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From: TSS ()
Subject: Potential and Proven Pathways for TSE, Waterborne zoonoses, dead stock downer slaughter disposal, vaccines and plume
Date: June 22, 2005 at 1:59 pm PST

Section VII

Prevention and control of

waterborne zoonoses

snip...

24.5 ARE TSES POTENTIAL WATERBORNE

PATHOGENS?

24.5.1 Characteristics of TSEs

TSEs are a group of infectious diseases characterized by slow and progressive

degenerative changes in the central nervous system. TSEs affecting humans

include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker

syndrome, kuru, and fatal familial insomnia; those affecting animals include

scrapie in sheep and goats, feline spongiform encephalopathy, transmissible

mink encephalopathy, chronic wasting disease (CWD) in elk and deer, and

Control in animal reservoirs 395

bovine spongiform encephalopathy (BSE) (Dormont 2002). It is hypothesized

that these unique infectious agents are aberrant forms of a normal host protein.

Prusiner (1982) first proposed the existence of this self-propagating protein,

which he termed a "prion," as the causative agent of TSEs. Although the theory

that prions are responsible for TSEs is now accepted by the majority of the

scientific community, some scientists are still not convinced and suggest that an

infectious agent such as viruses or virinos may be responsible (Manuelidis

2003). The normal prion protein is found in neural as well as many other body

tissues and is thought to be a membrane-bound glycoprotein involved in copper

transport into host cells and protection of these cells against oxidative stress

(Clarke et al. 2001; Collinge 2001). The infectious form of the prion is thought

to occur when the -helical structure of the native protein is somehow converted

to the -sheet isoform. The altered prion protein differs from the native form in

three important respects. Firstly, it is highly resistant to proteases and other

physical and chemical agents, such as heat, ultraviolet (UV) light, and oxidants

(Dormont 2002). Secondly, it is postulated that it catalyses the transformation of

native prion protein to the infectious form using the infectious form of prion as a

template, perhaps with the addition of an accessory factor termed "protein X."

Finally, the highly resistant form of the protein accumulates over time in the

host tissues and in some way leads to the characteristic neural pathology

associated with TSEs. It is possible that the accumulation of the aberrant form of

the prion protein leads to a failure of the normal prion protein role in the

protection of cells against oxidative stress and to calcium cytotoxicity (Hur et al.

2002), but this is not certain.

BSE was first diagnosed in 1986 at the Central Veterinary Laboratory in

Weybridge in the United Kingdom. It is thought that BSE may have originated

spontaneously in cattle or as a rare type of scrapie present in sheep.

Subsequently, cattle became infected as a result of feeding bovine- or ovinederived

BSE-contaminated meat and bone meal (MBM) to cattle. Once cattle

became infected, they in turn contributed further to the contamination of MBM

with the BSE agent. The highly resistant nature of the prion protein is thought to

have allowed it to survive an altered rendering process used at the time in the

production of MBM.

The protease and acid resistance of the prion may also allow it to pass

through the stomach and into the intestinal tract. Once in the intestine, it is

thought to be taken up by gut-associated lymphoid tissues and subsequently

passed to lymphoid tissues such as the spleen and tonsils, where it enters the

lymphoid-associated peripheral nervous system. It then makes its way to the

central nervous system over the course of many months and years, depending on

the TSE strain and the host species and genotype. The resistant nature of the

protein may also be responsible for the ability of TSEs such as scrapie from

396 Waterborne Zoonoses

sheep to persist in soils for more than 3 years (Brown and Gajdusek 1991).

There is strong epidemiological evidence supporting lateral transfer of scrapie

and CWD in sheep and deer, respectively.

24.5.2 Risks of acquiring BSE from drinking-water sources

In 1997, evidence was presented that BSE was a zoonotic agent (Bruce et al.

1997). The BSE-associated disease in humans was termed "variant

Creutzfeldt-Jakob disease" (vCJD) because of its similarity to the well

recognized human TSE, CJD. It is assumed that humans with vCJD acquired the

infection through the consumption of bovine nervous tissues (bovine offal, beefon-

the-bone) containing high levels of the infectious BSE agent. Shortly after

this finding, it was suggested that nearly a million cattle in the United Kingdom

would have to be culled and disposed of to control the BSE and vCJD epidemics

in cattle and humans, respectively. As a result of this impending action, concern

was expressed that the BSE agent present in infected material from the cattle to

be slaughtered could enter surface water and groundwater (from

slaughterhouses, rendering plants, and landfills) and pose a public health risk.

The following is a list of some of the key components of this risk assessment

(Gale 1998, 2001; Gale et al. 1998):

(1) Concentration of BSE agent in bovine neural tissue. It was assumed that

the level of infectious material in the nervous tissues of cattle would be

equivalent to that which occurred at the peak of the BSE outbreak as a

worst-case scenario.

(2) Infectious dose models for BSE. It can be postulated that a certain

threshold dose level of the BSE agent is required to cause vCJD in

humans and that this dose is much less likely to be achieved as a result

of a single consumption event of water rather than of bovine nervous

tissue. This is because the agent is likely to be highly dispersed in water

and concentrated in nervous tissues in beef. However, it is also possible

that the threshold could be reached by a susceptible individual after

years or months of low-level long-term exposure. However, even if this

assumption is accepted, Gale et al. (1998) calculated that a threshold

dose from the agent in water would be reached only after approximately

45 million years. Alternatively, it is possible that a specific threshold

does not exist for the population and that a very low dose of the BSE

agent could result in infection in a correspondingly small proportion of

the population — i.e., those most susceptible would have a lower

threshold dose. If this assumption is accepted and it is considered that

the prion ID50 is divisible and cumulative, according to Gale et al.

Control in animal reservoirs 397

(1998), one arrives at similar levels of risk for drinking water and eating

beef-on-the-bone (10-8 versus 10-9 per person per year).

(3) The interspecies barrier. Mice can be infected with BSE by feeding

them infected bovine nervous tissue; however, the ID50 by the oral route

for mice is approximately 1000 times greater on an equivalent-weight

basis than it is for cattle. A large part of the interspecies difference in

ID50 may be related to the ability of the prion material to pass through

the gastrointestinal tract and then enter gut-associated lymphoid and

nervous tissues. While pigs can be infected with BSE-infected nervous

tissue by the combined intracranial, intravenous, and intraperitoneal

routes, they appear to be completely refractory to infection with this

TSE by the oral route (Wells et al. 2003). Martinsen et al. (2002)

recently reported that the BSE ID50 in mice can be decreased by

lowering concentrations of hydrochloric acid in the stomach of mice

using ranitidine. It is therefore conceivable that some humans may be

more susceptible to infection than others and that this susceptibility

could change with the physiology of the gastrointestinal tract.

(4) Susceptibility to TSEs based on genotype. It is known that there are

differences in the genotype of prion proteins within sheep, mice, and

human populations that make them resistant or susceptible to specific

TSEs. Humans that are homozygous for methionine at codon 129 of the

prion protein gene are more susceptible to CJD, and all cases of vCJD

described thus far have this genotype (Will et al. 2000).

(5) Dilution in water. As mentioned above, humans with vCJD are thought

to have acquired the infection through the consumption of bovine

nervous tissues containing high concentrations of the BSE agent. The

human ID50 has been calculated to be equivalent to 1013 BSE prion

proteins (Gale et al. 1998). As mentioned above, it is thought that in

contrast to beef products, the BSE agent is likely to be highly dispersed

in water. Therefore, the daily intake of infectious prions by consumers

of water is likely to be very low by nature of dilution when compared

with BSE-contaminated nervous tissue in beef-on-the-bone.

(6) Transport and solubility in water. The prion protein is a typical

membrane protein and has both hydrophilic and hydrophobic domains.

This property limits its solubility in water and favours the formation of

insoluble aggregates, promotes adhesion to hydrophobic particles, and

would be predicted to limit its mobility in surface water or groundwater.

Further, Brown and Gajdusek (1991) showed that a closely related TSE

agent, scrapie, has very limited mobility in soils. Thus, risks of

infectious prions entering groundwater or surface water from cattle

carcasses buried for disposal are likely very low.

398 Waterborne Zoonoses

In support of these risk assessments, Cousens et al. (2003) reported that

vCJD cases in the United Kingdom have not been geographically clustered, as

would be expected if the source of infection was from an environmental source

such as soil or water.

While much of the evidence suggests that the risks of infection with the BSE

agent from drinking-water are negligible (Gale 2001), further research on our

levels of exposure to TSEs in the environment and parameters affecting the

infective dose in humans is required. A reasonable estimate of the ID50 for

humans of BSE-infected material is required before a meaningful quantitative

risk assessment can be conducted. However, essential elements necessary for

this risk assessment model, such as the nature of the interspecies barrier for BSE

infection in humans, are not known. In addition, a lack of understanding of the

genotypic and physiological differences in susceptibility to this TSE within the

human population has further complicated this task.

24.5.3 BSE eradication plan

The epidemic in the United Kingdom has resulted in 180 121 cases of BSE in

cattle (http://www.defra.gov.uk/animalh/bse/index.html). The BSE epidemic

appears to have reached its peak in 1992, and the number of cases has declined

since then. At the time of this writing, 137 deaths have been associated with

vCJD in the United Kingdom, and the peak of the epidemic appears to have

been in 2000 (http://www.doh.gov.uk/cjd/cjd_stat.htm). In the United Kingdom,

a number of steps have been taken to control the BSE outbreak in cattle and the

vCJD epidemic in humans. The MBM ban for ruminant feed and culling of

animals from infected herds were likely to have been the most important steps in

controlling these epidemics. Many other countries have adopted similar

measures to combat and/or prevent the entry of BSE. The MBM ban has been

expanded to include all food-producing animals in certain countries. Measures

to protect the human population from vCJD have included removal of specified

risk materials (offal, heads, and spines) of bovine origin from the food-chain,

restriction of slaughter of animals for human consumption to those under 30

months of age, and banning the importation of cattle or beef from countries with

BSE. Both BSE and vCJD cases have declined due to these measures.

24.5.4 Scrapie eradication plan

Scrapie is a TSE endemic in sheep populations throughout most of the world

(Australia and New Zealand are notable exceptions to this, with their sheep

scrapie-free). It is often stated that scrapie has existed in sheep in the United

Control in animal reservoirs 399

Kingdom for more than two centuries without an apparent public health impact

(Baylis et al. 2002). However, as stated above, it has been hypothesized that

BSE may be a rare strain of scrapie that has existed for some time at low levels

in the sheep population in the United Kingdom prior to causing BSE in the

cattle population. It is also certain that some sheep consumed MBM

contaminated with the BSE agent before the MBM feed ban took place. It

therefore seems likely that some sheep may have become infected with BSE

through MBM and may pose a public health risk (Butler 1998).

Further, there is concern that the public health risk from BSE in sheep could

be potentially greater than is posed by BSE in cattle. Firstly, the scrapie agent is

distributed more widely in body tissues of sheep than is BSE in the tissues of

cattle. Therefore, BSE in sheep could present a greater risk for acquiring a TSE

for human consumers of mutton. Secondly, the epidemiology of scrapie in sheep

is quite different from that of BSE in cattle. Studies on BSE in cattle suggest

that there is little or no spread of the agent horizontally to herd mates and

vertically to offspring; in scrapie in sheep and CWD in cervids, however, there

is both vertical and horizontal spread of the agent within flocks and herds, and

these agents appear to persist in pastures and act as a source of infection for

other susceptible animals (Baylis et al. 2002; Detwiler and Baylis 2003; Salman

2003). This raises the possibility that BSE not only could be transmitted by

consumption of mutton but also could become more widely dispersed in the

environment. In response to this potential public health threat, a National

Scrapie Plan has been implemented in the United Kingdom with the aim of

eradicating scrapie (and BSE, if it exists) from the national sheep flock. The

plan will use selective breeding for the scrapie/BSE-resistant prion genotype of

sheep ARR/ARR (Houston et al. 2003).

24.6 SUMMARY AND CONCLUSIONS

The risk of zoonotic waterborne diseases can be resolved to some extent by

minimizing the entry of animal wastes to source waters, by controlling animal

movements, proper storage and disposal of farm animal wastes, using

procedures that will minimize the survival of zoonotic pathogens, and limiting

transport of these wastes in surface water runoff.

Control and, in some cases, eradication of zoonotic agents in animal

reservoirs may be an efficient and cost-effective means of controlling drinkingwater

source and recreational water contamination with zoonotic pathogens.

Most zoonotic pathogens are not uniformly distributed through animal

populations but rather are present in specific animal species reservoirs. Further

specific age classes or animals such as young calves may shed these organisms

in much higher numbers than adults.

400 Waterborne Zoonoses

Control measures for domestic animals centre around the issue of increased

biosecurity. This can be brought about by measures such as limiting access of other

animal species through physical barriers, limiting cross-contamination among animals

by using good sanitation practices and raising susceptible animals away from animals

that may be carriers of zoonotic agents, keeping "closed herds," "all-in all-out"

procedures, quarantine of new animals and surveillance-based test and slaughter

procedures, providing food and water free of zoonotic agents, competitive exclusion,

bacteriophage therapy, other feed additives, and active and passive immunization.

These strategies can be applied with success at the farm level but are more effective on

a national level with economic incentives for compliance.

Control of zoonotic diseases in domestic animal populations, while difficult, is

more easily addressed than control of these diseases in wild animal populations.

Wherever it is possible, there should be physical separation of wildlife from domestic

animals; in addition, population control of wild species should be considered only in

selected areas where there is a high rate of infection with a zoonotic agent in a

reservoir population and there is a clear risk of contamination of surface water with

pathogens and/or transfer of these pathogens to domestic livestock. Wildlife

vaccination schemes to limit infection with specific zoonotic agents or for

immunocontraception represent possible strategies for limiting certain zoonotic

waterborne diseases.

The sudden emergence of zoonotic pathogens responsible for the outbreak of BSE

in cattle and vCJD in humans in the United Kingdom has been a cause of concern for

most public health authorities. A ban on feeding MBM to food-producing animals and

a rigorous test and slaughter policy have brought both the BSE epidemic in cattle and

the vCJD epidemic in humans under control in the United Kingdom. The small size

and extreme resistance of these TSE agents to proteases, heat, UV light, and chemical

treatments suggest that current water treatment technologies would have little effect in

controlling these zoonotic agents, and TSE agents have been shown to persist in soils

for years. However, the insoluble nature of prions is likely to limit their movement into

water systems. Further, it is felt that a relatively small quantity of prions would be

released following slaughter or rendering of cattle and that these prions would be

diluted in the environment and would be highly unlikely to constitute an infective dose

for a human over a lifetime.

24.7 RECOMMENDATIONS

Many zoonotic agents associated with waterborne disease are also associated with

foodborne disease in humans. However, they frequently do not cause overt clinical

disease in domestic animal populations. National and international agencies with

health mandates that address control of waterborne and foodborne diseases should

coordinate their activities and share resources to accomplish specific zoonotic

Control in animal reservoirs 401

pathogen reduction targets. Programme objectives can be accomplished only by

working with agricultural and conservation stakeholder groups and veterinary

authorities that have experience in disease control in animal populations.

Agencies with health mandates that encompass control of waterborne diseases

should also coordinate their activities and share resources to control contamination of

water with animal wastes by working with agricultural and environmental stakeholder

groups and agencies.

Control of waterborne zoonotic pathogens depends on the use of tools such as

HACCP in water safety plans and risk assessments. Cost/benefit analyses must be

performed before strategies are implemented, and the solutions proposed to limit

waterborne disease must be communicated and found to be acceptable by

stakeholders.

The most important component of any water treatment strategy is likely to be

source protection. This can best be accomplished by taking steps to control zoonotic

pathogens in animal populations (as outlined above), proper storage and disposal of

animal wastes, and limiting physical access of animals to source waters.

Efforts should be focused on improving water treatment in rural areas and in small

communities and improving the safety of water used in the irrigation of crops, in

particular raw edible field crops.

Members of communities that are most at risk of waterborne diseases need to be

identified and protected from waterborne disease. Those most at risk include the very

young, the aged, the immunocompromised, individuals who are genetically most

susceptible, and those with increased occupational or recreational exposure to

waterborne pathogens.

24.8 REFERENCES

snip...

http://www.who.int/water_sanitation_health/diseases/zoonosessect7.pdf

National Renderers Association Public Response to USDA-APHIS

ANPR “Risk Reduction Strategies for Potential BSE Pathways Involving Downer Cattle and Dead Sock of Cattle and Other Species”

Docket No. 01-68-1, Federal Register, Vol.68, No.13: 2703 – 2711, 01/21/2003

APPENDICES I - III

APPENDIX I

snip...

In spite of the concerted efforts by all participants in animal production, there are, and always will be, a significant number of on-farm mortalities. While the vast majority of livestock enter the food chain, a small portion die due to various non-infectious (accidents, injuries, etc.) causes and infectious, including major zoonotic, conditions or is condemned at time of slaughter. Add to these the already huge amounts of animal material derived from normal processing. Animals that succumb to either disease or accident prior to slaughter, making them unfit for human consumption, and living animals in a condition that doesn’t meet certain minimum standards are diverted away from the food chain. The data in Tables 3 – 12, gathered by the Sparks Companies (ref.36) on behalf of NRA, are revealing. In the year 2000 for example, the combined

poultry and livestock mortalities in the U.S. amounted to 105,345,700 heads, with a total weight of more than 3.3 billion pounds. There is also a significant volume of animal by-

products coming from various sectors of food processing, retail and catering business, as well as from free-roaming wildlife. The effective and safe utilization of these by-products is important to the overall food animal production, processing and consumption cycle.

snip...

Table 12: Estimated Number of Dead Stock Rendered in the United States in 2000 (Source: ref.36)

------------------------------------------------------------------------------------------------------------

Species Dead Stock (lbs) % of Deaths Meat and Bone Meal (lbs)1

Cattle 869,480,910 45.0 241,715,690

Pre-weaned Hogs 35,261,690 53.1 9,802,750

Weaned Hogs 622,369,300 68.0 173,018,700

Sheep, Lamb & Goats 32,052,800 45.0 8,910,680

------------------------------------------------------------------------------------------------

Total 1,559,164,800 lbs 52.4% 433,447,790 lbs

------------------------------------------------------------------------------------------------------------

1 assumes MBM yield of 27%

http://www.rendermagazine.com/news/USDA-ANPRDownersApendices.doc

ONE OTHER THING i must comment on.


PLUME and TSE

WITH all the open pit pyres and even down to say bones (spinal cord) surgery and grinding and the plume that is caused by that. It would be nice to see more studies there. a new study, a small abstract;

EM 47 The study of a lab-scale contaminant plume

Helen Rees1, Steven Banwart1, Sascha Oswald2, Roger Pickup3 & David Lerner1

1Groundwater Protection & Restoration Group, Dept of Civil & Structural

Engineering, University of Sheffield, Mappin Street, S1 3JD; 2Centre for

Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany;

3Centre for Ecology and Hydrology, Lancaster Environment Centre,

Library Avenue, Bailrigg, Lancaster LA1 4AP

see full text of ;

Microbiology s o c i e t y f o r g e n e r a l

156th Meeting

4–7 April 2005

Heriot-Watt University,

Edinburgh

http://www.socgenmicrobiol.org.uk/meetings/pdfabstracts/hw2005abs.pdf

SEEMS THEY HAVE BEEN WRONG about a lot of things ;

The implications remain however disquieting, since it is clear

that cases of BSE were not detected initially and have entered

the human and animal food chain.

Milk and milk products are considered safe. Tallow and

gelatin are considered safe if prepared by a manufacturing

process which has been shown experimentally to inactivate the

transmissible agent. No infectivity has yet been detected in

skeletal muscle tissue. Reassurance can be provided by removal

of visible nervous and lymphatic tissue from meat.

. Human and veterinary vaccines prepared from bovine

materials may carry the risk of transmission of animal TSE

agents. The pharmaceutical industry should ideally avoid the

use of bovine materials and materials from other animal species

in which TSEs naturally occur. If absolutely necessary, bovine

materials should be obtained from countries which have a

surveillance system for BSE in place and which report either

zero or only sporadic cases of BSE. These precautions apply to

the manufacture of cosmetics as well.

. vCJD has never been known to have developed in a recipient

of vCJD patient’s blood, but studies are limited in scope and

should continue. Blood donation should not be taken from

donors treated with human pituitary gland extracts, donors

with family history of CJD, GSS or FFI, or donors receiving a

human dura mater graft.

http://www.who.dk/document/eehc/eurobulletinmay2001.pdf

THEY would not listen to there own concerns and kept there concerns SECRET from the public...TSS

-------- Original Message -------- Subject: Re: MMR vaccine
Date: Wed, 04 Jun 2003 11:42:31 -0500
From: "Terry S. Singeltary Sr."


8. The Secretary of State has a number of licences. We understand that
the inactivated polio vaccine is no longer being used. There is a stock
of smallpox vaccine. We have not been able to determine the source
material. (Made in sheep very unlikely to contain bovine ingredients).

http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdf

http://www.bseinquiry.gov.uk/report/volume7/chapted2.htm

http://www.bseinquiry.gov.uk/files/yb/1989/02/14011001.pdf

although 176 products do _not_ conform to the CSM/VPC
guidelines.

http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf

5.23 This alerted Sir Donald Acheson to the fact that concerns about the
safety of vaccines had not yet been resolved. He contacted Dr Pickles,
and their conversation led him to ask Dr Harris to look into the matter:
My attention has been drawn to a sentence in Dr Pickles' draft of a
submission to the Secretary of State on this matter. It reads: 'At the
present time we can't give any complete guarantee of safety for human
medicines that use bovine materials in manufacture such as most
vaccines.' Having looked at the report I am not able to find any
statement which supports this statement of concern. I have, however,
therefore spoken to Dr Pickles on the telephone and she reports to me
that for some considerable time she has had serious concern about the
safety of bovine-based vaccines in the light of the fact it has been
discovered that contamination with placental material (which is known to
be heavily infected with the BSE particle) is a distinct possibility in
the preparation of material for human vaccines derived from foetal
serum. This matter as described to me by Dr Pickles gives me sufficient
cause for concern to ask you to look into it urgently together with
Medicines Division. I shall amend the submission to indicate that the
question of the safety of vaccines derived from bovine material is a
matter which has not been dealt with directly by Southwood's group, but
is one in which I am making urgent enquiries. 22

http://www.bseinquiry.gov.uk/report/volume7/chapted2.htm

WHO/CDS/CSR/APH/2000.2

3.5 Animal vaccine-related Transmissible Spongiform Encephalopathy risks:

Scrapie outbreak in Italy

Maurizio Pocchiari:

Historically, Italy has had a low incidence of scrapie; however, in 1997
there was a dramatic increase in the number of reported flocks. This
increase in reports included a relatively high proportion of goat
flocks, generally considered more resistant to natural scrapie than
sheep. Details of the timing of the flock outbreaks, composition of the
flocks and vaccination status were provided. It was noted that
vaccination for Mycoplasma agalactiae was provided to a large proportion
of the flocks developing scrapie, and that this vaccine is made from
sheep brain and mammary gland. Small batches of brain and mammary glands
are mixed, and given subcutaneously to adult and young animals,
providing considerable possible exposure to contaminated material. Some
flocks receiving this vaccine did not develop scrapie, and western blot
and transmission experiments are underway. However, the consultation
agreed that the epidemiologic evidence points toward a vaccine origin
for the scrapie disease seen in some of the flocks.

snip...

7.6 Could vaccines prepared from animal brain tissue pose a risk of
transmission of Transmissible Spongiform Encephalopathies to humans?
François Meslin:

Over 40,000 deaths due to rabies are reported annually worldwide and
each year seven to eight million people receive antirabies vaccine
treatment following dog bites. Dog rabies poses a significant public
health problem in Asia, as 85% of the human deaths due to rabies
reported worldwide and 80% of the vaccine doses applied in
developing countries come from this part of the world.
In many Asian countries such as Bangladesh, India, Nepal and Pakistan,
sheep-brain based Semple vaccine 15 is the only vaccine available free
of cost. It represents 50 to 95% of all vaccine doses used for rabies
post-exposure treatment, depending upon the country. A complete
treatment consists of 10 subcutaneous daily injections
of 2 to 5 ml (depending mainly on patient size and nature of the
exposure) plus booster doses; that is a total of 25 to 50 ml of the 5 %
sheep brain suspension injected over a 10-day period.
According to the literature, the reported rate of neuroparalytic
complications following the use of this vaccine varies from 1:600 to
1:1575 administrations, and 20-25% of these lead to death. The exact
incidence of neuroparalytic complications throughout India or other
countries in the area is not known. However, in the State of
Karnataka, India, 112 cases of neuroparalytic accidents were admitted in
the past 20 years following Semple vaccine administration. In contrast,
the newly developed cell culture or embryonating egg vaccines are
effective and safe, with lower and less severe complication rates.
In many Asian countries, Semple type vaccine has been used for the past
90 years. In India forty million ml of this vaccine are produced in this
country to treat at least 500 000 persons each year. In Pakistan 450 000
and in Bangladesh 60 000 people receive Semple type vaccine after
possible exposure to rabies. There is a theoretical risk of TSE
transmission to humans through parenteral administration of
these products. Although there is to date no evidence of such
occurrences in human medicine, recent events in the TSE field have
demonstrated that an animal TSE agent could affect human beings.
The situation is very similar regarding rabies vaccines for animal use.
For example various Indian veterinary vaccine institutes prepare 100
million ml of Semple vaccine for use in both rabies pre-and
post-exposure prophylaxis in dogs and food production animals each year.
Scrapie could be theoretically transmitted to animal vaccine recipients,
especially ruminants, through sheep-brain based vaccines such as
Semple type vaccine. This could happen because scrapie infectivity, if
present, would not be inactivated by the manufacturing process. In this
connection, a recent 15 Ãx-propiolactone inactivated or phenolized
antirabies vaccine containing 5% suspension of sheep brain infected with
a fixed strain of rabies virus.

WHO/CDS/CSR/APH/2000.2

34 WHO Consultation on Public Health and Animal TSEs
Epidemiology, Risk and Research Requirements

publication strongly suggests that scrapie was transmitted to sheep and
goats through the administration of a veterinary vaccine whose method of
preparation is similar to the Semple type vaccine. In addition, various
Asian countries have begun to use animal tissues as feed supplement for
intensive sheep and dairy cattle production. This introduces an
additional, though still theoretical, possibility that scrapie, or even
BSE, could spread among the sheep population and enter the sheep flocks
that are used as a source of rabies vaccine production for human or
animal use. In areas where the status of animal TSE is not well
documented, this risk cannot be totally ruled out, though it may be
remote, as there is no test available at present to detect
pre-clinical cases of prion disease in sheep.

snip...

Recommendation 25

Human vaccines prepared from whole ruminant brains may carry the risk of
transmission of animal TSE agents, because the inactivation processes
usually applied to these products do not inactivate TSE agents. In
particular, considering the recent emergence of vCJD in humans related
to BSE in cattle, the consultation recommends that the use of these
vaccines should be avoided if suitable alternatives can be made
available. The Consultation strongly supported the recommendation made
by WHO Expert Committee on Rabies, which states:

"The (Expert) Committee reiterated, as stated in its 1983 report, its
support for the trend to limit or abandon completely - where
economically and technically possible - the production of
encephalitogenic brain-tissue vaccines, and strongly advocated the
production and use of inactivated cell-culture rabies vaccines in both
developed and developing countries."

Recommendation 26

The use of veterinary vaccines prepared from whole ruminant brains, for
use in ruminants, should be avoided unless the process ensures TSE
inactivation and/or removal, or the source animals have been
demonstrated to be free of any TSE.

snip...

http://www.who.int/emc-documents/tse/docs/whocdscsraph20002.pdf

http://216.239.37.100/search?q=cache:ha1lZiMaWG4C:www.who.int/emc-documents/tse/docs/whocdscsraph20002.pdf+Acquisition+of+spongiform+encephalopathies+in+India+through+sheep-brain+rabies+vaccination.&hl=en&ie=UTF-8

55
III.3. IATROGENIC TRANSMISSION
Iatrogenic transmission of BSE has not been reported, or even suspected,
in cattle but there are some definite occurrences of scrapie in sheep
that have been reliably attributed to the use of non-commercial vaccines
containing ovine starting materials. For this reason, the issue is
discussed below. Other forms of iatrogenic transmission of TSE have been
restricted to humans and human tissues. For the sake of completeness and
convenience, these subjects are briefly discussed below.

III.3.1 VACCINES
Reference has already been made to the occurrence of at least several
hundred cases of scrapie in British sheep as a direct result of the use
of a vaccine against the tick transmitted, viral disease, louping-ill
(Gordon, Brownlee and Wilson, 1939, Gordon, 1946 and Greig, 1950). This
occurrence resulted from the accidental use of scrapie-infected source
material and processing methods that did not inactivate the scrapie
agent that was unknowingly present. A more recent possible occurrence of
possible iatrogenic scrapie has recently been reported in Etna Silver
crossbred goats in Italy by Cappucchio et al., (1998). The goats were
kept at grass and concentrate rations were not fed, thus eliminating a
source of infection from feed via mammalian proteins. Animals over two
months old were annually vaccinated against contagious agalactia caused
by Mycoplasma agalactiae. The vaccine included central nervous system
from pathogen-free sheep. The mortality rate in the goats reached
28% in 1 herd, 60% in the second and 5.5% in a third herd. About half
the 56 goats were between 2.5 - 3 years old. Only 1.15% of sheep that
were kept with the goats developed scrapie. Scrapie was confirmed by
microscopic examination of the brain and by detection of PrPSc including
by immunocytochemistry. PrPSc was widespread in the brain and beyond
sites of vacuolar change. The high mortality, severe loss of weight and
simultaneous appearance in the three herds were distinctly unusual
features in this outbreak. The source of infection remains uncertain and
unproven but iatrogenic transmission must be considered.
A larger epidemic involving 20 outbreaks of scrapie in sheep and goats,
also in Italy, has been even more recently reported by Agrimi et al.,
(1999). The annual incidence ranged from 1% to 90% with a mean incidence
for goats of 26% and for sheep of 10%. The total number of cases in
sheep and goats together was 1040. The clinical disease was confirmed by
microscopic examination of the brain and PrP immunocytochemistry or
Western blotting. The high incidence in goats, the high
within-flock/herd incidence, the temporal clustering, absence of
commercial concentrate feeding in eight flocks and association with the
use of a sub-cutaneously administered M. agalactiae vaccine, prepared
locally using brain and mammary tissue from clinically healthy sheep,
strongly suggests an iatrogenic origin. Scrapie appeared between 23 and
35 months after the vaccine was administered. A third outbreak in
southern Italy attributed also to the same vaccine has been described by
Caramelli et al, (2001) in a mixed flock of Comisana sheep and half-bred
goats in an upland area of southern Italy. High crude mortality and
scrapie incidence occurred in both species and a large proportion of
aged animals were affected. The neuropathology was similar to that in
other sheep in Italy with iatrogenic disease but different from
conventional natural scrapie. Affected sheep were all of the most
susceptible genotype (Codon 171 QQ). It is stressed that the vaccines
incriminated in the transmission of scrapie in all these incidents are
not commercially produced. They have been prepared and distributed
locally within the country. Dr Subash Arya has repeatedly drawn
attention to the possible risk of transmitting CJD to humans vaccinated
with sheep-brain derived vaccines in India, e.g. Arya, (1994). However,
neither Dr Arya nor any of his colleagues has yet found any such case.
The episodes of scrapie resulting from the use of vaccines prepared from
infected sheep tissues emphasises the need for caution and mandatory
selection of safe sources for starting materials used in the manufacture
of vaccines. Such vaccines could theoretically at least, be used in
cattle thus creating a potential risk, though it is most unlikely that
they would be licensed for this purpose in Europe. Vaccines have not
been incriminated in the transmission of BSE (Wilesmith et al., 1988,
J.W.Wilesmith, personal communication). Furthermore, large numbers of
doses of commercially produced vaccines that have used bovine starting
materials, have been inoculated by parenteral and oral routes into
cattle throughout the world and a substantial proportion have been
produced in Europe, but no incident of BSE has been attributed to their
use. This is important because, since there is no species barrier, any
chink in the armour protecting vaccines from contamination would have
been revealed, but none has.

III.3.2.OTHER MEDICINAL PRODUCTS DERIVED FROM TSE-SUSCEPTIBLE SPECIES
Animal sources of material used in medicinal products vary, but mostly
are derived from cattle. There is thus at least a possibility that
unless strict precautions are taken, disease could be transmitted in
this way. It cannot be ruled out that no case ever arose by this means,
but it is clear that the majority did not, even at the very beginning of
the BSE epidemic before publication of information on BSE, and before
any legislation was in place (Wilesmith et al., 1988). The highest risk
tissue is bovine brain from a clinically affected animal or one in the
immediate pre-clinical phase. Posterior pituitary extract (now prepared
biosynthetically), was available and used in veterinary practice mainly
in adult female cattle at the time of parturition, to assist treatment
of retained placenta or to assist in milk let down. However, no
association was found between its use and the occurrence of BSE
(Wilesmith et al., 1988).

http://europa.eu.int/comm/food/fs/sc/ssc/out236_en.pdf

Indian J Pediatr 1991 Sep-Oct;58(5):563-5

Arya SC.

Centre for Logistical Research and Innovation, Greater Kailash, New Delhi.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1813404&dopt=Abstract

BMJ 1996 Nov 30;313(7069):1405

Comment on:

* BMJ. 1996 Aug 24;313(7055):441.


Blood donated after vaccination with rabies vaccine derived from
sheep brain cells might transmit CJD.

Arya SC.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8956737&dopt=Abstract

BMJ 1996;313:1405 (30 November)
Letters
Blood donated after vaccination with rabies vaccine derived from sheep
brain cells might transmit CJD
EDITOR,--Janet Morgan reports that the National Blood Authority in
Britain has decided to tighten the donor screening programme to exclude
transmission of Creutzfeldt-Jakob disease or its variant through blood
donations.1 Prospective donors will be prevented from donating blood if
they have a history of treatment with human growth hormone or if one of
their siblings, parents, or grandparents developed the disease. I would
point out that similar care should also be taken when immigrants from
Asia and Africa offer to donate blood, in case they received rabies
vaccine derived from culture of sheep brain cells when they were living
in their country of origin.

In many countries in Asia and Africa limited supplies of imported rabies
vaccines derived from culture of human cells have been available. Many
people continue to be offered indigenously produced sheep brain vaccine
after exposure to a rabid animal. Scrapie is known to exist in sheep
around many centres where the vaccine is produced. In the mountain sheep
of the Kumaon foothills in the Himalayas, for example, scrapie was
established more than four decades ago and 1-10% of the flock was
reported to have the disease in 1961.2 In the Himalayan foothills the
Central Research Institute continues to produce four to five million
doses of sheep brain vaccine annually. Transmission of abnormal prion
protein, PrPsc, in sheep brain vaccine might have occurred in some of
the 30 documented cases of Creutzfeldt-Jakob disease in different
regions in India.3 Because Creutzfeldt-Jakob disease has a latency of
about 20 years, many recipients of sheep brain rabies vaccine could
emigrate to Britain before becoming ill.

Before accepting blood donations from immigrants it would be desirable
to ask the potential donors whether they were exposed to a rabid animal
and immunised with sheep brain rabies vaccine in their country of
origin. Furthermore, indirect assessment should be possible through, for
example, assay looking for antibodies specific to rabies.

Clinical microbiologist Centre for Logistical Research and Innovation,
M-122 (of part 2), Greater Kailash-II, New Delhi-110048, India

Subhash C Arya

http://bmj.com/cgi/content/full/313/7069/1405/a

: Neuroepidemiology 1991;10(1):27-32

Creutzfeldt-Jakob disease in India (1971-1990).

Satishchandra P, Shankar SK.

Department of Neurology, National Institute of Mental Health and
Neurosciences (NIMHANS), Bangalore, India.

Thirty cases including 20 definite and 10 probable cases of
Creutzfeldt-Jakob disease (CJD) seen in India between 1971 and 1990 are
reported. Demographic analysis has shown similarities to the previously
published reports from other parts of the world. Though 21 (70%) of
cases were from two centers--Bombay and Bangalore-, suggesting
clustering, this seems to be more apparent than real. One subject worked
in the medical field, where possibility of iatrogenic transmission could
not be ruled out. None of the cases had positive family history of CJD.
There is no epidemiological data of CJD from India so far and hence this
report is one such pilot study.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2062414&dopt=Abstract

i recieved the 1947 report of the Louping-ill vaccine
incident and posted on www here;

Louping-ill vaccine (scrapie transmission by vaccine)

THE VETERINARY RECORD
516 No 47. Vol. 58
November 23rd, 1946

NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND

ANNUAL CONGRESS, 1946

snip...

The enquiry made the position clear. Scrapie was developing in
the sheep vaccinated in 1935 and it was only in a few instances
that the owner was associating the occurrence with louping-ill
vaccination. The disease was affecting all breeds and it was
confined to the animals vaccinated with batch 2. This was clearly
demonstrated on a number of farms on which batch 1 had been
used to inoculate the hoggs in 1935 and batch 2 to inoculate
the ewes. None of the hoggs, which at this time were three-
year-old ewes. At this time it was difficult to forecast whether all
of the 18,000 sheep which had received batch 2 vaccine would
develop scrapie. It was fortunate, however, that the majority of
the sheep vaccinated with batch 2 were ewes and therfore all
that were four years old and upwards at the time of vaccination
had already been disposed of and there only remained the ewes
which had been two to three years old at the time of vaccination,
consequently no accurate assessment of the incidence of scrapie
could be made. On a few farms, however, where vaccination was
confined to hoggs, the incidence ranged from 1 percent, to 35 percent,
with an average of about 5 percent. Since batch 2 vaccine
had been incriminated as a probable source of scrapie infection,
an attempt was made to trace the origin of the 112 sheep whose
tissues had been included in the vaccine. It was found that they
had been supplied by three owners and that all were of the
Blackface or Greyface breed with the exception of eight which
were Cheviot lambs born in 1935 from ewes which had been in
contact with scrapie infection. Some of these contact ewes
developed scrapie in 1936-37 and three surviving fellow lambs to
the eight included in the batch 2 vaccine of 1935 developed
scrapie, one in September, 1936, one in February, 1937, and one
in November, 1937. There was, therefore, strong presumptive
evidence that the eight Cheviot lambs included in the vaccine
althought apparently healthy were, in fact, in the incubative stage
of a scrapie infection and that in their tissues there was an
infective agent which had contaminated the batch 2 vaccine,
rendering it liable to set up scrapie. If that assumption was
correct then the evidence indicated that:-

(1) the infective agent of scrapie was present in the brain, spinal
cord and or spleen of infected sheep:
(2) it could withstand a concentration of formalin of 0-35 percent,
which inactivated the virus of louping-ill:
(3) it could be transmitted by subcutaneous inoculation;
(4) it had an incubative period of two years and longer.

Two Frenchmen, Cuille & Chelle (1939) as the result of experiments
commenced in 1932, reported the successful infection of
sheep by inoculation of emulsions of spinal cord or brain material
by the intracerebral, epidural, intraocular and subcutaneous routes
The incubation period varied according to the route employed,
being one year intracerebrally, 15 months intraocularly and 20
months subcutaneously. They failed to infect rabbits but succeeded
in infecting goats. Another important part of their work
showed that the infective agent could pass throught a chamberland
1.3 filter, thus demonstrating that the infective agent was a
filtrable virus. It was a curious coincidence that while they
were doing their transmission experiments their work was being
confirmed by the unforeseeable infectivity of a formalinized tissue
vaccine.

As a result of this experience a large-scale transmision experiment
involving the ue of 788 sheep was commenced in 1938 on a
farm specially taken for the purpose by the Animal Diseases
Research Association with funds provided by the Agricultural
Research Council. The experiment was designed to determine the
nature of the infective agent and the pathogenesis of the disease.
It is only possible here to give a summary of the result which
showed that (1) saline suspensions of brain and spinal cord tissue
of sheep affected with scrapie were infective to normal sheep
when inoculatted intracerebrally or subcutaneously; (2) the incubation
period after intracerebral inoculation was seven months and
upwards and only 60 percent of the inoculated sheep developed
scrapie during a period of four and a half years; (3) the incubation
period after subcutaneous inoculation was 15 months and upwards
and only about 30 percent of the inoculated sheep developed
the disease during the four and a half years: (4) the infective
agent was of small size and probably a filtrable virus.

The prolonged incubative period of the disease and the remarkable
resistance of the causal agent to formalin are features of
distinct interest. It still remains to determine if a biological test
can be devised to detect infected animals so that they can be
killed for food before they develop clinical symptoms and to
explore the possibilities of producing an immunity to the disease...

http://www.vegsource.com/talk/lyman/messages/7634.html

USA IMPORTS VACCINE PRODUCTS FROM BSE COUNTRIES

http://www.mad-cow.org/00/may00_news.html

Furthermore, we showed that
the strain responsible for iCJD is closely related to that of one
patient with sCJD, and, more unexpectedly, that these agents were
similar to the French scrapie strain studied (but different from the
U.S. scrapie strain).

http://www.pnas.org/cgi/content/full/041490898v1

Human vaccine prepared in animal brains

http://www.mad-cow.org/00/nov00_late_news.html#fff

http://www.whale.to/v/singeltary7.html

http://www.mad-cow.org/00/may00_news.html

http://www.mad-cow.org/00/jul00_dont_eat_sheep.html#hhh

STUDY DESIGN AND METHODS: BSE was passaged through macaque monkeys and
then adapted to the prosimian microcebe (Microcebus murinus ). Brain
homogenate and buffy coat from an affected microcebe were separately
inoculated intracerebrally into three healthy microcebes (two animals
received brain and one received buffy coat).

RESULTS: All three inoculated microcebes became ill after incubation
periods of 16 to 18 months. Clinical, histopathologic, and
immunocytologic features were similar in each of the recipients.

CONCLUSION: Buffy coat from a symptomatic microcebe infected 17 months
earlier with BSE contained the infectious agent. This observation
represents the first documented transmission of BSE from the blood of an
experimentally infected primate, which in view of rodent buffy coat
infectivity precedents and the known host range of BSE is neither
unexpected nor cause for alarm.

http://www.blackwell-synergy.com/servlet/useragent?func=synergy&synergyAction=showAbstract&doi=10.1046/j.1537-2995.2002.00098.x

Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy BSE-L
To: BSE-L

snip...

[host Richard Barns]
and now a question from Terry S. Singeltary of
CJD Watch.

[TSS]
yes, thank you,
U.S. cattle, what kind of guarantee can you
give for serum or tissue donor herds?

[no answer, you could hear in the back ground,
mumbling and 'we can't. have him ask the question
again.]

[host Richard]
could you repeat the question?

[TSS]
U.S. cattle, what kind of guarantee can you
give for serum or tissue donor herds?

[not sure whom ask this]
what group are you with?

[TSS]
CJD Watch, my Mom died from hvCJD and we are
tracking CJD world-wide.

[not sure who is speaking]
could you please disconnect Mr. Singeltary

[TSS]
you are not going to answer my question?

[not sure whom speaking]
NO

snip...

http://vegancowboy.org/TSS-part1of8.htm

Meanwhile, health officials with the Food and Drug Administration say
the method of manufacturing the old vaccine, called Dryvax, which was
made by Wyeth using calf skin, is "no longer considered optimal."
Instead, the agency says the new smallpox vaccine "will be prepared in
MRC-5 cells"  a line of aborted fetal cells dating back to 1966 
because that method is more efficient.

"The MRC-5 line was developed & from lung tissue taken from a 14-week
fetus aborted for psychiatric reasons from a 27-year-old physically
healthy woman," said a description of the cell tissue by the Coriell
Institute for Medical Research at the University of Medicine and
Dentistry of New Jersey, where the line is maintained. The institute
further describes it as "normal human fetal lung fibroblast."

http://www.worldnetdaily.com/news/article.asp?ARTICLE_ID=25362

SMALLPOX VACCINE, Dried, Calf Lymph Type
Summary of Package Insert

Dryvax, Wyeth Laboratories, Marietta, PA (1960)

Ingredients
brilliant green:

calf lymph

chloriatracycline hydrochloride;
dihydrostreptomycin sulfate;
glycerin;
neomycin sulfate;
phenol;
polymixin B sulfate.

http://www.vaccineawareness.org/IllinoisIssues/SmallpoxInsert.htm

TSS

########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

-------- Original Message --------

Subject: CJD AND BLOOD PRODUCTS DATA
Date: Fri, 10 Sep 2004 14:44:27 -0500
From: "Terry S. Singeltary Sr."


The World Market for Human Blood, Prepared Animal Blood, Toxins, Cultures of Micro-Organisms, and Similar Products Excluding Yeasts: A 2004 Global Trade Perspective

In what follows, Chapter 2 begins by summarizing the regional markets for imported and exported human blood, prepared animal blood, toxins, cultures of micro-organisms, and similar products excluding yeasts. The total level of imports and exports on a worldwide basis, and those for each region, is based on a model which aggregates across country markets and projects these to the current year. From there, each country represents a percent of the world market. This market is served from a number of competitive countries of origin. Based on both demand- and supply-side dynamics, market shares by country of origin are then calculated across each country market destination. These shares lead to a volume of import and export values for each country and are aggregated to regional and world totals. In doing so, we are able to obtain maximum likelihood estimates of both the value of each market and the shares that countries are likely to receive this year. From these figures, rankings are calculated to allow managers to prioritize markets. In this way, all the figures provided in this report are forecasts that can be combined with internal information for strategic planning purposes.

U.S. $795.00 [sorry, can't help you there...TSS)

http://www.marketresearch.com/researchindex/918108.html

BLOOD PRODUCTS ADVISORY COMMITTEE SIXTYSIXTH
MEETING
VOLUME I

Thursday, June 15, 2000
8:00 a.m.

snip...

They looked at estimates of possible human
7 exposure to the agent elsewhere in the European Union and
8 heard results of a very interesting assessment by Canadian
9 authorities of the risk of new variant CJD in Canadians who
10 had traveled to the United Kingdom and to France, and
11 finally reviewed the effects of recent policies on the
12 supply of blood and blood products in the United States.
13 [Slide]
14 When asked if the committee thought that the
15 available scientific data on the risk of transmitting CJD
16 and new variant CJD warranted a change in the current FDA
17 policy regarding deferrals of blood and plasma donors and
18 product retrievals based on their travel or residence in the
19 United Kingdom, the committee members voted three in favor
20 and 15 opposed. The members felt that insufficient time had
21 passed since the implementation of the new policy to assess
22 its effects on supply and they were, therefore, reluctant to
23 advise any further changes at the moment. There were a
24 couple of contingent questions concerning it. They felt
25 comfortable staying with the current policy concerning
43
1 deferral of donors resident in the U.K.
2 [Slide]
3 When asked if FDA should recommend deferral from
4 blood or plasma donations for persons with a history of
5 travel or residence in France, the vote was 17 against such
6 deferral and only one in favor. The committee seemed
7 impressed that both the assessments of exposure to U.K. beef
8 and beef products in France and the rates of new variant CJD
9 both suggested that the risk to residents of France was only
10 about 5 percent of that in the U.K. The apparently
11 concluded that such a risk was not sufficiently significant
12 to recommend any deferral even for much longer periods of
13 residence in France.
14 [Slide]
15 Essentially the same advice was offered for donors
16 resident in other BSE countries, although there was concern
17 about the lack of information concerning potential exposures
18 to BSE in some of those countries.
19 [Slide]
20 The secondary issue of possible effects of
21 leukoreduction on CJD risk was addressed. Since a large
22 part of the infectivity in blood of rodents experimentally
23 infected with TSE's is in the buffy coat, it has been
24 proposed that leukofiltration might reduce the risk of
25 blood-borne transmission of CJD, and several European
44
1 countries have decided to do that as a precautionary measure
2 to reduce the risk of transmitting CJD. So, the committee
3 was asked to consider evidence that leukoreduction might be
4 expected to reduce the theoretical risk of transmitting CJD
5 and new variant CJD by human blood, blood components and
6 plasma derivatives and whether the reduction in risk is
7 likely to be substantial enough to have practical value and,
8 consequently, whether universal leukoreduction of blood and
9 blood components should be recommended by the FDA for that
10 purpose.
11 [Slide]
12 The committee reviewed information on the work of
13 this committee, that is, recent recommendations and
14 prospects for the implementation of universal leukoreduction
15 techniques and theoretical applications of leukoreduction to
16 remove TSE agents from blood, and the possible role of
17 leukocytes in experimental pathogenesis of TSEs in rodents
18 and the implications for human blood, the main one being
19 that since circulating cells of lymphoid origin seemed to be
20 obligatory for pathogenesis of TSEs in rodents, it was to be
21 expected that there would be infected cells in the blood of
22 humans as well, although that has never been convincingly
23 demonstrated. They also looked at TSE infectivity in the
24 blood of experimentally infected rodents and that
25 implementation for human disease as a model. The available
45
1 information was very limited and one small but troubling
2 study even suggested that animals infected by the
3 intravenous route cleared infected cells better than they
4 did the same amount of infectivity presented in a cell free
5 form.
6 [Slide]
7 So, when asked if leukoreduction can be expected
8 to reduce significantly the infectivity theoretically
9 present in blood of persons during the course of CJD and new
10 variant CJD, the committee concluded that available data
11 were simply insufficient to decide and, with two dissenting
12 votes, they advised that leukoreduction not be recommended
13 as a precaution to reduce the risk of transmitting CJD until
14 its potential effects are better understood. Thank you very
15 much.

http://www.fda.gov/ohrms/dockets/ac/00/transcripts/3620t1.pdf

Variant Creutzfeldt-Jakob Disease and Haemophilia
A Risk Assessment of Plasma-derived Products
Prepared by Albert Farrugia, BSc, PhD, on behalf of the
WFH Task Force on TSEs
Revised November 15, 2001

snip...

The following table includes European countries that contribute plasma to products available
for the treatment of haemophilia A and von Willebrand disease on the export market (6).
Products manufactured by national fractionators solely for domestic use are not considered at
this stage. It is felt that any donor deferral measures emanating from the U.S. Food and Drug
Administration (FDA) are more likely to impact on the supply export-directed products in the
first instance, given the worldwide influence of the FDA. In January, an Advisory Committee
of the FDA met to discuss whether the FDA should reconsider its policies on the suitability of
blood donors who lived or travelled in countries where BSE has been identified, and the risks
of CJD and vCJD transmission by human cells, tissues, and cellular and tissue-based
products. The Advisory Committee recommended tightening restrictions on blood donors and
donations from France, Portugal, and Ireland. The Committee decided that the number of
BSE cases elsewhere in Europe was too small to justify adding other countries to the blood
donation ban.

full text;

http://www.wfh.org/Content_Documents/Blood_Safety/vCJD_Bulletin2_revised.pdf

ACTION TAKEN BY THE UK MEDICINES CONTROL
AGENCY ON BOVINE INGREDIENTS IN MEDICINAL
PRODUCTS

6.1 Information is held on a especial data base from the initial BSE
survey in 1989. More current products, which were vetted during
their initial licensing assessment, after the UK BSE quideline was
published, may not appear in the listing, since BSE was considering
in their initial licensing assessment.

http://www.bseinquiry.gov.uk/files/yb/1994/09/01003001.pdf

RESTRICTED-COMMERCIAL..............CSM/BIOLS/94/6th Meeting

NOT FOR PUBLICATION

COMMITTEE ON SAFETY OF MEDICINES

SUB-COMMITTEE ON BIOLOGICALS

snip...

1.1 The chairman reminded the Sub-Committee that the papers and
proceedings were confidential and should not be disclosed...

snip...

4.6 BOVINE SERA

4.6.1 There was a discussion of the problem of the paper trail audit,
and countries of sourcing for bovine sera. Concern was expressed about
the fact that bogus certificates of origin had been produced and circulated.
It was noted that in the USA bovine protein was still being fed to cattle.
Sera from the USA could be used in the initial production and subsequent
large scale manufacture of hybridomas, rDNA products and vaccines
(some of which may be used in healthy children)...

http://www.bseinquiry.gov.uk/files/yb/1994/09/14003001.pdf

RESTRICTED-COMMERCIAL CSM/94/8th Meeting

NOT FOR PUBLICATION

COMMITTEE ON SAFETY OF MEDICINES

(7 blank pages to follow...TSS)

http://www.bseinquiry.gov.uk/files/yb/1994/09/22006001.pdf

http://www.bseinquiry.gov.uk/files/yb/1994/09/22007001.pdf

Variant CJD and BPL Plasma Products





February 1, 2001

Dr. P.L.F. Giangrande
Vice President Medical
World Federation of Hemophilia

The World Federation of Hemophilia has received several enquiries about a recent problem which has arisen in the United Kingdom. As a physician working in the UK, I have been very closely involved in this matter and am writing this to set out the facts.

A volunteer donor in the UK who gave blood in 1996 and 1997 has recently died of variant CJD (vCJD). The plasma from this donor was used by Bio-Products Laboratory (BPL) in the manufacture of several batches of various factor VIII and IX concentrates, including 8Y, Replenate and Replenine. These products were used in the UK in 1997 and 1998. All patients who were treated with the implicated batches have already been traced, and will be notified of this problem which has arisen. The Haemophilia Society in the UK has also issued a statement, which has been circulated to members.

Of course, I recognise that this news may generate some anxiety amongst the haemophilia community, particularly in the UK. However, it must be emphasised that there is no evidence that vCJD is transmitted by blood products and no person with haemophilia in the world has ever been reported to have developed either the classical or variant form of CJD.

Furthermore, BPL has assured me that none of the implicated batches have been exported from the UK for use abroad. Although BPL continues to export a number of blood products (including coagulation factor concentrates), it must be appreciated that these are now manufactured with plasma imported from North America.

--------------------------------------------------------------------------------

http://www.wfh.org/ShowDoc.asp?Rubrique=30&Document=110

7.4 The Committee was informed that, since the publication of Hunter et al.
(2002), two further sheep had succumbed to BSE; one of these sheep had
been transfused with buffy coat, while the other had been transfused with
whole blood. Of the remaining 20 sheep that received transfusions, one died
of unrelated causes and 19 animals remain apparently healthy. The healthy
animals are at varying times post-transfusion – ranging from less than 100 to
over 1000 days.
7.5 Members were informed that among the 21 sheep transfused with blood from
scrapie infected animals (761 to 1080 days of age), 4 had developed scrapie
between 614 and 737 days post-transfusion. One animal received the buffy
coat preparation from the blood of an animal with clinical disease. The
remaining 3 animals received whole blood from donors not yet showing clinical
signs. Of the remaining 17 transfused sheep, one died of unrelated causes
and two further sheep were showing clinical signs of scrapie; one of these had
received buffy coat, while the other had received whole blood.
7.6 The Committee noted that it would not be possible to confirm that the negative
controls are free of TSEs until the end of the study, when they would be culled
and analysed post mortem for signs of subclinical infection. Of the 10 positive
controls that received BSE-infected cattle brain homogenate intravenously, 5
have developed disease or appear to be in the early stages of the disease.
3 Hunter, N., Foster, J., Chong, A., McCutcheon, S., Parnham, D., Eaton, S., MacKenzie, C. and Houston, F.
(2002). Transmission of prion disease by blood transfusion. Journal of General Virology 83.
www.socgenmicrobiol.org.uk/JGVDirect/18580/18580ft.pdf

CJD: Transmission

Lord Lucas asked Her Majesty's Government:


Further to the Written Answer by Lord Hunt of Kings Heath on 27 March (WA 59), what is the "strong epidemiological evidence to suggest that classic CJD is not transmitted through blood"; which of the many variants of "classic CJD" this evidence applies to; and whether they will place copies of the relevant papers in the Library of the House.[HL1864]

The Parliamentary Under-Secretary of State, Department of Health (Lord Hunt of Kings Heath): The following, peer reviewed articles, relate to this subject and will be placed in the Library:

T F G Esmonde et al, 1993, Creutzfeldt-Jakob disease and blood transfusion, Lancet 341; 205-207;


P Brown, 1995, Can Creutzfeldt-Jakob disease be transmitted by transfusion?, Current Opinion in Haematology, vol 2, pp 472-477;


C M van Duijn et al, 1998, Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95, Lancet 351: 1081-1085;

11 Apr 2000 : Column WA32

Ricketts MN et al: Is Creutzfeldt-Jakob Disease transmitted in blood?, Energ Infect Dids 1997:3, 155-166; and


Heye N et al: Creutzfeldt-Jakob Disease and blood transfusion, Lancet 1994; 343; 298-299.

These studies cover all types of CJD. Sporadic (classic) CJD, however, accounts for some 85 per cent of non-variant cases.

The European Committee for Proprietory Medicinal Products (CPMP) reviewed the evidence in December 1995 and advised that there was no experimental or epidemiological evidence that classical CJD is transmitted by blood transfusions or plasma-derived products. A recall policy was not considered justified for plasma derived products from plasma pools incorporating a donation implicated for classical CJD. It reaffirmed that advice in March 1997. CPMP concluded on the basis of currently available information from epidemiological and experimental studies that there is no scientific justification for changing from the current CPMP position on classical CJD. CPMP further stated there to be no evidence that classical CJD is transmitted via blood or plasma derived products. This issue was also subsequently considered by the US Food and Drugs Administration, which came to the same conclusion.

New-variant CJD

Lord Lucas asked Her Majesty's Government:


Further to the Written Answer by Lord Hunt of Kings Heath on 27 March (WA 55-6), whether they will provide data on those who have died from, or been diagnosed with, new-variant CJD in the United Kingdom as to:


(a) the status of nucleotide-21 preceding the prion ATG start codon;

(b) the status of codons 26, 56 and 174 of doppel;

(c) the dates of onset and confirmation for those patients diagnosed with new-variant CJD but still living;

(d) the definition of "onset"; and

(e) the age of the patients at onset to the nearest month.[HL1807]


Lord Hunt of Kings Heath: The genetic information requested is not available. However, extensive studies of polymorphisms in and around the prion protein and doppel genes have been under way for some time at the St Mary's Prion Unit, London. The results of these investigations will be published in the scientific literature, subject to peer review, in due course.

Confirmation of a diagnosis of vCJD is currently obtained by postmortem neuropathology. There are therefore no "confirmed" patients still living. The dates of onset for patients still living and defined as "probable" to the nearest month are as follows:


http://www.publications.parliament.uk/pa/ld199900/ldhansrd/vo000411/text/00411w02.htm


25 Apr 2002 : Column WA58

Bovine Embryos and Live Cattle: Imports from North America

The Earl of Caithness asked her Majesty's Government:


When the ban on the importation of embryos and live cattle from North America will be lifted; and [HL3912]
What is the scientific evidence for the imposition of a ban on the importation of embryos and live cattle from North America. [HL3913]


Lord Whitty: Her Majesty's Government have not imposed a ban on imports of bovine embryos and live cattle from North America.

The European Parliament and European Council introduced legislation in May last year laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies (TSEs). The legislation was introduced in response to the recommendations of the Office International des Epizooties (OIE—the international animal health organisation) and advice from the Commission's scientific comittees. The legislation (and the transitional measures which came into effect in October last year) includes requirement that imports into the EU of bovine embryos and live cattle must be accompanied by certification confirming that the feeding of ruminants with protein derived from mammals has been banned and that the ban has been effectively enforced. Some exporting countries, such as Canada and the USA, are currently unable to meet these new requirements.

http://www.publications.parliament.uk/pa/ld199900/ldhansrd/pdvn/lds02/text/20425w04.htm

BSE: US Export of Specified Risk Material

Lord Kennet asked Her Majesty's Government:


Whether the United States contends that under the provisions enforceable by the World Trade Organisation the European Union may not ban the import into Europe from the United States of "specified risk material" (that is, material at possible risk of BSE infection).

Lord Donoughue: Yes. But their position on the Specified Risk Material legislation is based on the assumption that the United States can safely be regarded as a "BSE free" country. Their case for such treatment has not been accepted by the EU Commission's Scientific Veterinary Committee.

http://www.publications.parliament.uk/pa/ld199798/ldhansrd/vo971215/text/71215w02.htm

Baroness Masham of Ilton: My Lords, as blood products which infected haemophiliacs with HIV came from the USA, is the Minister confident that something else nasty may not come again from imported blood from the USA? Is he aware that there are ways of cleaning blood to make it safer? I know that that is done in Vienna, in Austria. Will the Minister look into that? Following the question asked by the noble Lord, Lord Clement-Jones, about people using their own blood, I am sure that, when this Statement goes out into the wider community, people will want to know that information.

http://www.publications.parliament.uk/pa/ld199900/ldhansrd/pdvn/lds03/text/31217-09.htm

However, the Bio Products Laboratory who produce plasma products did export surplus products, under the Income Generation Regulations for the NHS, and used the income for the benefit of the health service.[21]

http://www.publications.parliament.uk/pa/cm200001/cmselect/cmpubacc/207/20703.htm#n21

43. Do you sell any of it abroad at all?
(Mr Gorham) No. The only circumstances in which we would export blood would be if there was an approach to the British Government and the British Government felt that it was appropriate to support an international emergency or something like that. We do supply the British Forces. We occasionally help out our colleagues in Wales and Scotland and they would reciprocate with us if that was appropriate. At the moment it is more or less totally contained within the United Kingdom.

http://www.publications.parliament.uk/pa/cm200001/cmselect/cmpubacc/207/1012904.htm

Blood and Blood Products

Mr. Hinchliffe: To ask the Secretary of State for Health what estimate he has made of the number of persons who have been inoculated with blood or blood products over the past three years in the United Kingdom. [61681]

Ms Jowell [holding answer 2 December 1998]: It is estimated that about one million people in the United Kingdom receive blood and blood products every year.

http://www.parliament.the-stationery-office.co.uk/pa/cm199899/cmhansrd/vo990210/text/90210w02.htm


CJD blood products given to 3,000 patients
December 16 1997 BY AUDREY MAGEE AND IAN MURRAY
UP TO 3,000 people treated in 100 British hospitals may have been injected with blood products taken from a donor who died six weeks ago from new variant Creutzfeldt-Jakob disease, the human form of BSE. None of them is to be told because the Health Department believes the risk of them developing the disease is so slight that there is no reason to cause alarm.

Although hospitals have been advised to return the product, used in X-ray screenings to detect lung disease, so far only 15 per cent has been recovered. There is no order obliging hospitals to return it and some clinicians may go on using up stocks on the basis that patients are far more likely to die from infections or cancer that can be diagnosed with the product than from CJD.

Another 268 patients in Ireland are known to have been given injections from the same batch of the product. The Irish Health Ministry has decided to notify all the patients concerned.

Even though the identity of all those who have been given an injection of the product is known, it was decided not to tell them because there is no evidence that the illness can be transmitted through the blood or the serum derived from it to make the product and the risk of developing CJD is regarded as negligible.

"You are putting an enormous burden on people by telling them they have a remote risk of contracting the disease," the department said last night. "The ethics committee which advises us on these matters decided it was just not appropriate to tell them."
The blood from the donor was sent 18 months ago to the National Blood Authority laboratory, where it was split into a number of different products. The donor's plasma was mixed with some taken from 49,000 other donors to make 8,174 bottles of albumin, the water-soluble protein found in blood.

Many were exported but 210 of the 50ml bottles remained in Britain and were sent to eight different hospitals and companies. Some of the bottles were used intravenously to rehydrate burn victims.

One bottle was sent to Nycomed Amersham which used it to produce 14,000 vials of Amerscan Pulmonate II, an agent which is injected into the lungs so that infections and cancer show up under X-ray. The company sent almost 3,700 vials to 100 British hospitals.

At the end of October the European Committee on Proprietary Medicinal Products called for the withdrawal of blood products derived from donors who were confirmed CJD cases. On November 1 the Blood Transfusion Service was notified that one of its donors had died from the disease so the Amersham company was told.

In turn the company got in touch with the Medicines Control Agency which informed the Health Department and it recommended withdrawal of the product on November 17.

Despite regular alarms, there has never been any convincing evidence that blood or blood products can transmit CJD (Nigel Hawkes writes). Unless new variant CJD, the human form of "mad cow" disease, is more easily transmitted than classic CJD via blood or blood products, there does not appear to be any cause for concern. [This is no medical basis for this statement -- webmaster]

For classic CJD the risk seems negligible. About 50 people a year die of the disease, so it is certain that every year some of them give blood after they have the infection but before its symptoms appear. Studies show that classic CJD can be passed on in human tissue, but not - so far as we know - in blood. [This is not an accurate summary of current scientific knowledge -- webmaster]


http://www.mad-cow.org/~tom/dec15_news.html


South Africa has been exporting plasma for many years. From 1983-86, human plasma was falsely labelled "animal plasma" and illegally exported to Europe. This illegal practice resulted in a court case and one conviction in Belgium. In 1996, Austrian police seized 4000 L of infected blood from a Linz-based company, Albovina.

The Sunday Times report said that Austrian officials have investigated two British companies, based in Guernsey and Berkshire. Police are still trying to find out where the companies' plasma products were used. Johann Kurz, head of unit for biologicals with the federal Ministry of Social Security & Generation in Vienna, Austria, told The Lancet, "We suspect that in 1996 and earlier, some products coming from South Africa were transferred to India, China, and Hong Kong, among other countries". The products were albumin and intravenous immunoglobulins.

Nevertheless, Luc Noel, Coordinator of Blood Safety with the WHO in Geneva, Switzerland, emphasised that: "There should not be any confusion of the transfusion services in South Africa--which are now world class--with these criminal activities". While it is important that this trafficking is exposed, the public can be confident in their blood services, Noel added.

Sanjay Kumar

Kirsten Myhr, MScPharm, MPH Bygdøy alle 58B 0265 Oslo, Norway Tel.: +47 22 56 05 85, fax: +47 22 24 90 17 myhr@online.no

http://www.freerepublic.com/focus/f-news/889385/posts


Greetings,

WITH the amount of diseased dead stock downer livestock that is being disposed in the USA and other countries in various ways, the potential amplification and transmission to humans and animals of this agent via a multitude of routes and sources is enormous. to flounder and continue to insist on finding reasons why we should NOT impliment this or that rule for human/animal safety due to economic consequenses, with an agent that is so unusual and deadly as the TSE agent, and with an agent with an incubation period as long as the TSE agent, would be the most inhumane and immoral thing any governing body could do for there human and animal population, especially with the science documented to date. sadly, it will be politics as usual. the agent will continue to spread, while we find ourselves with a new cause for all of these TSE agents now, the cause, spontaneous TSE. it's nobody's fault, there is no route and source for any of this, ignore all transmission studies, just happens. right$ i have yet to hear from any of these spontaneous folks, a figure of what they call spontaneous VS a figure of the other multitude of proven routes and sources? like, how much of the 85%+ of all CJD 'sporadic', is this so called spontaneous TSE? 1%, 2%, or 80%? another odd thing that most are refusing to see, the 'spontaneous' TSE to date that stan proved to be infectious, looked like no other TSE he had seen in human or animal documented to date. SO could someone please show me this data that shows that any natural TSE has ever been proven spontaneous? show me the data...

TSS

Terry S. Singeltary Sr.




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