Evolution of the Mad Cow Disease in the

United States

Denish Moorthy, Eugene Shubnikov, Ron LaPorte

The Supercourse Network of the Global Health University

www.pitt.edu/~super1/

Outline of Presentation1. The Mad Cow Disease – What is It?2. What Causes it?3. How is it Diagnosed?4. How Does it Spread?5. Should Humans Be Worried?6. What is Creutzfeld-Jakob Disease (CJD)?7. What Happens in CJD?8. Is there a Cure?9. Epidemiology10.Implication for World Trade 11.The UK Story12.We are faced with a potential problem

The Mad Cow Disease in Cows, Scrapie in Sheep, the Creutzfeldt-Jakob Disease in human beings belong to a class of disease called Transmissible Spongiform Encephalopathy (TSEs)

Initially thought to be due to “slow viruses”, due to the long incubation period between time of infection and appearance of disease, these are now known to be caused by agents called prions.

Mad Cow Disease: What is it?

Transmissible Spongiform Encephalopathy (TSE) What Are

They? Transmissible Spongiform Encephalopathy (TSEs) are rare forms of progressive neurodegenerative disorders that affect both humans & animals

They are caused by similar agents (prions)

They are called so because they produce spongiform changes in the brain

Also, the agent causing the disease is found at the highest titre in the brain

Mad Cow DiseaseScientific Name: Bovine Spongiform Encepalopathy

It is found on any type of cloven hoofed animals such as: pigs, sheep, and cattle

Sheep: Scrapie Spongiform Encepalopathy.

There is a human form called Creutzfeldt-Jakobs Disease

• Bovine Spongiform Encephalopathy (BSE) is so named because of the spongy appearance of the brain tissue of infected cattle (and also in the human beings) when sections are examined under a microscope

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

What Causes

Mad Cow Disease?

Initially thought to have been caused by a “slow” viruses, these were classified as “slow Viral Diseases

Now there is evidence to point out Prions as the causative factor

Prions- Shortened form of Proteinaceous infectious

particles- Prions are single molecules containing about

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

Prion Hypothesis PrP is a normal cellular protein referred to as PrPc

Diseased brain contains aberrant PrP which is referred to as PrPSc

PrPSc has the ability to convert PrPc to itself A chain reaction follows, resulting in a cluster of

tangled, nonfunctional proteins called plaques, which are aggregates of PrPSc in the brain

The body defences remove these PrPSc aggregates leaving behind holes

This causes degeneration of the brain cells leading to mental changes and ultimately, death

Variant CJD in humans: section of cerebral cortex stained to show aggregates of PrPSc within plaques and more finely distributed throughout the grey matter (PrP stains brown)

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

Prion Characteristics

How is it Diagnosed in Cattle?

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

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).

Clinical Signs - 2

DiagnosisCurrently, there is no test

to detect the disease in a live animal or in humans

Veterinary pathologists confirm BSE by postmortem microscopic examination of brain tissue or by the detection of the abnormal form of the prion protein

Histological findings include

Vacuolation of the neurones and neuronal ground substance in cerebella/cortex

Perivascular fibrils of amyloid in which PrPsc can be demonstrated by immunostaining and congo red bifringence

Astrocyte infiltration.

Histological Findings on Post Mortem

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

Sheep with Scrapie used in Meat and Bone Meal (MBM) – known as “Offal”

MBM fed to cattle

Infected Beef eaten by humansNot affected by cooking

Should Humans

be Worried?

Mad Cow Disease in HumansWhen cattle brains and

other cattle byproducts infected with BSE are ingested by humans, there is a risk of developing the Creutzfeldt-Jakob Disease

What is Creutzfeldt-Jakob

Disease (CJD)?

Bovine Spongiform Encephalopathy (BSE) was first described in the UK in 1985 as a prion-based disease that affected cattle.

In 1996 it was first detected in a human being

It was suspected at that time (which turned out to be correct) that humans were contracting the disease from eating cows that had been infected with BSE

In humans, it is has been named the Creutzfeldt-Jakob Disease (CJD)

Origins of CJD

CJD is classified into 2 forms: Classic CJD & Variant CJD

Classic CJD can be transmitted to other species, however other animals cannot carry it.

Sub classified into: Sporadic CJD and Iatrogenic CJD

Sporadic CJD - >85% of Classic CJD cases

Most common between 50 – 75 years

Characterized by rapidly increasing dementia

Iatrogenic CJD - < 5% Classic CJD cases

Transmission of prion via medications & surgical equipment

Types of CJD

What is vCJDVariant Creutzfeldtt-Jakob

Disease (vCJD), is caused by the consumption of BSE infected meat products

The first 10 cases of variant CJD were observed in 1996, ten years after the outbreak of BSE in the UK

Variant CJD seems to affect mostly young patients

CJD causes fatal degradation of brain tissue & the nervous system

The symptoms include loss of expressiveness, muscular tremble, spasm, impaired muscle coordination, loss of memory & dementia

vCJD patients also display unusual psychiatric problems

There is no cure for CJD

The condition of the patient deteriorates, finally resulting in death

Clinical Symptoms

Is there a Cure?

At Present, there is no Cure for the Mad Cow Disease

(Bovine Spongiform Encephalitis) and for the Creutzfeldt-Jakob Disease

Prevention is the only available option

Don’t feed cattle animal bi-products

Watch to make sure you are feeding your animals safe feeds

Always vaccinate cattle properly

Prevention

USDA requires all imported meat to be inspected

US will not import cattle from Britian

Animals suspected of the disease are quarantined

Prevention

Epidemiology

Mad Cow Disease in the worldMad 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

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

Mad Cow Disease in Europe

The number of people who have died from variant Creutzfeldt Jacobs Disease (vCJD), is also growing

By the end of 2000, nearly 90 people had either died or were dying from the disease in the UK

Deaths from vCJD have also been reported in France & Italy

vCJD in Europe

France160 cases of BSE were diagnosed in 2000Beef sales dropped by > 25%

GermanyConfirmed 20 cases of BSE in 2001Beef sales dropped by 50 percent

United KingdomSingle largest source of BSE1,277 cases confirmed in 2000

vCJD in Europe

Implications for World Trade

Consumer Perception of BSE

Beef Consumption

UK and EU decreased by 30%US – Steady OverallWorld – slight increase

Fast Food Chains

Demand BSE Free

Implications for World Trade

Increased Demand for Grass Fed and Grain Fed Beef due to low possibility of BSE

Reduced trade in products made from Beef by-productsMake upDiet SupplementsHealth Products

The United Kingdom (UK) Story

BSE was discovered in ataxic cows by the Central Veterinary Laboratory in November 1986 by observing vacuolation of brains by histopathology

BSE considered to be caused by a single strain of scrapie

BSE First Discovered in the UK

Feed ban introduced

First histopathological

confirmation

Confirmed cases of BSE plotted by month and year of clinical onset

1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

A further 750,000 cases of subclinical BSE may have occurred and been culled before the peak age for clincal disease of 5.5yr

Brains and spinal cords from 440,000 of these could have contributed to the human food chain before the offal regulations of 1989

The disease should be almost extinct in the year 2001 when no animals fed on Meal and Bone Mill (or MBM) are left

BSE in the UK

Effects on the U.S.Caused great worries for many beef consumers

Caused cattle ranchers to take many precautionary steps

“This disease has not been known to be in the US…”

“…And chances are, it never will because the US has so many safety standards”