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Bovine Spongiform Encephalopathy Mad Cow Disease

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  Slowly Progressive, Degenerative, Fatal Disease affecting the CNS of adult cattle

  Behavior / temperament changes   Tremors, incoordination,

falling, and difficulty in rising

  Decreased milk production

  Apprehensive to aggression

  Small % “Mad Cow”

  Incubation period – 2 to 8 years

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Economic Impact   Export Markets Closed

  Domestic Consumption

  Consumer Confidence

  Fast Food Chains Demand BSE Free

  BSE Cases - UK

  Since 1986 – 180,000

  Peaked 1993 – 1,000 cases per week

  2000 - 1352

  2003 - 154

  Increased Demand for Grass/Grain Fed Beef

  Reduced trade in Beef by-product goods

  Make up

  Diet Supplements

  Health Products

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Etiology   Not Yet Fully Characterized

 Protein only hypothesis

  Dr. Stanley Prusiner, Nobel 1997  Prion = Proteinaceous infectious particle

 Smaller than smallest known virus

PrPC PrPSc

(Normal cellular surface protein) (prion)

conformational change

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Normal protein   Secondary structure

dominated by α helices

  Easily soluble

  Easily digested by proteases

  Encoded by PRNP gene (in humans)

 Located on human chromosome 20

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Abnormal Protein   Insoluble

  Highly resistant to proteases

 Survives in tissues post-mortem

  Extremely resistant

 Heat, normal sterilization processes, sunlight

  No detectable immune response

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Abnormal Protein   PrPSc (Sc: scrapie)

 aa sequence & primary structure =normal protein

 Secondary structure dominated by β conformation

  When PrPSc contacts PrPC

 Converts it to the abnormal form

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PrPc

PrPsc

PrPc

PrPc

PrPc

PrPc

PrPc

PrPc

PrPc

PrPc PrPc

PrPc

PrPc

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PrPC

PrPSC

PrPC

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PrPsc fibrils

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Plaque

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Epidemiology

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Geographic Distribution

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The spread of BSE

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Geographic Distribution   95% of all BSE cases in U.K.

  Outside U.K. due to importation or contaminated feed

  No cases reported from   Australia, New Zealand, Central America, South

America

  2003   Canada and U.S. reported single cow

  2005   Additional Canadian cases   U.S. reported single case - June

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Animal Transmission   Reasons for emergence

under debate

  Feed contaminated with scrapie or unknown BSE

  Spontaneous

  Changes in feed processing

  Current thought

  Spread via ingestion of BSE contaminated feed

  High Risk Products

  Brain and spinal cord tissue

  Meat and Bone meal (MBM)

  Not in Muscle cuts, Steaks & Roast

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Transmission   BSE contaminated feed

  No Horizontal Transmission

 Contact - Cattle to cattle or cattle to other species

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Pathogenesis   Details are unknown

Oral exposure

Peyer’s patches

Peripheral nerves

CNS

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Human Transmission   Humans consuming cattle

products infected with BSE can develop vCJD

 Brain and spinal tissue

  Dose required not known

  Genetic susceptibility

 All human cases have been homozygous for methionine at codon 129 of PrPC

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Human Transmission   Possible modes

 Transmission from surgical instruments used on tonsils, appendix, or brain tissue

 Growth hormone injections

 Vaccines

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Clinical signs

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Clinical Signs   Incubation: 2-8 years

  Initial neurological signs  Anxiety, fear, easily

startled, depressed

  Final stages  Excitable, hyperreflexia,

hypermetria, ataxia, muscle fasciculation, tremors and myoclonus

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Clinical Signs   Terminal state

 Decreased rumination

 Loss of body weight and condition, despite good appetite

  No treatment for BSE

  Affected herds  2% morbidity

 100% mortality

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Diagnosis   Slowly progressive, fatal neurologic

disease

  Differentials

 Nervous ketosis, hypomagnesemia, listeriosis, polioencephalomalacia, rabies, brain tumor, lead poisoning spinal cord trauma

  No ante mortem testing available

  Brain, medulla, spinal cord, brain stem

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Sampling

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Obex

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HP: H&E   Spongiform

changes in gray matter

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HP: IHC   Detection of PrPSc

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Post Mortem   IHC/IHK “gold

standard”  Expensive  Labor intensive

  Various rapid diagnostic tests have been developed  Western blotting  ELISA

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Humans   Initial symptoms

  Depression and schizophrenia-like psychosis

  Neurological signs   Unsteadiness, difficulty

walking, and involuntary muscle movements

  Progression   Become completely

immobile and mute

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Public Health   1996-2004

 172 cases of vCJD worldwide

 156 from UK

  No cases of indigenous vCJD in U.S.

  Unknown incubation period and consumption

 Possibly more cases of vCJD in future

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Kuru   Cannibalism, Papua

  Affected mostly women and children, with a small amount of men

  Mortality: 5-10 %

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Prevention and Control   Import restrictions

 Live ruminants and products

  Ban most mammalian proteins as food source for ruminants

  Test all cattle at slaughter  downer cattle

  Surveillance

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Recommended Actions   Notify authorities immediately

of any suspicious cases

  Submit brain, medulla

  Incinerate the carcass

  Quarantine the premises

  Confirmatory diagnosis

  Depopulation and trace backs

 Proper disposal of suspect animals SS 10/13/14

Disinfection   Porous load autoclaving

  134-138 oC for 18 minutes

  Not always effective

  Disinfectant   Sodium hypochlorite, 2% chlorine

  2-N sodium hydroxide

  1 hour at 20oC on surfaces, 8 hours equipment

  Rendering at 133oC, 3 bar for a min of 20 min

  Resistant in tissues, dried organic material, at high titer

  http://www.oie.int/eng/maladies/fiches/a_B115.htm

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Food Safety, US   Mammalian byproducts Banned from

Feeding to Ruminants

  Surveillance of cattle over 30 Months of Age

 Tested over 20,000 samples in 2003

 Targets non-ambulatory cows

  Import Ban on live ruminants and products

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Japan; beef number on the package

• When the cattle was born or imported ? (age: 20 mos) • Gender　 • Mother’s number • Where did it grow up? •  When did its feeding start and end? • Slaughtered date, or imported date • For imported ones, it tells which country did the beef come from? • Name of the slaughter house and its location

Source: Dr. Tanguchi, Kitasato University, Japan-2005.

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National Animal ID System   USA, Canada

  Interstate movement

  RFID – Radio Frequency Identification

  Complete & Thorough Investigation

  Trace Forward & Trace Back

  http://www.aphis.usda.gov/traceability/index.shtml

  http://www.canadaid.com/about_us/about_us.html

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National Animal Identification System (NAIS)

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Animal Identification   Individual animals

  Animal ID Number (AIN)   15 digits – starts with 840

  Group/Lots   Premises ID, plus date & count   Example: A23T567 103002 01

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Animal Identification   9 mfrs/ 29 AIN devices

  11 visual eartags

  16 RFID eartags

  2 RFID injectable transponders

  2 Slaughter Swine Premises ID Tags

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Scrapie

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