Salmonella anatum: Dose Response Models

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Salmonella anatum

Author: Sushil Tamrakar


General overview of Salmonella and Salmonellosis

Salmonella, a genus of rod-shaped, gram-negative, non-spore forming, and predominantly motile enterobacteria, causes more than 104 cases of infections per year in United States. Salmonellosis is an important medical problem, as well as infection with non-typhi Salmonella which often causes mild self-limited illness, Severe sequelae including death may occur, particularly in immunocompromised hosts. It has been reported that the incidence of salmonellosis is higher in developing countries, where food handlers may be a reservoir for further transmission of infection. [1]

Salmonella anatum is a common cause of salmonellosis, an important infectious disease in humans and animals. [2] Additionally, unpasteurized fruit juices have been associated with outbreaks of gastrointestinal diseases caused by infection with Salmonella anatum [3]



Summary Data

McCullough, N. B. and C. W. Elsele (1951) inoculated human volunteers orally with the Salmonella anatum strain I,II and III.[4]


Experiment serial number Reference Host type Agent strain Route # of doses Dose units Response Best fit model Optimized parameter(s) LD50/ID50
232, 233* [4] human strain I oral, with eggnog 16 CFU positive stool culture beta-Poisson α= 3.18E-01 , N50 = 3.71E+04 3.71E+04
232 [4] human strain I oral, with eggnog 8 CFU positive stool culture beta-Poisson α = 2.91E-01 , N50 = 4.44E+04 4.44E+04
233 [4] human strain II oral, with eggnog 8 CFU positive stool culture beta-Poisson α = 2.3E-01 , N50 = 4.91E+03 4.91E+03
*This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.


*Recommended Model

The pooled model of experiment number 232 and 233 is the recommended model as more data points in the model result into improvement in fits.



Exponential and betapoisson model.jpg

Optimization Output for experiment 232, 233 (Salmonella anatum)

Human/ Salmonella anatum strain I & II pooled data [4]
Dose Positive stool culture No positive stool culture Total
12000 2 3 5
24000 3 3 6
66000 4 2 6
89000 5 1 6
93000 1 5 6
141000 3 3 6
256000 5 1 6
448000 4 2 6
587000 4 2 6
860000 6 0 6
1040000 6 0 6
3.9E+06 4 2 6
1E+07 6 0 6
2.39E+07 5 1 6
4.45E+07 6 0 6
6.73E+07 8 0 8


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 138 119 15 3.84
0
25
0
Beta Poisson 18.9 14 23.7
0.168
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 3.18E-01 1.35E-01 1.71E-01 1.92E-01 5.70E-01 6.66E-01 9.56E-01
N50 3.71E+04 1.40E+03 5.50E+03 8.86E+03 8.82E+04 1.00E+05 1.30E+05


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 232 (Salmonella anatum)

Human / Salmonella anatum strain I data [4]
Dose Positive stool culture No positive stool culture Total
12000 2 3 5
24000 3 3 6
66000 4 2 6
93000 1 5 6
141000 3 3 6
256000 5 1 6
587000 4 2 6
860000 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 20.5 11 7 3.84
0.000922
14.1
0.00457
Beta Poisson 9.53 6 12.6
0.146
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 2.91E-01 9.77E-04 9.77E-04 4.11E-02 1.68E+00 5.36E+00 1.20E+03
N50 4.44E+04 6.74E-02 8.03E+02 4.15E+03 1.64E+05 6.89E+06 9.07E+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


Optimization Output for experiment 233 (Salmonella anatum)

Human/ Salmonella anatum strain II data [4]
Dose Positive stool culture No positive stool culture Total
89000 5 1 6
448000 4 2 6
1040000 6 0 6
3.9E+06 4 2 6
1E+07 6 0 6
2.39E+07 5 1 6
4.45E+07 6 0 6
6.73E+07 8 0 8


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 62.8 54.2 7 3.84
1.84e-13
14.1
4.22e-11
Beta Poisson 8.6 6 12.6
0.198
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 2.3E-01 3.63E-02 5.29E-02 6.00E-02 5.51E-01 6.70E-01 1.40E+00
N50 4.91E+03 2.59E-10 2.73E-08 4.91E-06 8.72E+04 1.23E+05 2.29E+05


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. Chalker RB, Blaser MJ (1988) A review of human salmonellosis: III. Magnitude of Salmonella infection in the United States. Reviews of Infectious Diseases 10(1): 111-124.
  2. Hartmann FA, West SE (1995) Antimicrobial susceptibility profiles of multidrug-resistant Salmonella anatum isolated from horses. Journal of Veterinary Diagnostic Investigation 7: 159-162.
  3. Krause G, Terzagian R, et al. (2001) Outbreak of Salmonella Serotype Anatum Infection Associated With Unpasteurized Orange Juice. Southern Medical Journal 94(12): 1168&hyhen;1172.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 McCullough NB, Elsele CW (1951) Experimental Human Salmonellosis: I. Pathogenicity of Strains of Salmonella meleagridis and Salmonella anatum Obtained from Spray-Dried Whole Egg. The Journal of Infectious Diseases 88(3): 278-289. Cite error: Invalid <ref> tag; name "McCullough_and_Elsele.2C1951" defined multiple times with different content Cite error: Invalid <ref> tag; name "McCullough_and_Elsele.2C1951" defined multiple times with different content Cite error: Invalid <ref> tag; name "McCullough_and_Elsele.2C1951" defined multiple times with different content

Chalker RB and Blaser MJ (1988) A Review of Human Salmonellosis: III. Magnitude of Salmonella Infection in the United States. Reviews of Infectious Diseases 10(1), 111-124.

Hartmann FA and West SEH (1995) Antimicrobial Susceptibility Profiles of Multidrug-Resistant Salmonella Anatum Isolated from Horses. Journal of Veterinary Diagnostic Investigation 7(1), 159-161.

Krause G, Terzagian R and Hammond R (2001) Outbreak of Salmonella serotype Anatum infection associated with unpasteurized orange juice. Southern medical journal 94(12), 1168-1172.

McCullough NB and Elsele CW (1951) Experimental Human Salmonellosis: I. Pathogenicity of Strains of Salmonella meleagridis and Salmonella anatum Obtained from Spray-Dried Whole Egg. The Journal of Infectious Diseases 88(3), 278-289.