Enteroviruses
Author: Yin Huang
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General overview
Enterovirus, a kind of small (30 nm), nonenveloped, singlestranded 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 fecaloral transmission and less commonly by respiratory droplets. While no known nonhuman reservoirs have been identified, waterborne, foodborne, and bloodborne 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.
Experiment serial number 
Reference 
Host type 
Agent strain 
Route 
# of doses 
Dose units 
Response 
Best fit model 
Optimized parameter(s) 
LD_{50}/ID_{50}

63* 
^{[1]} 
pig 
porcine, PE705i 
oral 
3 
pfu 
infection 
exponential 
k = 3.74E03 
1.85E+02

62 
^{[1]} 
pig 
porcine, PE3ECPO6 
oral 
3 
pfu 
infection 
exponential 
k = 2.96E04 
2.34E+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
It is recommended that experiment 63 should be used as the best doseresponse model. A more virulent strain in experiment 1 can be more meaningful for emergency preparedness.
a:
Optimization Output for experiment 63
pigs/ Porcine enterovirus type 7 ^{[1]}
Dose 
infected 
Noninfected 
Total

250 
4 
2 
6

250 
3 
3 
6

1000 
5 
0 
5


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

0.614

5.49e05

2

3.84 1

5.99 0.736

Beta Poisson

0.614

1

3.84 0.433

Exponential is preferred to betaPoisson; cannot reject good fit for exponential.


Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter

MLE estimate

Percentiles

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

k 
3.74E03 
1.83E03 
2.19E03 
2.19E03 
5.62E03 
5.62E03 
5.62E03

ID50/LD50/ETC* 
1.85E+02 
1.23E+02 
1.23E+02 
1.23E+02 
3.16E+02 
3.16E+02 
3.79E+02

*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 62
Pigs/ Porcine enterovirus type 3 Strain model data ^{[1]}
Dose 
infected 
Noninfected 
Total

100 
0 
3 
3

250 
0 
6 
6

1000 
2 
4 
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

1.24

0.000314

2

3.84 1

5.99 0.537

Beta Poisson

1.24

1

3.84 0.265

Exponential is preferred to betaPoisson; cannot reject good fit for exponential.


Optimized k parameter for the exponential model, from 10000 bootstrap iterations
Parameter

MLE estimate

Percentiles

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

k 
2.96E04 
2.40E17 
2.40E17 
2.40E17 
7.19E04 
7.19E04 
1.02E03

ID50/LD50/ETC* 
2.34E+03 
6.77E+02 
9.64E+02 
9.64E+02 
2.89E+16 
2.89E+16 
2.89E+16

*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
Summary
The different LD_{50} for these two experiments indicates various virulence between pathogen strains.
References
 ↑ ^{1.0} ^{1.1} ^{1.2} ^{1.3} Cliver, D. O. (1981). "Experimental infection by waterborne enteroviruses." Journal of Food Protection 44: 861865.
Cliver, D. O. (1981). "Experimental infection by waterborne enteroviruses." Journal of Food Protection 44: 861865.
Stalkup, J. R. and S. Chilukuri (2002). "Enterovirus infections: a review of clinical presentation, diagnosis, and treatment." Dermatologic clinics 20(2): 217223.