Listeria monocytogenes (Stillbirths in animals)
Author: Sushil Tamrakar
General overview of Listeria monocytogenes
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 (Smith, Takeuchi et al. 2008).
http://www.cdc.gov/listeria/
Summary Data
Smith et al.(2008) studied dose-response model for Listeria monocytogenes induced stillbirths in nonhuman primates (Smith, Takeuchi et al. 2008) . 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 (Williams, Irvin et al. 2007; Williams, Castleman et al. 2009). 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.
| Experiment serial number |
Reference |
Host type |
Agent strain |
Route |
# of doses |
Dose units |
Response |
Best fit model |
Optimized parameter(s) |
LD50/ID50
|
| 289,290* |
[1][2] |
pooled |
|
oral |
13 |
CFU |
stillbirths |
beta-Poisson |
α = 4.22E-02 , N50 = 1.78E+09 |
1.78E+09
|
| 289 |
[1] |
rhesus monkeys |
|
oral |
8 |
CFU |
stillbirths |
beta-Poisson |
α = 4E-02 , N50 = 8.26E+08 |
8.26E+08
|
| 290 |
[2] |
guinea pig |
|
oral |
5 |
CFU |
fetal mortality |
beta-Poisson |
α = 9.36E-02 , N50 = 4.67E+07 |
4.67E+07
|
| *This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.
|
|
*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.
Optimization Output for pooled data (experiment 289 and 290)
Rhesus monkey/Listeria monocytogenes
| Dose |
Stillbirths |
Not stillbirths |
Total
|
| 316 |
0 |
1 |
1
|
| 1580 |
2 |
6 |
8
|
| 1E+04 |
0 |
4 |
4
|
| 2E+04 |
0 |
3 |
3
|
| 1E+05 |
2 |
9 |
11
|
| 126000 |
1 |
4 |
5
|
| 1E+06 |
2 |
7 |
9
|
| 1580000 |
2 |
4 |
6
|
| 1E+07 |
3 |
6 |
9
|
| 1.26E+07 |
2 |
3 |
5
|
| 1E+08 |
3 |
1 |
4
|
| 1.26E+08 |
2 |
2 |
4
|
| 3.98E+10 |
1 |
0 |
1
|
|
Goodness of fit and model selection
| Model |
Deviance |
Δ |
Degrees
of freedom |
χ20.95,1
p-value |
χ20.95,m-k
p-value
|
| Exponential
|
71.8
|
63.9
|
12
|
3.84
1.33e-15
|
21
1.49e-10
|
| Beta Poisson
|
7.88
|
11
|
19.7
0.724
|
| Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.
|
|
Optimized parameters for the beta-Poisson model, from 500 bootstrap iterations
| Parameter
|
MLE estimate
|
Percentiles
|
| 0.5% |
2.5% |
5% |
95% |
97.5% |
99.5%
|
| α
|
4.22E-02
|
1.14E-02 |
1.54E-02 |
1.78E-02 |
1.26E-01 |
1.51E-01 |
2.71E-01
|
| N50
|
1.78E+09
|
1.74E+06 |
4.42E+06 |
7.04E+06 |
2.28E+15 |
8.63E+16 |
8.36E+20
|
|
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters. 
beta Poisson model plot, with confidence bounds around optimized model
Optimization Output for experiment 289
Rhesus monkey/Listeria monocytogenes [1]
| Dose |
Stillbirths |
Not stillbirths |
Total
|
| 316 |
0 |
1 |
1
|
| 1580 |
2 |
6 |
8
|
| 2E+04 |
0 |
3 |
3
|
| 126000 |
1 |
4 |
5
|
| 1580000 |
2 |
4 |
6
|
| 1.26E+07 |
2 |
3 |
5
|
| 1.26E+08 |
2 |
2 |
4
|
| 3.98E+10 |
1 |
0 |
1
|
|
Goodness of fit and model selection
| Model |
Deviance |
Δ |
Degrees
of freedom |
χ20.95,1
p-value |
χ20.95,m-k
p-value
|
| Exponential
|
51.4
|
47.7
|
7
|
3.84
4.95e-12
|
14.1
7.71e-09
|
| Beta Poisson
|
3.68
|
6
|
12.6
0.72
|
| Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.
|
|
Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
| Parameter
|
MLE estimate
|
Percentiles
|
| 0.5% |
2.5% |
5% |
95% |
97.5% |
99.5%
|
| α
|
4E-02
|
9.86E-04 |
9.94E-04 |
1.02E-02 |
1.22E-01 |
1.96E-01 |
3.05E-01
|
| N50
|
8.26E+08
|
1.94E+03 |
4.54E+04 |
5.30E+05 |
8.90E+18 |
6.18E+22 |
4.86E+65
|
|
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters. 
beta Poisson model plot, with confidence bounds around optimized model
Optimization Output for experiment 290
Guinea pig/Listeria monocytogenes [2]
| Dose |
Fetal mortality |
Not fetal mortality |
Total
|
| 1E+04 |
0 |
4 |
4
|
| 1E+05 |
2 |
9 |
11
|
| 1E+06 |
2 |
7 |
9
|
| 1E+07 |
3 |
6 |
9
|
| 1E+08 |
3 |
1 |
4
|
|
Goodness of fit and model selection
| Model |
Deviance |
Δ |
Degrees
of freedom |
χ20.95,1
p-value |
χ20.95,m-k
p-value
|
| Exponential
|
19.3
|
17.6
|
4
|
3.84
2.71e-05
|
9.49
0.000677
|
| Beta Poisson
|
1.72
|
3
|
7.81
0.632
|
| Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.
|
|
Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
| Parameter
|
MLE estimate
|
Percentiles
|
| 0.5% |
2.5% |
5% |
95% |
97.5% |
99.5%
|
| α
|
9.36E-02
|
1.19E-02 |
2.03E-02 |
2.95E-02 |
1.10E+00 |
1.02E+02 |
8.41E+02
|
| N50
|
4.67E+07
|
9.56E+05 |
2.12E+06 |
3.23E+06 |
8.13E+11 |
4.28E+14 |
2.83E+23
|
|
Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters. 
beta Poisson model plot, with confidence bounds around optimized model
References
- ↑ 1.0 1.1 1.2 Smith, M. A., K. Takeuchi, et al. (2008). "Dose-Response Model for Listeria monocytogenes-Induced Stillbirths in Nonhuman Primates." Infection and Immunity 76(2): 726-731
- ↑ 2.0 2.1 2.2 Williams, D., E. A. Irvin, et al. (2007)."Dose-Response of Listeria monocytogenes after Oral Exposure in Pregnant Guinea Pigs." Journal of Food Protection 70(5): 1122-1128
Williams D, Castleman J, et al. (2009) Risk of Fetal Mortality After Exposure to Listeria monocytogenes Based on Dose-Response Data from Pregnant Guinea Pigs and Primates. Risk Analysis 29(11): 1495-1505.
