GENERAL INTRODUCTION: PRION DISEASES

PRION DISEASES

A General Introduction has been added to each disease chapter in an attempt to give a brief updated overview of the taxonomic, biological and other characteristics of the virus family or group of bacteria/protozoa that cause disease in livestock and, where relevant, involve wildlife. As the text of the three-volume book Infectious Diseases of Livestock is currently under revision the Editors are aware that there are inconsistencies between the updated introductions to chapters and the content of the chapters themselves. Once the chapters have been updated – a process that is currently underway – these inconsistencies will be removed.

There is strong scientific evidence that a group of infectious neurodegenerative diseases of humans and some other mammals – known collectively as the transmissible spongiform encephalopathies (TSEs; Table 1) – are caused by prions, i.e. transmissible mis-folded variants (PrPSc) of the normal cell-membrane protein designated PrPC. PrPSc, after a long incubation period, accumulates in the brains of infected individuals as microscopic fibrils, disturbing the architecture through characteristic vacuole and plaque formation, accompanied by neuronal loss. The resulting is an invariably fatal illness. Prions have no associated nucleic acid as is the case with other infectious agents.3

Transmission usually occurs horizontally, mostly by the oral route but in some TSEs transmission can also be vertical. The epidemiology of TSEs is often complicated by genetic predisposition. Furthermore, because prions are not recognised as foreign by the adaptive immune system of the host, PrPSc does not induce immunological responses. That probably contributes to the pathogenicity of TSEs and renders laboratory diagnosis more difficult than for most other infectious diseases.

Despite the fact that scrapie in sheep was recognised as long ago as the 1732, why and how the mis-folding of PrPC occurs is still a subject of fundamental research.

Prior to the 1980s TSEs were of limited practical importance. However, the so-called mad-cow disease (bovine spongiform encephalopathy - BSE) pandemic, centred on the United Kingdom (UK) from about 1985 caused the most complex, financially costly and frightening zoonotic crises in the modern era. At the height of the pandemic in 1992, more than 36 000 cases of BSE occurred in cattle in the UK; that, together which demonstration of the zoonotic potential of the disease in 1996,1 resulted in widespread consternation. However, the recorded human death toll worldwide due to variant Creutzfeldt-Jakob (vCJD) disease currently stands at only 228. Of those, 77 per cent occurred in the UK (www.cjd.ed.ac.uk/sites/default/files/worldfigs_0.pdf). The effort and expense required to eliminate the pandemic – for all practical purposes now achieved – was unprecedented in recent times. It has been estimated that the eventual cost to the European Union for managing the pandemic will reach € 92 billion.2 Ironically, the threat of BSE will probably never be finally eliminated because sporadic, atypical cases of most TSEs, BSE and scrapie included, occur at extremely low prevalence rates. Therefore, if in future, the same set of circumstances that precipitated the 1985 BSE pandemic were to recur, the pandemic would likely be repeated.

Table 1 Known transmissible spongiform encephalopathies

Disease

Host species (unusual hosts)

Mechanism of transmission

Classical scrapie

Sheep, goats

Mostly via oral exposure to excretions/ secretions from infected animals

Bovine spongiform encephalopathy

Cattle (some African antelope & various domestic & wild felids, goats)

Consumption of tissues from infected cattle – usually in the form of meat and bone meal  in feed concentrates (cattle and antelope) or beef carcass material (felids)

Atypical scrapie

Sheep, goats

Uncertain (sporadic disease?)

Atypical bovine spongiform encephalopathy

 Cattle

 Uncertain (sporadic disease?)

Chronic wasting disease

Deer, elk, moose

Mostly via oral exposure to excretions/ secretions from infected animals

Kuru

Human

Ritual cannibalism

Transmissible mink encephalopathy

Mink

Consumption of contaminated feedstuffs but source uncertain (cattle, sheep?)

Creutzfeldt-Jakob Disease

Human

Iatrogenic & genetic andsporadic forms

Variant Creutzfeldt-Jakob Disease

Human

Consumption of contaminated beef or beef products

Gerstmann-Sträussler- Scheinker Syndrome

Human

Genetic

Fatal familial insomnia

Human

Genetic and sporadic

Proteinase-sensitive prionopathy

Human

Sporadic

References

  1. COLLINGE, J., SIDLE, K. C., MEADS, J., IRONSIDE, J. & HILL, A. F., 1996. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature, 383(6602), 685-90.
  2. CUNNINGHAM, E. P., 2003. After BSE: A future for the European Livestock Sector, pp 90. Wageningen Academic Pub., Netherlands.
  3. MACLACHLAN, N. J. & DUBOVI, E. J., (eds.) 2016. Veterinary Virology, 5th edition, Academic Press.