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General Overview

Listeria monocytogenes is a food-borne pathogen responsible for the illness listeriosis. This disease is especially severe for susceptible people, including fetuses and immunocompromised individuals .


http://www.cdc.gov/listeria/

Summary Data

Smith et al.(2008) studied dose-response model for Listeria monocytogenes induced stillbirths in nonhuman primates . Thirty-three pregnant rhesus monkeys (Macaca mulatta) were identified at 30 gestation days (gd) and L. monocytogenes was administered by nasogastric intubation. Animals were observed daily for changes in behavior or activity or signs of illness such as diarrhea. Similarly, Williams et al ( 2007 and 2009) explored fetal mortality in guinea pigs after oral exposure . Timed-pregnant guinea pigs were inoculated L. monocytogenes with whipping cream and the doses ranges from 104 CFU to 108 CFU. The animals were sacrificed on gestation day.

Recommended Model

It is recommended that pooled model of experiment 289 and 290 pooled should be used as the best dose response model. More data means better fit.

Exponential and betapoisson model.jpg

ID Exposure Route # of Doses Agent Strain Dose Units Host type Μodel LD50/ID50 Optimized parameters Response type Reference
289 intubation 8.00 CFU rhesus monkey beta-Poisson 8.26E+08 a = 0.04 N50 = 8.26E+08 stillbirths
290 intubation 5.00 CFU guinea pig beta-Poisson 4.67E+07 a = 0.0936 N50 = 4.67E+07 fetal mortality
292 oral 6.00 F5817 CFU beta-Poisson a = 0.253 N50 = 277 infection
Exposure Route:
intubation
# of Doses:
8.00
Agent Strain:
Dose Units:
CFU
Host type:
rhesus monkey
Μodel:
beta-Poisson
LD50/ID50:
8.26E+08
Optimized parameters: a = 0.04 N50 = 8.26E+08
Response type:
stillbirths
Reference:
Exposure Route:
intubation
# of Doses:
5.00
Agent Strain:
Dose Units:
CFU
Host type:
guinea pig
Μodel:
beta-Poisson
LD50/ID50:
4.67E+07
Optimized parameters: a = 0.0936 N50 = 4.67E+07
Response type:
fetal mortality
Reference:
Exposure Route:
oral
# of Doses:
6.00
Agent Strain:
F5817
Dose Units:
CFU
Host type:
Μodel:
beta-Poisson
LD50/ID50:
Optimized parameters: a = 0.253 N50 = 277
Response type:
infection
Reference:

 

Goodness of Fit and Model Selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value 		χ20.95,m-k 
p-value
Exponential 9.88 6.48 5 3.84 
0.011 		11.1
0.0788
beta Poisson 3.4 4 9.49
0.494
beta-Poisson fits better than exponential; can not reject good fit for beta-Poisson

 

 

 

 

 

 

 

Bootstrapped Parameter Estimates
Parameter MLE Estimate 0.5% 2.5% 5% 95% 97.5% 99.5%
α 6.95E-01 2.69E-01 3.39E-01 3.78E-01 2.56E+0 2.28E+01 1.18E+03
N50 3.39E+03 3.58E+01 2.47E+02 4.67E+02 1.09E+04 1.26E+04 1.85E+04

 

 

 

 

 

 

References