Listeria monocytogenes (Stillbirths): Dose Response Models

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 [1].

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

Summary Data

Smith et al.(2008) studied dose-response model for Listeria monocytogenes induced stillbirths in nonhuman primates [1]. 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 [2]. 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

References

Smith, M. A., Takeuchi K., Anderson G., Ware G. O., McClure H. M., Raybourne R. B., et al. (2008). Dose-Response Model for Listeria monocytogenes-Induced Stillbirths in Nonhuman Primates. Infection and Immunity. 76, 2.
Williams, D., Irvin E. A., Chmielewski R. A., & May) F. J. F.( (Submitted). Dose-Response of Listeria monocytogenes after Oral Exposure in Pregnant Guinea Pigs. Journal of Food Protection. 70, 5.

ID	Exposure Route	# of Doses	Agent Strain	Dose Units	Host type	Μodel	LD50/ID50	Optimized parameters	Response type
292	oral	6	F5817	CFU		beta-Poisson		α = 0.253 N₅₀ = 277	infection
289	intubation	8		CFU	rhesus monkey	beta-Poisson	8.26E+08	α = 0.04 N₅₀ = 8.26E+08	stillbirths
290	intubation	5		CFU	guinea pig	beta-Poisson	4.67E+07	α = 0.0936 N₅₀ = 4.67E+07	fetal mortality

Experiment ID:

292

# of Doses:

Agent Strain:

F5817

Dose Units:

CFU

Host type:

Μodel:

beta-Poisson

Optimized parameters: a = 0.253

N₅₀ = 277

Reference:

**Goodness of Fit and Model Selection**
Model	Deviance	Δ	Degrees of freedom	χ²_0.95,1 p-value	χ²_0.95,m-k p-value
Exponential	9.88	6.48	5	3.84 0.011	11.1 0.0788
beta Poisson	3.4	6.48	4	3.84 0.011	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

Experiment ID:

289

# of Doses:

Agent Strain:

Dose Units:

CFU

Host type:

rhesus monkey

Μodel:

beta-Poisson

Optimized parameters: a = 0.04

LD₅₀/ID₅₀ = 8.26E+08
N₅₀ = 8.26E+08

Reference:

Experiment ID:

290

# of Doses:

Agent Strain:

Dose Units:

CFU

Host type:

guinea pig

Μodel:

beta-Poisson

Optimized parameters: a = 0.0936

LD₅₀/ID₅₀ = 4.67E+07
N₅₀ = 4.67E+07

Reference:

Listeria monocytogenesDose Response Experiments

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General Overview

Summary Data

Recommended Model

References