep : sheep TMETME (transmissible mink encephalopathy): mink (transmissible mink encephalopathy): mink CWDCWD (chronic wasting disease): muledeer, elk (chronic wasting disease): muledeer, elk BSEBSE (bovine spongiform encephalopathy): cows (bovine spongiform encephalopathy): cows

Control and PreventionControl and Prevention avoid beef and beef products altogether. avoid beef and beef products altogether. if eating meat, then select beef or beef products if eating meat, then select beef or beef products

that have less opportunity for contamination from that have less opportunity for contamination from nervous tissue (solid muscle cuts vs. processed nervous tissue (solid muscle cuts vs. processed sausages or hamburgers). sausages or hamburgers).

milk or milk products are not believed to pose milk or milk products are not believed to pose any risk from the BSE agent. any risk from the BSE agent.

Diagnostic Tests and SurveillanceDiagnostic Tests and Surveillance There is no approved laboratory test able to There is no approved laboratory test able to

detect the disease in live animals. detect the disease in live animals. Veterinary pathologists confirm BSE by Veterinary pathologists confirm BSE by microscopic examination of brain tissue. microscopic examination of brain tissue.

New enzyme can destroy mad cow disease New enzyme can destroy mad cow disease proteinprotein KAGOSHIMA (Kyodo) A Kagoshima KAGOSHIMA (Kyodo) A Kagoshima

University research team has discovered a University research team has discovered a new enzyme that is capable of breaking new enzyme that is capable of breaking down a protein particle believed to be the down a protein particle believed to be the transmitter of mad cow disease, university transmitter of mad cow disease, university sources said Saturday. sources said Saturday.

Treatment / Cure?Treatment / Cure? There is no cure for BSE or CJDThere is no cure for BSE or CJD