Description

Červa (1967a,b) studied white mice of the Czechoslovak H-strain weighing 13-15 grams inoculated intranasally by placing 0.02 mL of the A1 strain of Acanthamoeba over the nares of the ethyl-ether anesthetized mice (Cerva, 1967b).

The beta-Poisson model provided the best fit to the data. 

 

Cerva, L. (1967b). Intranasal, Intrapulmonary, and Intracardial Inoculation of Experimental Animals with Hartmanella castellanii. Folia Parasitologica (Praha), 14, 207–215.

# of Doses
6.00
Μodel
N50
14,690 or 14,538
Dose Units
Response
Exposure Route
Contains Preferred Model
Status
fitted
a
0.161
Agent Strain
A. culbertsoni (A1)
Experiment ID
Acanth_Intranasal1
Host type
Experiment Dataset
Dose (no. of organisms) Positive Response Negative Response Total Subjects/Responses
3 0 20 20
30 2 18 20
300 1 19 20
3000 9 11 20
Description

Culbertson et al. (1966) studied the pathogenicity of the HN-3 strain of A. castellanii (Culbertson et al., 1966; Marciano-Cabral & Cabral, 2003) on ether-anesthetized-specific-pathogen-free (SPF) mice. Cultures of amebae were grown in trypticase soy broth and diluted so that 0.03 mL of a concentrated suspension could be instilled intranasally into the mice by placing fluid over the nares (Culbertson et al., 1966; Culbertson, Ensminger, & Overton, 1965a; Culbertson, Ensminger, & Overton, 1965b).

The exponential model provided the best fit to the data. 

Figure 1: Plot of exponential model fit to Experiment 6 with upper and lower 95% and 99% confidence
Figure 1: Plot of exponential model fit to Experiment 6 with upper and lower 95% and 99% confidence
Figure 2: Histogram of the 10,000 bootstrap replicates of k for the best fitting exponential model fit to Experiment 6
Figure 2: Histogram of the 10,000 bootstrap replicates of k for the best fitting exponential model fit to Experiment 6

 

Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.

# of Doses
3.00
Μodel
LD50/ID50
2.67E+03
Dose Units
Exposure Route
Contains Preferred Model
Status
fitted
k
2.60E-04
Agent Strain
A. castellanii HN-3
Experiment ID
Acanth_Intranasal4
Host type
Experiment Dataset
Dose (no. of organisms) Positive Response Negative Response Total Subjects/Responses
100 2 78 80
500 9 71 80
1000 21 59 80
Description

Culbertson et al. (1966) studied the pathogenicity of the HN-3 strain of A. castellanii (Culbertson et al., 1966; Marciano-Cabral & Cabral, 2003) on ether-anesthetized-specific-pathogen-free (SPF) mice. Cultures of amebae were grown in trypticase soy broth and diluted so that 0.03 mL of a concentrated suspension could be instilled intranasally into the mice by placing fluid over the nares (Culbertson et al., 1966; Culbertson, Ensminger, & Overton, 1965a; Culbertson, Ensminger, & Overton, 1965b).

The exponential model provided the best fit to the data. 

Figure 1: Plot of exponential model fit to Experiment 5 with upper and lower 95% and 99% confidence
Figure 1: Plot of exponential model fit to Experiment 5 with upper and lower 95% and 99% confidence

Culbertson, C. G., Holmes, D. H., & Overton, W. M. (1965b). Hartmanella castellani (Acanthamoeba sp.). The American Journal of Clinical Pathology, 43(4), 361–364.

Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.

Figure 2: Histogram of the 10,000 bootstrap replicates of k for the best fitting exponential model fit to Experiment 5
Figure 2: Histogram of the 10,000 bootstrap replicates of k for the best fitting exponential model fit to Experiment 5
# of Doses
3.00
Μodel
LD50/ID50
749
Dose Units
Response
Exposure Route
Contains Preferred Model
Status
fitted
k
9.26E-04
Agent Strain
A. castellanii HN-3
Experiment ID
Acanth_Intranasal3
Host type
Experiment Dataset
Dose (no. of organisms) Positive Response Negative Response Total Subjects/Responses
100 7 73 80
500 31 49 80
1000 43 37 80
Description

Culbertson et al. (1966) studied the pathogenicity of the HN-3 strain of A. castellanii (Culbertson et al., 1966; Marciano-Cabral & Cabral, 2003) on ether-anesthetized-specific-pathogen-free (SPF) mice. Cultures of amebae were grown in trypticase soy broth and diluted so that 0.03 mL of a concentrated suspension could be instilled intranasally into the mice by placing fluid over the nares (Culbertson et al., 1966; Culbertson, Ensminger, & Overton, 1965a; Culbertson, Ensminger, & Overton, 1965b).

The exponential model provided the best fit to the data. 

 

Figure 1. Parameter histogram for exponential model (uncertainty of the parameter)
Figure 1. Parameter histogram for exponential model (uncertainty of the parameter)
Figure 2. Exponential model plot, with confidence bounds around optimized model
Figure 2. Exponential model plot, with confidence bounds around optimized model

Culbertson, C. G., Holmes, D. H., & Overton, W. M. (1965b). Hartmanella castellani (Acanthamoeba sp.). The American Journal of Clinical Pathology, 43(4), 361–364.

Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.

# of Doses
3.00
Μodel
LD50/ID50
5.28E+03
Dose Units
Response
Exposure Route
Contains Preferred Model
Status
fitted
k
1.31E-04
Agent Strain
A. castellanii HN-3
Experiment ID
Acanth_Intranasal2
Host type
Experiment Dataset
Dose (no. of organsims) Positive Responses Negative Responses Total Subjects/Responses
100 2 78 80
500 4 76 80
1000 10 70 80
Description
myco
Host
C57BL/6 beige mice/NS
# of Doses
5.00
Μodel
LD50/ID50
2.22E+8
Dose Units
Response
Exposure Route
Contains Preferred Model
Status
fitted
k
3.12E-9
Agent Strain
MAC 101 (human-derived)
Experiment ID
myco_intravenous_2
Host type
Experiment Dataset
Description
Mycobacterium_Avium_1
Host
Female C57BL/6 beige Mice/5 weeks
# of Doses
5.00
Μodel
LD50/ID50
6.30E+5
Dose Units
Response
Exposure Route
Contains Preferred Model
Status
fitted
k
1.10E-6
Agent Strain
M. avium serovar 1, human non- AIDS isolates: pooled strains N-289, N-356, N-357, N-364, N-445, N458, N-461; Serovar 9 strains N-254, N-302
Experiment ID
myco_intravenous
Host type
Experiment Dataset
Description
T3 Strain for serotype PEN 3 model data 
Dose Infected Non-infected Total
1E+04 2 3 5
1E+05 4 1 5
1E+06 2 3 5
1E+07 3 2 5
1E+08 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 45.6 40.2 4 3.84
2.25e-10
9.49
2.92e-09
Beta Poisson 5.41 3 7.81
0.144
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 1.17E-01 1.06E-02 1.79E-02 2.48E-02 2.79E-01 3.29E-01 4.72E-01
N50 3.14E+04 3.29E-09 2.55E-05 2.53E-02 4.21E+05 9.69E+05 3.68E+06

 

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

# of Doses
5.00
Μodel
N50
3.14E+04
LD50/ID50
3.14E+04
Dose Units
Response
Exposure Route
Contains Preferred Model
a
1.17E-01
Agent Strain
type strain for serotype PEN 3
Experiment ID
186
Host type
Description
T2 Strain for serotype PEN 2 model data 
Dose Infected Non-infected Total
1E+04 1 4 5
1E+05 3 2 5
1E+06 4 1 5
1E+07 4 1 5
1E+08 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 25.4 24.5 4 3.84
7.59e-07
9.49
4.13e-05
Beta Poisson 0.969 3 7.81
0.809
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 3.19E-01 8.29E-02 1.26E-01 1.49E-01 1.05E+01 5.53E+02 1.52E+03
N50 6.68E+04 4.06E+02 5.55E+03 1.04E+04 3.58E+05 4.65E+05 8.48E+05

 

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

# of Doses
5.00
Μodel
N50
6.68E+04
LD50/ID50
6.68E+04
Dose Units
Response
Exposure Route
Contains Preferred Model
a
3.19E-01
Agent Strain
type strain for serotype PEN 2
Experiment ID
185
Host type
Description
T1 Strain for serotype PEN 1 data 
Dose Infected Non-infected Total
1 0 5 5
100 0 5 5
1E+04 0 5 5
1E+06 3 2 5
1E+08 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 0.0918 -0.000599 4 3.84
1
9.49
0.999
Beta Poisson 0.0924 3 7.81
0.993
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 9.01E-07 4.61E-08 2.21E-07 2.21E-07 4.61E-06 4.61E-06 4.61E-06
ID50/LD50/ETC* 7.69E+05 1.51E+05 1.51E+05 1.51E+05 3.14E+06 3.14E+06 1.51E+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
5.00
Μodel
LD50/ID50
7.69E+05
Dose Units
Response
Exposure Route
Contains Preferred Model
k
9.01E-07
Agent Strain
type strain for serotype PEN 1
Experiment ID
184
Host type
Description

The same exposure route and endpoint was evaluated for Experiments 3 and 4 (Cerva, 1967b; Culbertson et al. 1966)[6] [5]. A pooling analysis was attempted and successful. The beta-Poisson model provided a good fit to the pooled data and is shown below in Figure 1. Note: both the exact and approximate beta-Poisson models were fit to the data. The figures shown below and the csv file of bootstrapped parameter replicates are for the best fitting parameters of the exact beta-Poisson model. The successful pooling of multiple datasets generally increases the confidence in the estimated model parameters. 

Figure 1: Plot of the beta-Poisson model fit to the pooled Experiments 3 and 4 with upper and lower 95% and 99% confidence
Figure 1: Plot of the beta-Poisson model fit to the pooled Experiments 3 and 4 with upper and lower 95% and 99% confidence

 

Figure 2: Uncertainty plot of the 10,000 paired bootstrap replicates of alpha and beta for the pooled beta-Poisson model.
Figure 2: Uncertainty plot of the 10,000 paired bootstrap replicates of alpha and beta for the pooled beta-Poisson model.

 

 

[6] Cerva, L. (1967b). Intranasal, Intrapulmonary, and Intracardial Inoculation of Experimental Animals with Hartmanella castellanii. Folia Parasitologica (Praha), 14, 207–215.

[5] Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.

# of Doses
9.00
Μodel
N50
19357
Dose Units
Response
Exposure Route
Contains Preferred Model
Status
pooled
Resampled Parameters
a
0.245
Agent Strain
A. castellanii HN-3 and A culbertsoni A1
Experiment ID
Acanth_Intranasal_Pooled
Host type
Experiment Dataset