Listeria monocytogenes (Infection)
Author: Sushil Tamrakar
General overview of Listeria monocytogenes
Listeria monocytogenes is a gram-positive rod-shaped bacterium. It is the causative agent of listeriosis, a serious infection caused by eating food contaminated with the bacteria. The disease generally affects older adults, pregnant women, newborns, and adults with weakened immune systems. However, rarely, persons without these risk factors can also be affected [1] [2]
The overt form of the disease has mortality greater than 25 percent. The two main clinical manifestations are sepsis and meningitis. Meningitis is often complicated by encephalitis, a pathology that is unusual for bacterial infections [2].
Summary Data
Golnazarian et al.(1989)[3] also compared infectious dose in normal and compromised C57BL/6J mice with pathogens (strain F5817) via oral route and responses were recorded as death and infection separately. Audurier et al.(1980) [4] conducted an experiment on Swiss female mice (OF1) via oral route and infection was observed after 28 days of inoculation.The dose-response analysis of both cases were published by Haas, Thayyar-Madabusi in 1999 [4] [5]
| Experiment serial number |
Reference |
Host type |
Agent strain |
Route |
# of doses |
Dose units |
Response |
Best fit model |
Optimized parameter(s) |
LD50/ID50
|
| 292,295 Pooled* |
[3] |
C57Bl/6J mice |
F5817 |
oral |
10 |
CFU |
infection |
beta-Poisson |
α = 2.53E-01 , N50 = 2.77E+02 |
2.77E+02
|
| 292 |
[3] |
C57Bl/6J mice |
F5817 |
oral |
6 |
CFU |
infection |
beta-Poisson |
α = 6.95E-01 , N50 = 3.39E+03 |
3.39E+03
|
| 295 |
[3] |
C57Bl/6J mice |
F5817 |
oral |
4 |
CFU |
infection |
beta-Poisson |
α = 1.2E-01 , N50 = 1.16E+03 |
1.16E+03
|
| 296 |
[4] |
OF1 mice |
strain 10401 |
oral |
5 |
CFU |
infection |
beta-Poisson |
α = 1.72E-01 , N50 = 2.06E+06 |
2.06E+06
|
| *This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.
|
|
Optimization Output for experiment 292 and 295 (Pooling)
Pooled C57Bl/6J mice/Listeria monocytogenes [3]
| Dose |
Infected |
Non-infected |
Total
|
| 2 |
0 |
6 |
6
|
| 5 |
1 |
5 |
6
|
| 110 |
2 |
4 |
6
|
| 5500 |
7 |
3 |
10
|
| 32400 |
7 |
3 |
10
|
| 39000 |
4 |
2 |
6
|
| 55000 |
9 |
1 |
10
|
| 251000 |
10 |
0 |
10
|
| 550000 |
10 |
0 |
10
|
| 2820000 |
10 |
0 |
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
|
35.7
|
26.9
|
9
|
3.84
2.12e-07
|
16.9
4.52e-05
|
| Beta Poisson
|
8.75
|
8
|
15.5
0.364
|
| 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
|
2.53E-01
|
1.51E-01 |
1.62E-01 |
1.78E-01 |
6.47E-01 |
8.62E-01 |
1.79E+00
|
| N50
|
2.77E+02
|
3.39E+01 |
5.48E+01 |
6.67E+01 |
4.48E+03 |
7.53E+03 |
1.29E+04
|
|
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 292
C57Bl/6J mice/Listeria monocytogenes [3]
| Dose |
Infected |
Non-infected |
Total
|
| 5500 |
7 |
3 |
10
|
| 32400 |
7 |
3 |
10
|
| 55000 |
9 |
1 |
10
|
| 251000 |
10 |
0 |
10
|
| 550000 |
10 |
0 |
10
|
| 2820000 |
10 |
0 |
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
|
9.88
|
6.48
|
5
|
3.84
0.0109
|
11.1
0.0788
|
| Beta Poisson
|
3.4
|
4
|
9.49
0.494
|
| 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
|
6.95E-01
|
2.69E-01 |
3.39E-01 |
3.78E-01 |
2.56E+00 |
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
|
|
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 295
C57Bl/6J mice/Listeria monocytogenes [3]
| Dose |
Infected |
Non-infected |
Total
|
| 2 |
0 |
6 |
6
|
| 5 |
1 |
5 |
6
|
| 110 |
2 |
4 |
6
|
| 39000 |
4 |
2 |
6
|
|
Goodness of fit and model selection
| Model |
Deviance |
Δ |
Degrees
of freedom |
χ20.95,1
p-value |
χ20.95,m-k
p-value
|
| Exponential
|
25.8
|
24.9
|
3
|
3.84
6.09e-07
|
7.81
1.06e-05
|
| Beta Poisson
|
0.897
|
2
|
5.99
0.639
|
| 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
|
1.2E-01
|
1.86E-02 |
3.62E-02 |
4.68E-02 |
1.85E+00 |
1.84E+01 |
1.29E+02
|
| N50
|
1.16E+03
|
2.63E+01 |
6.05E+01 |
8.54E+01 |
2.68E+06 |
5.35E+07 |
1.51E+14
|
|
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 296
OF1 mice/Listeria monocytogenes [4]
| Dose |
Infected |
Non-infected |
Total
|
| 970000 |
2 |
3 |
5
|
| 9.7E+06 |
3 |
2 |
5
|
| 9.7E+07 |
4 |
1 |
5
|
| 9.7E+08 |
5 |
0 |
5
|
| 9.7E+09 |
8 |
2 |
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
|
86.8
|
84.2
|
4
|
3.84
0
|
9.49
0
|
| Beta Poisson
|
2.6
|
3
|
7.81
0.458
|
| 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
|
1.72E-01
|
1.81E-02 |
2.45E-02 |
3.24E-02 |
6.06E-01 |
9.07E-01 |
6.14E+00
|
| N50
|
2.06E+06
|
1.03E-10 |
7.25E-06 |
8.26E-03 |
2.04E+07 |
3.39E+07 |
7.13E+07
|
|
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
Summary
As the two data set of C57 Bl/6 J mice inoculated with L. monocytogenes [3] could be pooled. The pooled model is recommended to use as recommended model. However, according to Haas, Thayyar-Madabusi et al.(1999), the dose-response model of the experiment number 296 [4] showed consistence result to some reported outbreaks.
References
- ↑ CDC
- ↑ 2.0 2.1 Todar
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Golnazarian, C. A., C. W. Donnelly, et al. (1989). "Comparison of infectious dose of Listeria monocytogenes F5817 as determined for normal versus compromised C57B1/6J mice." Journal of food protection 52(10): 696-701. Cite error: Invalid
<ref> tag; name "Golnazarian" defined multiple times with different content Cite error: Invalid <ref> tag; name "Golnazarian" defined multiple times with different content Cite error: Invalid <ref> tag; name "Golnazarian" defined multiple times with different content
- ↑ 4.0 4.1 4.2 4.3 4.4 Audurier, A., P. Pardon, et al. (1980). "Experimental infection of mice with Listeria monocytogenes and L. innocua." Annales de microbiologie 131B(1): 47-57.
- ↑ Haas CN, Thayyar-Madabusi A, et al. (1999) Development and Validation of Dose-Response Relationship for Listeria monocytogenes. Quantitative Microbiology 1(1): 89-102.
