Listeria monocytogenes (Infection): Dose Response Models

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Listeria monocytogenes (Infection)

Listeriosis
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 are also infected [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].


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


Summary Data

Golnazarian et al.(1989)[3] 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.


Exponential and betapoisson model.jpg

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 sets using C57 Bl/6 J mice inoculated with L. monocytogenes [3] could be pooled, the pooled model is recommended to use as recommended model. According to Haas, Thayyar-Madabusi et al.(1999), the dose-response model of the experiment number 296 [4] showed consistent with reported outbreaks.

References

  1. CDC
  2. 2.0 2.1 Todar
  3. 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. 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.
  5. Haas CN, Thayyar-Madabusi A, et al. (1999) Development and Validation of Dose-Response Relationship for Listeria monocytogenes. Quantitative Microbiology 1(1): 89-102.