Listeria monocytogenes (Death as response): Dose Response Models

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Listeria monocytogenes (Death as response)

Author: Sushil Tamrakar
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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 (CDC 2012; Todar 2012).

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 (Todar 2012).





Summary Data

Czuprynski et al. ( 2003) studied susceptibility of C57BL/6 mice and A/J mice to Listeria monocytogenes (strain Scott A) inoculating them intragastrically (Czuprynski, Faith et al. 2003). Similarly, Golnazarian et al. (1989) also compared infectious dose in normal and compromised C57BL/6J mice with pathogens( strain F5817) via oral route (Golnazarian, Donnelly et al. 1989).


Experiment serial number Reference Host type Agent strain Route # of doses Dose units Response Best fit model Optimized parameter(s) LD50/ID50


291* [1] C57B1/6J mice F5817 oral 6 CFU death exponential k = 1.15E-05 6.05E+04
293 [2] A/J Mice Scott A intragastric 3 CFU death exponential k = 5.71E-07 1.21E+06
294 [2] C57BL/6 Mice Scott A intragastric 3 CFU death beta-Poisson α = 2.71E-01 , N50 = 7.89E+07 7.89E+07
*This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.



a:
Exponential and betapoisson model.jpg

Optimization Output for experiment 291

C57BL/6J mice/Listeria monocytogenes [3]
Dose DEATH NOT DEATH Total
5500 1 9 10
32400 2 8 10
55000 4 6 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 2.22 -0.000453 5 3.84
1
11.1
0.818
Beta Poisson 2.22 4 9.49
0.695
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.


Optimized k parameter for the exponential model, from 500 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 1.15E-05 7.13E-06 7.83E-06 7.96E-06 1.71E-05 1.85E-05 2.07E-05
ID50/LD50/ETC* 6.05E+04 3.35E+04 3.75E+04 4.06E+04 8.71E+04 8.85E+04 9.73E+04
*Not a parameter of the exponential model; however, it facilitates comparison with other models.



Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model





Optimization Output for experiment 293

A/J mice/Listeria monocytogenes [3]
Dose DEATH NOT DEATH Total
1E+05 1 5 6
1E+06 2 4 6
1E+07 6 0 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 1.25 -0.0018 2 3.84
1
5.99
0.536
Beta Poisson 1.25 1 3.84
0.264
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.


Optimized k parameter for the exponential model, from 500 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 5.71E-07 2.31E-07 2.31E-07 2.98E-07 1.30E-06 1.49E-06 2.19E-06
ID50/LD50/ETC* 1.21E+06 3.17E+05 4.64E+05 5.35E+05 2.32E+06 3.00E+06 3.00E+06
*Not a parameter of the exponential model; however, it facilitates comparison with other models.



Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model



Optimization Output for experiment 294

C57BL/6 mice/Listeria monocytogenes [3]
Dose DEATH NOT DEATH Total
1E+07 1 5 6
1E+08 4 2 6
1E+09 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 10.7 9.97 2 3.84
0.0016
5.99
0.00471
Beta Poisson 0.752 1 3.84
0.386
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 2.71E-01 9.85E-04 9.98E-04 1.01E-03 1.46E+00 5.95E+01 2.41E+05
N50 7.89E+07 9.28E-03 2.42E+02 2.56E+03 7.18E+08 1.90E+09 1.99E+14



Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
File:BPmodel ID294.png
beta Poisson model plot, with confidence bounds around optimized model





Summary

Although different experiments resulted into different risk the the experiment 291 was preferred as model for death as an endpoint of experiment.

References

  1. 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.
  2. 2.0 2.1 Czuprynski, C. J., N. G. Faith, et al. (2003). "A/J Mice Are Susceptible and C57BL/6 Mice Are Resistant to Listeria monocytogenes Infection by Intragastric Inoculation." Infection and Immunity 71(2): 682-689.
  3. 3.0 3.1 3.2 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 ".7B.7B.7Brefer.7D.7D.7D" defined multiple times with different content Cite error: Invalid <ref> tag; name ".7B.7B.7Brefer.7D.7D.7D" defined multiple times with different content

CDC (2012) "Listeria (Listeriosis)."

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.

Todar, K. (2012). Todar's Online Textbook of Bacteriology.

Czuprynski, C. J., N. G. Faith, et al. (2003). "A/J Mice Are Susceptible and C57BL/6 Mice Are Resistant to Listeria monocytogenes Infection by Intragastric Inoculation." Infection and Immunity 71(2): 682-689.

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.