Difference between revisions of "Enteroviruses: Dose Response Models"

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(Optimized Models and Uncertainty and Fitting Analyses)
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[[File:Cliver1981(2)_Enterovirus_ExpHist.png|thumb|left|500px|<center>'''(a)'''</center>]][[File:Cliver1981(2)_Enterovirus_ExpModel.png|thumb|none|500px|<center>'''(b)'''</center>]]
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==='''Summary'''===
 
==='''Summary'''===

Revision as of 15:55, 15 February 2011

Enteroviruses

Author: Yin Huang
If you want to download this chapter in pdf format, please click here
If you want to download the excel spreadsheet of tables, please click the captions of tables. If you want to download a specific figure, just click on the figure


General overview

Enterovirus, a kind of small (30 nm), nonenveloped, single-stranded RNA viruses, belongs to the family Picornaviridae. While most of the enterovirus infections are relatively mild and result in complete recovery of the patient, they can also cause severe and fatal diseases such as meningitis, encephalitis, myocarditis, neonatal sepsis, and polio. Infection occurs mainly via fecal-oral transmission and less commonly by respiratory droplets. While no known non-human reservoirs have been identified, water-borne, foodborne, and blood-borne transmissions have been reported (Stalkup and Chilukuri 2002).




Summary Data

Cliver (1981) challenged pigs with Porcine enterovirus type 3 and 7 via oral exposure route.

Table 20.1. Summary of the enterovirus data and best fits
Experiment number Reference Host type/pathogen strain Route/number of doses Dose units Response Best-fit model Best-fit parameters LD50
1 Cliver, 1981 pigs/ Porcine enterovirus type 3 oral/3 pfu infection Beta-Poisson k=0.00030 2340.15
2 Cliver, 1981 pigs/ Porcine enterovirus type 7 oral/3 pfu infection Beta-Poisson k=0.0037 185.10

The data from different experiments were not able to be statistically pooled.



Optimized Models and Uncertainty and Fitting Analyses

Output for experiment 1.

Table 20.2: Dose response data
Dose (pfu) death survival Total
1.00E+02 0 3 3
2.50E+02 0 6 6
1.00E+03 2 4 6
Cliver, 1981.


Table 20.3: Goodness of fit and model selection
Model Deviance Δ DF χ20.95,df χ20.95,1
Exponential 1.24 0 2 5.99 3.84
Beta Poisson* 1.24 1 3.84
*Conclusion: Both models fit well, but the exponential model is better than beta-Poisson.
Table 20.4: Parameters for the best-fit model (exponential ), obtained from 1E4 bootstrap iterations
Parameter or value MLE Estimate Percentiles
0.50% 2.5% 5% 95% 97.5% 99.5%
k 0.000296 2.40E-17 2.40E-17 2.40E-17 0.000719 0.000719 0.001025
LD50 (spores) 2340.15 676.5683 963.8791 963.8791 2.89E+16 2.89E+16 2.89E+16


(a)
(b)


Fig 20.1. Models plot for experiment 1. (a) Uncertainty plot of exponential model; (b) Plot of exponential model with upper and lower 95% and 99% confidence.




Output for experiment 2.

Table 20.5: Dose response data
Dose (pfu) death survival Total
2.50E+02 4 2 6
2.50E+02 3 3 6
1.00E+03 5 0 5
Cliver, 1981.


Table 20.6: Goodness of fit and model selection
Model Deviance Δ DF χ20.95,df χ20.95,1
Exponential 0.61 0 2 5.99 3.84
Beta Poisson* 0.61 1 3.84
*Conclusion: Both models fit well, but the exponential model is better than beta-Poisson.
Table 20.7: Parameters for the best-fit model (exponential ), obtained from 1E4 bootstrap iterations
Parameter or value MLE Estimate Percentiles
0.50% 2.5% 5% 95% 97.5% 99.5%
k 0.0037 0.001829 0.002191 0.002191 0.005619 0.005619 0.005619
LD50 (spores) 185.10 123.3551 123.3551 123.3551 316.3171 316.3171 378.9585


(a)
(b)



Fig 20.2. Models plot for experiment 2. (a) Uncertainty plot of exponential model; (b) Plot of exponential model with upper and lower 95% and 99% confidence.



Summary

The different LD50 for these two experiments indicates various virulence between pathogen strains.




References

Cliver, D. O. (1981). "Experimental infection by waterborne enteroviruses." Journal of Food Protection 44: 861-865.

Stalkup, J. R. and S. Chilukuri (2002). "Enterovirus infections: a review of clinical presentation, diagnosis, and treatment." Dermatologic clinics 20(2): 217-223.