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 (Gale 2006).

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 (Will et al. 1996; Smith and Bradley 2003).

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


General overview of prion and prion diseases

Diringer et al. (1998)[1] 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.

Jacquemot et al. (2005)[2] 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

Taylor et al. (1995)[3] 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.


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:
# of Doses:
Agent Strain:
scrapie strain C506M3
Dose Units:
LD50 i.c.
Host type:
Optimized parameters:
k = 2.4E-05
LD50/ID50 = 2.89E+04

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
Exponential 1.34 0.99 2 3.84 
Beta Poisson 0.35 1 3.84 
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