General Overview

Echoviruses, a member of the enterovirus genus, is a type of RNA virus that were shown to be a frequent cause of simple febrile illnesses and aseptic meningitis. Most infected persons experience no symptoms or have self-limited disease. Deaths and other adverse consequences are rare and limited to patients with severe echovirus encephalitis or to persons with B cell-deficiency syndromes who develop persistent infection (Modlin 1986).

Human echoviral infection occurs via fecal-oral transmission. Infants are particularly susceptible to echovirus infection. Both vertical transmission from an infected mother and nosocomial transmission via hospital personnel appear to be important sources of infection for the neonate. Severe disease and death may follow the infection that occurs with the first 10-14 days of life (Modlin 1986).

Summary Data

Schiff et al. (1984) challenged human volunteers lacking detectable serum antibody with echovirus-12 in chilled drinking water. The virus used in the study was originally recovered from a child with a clinical diagnosis of erythema infectiousum (fifth disease). The infection with echovirus-12 among volunteers was determined by intestinal shedding of virus and seroconversion.

Summary

The limited numbers of subjects under dose 33000 and 330000 might have contributed to their deviations from other dose groups and the unsuccessful fitting. By excluding these two outliner groups, significantly better fit was achieved (The reduction of deviance is substantially greater than the chi-square value at the degree of freedom of 2)

ID # of Doses Agent Strain Dose Units Host type Μodel Optimized parameters Response type Reference
112 6 strain 12 PFU human beta-Poisson a = 3.74E-01

LD50/ID50 = 1.01E+03
N50 = 1.01E+03
infection Suptel, E. A.. "Pathogenesis of experimental Coxsackie virus infection." Archive of Virology. 7 (1963): 61-66.
256 (excluding the outliers of exp 112) 4 strain 12 PFU human beta-Poisson a = 1.06E+00

LD50/ID50 = 9.22E+02
N50 = 9.22E+02
infection Schiff, G. M., et al. "Studies of echovirus-12 in volunteers: determination of minimal infectious dose and the effect of previous infection on infectious dose." The Journal of infectious diseases. 150 (1984): 6.
Experiment ID:
112
# of Doses:
6
Agent Strain:
strain 12
Dose Units:
PFU
Host type:
human
Μodel:
beta-Poisson
Optimized parameters: a = 3.74E-01

LD50/ID50 = 1.01E+03
N50 = 1.01E+03
Reference:
humans/ echovirus-12 strain [1]
Dose infected Non-infected Total
330 15 35 50
1000 9 11 20
3300 19 7 26
1E+04 12 0 12
33000 2 2 4
330000 2 1 3

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom
χ20.95,1 
p-value
χ20.95,m-k 
p-value
Exponential 122 110 5 3.84 
0
11.1 
0
Beta Poisson 11.7 4 9.49 
0.0196
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 3.74E-01 1.24E-01 1.81E-01 2.09E-01 7.79E-01 9.41E-01 2.01E+00
N50 1.01E+03 3.84E+02 5.32E+02 5.94E+02 1.75E+03 1.97E+03 2.54E+03

 

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

Best Fit
Experiment ID:
256 (excluding the outliers of exp 112)
# of Doses:
4
Agent Strain:
strain 12
Dose Units:
PFU
Host type:
human
Μodel:
beta-Poisson
Optimized parameters: a = 1.06E+00

LD50/ID50 = 9.22E+02
N50 = 9.22E+02
Reference:
humans/ echovirus-12 strain [1]
Dose infected Non-infected Total
330 15 35 50
1000 9 11 20
3300 19 7 26
1E+04 12 0 12

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom
χ20.95,1 
p-value
χ20.95,m-k 
p-value
Exponential 7.39 4.18 3 3.84 
0.041
7.81 
0.0605
Beta Poisson 3.21 2 5.99 
0.201
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 1.06E+00 3.07E-01 4.04E-01 4.69E-01 1.23E+01 6.22E+02 3.74E+04
N50 9.22E+02 4.68E+02 5.59E+02 6.15E+02 1.37E+03 1.49E+03 1.73E+03

 

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