Difference between revisions of "Salmonella nontyphoid: Dose Response Models"

From QMRAwiki
Jump to: navigation, search
m
m
Line 6: Line 6:
 
==='''General overview of ''Salmonella'' and Salmonellosis'''===
 
==='''General overview of ''Salmonella'' and Salmonellosis'''===
  
''Salmonella,'' a genus of rod-shaped, gram-negative, non-spore forming, predominantly motile enterobacteria, cause more than 10<sup>4</sup> cases of infections per year in United States. Salmonellosis is an important medical problem.  Infection with non-typhi ''Salmonella'' often causes mild self-limited illness; however, severe sequelae including death may occur, particularly in immunocompromised hosts. The incidence of salmonellosis is higher in developing than in developed countries and in developing countries food handlers may be a reservoir for further transmission of infection (Chalker and Blaser 1988).
+
''Salmonella,'' a genus of rod-shaped, gram-negative, non-spore forming, predominantly motile enterobacteria, cause more than 10<sup>4</sup> cases of infections per year in United States. Salmonellosis is an important medical problem.  Infection with non-typhi ''Salmonella'' often causes mild self-limited illness; however, severe sequelae including death may occur, particularly in immunocompromised hosts. The incidence of salmonellosis is higher in developing than in developed countries and in developing countries food handlers may be a reservoir for further transmission of infection <ref name="Chalker and Blaser 1988">
 +
Chalker RB, Blaser MJ (1988) [http://www.jstor.org/stable/4454281 A review of human salmonellosis: III. Magnitude of Salmonella infection in the United States.] Reviews of Infectious Diseases 10(1): 111-124.</ref>
  
  

Revision as of 13:19, 18 September 2012

Salmonella nontyphoid

Author: Yin Huang


General overview of Salmonella and Salmonellosis

Salmonella, a genus of rod-shaped, gram-negative, non-spore forming, predominantly motile enterobacteria, cause more than 104 cases of infections per year in United States. Salmonellosis is an important medical problem. Infection with non-typhi Salmonella often causes mild self-limited illness; however, severe sequelae including death may occur, particularly in immunocompromised hosts. The incidence of salmonellosis is higher in developing than in developed countries and in developing countries food handlers may be a reservoir for further transmission of infection [1]



Summary Data

Meynell G.G. and Meynell E.W. (1958) inoculated albino (PGMS) mice intraperitoneally with the Salmonella typhimurium strains 216 and 219 and challenged albino (Tuck) mice with Salmonella typhimurium strain 533 via the intraperitoneal route.


Experiment serial number Reference Host type Agent strain Route # of doses Dose units Response Best fit model Optimized parameter(s) LD50/ID50
246* [2] mice strain 216 and 219 intraperitoneal 10 CFU death beta-Poisson α= 2.1E-01 , N50 = 4.98E+01 4.98E+01
247 [2] mice strain 533 intraperitoneal 11 CFU death beta-Poisson α = 6.21E-02 , N50 = 3.46E+07 3.46E+07
248 [2] mice strain 533 intraperitoneal 7 CFU death beta-Poisson α= 1.08E-01 , N50 = 9.66E+06 9.66E+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 246

Mice/Salmonella strain 216 and 219 data [2]
Dose Dead Survived Total
5 7 8 15
25 4 11 15
125 7 8 15
630 9 6 15
3160 8 7 15
16000 13 2 15
8E+04 15 0 15
4E+05 15 0 15
2E+06 15 0 15
1E+07 15 0 15


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 133 113 9 3.84
0
16.9
0
Beta Poisson 20.5 8 15.5
0.00846
Neither the exponential nor beta-Poisson fits well; beta-Poisson is less bad.


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 2.1E-01 1.45E-01 1.58E-01 1.65E-01 2.92E-01 3.14E-01 3.63E-01
N50 4.98E+01 8.10E+00 1.40E+01 1.72E+01 1.31E+02 1.62E+02 2.34E+02


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 247

Mice/ Salmonella strain 533 data [2]
Dose Dead Survived Total
603 6 36 42
1910 3 39 42
6030 7 35 42
19100 5 42 47
60300 6 34 40
191000 3 29 32
603000 6 20 26
1910000 7 7 14
6030000 7 5 12
1.91E+07 10 2 12
6.03E+07 13 0 13


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 193 146 10 3.84
0
18.3
0
Beta Poisson 47.5 9 16.9
3.22e-07
Neither the exponential nor beta-Poisson fits well; beta-Poisson is less bad.


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 6.21E-02 3.53E-02 4.06E-02 4.32E-02 1.09E-01 1.25E-01 1.80E-01
N50 3.46E+07 9.76E+05 1.69E+06 2.40E+06 9.41E+08 2.13E+09 1.34E+10


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 248

Mice/ Salmonella strain 533 data [2]
Dose Dead Survived Total
1E+04 20 180 200
1E+05 17 153 170
1E+06 11 29 40
3160000 6 24 30
1E+07 12 8 20
3.16E+07 17 3 20
1E+08 19 1 20


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 214 165 6 3.84
0
12.6
0
Beta Poisson 48.7 5 11.1
2.56e-09
Neither the exponential nor beta-Poisson fits well; beta-Poisson is less bad.


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 1.08E-01 6.19E-02 7.06E-02 7.52E-02 1.79E-01 1.98E-01 2.44E-01
N50 9.66E+06 1.93E+06 2.43E+06 2.82E+06 5.38E+07 8.11E+07 2.13E+08


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

Noting the very different LD50 for different strains of host and pathogen, substantial variation of susceptibility is manifestly presented. Inconsistencies in the dose response pattern have been identified in the low-dose groups for all three experiments. The failure to successfully pool data from experiment 247 and 248 might be due to this variation and experimental errors. The mechanism behind this low dose variation is suggested for futher study.




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. 2.0 2.1 2.2 2.3 2.4 2.5 Meynell, G. G. and E. W. Meynell (1958). "The Growth of Micro-Organisms in vivo with Particular Reference to the Relation between Dose and Latent Period" Journal of Hygiene 56(3): 323-346

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.

Meynell GG, Meynell EW (1958) The Growth of Micro-Organisms in vivo with Particular Reference to the Relation between Dose and Latent Period Journal of Hygiene 56(3): 323-346