Listeria monocytogenes (Infection)
Author: Sushil Tamrakar
General overview of Listeria monocytogenes
Listeria monocytogenes is a grampositive rodshaped 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 doseresponse analysis of both cases were published by Haas, ThayyarMadabusi in 1999 ^{[4]} ^{[5]}
Experiment serial number 
Reference 
Host type 
Agent strain 
Route 
# of doses 
Dose units 
Response 
Best fit model 
Optimized parameter(s) 
LD_{50}/ID_{50}

292,295 Pooled* 
^{[3]} 
C57Bl/6J mice 
F5817 
oral 
10 
CFU 
infection 
betaPoisson 
α = 2.53E01 , N_{50} = 2.77E+02 
2.77E+02

292 
^{[3]} 
C57Bl/6J mice 
F5817 
oral 
6 
CFU 
infection 
betaPoisson 
α = 6.95E01 , N_{50} = 3.39E+03 
3.39E+03

295 
^{[3]} 
C57Bl/6J mice 
F5817 
oral 
4 
CFU 
infection 
betaPoisson 
α = 1.2E01 , N_{50} = 1.16E+03 
1.16E+03

296 
^{[4]} 
OF1 mice 
strain 10401 
oral 
5 
CFU 
infection 
betaPoisson 
α = 1.72E01 , N_{50} = 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 
Noninfected 
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 
χ^{2}_{0.95,1} pvalue 
χ^{2}_{0.95,mk} pvalue

Exponential

35.7

26.9

9

3.84 2.12e07

16.9 4.52e05

Beta Poisson

8.75

8

15.5 0.364

BetaPoisson fits better than exponential; cannot reject good fit for betaPoisson.


Optimized parameters for the betaPoisson model, from 10000 bootstrap iterations
Parameter

MLE estimate

Percentiles

0.5% 
2.5% 
5% 
95% 
97.5% 
99.5%

α

2.53E01

1.51E01 
1.62E01 
1.78E01 
6.47E01 
8.62E01 
1.79E+00

N_{50}

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 
Noninfected 
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 
χ^{2}_{0.95,1} pvalue 
χ^{2}_{0.95,mk} pvalue

Exponential

9.88

6.48

5

3.84 0.0109

11.1 0.0788

Beta Poisson

3.4

4

9.49 0.494

BetaPoisson fits better than exponential; cannot reject good fit for betaPoisson.


Optimized parameters for the betaPoisson model, from 10000 bootstrap iterations
Parameter

MLE estimate

Percentiles

0.5% 
2.5% 
5% 
95% 
97.5% 
99.5%

α

6.95E01

2.69E01 
3.39E01 
3.78E01 
2.56E+00 
2.28E+01 
1.18E+03

N_{50}

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 
Noninfected 
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 
χ^{2}_{0.95,1} pvalue 
χ^{2}_{0.95,mk} pvalue

Exponential

25.8

24.9

3

3.84 6.09e07

7.81 1.06e05

Beta Poisson

0.897

2

5.99 0.639

BetaPoisson fits better than exponential; cannot reject good fit for betaPoisson.


Optimized parameters for the betaPoisson model, from 10000 bootstrap iterations
Parameter

MLE estimate

Percentiles

0.5% 
2.5% 
5% 
95% 
97.5% 
99.5%

α

1.2E01

1.86E02 
3.62E02 
4.68E02 
1.85E+00 
1.84E+01 
1.29E+02

N_{50}

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 
Noninfected 
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 
χ^{2}_{0.95,1} pvalue 
χ^{2}_{0.95,mk} pvalue

Exponential

86.8

84.2

4

3.84 0

9.49 0

Beta Poisson

2.6

3

7.81 0.458

BetaPoisson fits better than exponential; cannot reject good fit for betaPoisson.


Optimized parameters for the betaPoisson model, from 10000 bootstrap iterations
Parameter

MLE estimate

Percentiles

0.5% 
2.5% 
5% 
95% 
97.5% 
99.5%

α

1.72E01

1.81E02 
2.45E02 
3.24E02 
6.06E01 
9.07E01 
6.14E+00

N_{50}

2.06E+06

1.03E10 
7.25E06 
8.26E03 
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, ThayyarMadabusi et al.(1999), the doseresponse 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): 696701. Cite error: Invalid
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 ↑ ^{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): 4757.
 ↑ Haas CN, ThayyarMadabusi A, et al. (1999) Development and Validation of DoseResponse Relationship for Listeria monocytogenes. Quantitative Microbiology 1(1): 89102.