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Home / Framework / Dose Response / Experiments / Cryptosporidium hominis: Dose Response Experiments
ID # of Doses Agent Strain Dose Units Host type Μodel Optimized parameters Response type Reference
108 8 Iowa strain oocysts human exponential
k = 4.19E-03
LD50/ID50 = 1.65E+02

infection DuPont, H. L., et al. "The infectivity of Cryptosporidium parvum in healthy volunteers." The New England journal of medicine. 332 (1995): 13.
139 8 Iowa isolate oocysts human exponential
k = 5.26E-03
LD50/ID50 = 1.32E+02

infection Messner, M. J., C. L. Chappell, and P. C. Okhuysen. "Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data." Water Research. 35 (2001): 16.
140 4 TAMU isolate oocysts human exponential
k = 5.72E-02
LD50/ID50 = 1.21E+01

infection Messner, M. J., C. L. Chappell, and P. C. Okhuysen. "Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data." Water Research. 35 (2001): 16.
141 4 UCP isolate oocysts human beta-Poisson a = 1.45E-01

LD50/ID50 = 1.79E+02
N50 = 1.79E+02
infection Coster, T. S., et al. "Immune response, ciprofloxacin activity, and gender differences after human experimental challenge by two strains of enterotoxigenic Escherichia coli." Infection and immunity. 75 (2007): 1.
181 4 *C. hominis*, TU502 oocysts human beta-Poisson a = 2.7E-01

LD50/ID50 = 1.68E+01
N50 = 1.68E+01
diarrhea Okhuysen, P. C., et al. "Infectivity of a Cryptosporidium parvum Isolate of Cervine Origin for Healthy Adults and Interferon-γ Knockout Mice." Journal of Infectious Diseases. 185 (2002): 9.
183 4 Moredun isolate oocysts human beta-Poisson a = 1.14E-01

LD50/ID50 = 4.55E+02
N50 = 4.55E+02
infection Blaser, M. J., et al. "Experimental Campylobacter jejuni Infection of Adult Mice." Infection and Immunity. 39 (1983): 2.
Experiment ID:
108
# of Doses:
8
Agent Strain:
Iowa strain
Dose Units:
oocysts
Host type:
human
Μodel:
exponential
Optimized parameters:
k = 4.19E-03
LD50/ID50 = 1.65E+02

Reference:
Iowa strain data [1]
Dose Infected Non-infected Total
30 1 4 5
100 3 5 8
300 2 1 3
500 5 1 6
1000 2 0 2
1E+04 3 0 3
1E+05 1 0 1
1E+06 1 0 1

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value		 χ20.95,m-k 
p-value
Exponential 0.503 0.131 7 3.84 
0.717		 14.1 
0.999
Beta Poisson 0.372 6 12.6 
0.999
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 4.19E-03 1.80E-03 2.22E-03 2.46E-03 7.52E-03 8.52E-03 1.12E-02
ID50/LD50/ETC* 1.65E+02 6.17E+01 8.14E+01 9.22E+01 2.82E+02 3.12E+02 3.84E+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

References

  1. The infectivity of Cryptosporidium parvum in healthy volunteers, DuPont, H. L., Chappell C. L., Sterling C. R., Okhuysen P. C., Rose J. B., and Jakubowski W. , The New England journal of medicine, Volume 332, p.13, (1995)
Experiment ID:
139
# of Doses:
8
Agent Strain:
Iowa isolate
Dose Units:
oocysts
Host type:
human
Μodel:
exponential
Optimized parameters:
k = 5.26E-03
LD50/ID50 = 1.32E+02

Reference:
Iowa isolate data [1]
Dose Infected Not infected Total
30 2 3 5
100 4 4 8
300 2 1 3
500 5 1 6
1000 2 0 2
1E+04 3 0 3
1E+05 1 0 1
1E+06 1 0 1

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value		 χ20.95,m-k 
p-value
Exponential 3.07 2 7 3.84 
0.157		 14.1 
0.879
Beta Poisson 1.07 6 12.6 
0.983
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 5.26E-03 2.25E-03 2.75E-03 3.08E-03 1.03E-02 1.19E-02 1.60E-02
ID50/LD50/ETC* 1.32E+02 4.33E+01 5.80E+01 6.72E+01 2.25E+02 2.52E+02 3.08E+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

References

  1. Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data, Messner, M. J., Chappell C. L., and Okhuysen P. C. , Water Research, Volume 35, p.16, (2001)
Best Fit
Experiment ID:
140
# of Doses:
4
Agent Strain:
TAMU isolate
Dose Units:
oocysts
Host type:
human
Μodel:
exponential
Optimized parameters:
k = 5.72E-02
LD50/ID50 = 1.21E+01

Reference:
TAMU data [1]
Dose Infected Non-infected Total
10 2 1 3
30 2 1 3
100 3 0 3
500 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 1.07 0.21 3 3.84 
0.647		 7.81 
0.783
Beta Poisson 0.864 2 5.99 
0.649
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 5.72E-02 1.80E-02 1.92E-02 2.46E-02 2.65E+00 2.65E+00 2.65E+00
ID50/LD50/ETC* 1.21E+01 2.61E-01 2.61E-01 2.61E-01 2.82E+01 3.61E+01 3.84E+01
*Not a parameter of the exponential model; however, it facilitates comparison with other models.

Exponential model plot, with confidence bounds around optimized model

Parameter histogram for exponential model (uncertainty of the parameter)

 

 

References

  1. Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data, Messner, M. J., Chappell C. L., and Okhuysen P. C. , Water Research, Volume 35, p.16, (2001)
Experiment ID:
141
# of Doses:
4
Agent Strain:
UCP isolate
Dose Units:
oocysts
Host type:
human
Μodel:
beta-Poisson
Optimized parameters: a = 1.45E-01

LD50/ID50 = 1.79E+02
N50 = 1.79E+02
Reference:
UCP isolate [1]
Dose Infected Non-infected Total
500 3 2 5
1000 2 1 3
5000 2 3 5
1E+04 4 0 4

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value		 χ20.95,m-k 
p-value
Exponential 11.5 6.99 3 3.84 
0.0082		 7.81 
0.00945
Beta Poisson 4.48 2 5.99 
0.107
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 1.45E-01 9.81E-04 4.63E-03 9.53E-03 1.27E+00 1.46E+02 9.10E+02
N50 1.79E+02 2.74E-13 7.60E-10 4.54E-09 2.62E+03 3.22E+03 6.10E+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

  1. Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data, Messner, M. J., Chappell C. L., and Okhuysen P. C. , Water Research, Volume 35, p.16, (2001)
Experiment ID:
181
# of Doses:
4
Agent Strain:
*C. hominis*, TU502
Dose Units:
oocysts
Host type:
human
Μodel:
beta-Poisson
Optimized parameters: a = 2.7E-01

LD50/ID50 = 1.68E+01
N50 = 1.68E+01
Reference:
TU502 data [1]
Dose Diarrhea Not diarrhea Total
10 2 3 5
30 3 2 5
100 5 2 7
500 3 1 4

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value		 χ20.95,m-k 
p-value
Exponential 11.6 11.5 3 3.84 
0.000708		 7.81 
0.00894
Beta Poisson 0.119 2 5.99 
0.942
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 2.7E-01 9.83E-04 9.85E-04 2.03E-03 6.60E+00 6.70E+02 3.19E+03
N50 1.68E+01 3.41E-16 9.86E-09 1.68E-06 7.15E+01 9.76E+01 6.59E+02

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

  1. Cryptosporidium Hominis: Experimental Challenge of Healthy Adults, Chappell, C. L., Okhuysen P. C., Langer-Curry R., Widmer G., Akiyoshi D. E., Tanriverdi S., and Tzipori S. , The American Journal of Tropical Medicine and Hygiene, Volume 75, p.5, (2006)
Experiment ID:
183
# of Doses:
4
Agent Strain:
Moredun isolate
Dose Units:
oocysts
Host type:
human
Μodel:
beta-Poisson
Optimized parameters: a = 1.14E-01

LD50/ID50 = 4.55E+02
N50 = 4.55E+02
Reference:
Moredunn isolate data [1]
Dose Infected Non-infected Total
100 2 2 4
300 2 3 5
1000 1 2 3
3000 3 1 4

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value		 χ20.95,m-k 
p-value
Exponential 7.37 6.16 3 3.84 
0.0131		 7.81 
0.0611
Beta Poisson 1.21 2 5.99 
0.546
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 1.14E-01 9.79E-04 9.81E-04 9.82E-04 1.17E+03 2.25E+03 5.52E+03
N50 4.55E+02 2.13E-09 2.19E-06 1.55E-05 5.62E+05 3.59E+09 1.43E+16

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

  1. Infectivity of a Cryptosporidium parvum Isolate of Cervine Origin for Healthy Adults and Interferon-γ Knockout Mice, Okhuysen, P. C., Rich S. M., Chappell C. L., Grimes K. A., Widmer G., Feng X., and Tzipori S. , Journal of Infectious Diseases, Volume 185, p.9, (2002)