Share on Facebook Share on Twitter Email
Answers.com

Transmissible spongiform encephalopathy

 
Encyclopedia of Public Health: Transmissible Spongiform Encephalopathy
Home > Library > Health > Public Health Encyclopedia

Bovine spongiform encepalopathy (BSE) is a transmissible, degenerative neurological disease of cattle that causes neither fever nor inflammation in the organs. Cattle infected with BSE experience a progressive degeneration of the nervous system. Symptoms include nervousness or aggression; abnormal posture, loss of coordination, and difficulty in standing; excessive itching or licking; decreased milk production; and loss of body weight despite continued appetite. The average age of symptom onset is five years, and death usually results within four months. The common name, "mad cow disease," is related to abnormal motor control and aggressiveness, which are also symptoms of rabies, which afflicts "mad dogs." Between 1986 and 2000, more than 170,000 cases of BSE were identified in cattle in the United Kingdom. The epidemic peaked in 1992–1993 at almost 1,000 cases per week.

The cause of BSE in British cattle was probably the use of commercial cattle feed containing meat and bone meal (MBM) derived from the rendered carcasses of sheep infected with scrapie, a degenerative disease of sheep. MBM is manufactured by rendering (melting) out the fat, and then drying the protein portion of by-products from the meat processing industry. Using MBM as a protein source in animal feed has been common for several decades. Apparently, the pre-1970 rendering methods, which included fat removal with solvents followed by a steam treatment, eliminated the infective agent in the rendered material before it was used in cattle feed. A change to "low temperature rendering" in the 1970s may have allowed the infective agent to remain in the protein portion that was dried and used as animal feed.

Natural transmission of BSE in cattle occurs when they eat infective material. The required oral dose for BSE transmission is small—five hundred to one thousand milligrams of BSE-infected brain tissue for calves. The BSE agent has been found only in the brain, spinal cord, retina, and the small intestines of cattle.

BSE and scrapie are transmissible spongiform encephalopathies, or TSEs. TSEs appear to be caused by an unconventional infectious agent known as a "prion" (proteinaceous infectious particle), an agent that contains no DNA or RNA. A prion is a normal protein (PrP) present on or in nerve cell membranes that can assume an abnormal (infective) physical shape referred to as PrPsc. One PrPsc molecule can induce normal PrP molecules to change shape into PrPsc.

Mutations in the PrP gene may make the conversion of normal PrP to disease-causing PrPsc more likely. There are at least twenty mutations in the PrP gene sequence resulting in "spontaneous" PrPsc formation. Once a few PrPsc molecules are formed, they rapidly convert other normal molecules to the infective form. Ingested PrPsc can travel to the central nervous system where it converts normal PrP to PrPsc.

The nerve cell attempts to break down the prion; however, PrPsc is very resistant to the enzymes that normally break proteins down. The cell can be cleaved into fragments, which fill up and kill the cell (leaving holes known as "spongiform" damage). These fragments aggregate and precipitate the formation of plaques.

Creutzfeldt-Jakob disease (CJD) is a human TSE that occurs primarily in those over sixty-five years of age. It produces rapidly progressing neurological symptoms and dementia. In 1995, a new form of CJD, variant, or new variant, CJD (vCJD), was recognized. Patients have behavioral and psychiatric disturbances (e.g., depression, personality change), failure of muscular coordination, and memory impairment. The original ten cases occurred in people under forty-two years of age and were fatal within thirteen months. The hypothesized cause was consumption of BSE-infected food materials. As of March 2001, ninety-five cases of vCJD had been identified in the United Kingdom, with a few isolated cases occurring in France and Ireland.

TSEs occur more often in specific subgroups of populations (certain breeds of sheep, cattle, mink, and human families) suggesting a genetic component. Some gene combinations are very resistant, while some are particularly susceptible to the disease. In addition, a TSE in a specific species can exist in several strains, with each producing specific symptoms, times of onset and progression, and lesions in the brain that are distinctly different from those produced by other strains. Recent evidence indicates that the TSE strain occurring in vCJD is not different from the strain responsible for BSE in cattle. If the TSE strain that causes BSE also causes vCJD, the question arises of whether there is likely to be an epidemic of vCJD. The chances of such an epidemic are reduced by the fact that the incubation period for CJD is relatively long in humans, and because much of the population is likely genetically resistant to the PrPsc that causes the disease. Further, while the infective dose in humans is not known, the dietary consumption of known infective tissues (brain, spinal cord, etc.) is low. However, it may be years before the full impact of this disease on the human population is known. As of 2001, no cases of BSE in cattle had been identified in the United States and no products had been imported that appear to pose potential risk to either human or animal health.

(SEE ALSO: Bovine Spongiform Encephalopathy; Epidemics; Prions; Veterinary Public Health)

Bibliography

Blanchfield, R. (1996). Bovine Spongiform Encephalopathy. IFST. Available at http://www.easynet.co.uk/ifst/PositionStatement.

Bruce, M.; Will, R. G.; Ironside, J. W.; McConnell, I.; Drummond, D.; Suttie, A.; McCardle, L.; Chree, A.; Hope, J.; Birkett, C.; Cousens, S.; Fraser, H.; and Bostock, C. J. (1997). "Transmissions to Mice Indicate that New Variant CJD Is Caused By the BSE Agent." Nature 389:498–501.

Hill, A. F.; Desbruslais, M.; Joiner, S.; Sidle, K. C. L.; Gowland, I.; Collinge, J.; Doey, L. J.; and Lantos, P.(1997). "The Same Prion Strain Causes vCJD and BSE." Nature 389:448–450.

United Kingdom Minister of Agriculture, Fisheries and Food (1997). Spongiform Encephalopathy Advisory Committee. SEAC Meeting Public Summary. Surrey, UK: MAFF.

—— (1998). Bovine Spongiform Encephalopathy: Number of Cases of BSE Reported. Available at http://www.oie.org/indemne/bse_a.htm#ru.

Prusiner, S. B. (1995). "Prion Diseases." Scientific American 272(1):48–57.

— M. SUSAN BREWER


Search unanswered questions...

Enter a question here...
Search: All sources Community Q&A Reference topics

Medical Dictionary: spongiform encephalopathy
Top
Home > Library > Health > Medical Dictionary

n.

Encephalopathy characterized by progressive diffuse vacuolation of the cerebral cortex.

Wikipedia: Transmissible spongiform encephalopathy
Top
Home > Library > Miscellaneous > Wikipedia
Transmissible spongiform encephalopathy
Classification and external resources
ICD-10 A81.
ICD-9 046
DiseasesDB 25165
eMedicine neuro/662
MeSH D017096

Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. According to the most widespread hypothesis they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection.[1] Mental and physical abilities deteriorate and myriad tiny holes appear in the cortex causing it to appear like a sponge (hence 'spongiform') when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen over time. Prion diseases of humans include classic Creutzfeldt-Jakob disease, new variant Creutzfeldt-Jakob disease (a human disorder related to mad cow disease), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia and kuru. These conditions form a spectrum of diseases with overlapping signs and symptoms.

Unlike other kinds of infectious disease which are spread by microbes, the infectious agent in TSEs is a specific protein called prion protein. Misshaped prion proteins carry the disease between individuals and cause deterioration of the brain. TSEs are unique diseases in that their aetiology may be genetic, sporadic or infectious via ingestion of infected foodstuffs and via iatrogenic means (e.g. blood transfusion).[2] Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare mutant prion allele, which expresses prion proteins that contort by themselves into the disease-causing conformation. Transmission occurs when healthy animals consume tainted tissues from others with the disease. In recent times a type of TSE called bovine spongiform encephalopathy (BSE) spread in cattle in an epidemic fashion. This occurred because cattle were fed the processed remains of other cattle, a practice now banned in many countries. The epidemic could have begun with just one cow with sporadic disease.

Prions cannot be transmitted through the air or through touching or most other forms of casual contact. However, they may be transmitted through contact with infected tissue, body fluids, or contaminated medical instruments. Normal sterilization procedures such as boiling or irradiating materials fail to render prions non-infective.

Contents

Classification

Mammalian agents of spongiform encephalopathies
ICTVdb Code Disease name Natural host Prion name PrP isoform
90.001.0.01.001. Scrapie Sheep and goats Scrapie prion OvPrPSc
90.001.0.01.002. Transmissible mink encephalopathy (TME) Mink TME prion MkPrPSc
90.001.0.01.003. Chronic wasting disease (CWD) Elk, White-tailed deer, Mule Deer and Red Deer CWD prion MDePrPSc
90.001.0.01.004. Bovine spongiform encephalopathy (BSE)
commonly known as "Mad Cow Disease"		 Cattle BSE prion BovPrPSc
90.001.0.01.005. Feline spongiform encephalopathy (FSE) Cats FSE prion FePrPSc
90.001.0.01.006. Exotic ungulate encephalopathy (EUE) Nyala and greater kudu EUE prion NyaPrPSc
90.001.0.01.007. Kuru Humans Kuru prion HuPrPSc
90.001.0.01.008. Creutzfeldt-Jakob disease (CJD) Humans CJD prion HuPrPSc
(New) Variant Creutzfeldt-Jakob disease (vCJD, nvCJD) Humans vCJD prion HuPrPSc
90.001.0.01.009. Gerstmann-Sträussler-Scheinker syndrome (GSS) Humans GSS prion HuPrPSc
90.001.0.01.010. Fatal familial insomnia (FFI) Humans FFI prion HuPrPSc

Features of TSE

The degenerative tissue damage caused by human prion diseases (CJD, GSS, and kuru) is characterised by four features: spongiform change, neuronal loss, astrocytosis and amyloid plaque formation. These features are shared with prion diseases in animals, and the recognition of these similarities prompted the first attempts to transmit a human prion disease (kuru) to a primate in 1966, followed by CJD in 1968 and GSS in 1981.These neuropathological features have formed the basis of the histological diagnosis of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the central nervous system in individual cases.[3]

The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as depression, lack of coordination, and/or an unsteady gait (ataxia). Patients also may experience involuntary jerking movements called myoclonus, unusual sensations, insomnia, confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment (dementia) and lose the ability to move or speak.[4]

Early neuropathological reports on human prion diseases suffered from a confusion of nomenclature, in which the significance of the diagnostic feature of spongiform change was occasionally overlooked. The subsequent demonstration that human prion diseases were transmissible reinforced the importance of spongiform change as a diagnostic feature, reflected in the use of the term "spongiform encephalopathy" for this group of disorders.

Prions appear to be most infectious when in direct contact with affected tissues. For example, Creutzfeldt-Jakob disease has been transmitted to patients taking injections of growth hormone harvested from human pituitary glands, and from instruments used for brain surgery (Brown, 2000) (prions can survive the "autoclave" sterilization process used for most surgical instruments). It is also believed that dietary consumption of affected animals can cause prions to accumulate slowly, especially when cannibalism or similar practices allow the proteins to accumulate over more than one generation. An example is kuru, which reached epidemic proportions in the mid 20th century in the Fore people of Papua New Guinea, who used to consume their dead as a funerary ritual.[5] Laws in developed countries now proscribe the use of rendered ruminant proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants.

Note that not all encephalopathies are caused by prions, as in the cases of PML (caused by the JC virus), CADASIL (caused by abnormal NOTCH3 protein activity), and Krabbe disease (caused by a deficiency of the enzyme galactosylceramidase). PSL -- which is a spongiform encephalopathy—is also probably not caused by a prion, although the adulterant which causes it among heroin smokers has not yet been identified.[6][7][8][9] This, combined with the highly variable nature of prion disease pathology, is why a prion disease cannot be diagnosed based solely on a patient's symptoms.

Genetics

Mutations in the PRNP gene cause prion disease. Familial forms of prion disease are caused by inherited mutations in the PRNP gene. Only a small percentage of all cases of prion disease run in families, however. Most cases of prion disease are sporadic, which means they occur in people without any known risk factors or gene mutations. Rarely, prion diseases also can be transmitted by exposure to prion-contaminated tissues or other biological materials obtained from individuals with prion disease.

The PRNP gene provides the instructions to make a protein called the prion protein (PrP). Normally, this protein may be involved in transporting copper into cells. It may also be involved in protecting brain cells and helping them communicate. 24 Point-Mutations in this gene cause cells to produce an abnormal form of the prion protein, known as PrPSc. This abnormal protein builds up in the brain and destroys nerve cells, resulting in the signs and symptoms of prion disease.

Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.

In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children.

Competing hypotheses

Protein-Only hypothesis

Protein could be the infectious agent, inducing its own replication by causing conformational change of normal cellular PrPC into PrPSc. Evidence for this theory:

  • infectivity titre correlates with PrPSc levels. However, this is disputed.[10]
  • PrPSc is an isomer of PrPC
  • Denaturing PrP removes infectivity [11]
  • Recombinant PrP is infectious [12]
  • PrP-null mice cannot be infected[13]

Viral hypothesis

This hypothesis postulates that an infectious viral agent is the cause of the disease. Evidence for this hypothesis is as follows:

  • Incubation time is comparable to a lentivirus
  • Strain variation of different isolates of PrPSc[14]
  • An increasing titre of PrPSc as the disease progresses suggests a replicating agent.

This hypothesis is largely discredited[citation needed], as no infectious, non-human nucleic acid has ever been isolated from the disease. It is largely based on the fact that infectious agents have previously been viral in origin, preferring this as more plausible than the infectious protein hypothesis.

Epidemiology

These spontaneous disorders in humans are very rare, affecting only about one person per million worldwide each year. However, transmissible TSEs can reach epidemic proportions, as was seen in the UK BSE outbreak of the 80s and 90s. It is very hard to map the spread of the disease due to the difficulty of identifying individual strains of the prions. This means that if animals start to show the disease after an outbreak on a nearby farm, you cannot show that it is the same strain affecting both, suggesting transmission, or that the second outbreak came from a completely different source.

Possible cure or vaccine

Recent research from the University of Toronto and Caprion Pharmaceuticals have discovered one possible avenue which might lead to quicker diagnosis, a vaccine or possibly even treatment for prion diseases. The abnormally folded proteins which cause the disease have been found to expose a side chain of amino acids which the properly folded protein does not expose. Antibodies specifically coded to this side chain amino acid sequence have been found to stimulate an immune response to the abnormal prions and leave the normal proteins intact.[15]

Another idea involves using custom peptide sequences. Since some research suggests prions aggregate by forming beta barrel structures, work done in vitro has shown that peptides made up of beta barrel-incompatible amino acids can help break up accumulations of prion. Yet a third idea concerns genetic therapy, whereby the gene for encoding protease-resistant protein is considered to be an error in several species, and therefore something to be inhibited.

References

Bibliography

Notes

  1. ^ Bastian FO, Sanders DE, Forbes WA, Hagius SD, Walker JV, Henk WG, Enright FM, Elzer PH (2007). "Spiroplasma spp. from transmissible spongiform encephalopathy brains or ticks induce spongiform encephalopathy in ruminants". J Med Microbiol. 56 (9): 1235–1242. doi:10.1099/jmm.0.47159-0. PMID 17761489. 
  2. ^ Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I, Fletcher A, Will RG, Pocchiari M, Cashman NR, d'Aignaux JH, Cervenakova L, Fradkin J, Schonberger LB, Collins SJ (2000). "Iatrogenic Creutzfeldt-Jakob disease at the millennium". Neurology 55 (8): 1075–81. PMID 11071481. 
  3. ^ Jeffrey M, Goodbrand IA, Goodsir CM (1995). "Pathology of the transmissible spongiform encephalopathies with special emphasis on ultrastructure". Micron 26 (3): 277–98. doi:10.1016/0968-4328(95)00004-N. PMID 7788281. 
  4. ^ Collinge J (2001). "Prion diseases of humans and animals: their causes and molecular basis". Annu Rev Neurosci 24: 519–50. doi:10.1146/annurev.neuro.24.1.519. PMID 11283320. 
  5. ^ Collins S, McLean CA, Masters CL (2001). "Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies". J Clin Neurosci 8 (5): 387–97. doi:10.1054/jocn.2001.0919. PMID 11535002. 
  6. ^ "hafci.org". http://www.hafci.org/infoline/enu/heroin.htm. Retrieved 2007-12-02. 
  7. ^ Kriegstein AR, Shungu DC, Millar WS, et al. (1999). "Leukoencephalopathy and raised brain lactate from heroin vapor inhalation ("chasing the dragon")". Neurology 53 (8): 1765–73. PMID 10563626. 
  8. ^ Chang YJ, Tsai CH, Chen CJ (1997). "Leukoencephalopathy after inhalation of heroin vapor". J. Formos. Med. Assoc. 96 (9): 758–60. PMID 9308333. 
  9. ^ Koussa S, Zabad R, Rizk T, Tamraz J, Nasnas R, Chemaly R (2002). "[Vacuolar leucoencephalopathy induced by heroin: 4 cases]" (in French). Rev. Neurol. (Paris) 158 (2): 177–82. PMID 11965173. 
  10. ^ Barron RM, Campbell SL, King D, et al. (December 2007). "High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrPSc in vivo". The Journal of Biological Chemistry 282 (49): 35878–86. doi:10.1074/jbc.M704329200. PMID 17923484. 
  11. ^ Supattapone S, Wille H, Uyechi L, et al. (April 2001). "Branched polyamines cure prion-infected neuroblastoma cells". Journal of Virology 75 (7): 3453–61. doi:10.1128/JVI.75.7.3453-3461.2001. PMID 11238871. 
  12. ^ Yang W, Yang H, Tien P (July 2006). "In vitro self-propagation of recombinant PrPSc-like conformation generated in the yeast cytoplasm". FEBS Letters 580 (17): 4231–5. doi:10.1016/j.febslet.2006.06.074. PMID 16831424. 
  13. ^ Sakudo A, Lee DC, Saeki K, et al. (August 2003). "Impairment of superoxide dismutase activation by N-terminally truncated prion protein (PrP) in PrP-deficient neuronal cell line". Biochemical and Biophysical Research Communications 308 (3): 660–7. doi:10.1016/S0006-291X(03)01459-1. PMID 12914801. 
  14. ^ Bruce ME (2003). "TSE strain variation". British Medical Bulletin 66: 99–108. doi:10.1093/bmb/66.1.99. PMID 14522852. 
  15. ^ Paramithiotis E, Pinard M, Lawton T, et al. (July 2003). "A prion protein epitope selective for the pathologically misfolded conformation". Nature Medicine 9 (7): 893–9. doi:10.1038/nm883. PMID 12778138. Lay summary – ScienceDaily (2003-06-02). 

External links

v • d • e
Infectious diseases - Prion diseases / Transmissible spongiform encephalopathy (A81, 046)
Prion diseases in humans

inherited/PRNP: fCJD · Gerstmann-Sträussler-Scheinker syndrome · Fatal familial insomnia

sporadic: sCJD

acquired/transmissible: Kuru · vCJD
Prion diseases in animals

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)

 
 

 

Copyrights:

Encyclopedia of Public Health. Encyclopedia of Public Health. Copyright © 2002 by The Gale Group, Inc. All rights reserved.  Read more
Medical Dictionary. The American Heritage® Stedman's Medical Dictionary Copyright © 2002, 2001, 1995 by Houghton Mifflin Company.  Read more
Wikipedia. This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article "Transmissible spongiform encephalopathy".  Read more