Lassa virus: Dose Response Experiments

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General Overview

Lassa virus is an RNA virus belonging to the family of Arenaviridae. As the causative agent of hemorrhagic fever, Lassa virus infects more than 200,000 people per year, causing more than 3,000 deaths with a mortality rate of about 15% among the hospitalized cases. Hemorrhagic fever is highly fatal disease mostly found in West Africa. The disease has an acute phase lasting 1 to 4 weeks, characterized by fever, skin rash with hemorrhages, sore throat, headache, and diarrhea. The U.S.

ID Exposure Route # of Doses Agent Strain Dose Units Host type Μodel LD50/ID50 Optimized parameters Response type Reference
15 inhalation 4.00 Josiah strain PFU guinea pig beta-Poisson 1.43E+04 a = 7.94E-02 N50 = 1.43E+04 death
Stephenson, E. H., Larson, E. W., & Dominik, J. W. (1984). Effect of environmental factors on aerosol-induced Lassa virus infection. Journal of Medical Virology, 14, 4. Retrieved from https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.1890140402
Exposure Route:
inhalation
# of Doses:
4.00
Agent Strain:
Josiah strain
Dose Units:
PFU
Host type:
guinea pig
Μodel:
beta-Poisson
LD50/ID50:
1.43E+04
Optimized parameters: a = 7.94E-02 N50 = 1.43E+04
Response type:
death
Reference:
Effect of environmental factors on aerosol-induced Lassa virus infection
Guinea pig/ Josiah strain model data 
Dose Dead Survived Total
5 1 7 8
48 1 7 8
724 3 5 8
5370 4 4 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 14.4 13.8 3 3.84 
0.000203 		7.81 
0.00237
Beta Poisson 0.633 2 5.99 
0.729
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 7.94E-02 9.77E-04 9.85E-04 9.87E-04 4.57E-01 1.19E+00 5.76E+02
N50 1.43E+04 2.13E-01 9.22E-01 2.90E+00 1.82E+13 3.06E+17 2.25E+34

 

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

Description
Human/Staphylococcus aureus 
Dose Infected Non-infected Total
2430000 4 16 20
6270000 8 12 20
1.27E+07 13 7 20
2.5E+07 14 6 20
3.34E+07 19 1 20
3.91E+07 20 0 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 5.52 5.36e-05 5 3.84 
0.994 		11.1 
0.356
Beta Poisson 5.52 4 9.49 
0.238
Exponential is preferred to beta-Poisson; 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 7.64E-08 5.67E-08 6.19E-08 6.41E-08 1.00E-07 1.02E-07 1.35E-06
ID50/LD50/ETC* 9.08E+06 2.70E+06 6.79E+06 6.93E+06 1.08E+07 1.12E+07 1.22E+07
*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

# of Doses
6.00
Μodel
exponential
LD50/ID50
9.08E+06
Dose Units
CFU/cm2
Response
infection
Exposure Route
subcutaneous
Contains Preferred Model
k
7.64E-08
Experiment ID
278
Host type
human
Description
Guinea pig/ Josiah strain model data 
Dose Dead Survived Total
0.02 1 9 10
0.2 4 6 10
2 10 0 10
24 10 0 10
2400 15 0 15
240000 5 0 5

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value 		χ20.95,m-k 
p-value
Exponential 0.42 -0.000621 5 3.84 
1 		11.1 
0.995
Beta Poisson 0.42 4 9.49 
0.981
Exponential is preferred to beta-Poisson; 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 2.95E+00 1.35E+00 1.61E+00 1.65E+00 5.43E+00 5.90E+00 7.52E+00
ID50/LD50/ETC* 2.35E-01 9.21E-02 1.17E-01 1.28E-01 4.21E-01 4.32E-01 5.14E-01
*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

# of Doses
6.00
Μodel
exponential
LD50/ID50
2.35E-01
Dose Units
PFU
Response
death
Exposure Route
subcutaneous
Contains Preferred Model
k
2.95E+00
Agent Strain
Josiah strain
Experiment ID
13
Host type
guinea pig
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