TSEHabeeb Shaikh

The objective

To discuss:

Basics of TSEBasics of TSE regulations

What is TSE?

Full form Linguistic break up

– Transmissible = communicable– Spongiform = which form sponge like structure– Encephalopathies = brain diseases

Encephalon = brain -pathy = pathological condition i.e. disease

Group of brain disease which causes formation of sponge like structure in brain

Medical definition

Types

Characteristics & symptoms

Histopathology Characteristics & symptoms

Self propagating Transmissible Rapidly progressive dementia Memory loss Psychological disorders Speech impairment Ataxia (balance & coordination

dysfunction) Hallucinations Seizures Death

Characteristics & symptoms

Facts about TSEs

Is it contagious or infectious? Transmission

• contaminated harvested human brain products• immunoglobulin• Tissue grafting• Genetic mutation• Consuming meat products contaminated with infectious prions• Blood transfusion

Diagnosis (Laboratory tests, EEG, MRI, Biopsy) Treatment (symptomatic) Who is vulnerable?

BSE prevalence in UK

CJD prevalence in UK

BSE world wide

TSE based humor

Cause

Prion or Spiroplasma? What is a prion (PrPc)? Prion (an acronym for

proteinaceous infectious particle)

Normal prion is a 35kD membrane glycoprotein

Misfolded, infectious, self replicating protein (PrPres)

Highly resistant to normal denaturation procedures

Mysteries of prion

Exact structure and properties How and why a normal prion gets misfolded? Is it a result of some infection or itself is an infection? Is it a self sustaining organism? Contain no nucleic acid? How it replicates itself in the body of victim? Prion is indestructible by heat up to 1000° F (350° C). Hot

enough to melt lead. Two Nobel prizes have been awarded for research in prion

diseases. In 1976, Carleton Gajdusek received the prize for proving that they are transmissible, and in 1997 Stanley Prusiner was given the prize for the prion hypothesis.

TSEs in humans

• Creutzfeldt-Jakob Disease (CJD)– sCJD (sporadic) most common of all CJDs– fCJD (familial) 15% of all CJD– vCJD (variant) 200 cases– iCJD (iatrogenic) 400 cases

• Fatal familial insomnia (FFI) Genetic 40 families worldwide, affecting about 100 people

• Gerstmann-Straüssler-Scheinker syndrome (GSS) Genetic 10-100 in 10 million

• Kuru in cannibals of Papua New Guinea• The most common of all is CJD affecting 1 out of a

million

What caused BSE epidemic?

What is rendered feed & protein?What are the sources of rendered feed?– Sick animals (cats, dogs, cows, pigs,

turkeys, chicken and ducks)– Dead animals– Rotten fish and shrimps– Zoo animals– Road kills– Maggot infested grains– hooves, skins, hair, fur, bones,

teeth, blood from slaughter houses

Why it is fed to animals?Bovine Somatotrophin

hormone

Few more uses of rendered protein and fats

Control of TSE

• 1988 – Rendered protein feed banned• 1989 – Specified bovine offal banned (offal:

decomposing animal flesh, waste material)

• July 1989 – First EU commission legislation on BSE introduced

• 1996 – Human consumption of sheep, goat and deer offal banned

Scientific principles of risk minimization

Scientific principles of TSE risk minimization are based on following procedures:

Control of animal feed Control of animals sourcing Control of organ sourcing for manufacturing of raw

materials Control of manufacturing procedures Control of quality systems

1. Control of animal feed

Control of feed to farmed animals and ruminants:a) processed animal protein;b) gelatin of ruminant origin;c) blood products;d) hydrolysed protein;e) dicalcium phosphate and tricalcium phosphate of

animal origin (dicalcium phosphate and tricalcium phosphate);

f) Feeding stuffs containing the proteins listed in points (a) to (e).

2. Control of animal sourcing

1. In-vivo diagnostic tests are cumbersome takes months to years2. If choice is available, non-animal or non-TSE animal source is preferred.

If unavoidable, use of TSE risk source should be justified3. The source animal and their geographical origin

OIE (Office International des Epizooties) The World Organisation for Animal Health has classified the world as:

http://www.oie.int/animal-health-in-the-world/official-disease-status/bse/list-of-bse-risk-status/

The World

A

(negligible risk)

B

(controlled risk)

C

(undetermined risk)

3. Control of organs sourcing

Animal

Category A (high infectivity tissues)

Category B (low infectivity tissues)

Category C (no detectable infectivity

tissues)

1. Category A tissues: Will not be used for manufacturing of medicines unless justified

2. Category B tissues: Tissues which are vulnerable for cross contamination during slaughtering and stunning of animals. Use of these tissues shall be subject to evaluation of risk.

3. Category C tissues: Tissues which are known to be not affected by Prions

4. Control of manufacturing procedures

1. Control at farms2. Control at slaughter houses3. Control at slaughter houses for cross-

contamination4. Control at RM manufacturing to avoid cross

contamination with high risk materials5. Defined manufacturing procedures which

takes control of TSE risk for specific animal origin RM

5. Control of quality systems

1. Production process and Quality system to ensure quality and traceability at slaughter houses and RM manufacturing sites

2. Implementation of HACCP and ISO systems3. Implementation of GDP

Specific considerations

Collagen:Hide, skins and tendons are safe.Bones are risky, the manufacturing procedure should be as per the guidelines.

Gelatin:Hides are safe, bones are riskyIf bone is the source for gelatin for parenteral use, bones of animals from category A and B countries only.If bones are the source of gelatin, the manufacturing procedure should be as per the guidelines.

Bovine blood and its derivatives:Foetal bovine serum is commonly used in cell cultures. Should be used with following considerations:1. Traceability of slaughterhouse and farms2. Should be sourced from category A countries. Can

be accepted from category B countries only if there is no risk of cross-contamination and age of animal is over 21 months

3. Stunning methods should not pose risk of cross-contamination

Specific considerations

Tallow derivatives:Glycerol and fatty acids and esters should be produced by using rigorous processes.Animal Charcoal:Charcoal produced by carbonization of tissues, such as bones, using temperatures higher than 800 °C is safe. Other methods must demonstrate compliance with the guidance.Milk and milk derivatives:Lactose, casein, cheese Safe

Specific considerations

Wool derivatives:Lanoline and wool alcohols are safe if collected from hairs of live animals.

Amino acids:Amino acids produced as per guidance note are safe. Other methods should demonstrate compliance.

Peptones:Peptones are partial hydrolysates of protein, achieved by enzymatic or acid digestion. They are used in microbiological culture media which might be used as seed stocks or in industrial scale fermentations for the production of human and veterinary medicinal products, including vaccines. Vegetable protein is a preferable source. If gelatin and casein are used as a source, the source should be derived as per guidance given above.

Specific considerations

Current BSE testing of animals

1 March 2013 – In GB, the requirement to test healthy slaughtered cattle for BSE ends on 1 March 2013. This applies to cattle born in EU Member States (except Bulgaria and Romania).From 1 March 2013, the following cattle must still be tested for BSE:1. Healthy cattle aged over 30 months slaughtered for human

consumption which were born in Romania, Bulgaria and all non-EU countries;

2. Cattle sent for emergency slaughter, cattle which are identified as sick at ante-mortem inspection, and fallen stock, i.e. cattle which die or are killed other than for human consumption:

aged over 48 months if born in EU Member States (except Bulgaria and Romania); or

aged over 24 months if they were born in Romania, Bulgaria and all non-EU countries.

Hilarious... but right

What is the moral of the story?

Greedy human nature Influential people must be morally at higher

levels New regulations are most often formed after

bitter experience Solution for human issues should be

scientifically and logically justifiable

Moral

Questions

Thanks for your presence and active participation