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General overview of prion and prion diseases

Prions are 'self-replicating' basic proteins of small molecular weight. Prions form a new class of infectious agents responsible for a number of slow degenerative central nervous system diseases of humans and other animal species. The transmissible spongiform encephalopathies (TSEs) are a group of progressive neurological prion diseases, including scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. [1]

Public awareness of prion diseases have been raised after an outbreak of BSE occurred among cattle in many European countries and scientific evidence indicated the foodborne transmission of BSE to humans. [2][3]

The disease is transmitted to humans via meats contaminated with the brain or spinal cords of infected carcasses.

http://www.cdc.gov/ncidod/dvrd/prions/

 

General overview of prion and prion diseases

Diringer et al. (1998) inoculated outbred Syrian hamsters orally with graded doses of scrapie agent. The infectious agent was prepared from the brains of scrapied hamsters at the terminal stage of disease.[4]

Jacquemot et al. (2005) exposed C57BL/6 mice to mouse-adapted scrapie strain C506M3 via the intraperitoneal route. The inoculum was a brain homogenate at 10% (wt/vol) in 5% glucose solution from a mouse with scrapie at the terminal stage of disease.[5]

Taylor et al. (1995)injected Weanling RIII/FaDk-ro mice with pooled BSE-infected brain. They measured the titer of infectivity by bioassay in mice. The infectious agent was prepared from the brains of 861cattle with suspected BSE obtained between August and November 1990 from five veterinary centers throughout England.[6]

References

  1. The infectivity of transmissible spongiform encephalopathy agent at low doses: the importance of phospholipid, Gale, P , Journal of applied microbiology, Volume 101, p.261–274, (2006)
  2. A new variant of Creutzfeldt-Jakob disease in the UK, Will, Robert G., Ironside JW, Zeidler Metal, Estibeiro K, Cousens SN, Smith PG, Alperovitch A, Poser S, Pocchiari M, and Hofman A , The Lancet, Volume 347, p.921–925, (1996)
  3. Bovine spongiform encephalopathy (BSE) and its epidemiology, Smith, Peter G., and Bradley Ray , British Medical Bulletin, Volume 66, p.185–198, (2003)
  4. Effect of repeated oral infection of hamsters with scrapie, Diringer, H., Roehmel J., and Beekes M. , Journal of General Virology, Volume 79, p.3, (1998)
  5. High Incidence of Scrapie Induced by Repeated Injections of Subinfectious Prion Doses, Jacquemot, C., Cuche C., Dormont D., and Lazarini F. , Journal of Virology, Volume 79, p.14, (2005)
  6. Inactivation of the bovine spongiform encephalopathy agent by rendering procedures, Taylor, D. M., Woodgate S. L., and Atkinson M. J. , Veterinary Record, Volume 137, p.24, (1995)
ID # of Doses Agent Strain Dose Units Host type Μodel Optimized parameters Response type Reference
251 3 scrapie strain C506M3 LD50 i.c. mice exponential
k = 2.4E-05
LD50/ID50 = 2.89E+04

death Taylor, D. M., S. L. Woodgate, and M. J. Atkinson. "Inactivation of the bovine spongiform encephalopathy agent by rendering procedures." Veterinary Record. 137 (1995): 24.
Experiment ID:
251
# of Doses:
3
Agent Strain:
scrapie strain C506M3
Dose Units:
LD50 i.c.
Host type:
mice
Μodel:
exponential
Optimized parameters:
k = 2.4E-05
LD50/ID50 = 2.89E+04

Reference:
mice/ scrapie strain C506M3 model data [2]
Dose Dead Survived Total
125 0 11 11
1250 1 9 10
12500 2 8 10

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value		 χ20.95,m-k 
p-value
Exponential 1.34 0.99 2 3.84 
0.32		 5.99 
0.512
Beta Poisson 0.35 1 3.84 
0.554
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

 

Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 2.4E-05 1.00E-13 1.00E-13 7.23E-06 5.47E-05 5.81E-05 7.44E-05
ID50/LD50/ETC* 2.89E+04 9.32E+03 1.19E+04 1.27E+04 9.58E+04 6.92E+12 6.92E+12
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

 

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model