What is Bovine Spongiform Encephalopathy
(BSE)?
BSE (bovine spongiform encephalopathy) is a
progressive neurological disorder of cattle, and has
been called “mad cow disease.” Its symptoms are similar to “scrapie,” a brain disease that occurs in
sheep.
Cattle affected by BSE experience progressive
degeneration of the nervous system. Affected cattle die.
There is
neither any treatment nor a vaccine to prevent the disease.
The incubation period (the time from when an
animal becomes infected until it first shows disease
signs) is from 2 to 8 years. Following the onset of
clinical signs, the animal’s condition deteriorates
until it either dies or is destroyed. This process
usually takes from 2 weeks to 6 months. Most cases
in Great Britain have occurred in dairy cows
between 3 and 6 years of age.
Learn more about Bovine Spongiform Encephalopahty.
Does BSE or a similar disease occur in
humans?
Yes. The human diseases are very rare and occur
sporadically worldwide at a rate of about one case
per one million people.
BSE belongs to a group of progressive degenerative neurological disease
known as transmissible spongiform
encephalopathies (TSEs). TSE diseases are always
fatal.
The TSE diseases include:
- Scrapie, which affects
sheep and goats
- Transmissible mink
encephalopathy
- Feline (cat) spongiform
encephalopathy
- Chronic wasting disease of deer
and elk
There are six TSE diseased that affect people:
What is Creutzfeldt-Jakob disease (CJD)?
CJD belongs to a group of neurological diseases
known as transmissible spongiform
encephalopathies (TSEs). TSE disease in humans is
very rare but fatal.
CJD is a slow degenerative
human disease of the central nervous system. It is
classified as a transmissible spongiform
encephalopathy because of the characteristic spongy
degeneration of the brain that occurs as the disease
progresses.
CJD occurs sporadically worldwide at a
rate of 1 case per 1 million people per year.
Learn more about Creutzfeldt-Jakob disease.
What is variant Creutzfeldt-Jakob disease
(vCJD)?
Variant Creutzfeldt- Jakob disease (vCJD) is another
rare and fatal human neurological disease that falls
into the category of transmissible spongiform encephalopathies (TSEs).
Like Creutzfeldt- Jakob
disease (CJD), vCJD causes a spongy degeneration of
the brain. vCJD is a new disease which was first
described in March 1996.
What is the association between BSE in cattle
and vCJD in humans?
Some cases of variant Creutzfeldt- Jakob disease
have been attributed to, among other possibilities,
eating beef products from cattle infected with the agent of BSE.
However, no evidence exist that cases
of vCJD are related to the use of vaccines, and no
cases of vCJD have ever been reported in United States.
Why are animal products used in the
manufacture of vaccines?
Vaccines contain either killed or weakened forms of
disease-causing bacteria or viruses, or components of
these that stimulate a response by the body’s immune system, which then protects against the
development of disease.
Although synthetic media
have been developed for growth of many medically important microorganisms, some still require
additional nutrients which are provided by animal-derived
products such as serum and blood. No
bovine material has ever been used as an active
ingredient of any vaccine.
In the late 19th century, microbiologist began to
grow bacteria in the laboratory. The early
bacteriologist tried to mimic as closely as possible
the infected person’s tissues by using sugars, salts,
and various meat extracts to make “growth media.”
These kinds of conditions were quite successful in
growing bacteria and then viruses in the lab, because
these media supplied the many necessary nutrients.
Which bovine derived materials are used in
vaccine manufacture?
Animal-derived products used in vaccine
manufacture can include:
- Amino acids
- Glycerol
- Detergents
- Gelatin
- Enzymes
- Blood
- Cow milk is
a source of amino acids, and sugars such as
galactose.
- Cow tallow derivatives used in vaccine
manufacture include glycerol.
- Gelatin and some
amino acids come from cow bones.
- Cow skeletal
muscle is used to prepare certain complex media.
- Many difficult to grow microorganisms required the
addition of serum from blood to the growth media.
Does all bovine material have the same risk of
transmitting the BSE agent?
Scientists have found that different bovine tissues
contain different amounts of the BSE agent. It is
generally believed that the highest amounts of infectivity are found in the brain and spinal cords
from animals in the final stages of clinical disease.
Some tissues such as skeletal muscle and milk have
never been shown to have any infectivity. However,
the slaughtering and butchering methods used to
obtain tissues and prepare materials can affect the
amount of infectivity that may be present.
Also the
production processes used to prepare bovine-derived
materials (such as heat sterilization and chemical
treatment) may reduce or remove infectivity.
Which countries are on the U. S. Department
of Agriculture list of countries where BSE is
known to exist or where a substantial risk for
BSE exists?
Initially, the USDA list included only countries and
other regions in which BSE was known to exist, such
as the United Kingdom, France, Switzerland, and the
Republic of Ireland.
In 1998, the USDA expanded the
list to include countries and other regions in which
BSE had not been documented but in which import
requirements were less restrictive than requirements
that would be acceptable for import into the United
States or in which there was inadequate BSE
surveillance.
Thus, all European countries, even
those that have had no reported cases of BSE, are
currently on the USDA list, which is published in the
Code of Federal Regulations, title 9, part 94 (9C.F.R.,
part 94).
What is the chance/risk that a vaccine on the
market in the US contains the BSE agent?
Both the FDA and its joint advisory committee
concluded that the risk for vCJD posed by vaccines
is theoretical and remote. Studies of the BSE agent have shown that infectivity depends on nature of
material used, how much is used and the route of
administration.
Other factors, such as the country of origin of the cattle used to supply the manufacturing
material, also have to be factored into any risk
estimate.
Both the European Community and the US Pharmaceutical industry have presented risk
assessment calculations which attempt to account for
all these factors.
In 1999, the Council on Scientific Affairs (CSA) of American Medical Association
considered the risk of BSE to public health and
determined that the current risk of transmission of
BSE in the US is minimal, concluding that adequate
guidelines exist to prevent high risk bovine materials
from contaminating products intended for human
use.
The report from the CSA did not address the
possibility that regulated industry might not follow
all of the recommendations made by the FDA. However, both FDA and the joint advisory
committee meeting have considered the risks posed
by bovine material in vaccines and concluded that any risk is remote and theoretical.
What is the risk of getting vCJD if a vaccine
contained the BSE agent?
There is no evidence to date that vaccines have
contributed to the cases of vCJD seen in Europe. Nor
is there evidence that any vaccines harbor the BSE
agent.
Vaccines are given a very limited number of
times via the intramuscular, subcutaneous or oral
route. Even in experimental studies, these routes of
administration are less effective at spreading the
agent than the intracerebral route usually used to
assess infectivity in animal studies.
The amount of
infectivity present and the efficiency with the BSE
agent passes from cow material to humans will also
affect the likelihood of infection.
How did FDA derive its risk estimates and
decide the risk of vCJD from vaccines was
remote and theoretical?
Scientists, regulatory authorities in Europe and the
pharmaceutical industry of the U.S. have considered
the risk of BSE in pharmaceutical products.
In estimating these risks it is necessary to consider the:
- Country of origin of any bovine material
- Type of
bovine tissue used
- Steps used to process the bovine tissue
- Amount of bovine derived material
used
- Stage of vaccine manufacture at which
the bovine material is used
Using previously published methods for calculating theoretical risk of
cased of vCJD from pharmaceutical products, FDA
has calculated a conservative estimation of the risk
of a vaccine causing a case of vCJD. These estimates
were presented in public session at the joint advisory
committee meeting on July 27, 2000.
FDA believes
these estimations are a realistic worst case scenario and that the real risk any US licensed vaccine could
cause vCJD is even lower than the estimates
presented (link to risk assessments and transcripts).
What steps has the FDA taken to ensure that
people are not exposed to the BSE agent in
vaccines?
FDA has taken a number of measures to minimize
any chance that the BSE could be introduced into
biologic products during manufacture.
Most
recently, FDA has directed manufactures not to use
products from animals born, living, or slaughtered in
countries where BSE has occurred, or countries where there is a high or unknown risk of BSE.
In this
recent action, the FDA has requested that vaccine
manufactures replace bovine-derived materials obtained from countries on the USDA list with
materials obtained from countries not on the USDA
list.
This recommendation, which is consistent with
existing FDA guidance first issued in 1993 on the
sourcing of bovine-derived materials, is intended to
reduce even the remote risk for vCJD from vaccines.
My child was just immunized. Should I be
worried?
No. The Public Health Service (PHS) recommends
that all persons continue to be vaccinated according
to current schedules. No evidence exists that cases of
vCJD are related to the use of vaccines, and no cases
of vCJD have ever been reported in the U.S.
In
addition, there is no evidence to date that vaccines
have contributed to the cases of vCJD seen in
Europe. Nor is there evidence that any vaccines
harbor the BSE agent.
As a result, PHS has no
preference for using one licensed vaccine product
over another based on the source of bovine-derived
materials used in vaccine production.
Why is the Food and Drug Administration now
requiring that vaccine manufacturers not use
bovine-materials from cattle born, raised, or slaughtered in countries where BSE is known
to exist or where there is a risk that BSE may
exist?
The FDA is taking this action as a precautionary
measure. This action is intended to reduce even the
remote risk for vCJD from vaccines.
When will vaccine manufactures finish
replacing cow-derived materials in vaccines
with materials obtained from countries free of
BSE?
All of the affected manufactures have agreed to
implement these changes or have already done so.
FDA anticipates that most of these changes will be completed in 2001.
Should I delay an immunization order to
reduce the chances of being exposed to the
BSE agent?
No. The Public Health Service (PHS) recommends
that all persons continue to be vaccinated according
to current schedules. No evidence exist that cases of
vCJD are related to the use of vaccines, and no cases
of vCJD have ever been reported in the U.S.
In
addition, there is no evidence that any vaccines
harbor the BSE agent. As a result, PHS has no
preference for using one licensed vaccine product
over another based on the source of bovine-derived
materials used in vaccine production.
Why is FDA leaving vaccine on the market that
did not follow its own recommendations
regarding sourcing of bovine derived
materials?
The FDA has looked at the benefit of vaccines and
the risk of vCJD from vaccine use. Vaccines have a
proven benefit in reducing the incidence of serious,
often life-threatening diseases.
Conversely, the
Public Health Service, FDA and the members of
FDA’s advisory committees on TSE and Vaccines
and Related Products (VRBPAC) believe the risk that
anyone will get vCJD from a vaccine is remote and
theoretical.
Failure to obtain recommended
vaccinations with licensed vaccines puts a person at
risk for serious disease. Without routine vaccination,
the incidence of disease would increase. This was
seen in Sweden, Japan and the UK when the number
of children vaccinated against pertussis decreased
due to concerns about vaccine adverse events
associated with the whole-cell DTP vaccine.
In addition, removal of safe and effective licensed
vaccines from the market could cause insufficient
supply and potentially increase the number of unvaccinated or under vaccinated individuals at risk
from preventable diseases.
Where can I obtain additional information?
Additional information about BSE or vaccines
manufactured with bovine-derived materials from
countries on the U.S. Department of Agriculture’s
list can be obtained from the FDA’s web site, www.fda.gov/cber/BSE/BSE.htm, or from
CBER’s Office Communication, Training and
Manufacturers Assistance, (800) 835-4709.
