Transmissible

Spongiform

Encephalopathies

(TSE)

TSE’s are rare forms of progressive neurodegenerative disorders that affect both humans and animals

and are caused by similar uncharacterized agents

that generally produce spongiform changes in the

brain. Specific examples of TSE’s include: scrapie,

which affects sheep and goats; bovine spongiform

encephalopathy (BSE), which affects cattle; transmissible mink encephalopathy; feline spongiform

encephalopathy; chronic wasting disease (CWD) of

mule deer, white-tailed deer, black-tailed deer, and

elk; and in humans, kuru, Creutzfeldt-Jakob disease,

Gerstmann-Straussler syndrome, fatal familial insomnia, and variant Creutzfeldt-Jakob disease (vCJD).

Diagnosis: TSE’s are insidious degenerative diseases of the central nervous system. Historically, the

diagnosis of TSE’s has been based on the occurrence of clinical signs of the disease, which was

confirmed only by postmortem examination of brain

tissue. More recently, identification of abnormal prion

protein, PrPres, by various techniques has improved

our ability to make a disease diagnosis.

Laboratory Testing: A characteristic feature of all

TSE’s is the lack of a measurable host immune

response to the agent meaning that there are no

antibodies produced. No conventional serologic test

can be used to identify infected animals. Scientists

usually diagnose TSE diseases in the laboratory by

histopathologic examination of the brain followed by

one or more supplemental tests. A description of

these tests is attached.

Scrapie: Scrapie was first diagnosed in the

United States in 1947. Control programs have been

in place since 1952. The latest program went into

effect in 1992. It involves a Flock Certification

Program and interstate movement regulations that

place restrictions on the movement of sheep and

goats from infected and source scrapie flocks. The

intent of the certification program is to monitor flocks

over a period of 5 years or more and identify flocks

that have not displayed evidence of scrapie. Flocks

are inspected yearly for compliance with the certification program standards. The older the flock’s status

date the lower the risk of that flock having scrapie.

APHIS has proposed a rule to strengthen the regulatory program by (1) requiring the identification of

mature sheep and goats in interstate commerce, (2)

restricting the interstate movement of sheep and

goats from the States that do not have effective

scrapie control programs, and (3) providing indemnity

for scrapie-positive and high-risk animals.

CWD: CWD is a TSE of deer and elk. Species

that have been affected include mule deer, whitetailed deer, black-tailed deer, and elk. The disease

occurs in free-ranging mule deer and elk in northeastern Colorado and southeastern Wyoming. In

1997, CWD was found in farmed elk herds in South

Dakota. Subsequently, CWD was diagnosed in

farmed elk in Nebraska, Oklahoma, Colorado, and

Montana. APHIS, in cooperation with the States and

industry, is currently developing a CWD program for

controlling and eliminating this disease in farmed

cervids. APHIS is also cooperating with State wildlife

agencies in Colorado and Wyoming where the disease occurs endemically in free-ranging cervids and

also with other wildlife agencies that are conducting

surveillance in nonendemic States to clearly define

the distribution of CWD in free-ranging cervids.

BSE: BSE is a TSE of cattle, which was first

diagnosed in 1986 in Great Britain. Epidemiological

data suggest that BSE in Great Britain is a common

source epidemic involving animal feed containing

contaminated meat-and-bone meal as a protein

source. There is no evidence that BSE spreads horizontally, i.e., by contact between unrelated adult cattle or from cattle to other species. BSE has not been

identified in native cattle outside of Europe, and more

than 95 percent of all BSE cases identified in the

world have been in the United Kingdom. BSE has

not been diagnosed in the United States, and USDA

has worked proactively to keep it that way. The

United States has one of the most aggressive BSE

surveillance programs in the world. Since 1989,

APHIS has prohibited the importation of live ruminants from countries where BSE is known to exist in

native cattle. Other products derived from ruminants,

such as fetal bovine serum, bonemeal, meat-andbone meal, bloodmeal, offal, fats, and glands, are

also prohibited entry, except under special conditions

with a USDA permit for scientific or research purposes.

Factsheet

Plant Protection and Quarantine July 2000

APHIS
TME: There is no official USDA program for TME.

We continue to monitor for reoccurrence of TME disease. The last known case of TME occurred in the

United States in 1985. There were other outbreaks

prior to 1964.

Testing Methods for TSE’s

Histopathology: Bilaterally symmetrical degenerative changes are usually seen in the gray matter of

the brain stem. These changes are characterized by

vacuolation or microcavitation of nerve cells in the

brain stem nuclei. The neural perikarya and axons of

certain brain stem nuclei contain intracytoplasmic vacuoles of various sizes, giving the impression of a

spongy brain. Hypertrophy of astrocytes (astrocytosis) often accompanies the vacuolation.

Electron Microscopy: A TSE diagnosis may also

be made when scrapie-associated fibrils (SAF) using

negative stain electron microscopy are detected.

Supplemental tests: Supplemental tests are available to enhance the diagnostic capabilities for TSE’s.

Research shows the partially protease-resistant form

of the prion protein (PrPres) is found in the brain of

TSE-infected animals. Two tests that have been used

routinely to detect PrPres in animals showing clinical

signs of a TSE are immunohistochemistry and a

Western-blot technique. In the past, if the brain tissue

was not harvested shortly after the animal’s death,

autolysis might make it very difficult to confirm a diagnosis by histopathology, but these tests permit a diagnosis of a TSE based on finding PrPres even if the

brain has been frozen or if autolysis has occurred.

Last year, the European Commission published a

preliminary report on the evaluation of four companies’ tests for the diagnosis of TSE in cattle brain

samples. These included a modified Western-blot test

developed by Prionics A.G. of Switzerland; a chemiluminescent ELISA test using a polyclonal antiPrP antibody for detection developed by Enfer Technology,

Ltd., of Ireland; a sandwich immunoassy for PrPres

developed by Commissariat a l’Energie Atomique

(CEA) of France; and a two-site noncompetitive

immunometric procedure using monoclonal antibodies

and DELFIA technology to generate a signal developed by E. G. & G. Wallace, Ltd., of the United

Kingdom. The Prionics test is currently being used in

Switzerland to test “fallen stock.” Other countries,

such as Germany and France, are going to start using

the Prionics test or one of the other three tests to

increase surveillance for BSE in cattle.

A number of tests have been proposed and are in

the initial process of being validated for the preclinical

diagnosis of TSE’s in sheep. These include 1)

immunohistochemistry testing of eyelid associated

lymphoid tissue and tonsil biopsies, 2) use of capillary

electrophoresis and fluorescent labeled peptides to

detect PrPres in the blood of animals infected with a

TSE, and 3) improved Western-blotting techniques

with very good sensitivity to detect PrPres in blood,

cerebrospinal fluid, or small pieces of biopsied tissues.

Agent Isolation: As the agents that cause TSE’s

have not been fully characterized or isolated, one

method used to detect infectivity in an animal is to

inoculate laboratory animals with brain material from

the affected animal and monitor them for evidence of

disease. This method may take more than 2 years to

produce results; hence, it is not practical for routine

testing. The most common animal used for this type

of bioassay is the mouse. Another problem with the

mouse bioassay method when testing cattle or sheep

samples is that the species barrier may prevent detection of low levels of infectivity.

The U.S. Department of Agriculture (USDA) prohibits discrimination

in all its programs and activities on the basis of race, color, national

origin, sex, religion, age, disability, political beliefs, sexual orientation, or marital or family status. (Not all prohibited bases apply to

all programs.) Persons with disabilities who require alternative

means for communication of program information (Braille, large

print, audiotape, etc.) should contact USDA’s TARGET Center at

(202) 720–2600 (voice and TDD).

To file a complaint of discrimination, write USDA, Director, Office of

Civil Rights, Room 326–W, Whitten Building, 1400 Independence

Avenue, SW, Washington, DC 20250–9410 or call (202) 720–5964

(voice and TDD). USDA is an equal opportunity provider and

employer.

United States Department of Agriculture • Animal and Plant Health Inspection Service • Safeguarding American Agriculture