Bovine Spongiform

Encephalopathy

G#12
Kashif Nawaz 09 layyah
Babar saqlain 19 layyah
Noman Bashir 44 layyah
Mad Cow Disease
Introduction
 BSE - Bovine Spongiform
Encephalopathy
“MAD COW DISEASE”
 What is it?
• Transmissible,
• slowly progressive,
• degenerative,
• fatal disease affecting the central
nervous system of adult cattle
 BSE - Bovine Spongiform
Encephalopathy
“MAD COW DISEASE”
 What is it?
– It is characterized by a long incubation period
of up to several years (2-8), during which
there is no visible incubation of the disease.

– It is invariable fatal; there is no known

treatment of cure.

– No test can detect prions in a live animal

 Susceptible species
The natural hosts are cattle.
Some cases have also occurred in antelopes
and feline (cats, tiger, puma etc.).

A range of other species including mice,

pigs, and sheep has been infected
experimentally.

Humans are thought to be susceptible.

 Causative Agent
 A prion is the most likely cause of B.S.E.

 A prion is a small protein-like material that

incorporates itself into the hosts’ DNA and
changes the structure of the alpha-helix.

 It is believed B.S.E. was begun by feeding

scrapie-infected sheep offal to cattle.
 What Are Prions?
 Shortened form of Proteinaceous infectious
particles
 Prions are single molecules containing about

200-250 amino acids.

 They are abnormal variants of proteins which

normally occur in cells

 Prions have the ability to convert the normal

forms that they come into contact with into

abnormal forms
 Basic Structure
 Normal prions contain
about 200-250 amino
acids,
 twisted into three
telephone chord-like coils
known as helices,
 with tails of more amino
acids.
 Basic Structure

 The mutated, and

infectious, form is
built from the
same amino acids
but take a different
shape.
 100 times smaller
than the smallest
known virus.
Normal Mutated
What is a the Prion theory?
One proposed method for prion
replication

Note that normal PrPC is involved in replication of mutated PrPSc

Brain Damage from Spongiform
Encephalopathy
vacuole
 Prion Characteristics
 No antibiotics can cure disease caused by prions
 They are not typical of a prokaryotic organism or a
eukaryotic organism
 All that is present in this pathogen is the protein PrPSc, the
mutation of PrPC
 PrPSc is resistant to any form of digestion
 Prions are non immunogens and do not induce an immune
response
 Prions are not easy to decompose biologically
 They are resistant to high temperatures & disinfectants
 Animal prion diseases
 Scrapie: sheep, goats; first described 1738
 Transmissible Mink Encephalopathy: minks;
1964
 Chronic Wasting Disease: mule, deer, elk;
1980
 Bovine Spongiform Encephalopathy: cattle;
1986
 Feline Spongiform Encephalopathy: cats; 1990
 human prion diseases
 Kuru

 Creutzfeldt-Jokob disease (CJD)

 New variant CJD

 Gerstmann-Straussler-Scheinker syndrome

 Fatal familial insomnia

 History
 1986
– First confirmed case in United Kingdom
 1988
– U.K. bans meat and bone meal from ruminants
in cattle feed
 1989
– USDA bans importation of ruminants from
countries with BSE
 History
 1993
– Peak of BSE in U.K
 1997
– U.S. and Canada ban feeding ruminant products
to ruminants
– U.S. importation ban extended to all of Europe
regardless of BSE status
 2001
– E.U. orders mandatory tests on cattle > 30
months old
 History: Canada
 1993: 1 case (imported from U.K.)
 2003: 2 cases (one living in U.S.)

 2004, 2005: 1 case each year

 2006: 5 cases

 2007: 3 cases

 2008: 4 cases

 2009: 1 case

 2010: 1 case
 History: U.S.
 December 2003
 Dairy cow from Washington state
 Confirmed by DNA tests
 6½ years old, imported from Canada
 Complications following calving and sent to
slaughter
 Definitively positive by U.K. lab
 History: U.S.
 June 2005
 12 year old Texas beef cow,
 Confirmed positive with new BSE
testing protocol
 March 2006
 10 year old Alabama beef cow
 “Down” on farm; veterinarian posted and
submitted obex for testing
 Both animals born before feed ban; neither
entered human food chain
 How BSE first occurred in
cattle…
 Rendered feed ingredients contaminated with an
infectious agent are believed to be the source of
BSE infection in cattle
 Some of the feed given to cattle includes
ingredients processed from remnants of
slaughtered animals, such as meat-and-bone
meal, which may harbor the agent that causes
BSE
 How Does it Progress?
 The incubation period (the time from when an
animal becomes infected until it first shows
disease signs) varies from 2 to 8 years.
 Following the onset of clinical signs, the
animals condition deteriorates until it either
dies or is destroyed.
 This process usually takes from 2 weeks to 6
months.
 Most cases in Great Britain (where it was first
detected) have occurred in dairy cows between
3 to 6 years of age.
There are three phases of BSE in cattle:
 The first phase:
 Low infectivity rate, and the cow does not pose a
large threat to humans at this level
 The second phase:
 Symptoms are not evident, but the infectivity level
is very high
 The prion agent is abundant in both the spinal chord
and the brain – the cow is a risk to public health
 The third phase:
 Clinical symptoms, & then death follows shortly
 Animal Transmission
 Origin unclear
– Feed contaminated
with scrapie or
unknown BSE
– Spontaneous mutation
– Changes in feed processing
 Maternal transmission
– Possible, low risk
– Retrospective offspring culling
 Likely spread ingestion of BSE contaminated feed
Center for Food Security and Public Health, Iowa State University,
2011
 Human Transmission
 Humans consuming cattle products
infected with BSE can develop vCJD
– Brain and spinal tissue
 Dose required unknown
 Genetic susceptibility

– All human cases have been homozygous for

methionine at codon 129 of PrPC
 Human Transmission
 Possible modes
– Transmission from surgical instruments
used on tonsils, appendix, or brain
tissue
– Growth hormone injections
– Vaccines
How Does it Spread?
 The Source of Prion
 Prion in cattle is mainly are
from the carcasses of scrapie-
infected sheep.
 After these infected sheep
having died , their brains and
other sheep byproducts infected
with scrapie is used to feed
cattle with the meat and bone
mill (MBM)
 How does it spread from
animal to animal?
 Feeding cattle animal bi-products such as meat-n-

bone mill that has an infected prion causes the

infection in the cattle
 The prions are concentrated in the brain, and spinal

cord of these animals

 There is no evidence that it is concentrated in the

muscle mass of cattle, and they are considered safe

as long as they are not in contact with the brain and
spinal cord during the slaughter process
 How did BSE Transfer to Humans
 Sheepwith Scrapie used in Meat and Bone Meal (MBM) – known as
“Offal”

 MBM fed to cattle

 Infected Beef eaten by humans

Not affected by cooking
Should Humans
be Worried?
 Mad Cow Disease in Humans
 When cattle brains and
other cattle byproducts
infected with BSE are
ingested by humans,
there is a risk of
developing the
Creutzfeldt-Jakob
Disease
 Clinical Signs
 Incubation: 2 to 8 years
 Initial neurological signs

– Often subtle
– Apprehension, fear, easily startled, depressed
 Final stages
– Excitable, hyperreflexia, hypermetria, ataxia,
muscle fasciculation, tremors

Center for Food Security and Public Health, Iowa State University,
2011
 Clinical Signs
 Terminal state
– Decreased rumination
– Loss of body weight and conditiondespite
good appetite
 There is no treatment for BSE
 Affected herds

– 2 to 3% morbidity
– 100% mortality
Center for Food Security and Public Health, Iowa State University,
2011
 Clinical Signs - 1
 Cattle affected by BSE
experience progressive
degeneration of the
nervous system. 

 Affected animals may display changes in

temperament,
such as nervousness or aggression, abnormal
posture, inco-ordination and difficulty in rising,
decreased milk production, or loss of body weight
despite continued appetite
 Clinical Signs
 The clinical signs are:
 Apprehension
 Hyperaesthesia
 Frequent licking with progressive
paresis, & ataxia
 No blindness or circling is seen
(At the London Zoo it was first
noticed by the public when a Puma
became ataxic).
 Symptoms
 Increased apprehension
 Poor coordination

 Difficulties walking

 Weight loss

 Agitation

 Nervousness
 Diagnosis
 Slowly progressive, fatal neurologic
disease
 Differentials

rabies, brain tumor, lead poisoning spinal cord

trauma
 No antemortem testing available
 Brain, medulla, spinal cord,
brain stem
 DIAGNOSIS
 The BSE testing protocol calls for an initial rapid test called an
Enzyme-Linked Immunosorbent Assay (ELISA).

 If the ELISA test is inconclusive, samples are sent for confirmatory

testing to the National Veterinary Services Laboratories (NVSL).

 An immunohistochemistry test is conducted at NVSL and,

concurrently, an OIE-approved Western Blot is conducted at the
National Animal Disease Center (NADC).

 These tests are designed to detect the presence of BSE-specific

abnormal prion protein in the brain tissue.
 Post Mortem Diagnosis
 Histopathology of brain
tissue
– Spongiform changes in
gray matter
 Detection of abnormal
prion protein

Center for Food Security and Public Health, Iowa State University,
2011
 Post Mortem Tests for BSE
 All are based on antibodies to detect prion
protein in tissue
 Immunohistochemistry (IHC) is considered

the gold standard

– Internationally recognized
– Expensive, labor intensive
 Rapid diagnostic tests
– Western blotting, ELISA
Center for Food Security and Public Health, Iowa State University,
2011
 Post Mortem Tests for BSE
 June 24, 2005
– New BSE confirmatory testing protocol
 IHC & Western Blot
– Confirmatory tests
– Performed with “inconclusive” BSE rapid
screening test results
– Positive result on either test
considered positive for BSE
Center for Food Security and Public Health, Iowa State University,
2011
 Rapid Diagnostic Tests
 NOT food safety tests
 NOT valid for assuring absence of prion

protein in individual animal

 Antibody-based tests can detect prion

protein before spongiform changes occur

Center for Food Security and Public Health, Iowa State University,
2011
Sampling
 Sampling
 Before collecting or sending any samples,
the proper authorities should be contacted
 Samples should only be sent under secure

conditions and to authorized laboratories

to prevent the spread of the disease

Center for Food Security and Public Health, Iowa

State University, 2011
 Sampling
 Collection sites
– State or Federal slaughter plants
– On farm
– Rendering facilities
– Veterinary diagnostic laboratories
– Animal feed slaughter facilities
 Pet food plants
– Sale barns, livestock auctions
– Sites utilized by accredited veterinarians
Center for Food Security and Public Health, Iowa State University,
2011
 Prevention
 Stop the feeding of rendered animal
products to other animals.
 Put bans on importation of animals from

infected countries.
 Establish high monitoring systems.
 Control in the UK
 Feed ban
 Selective Slaughter

 Surveillance Program

 Export ban
 Advances in prion control
• BSE-resistant cattle
• Bovine PrPc gene cloned, modified by site-directed
mutagenesis to produce BSE-resistance form
• Cattle were transformed with modified form of the gene,
targeted to replace natural PrPc gene
• Transgenic animals homozygous for mutant gene express
mutant copy and are resistant to BSE, but do not show
altered sleep/wake cycles as seen in knockout mice
• Depleting neuronal PrPc in prion infection prevents
disease and reverses spongiosis
• Using transgenic mice, first demonstration that prion
infection and pathology can be reversed by ceasing
expression of endogenous PrPc copy
 Vaccine?
 The development of a vaccine against the
infectious form of prions has proven to be
unsuccessful due to the lack of innate or
antigen-induced immune response against
the host-encoded protein.
 What is the U.S. doing to
Prevent BSE?
 On July 1989, a ban on importation of live
ruminants into the U.S. from United
Kingdom was enforced.
 Other regulatory methods have been

established to prevent importing live

animals and meat products from infected
and “high risk” countries.
 What is the U.S. doing to
Prevent BSE?
 On August 4, 1997, the Food and Drug
Administration developed regulations to
prevent the feeding of mammalian
proteins to ruminants
 How is the U.S. Monitoring?
 The U.S. has done monitoring on cattle in
42 states and has found zero traces of
BSE.
 Since 1990, there have been

1,250,880,700 cattle raised in the U.S.

 Since 1990, 11,700 cattle brains have been

checked for BSE.

Prevention
 Don’tfeed cattle animal
bi-products

 Watch to make sure you

are feeding your animals
safe feeds

 Alwaysvaccinate cattle
properly
 Prevention
 USDA requires all imported
meat to be inspected
 USwill not import cattle
from Britian
 Animals suspected of the
disease are quarantined
 Prevention Firewalls


 Test all cattle
Border

Ruminant-to- at slaughter

ruminant feed ban Remove all SRM
from food for
human consumption

Center for Food Security and Public Health, Iowa State University,
2011
Epidemiology
 Mad Cow Disease in the world
 Mad cow disease was first identified in
Britian in 1985
 The outbreak infected more than
100,000 cows across Europe in the
mid-1990s
 The recent resurgence of the disease
comes despite widespread beef import
restrictions and other measures
intended to protect the food supply
Mad Cow Disease in Europe
 Cases of BSE have now been
identified in 10 of the 15
European Union (EU) countries,
as well as Switzerland and
Liechtenstein
 Although the incidence is low, the
discovery of the disease across
the continent has had a dramatic
effect on beef consumption
 Beef consumption has has fallen
by 27% across the EU
 Infected and “High Risk”
Countries
 United Kingdom
 Western Europe

 Oman

 Romania

 Japan
The End