Giardia duodenalis: Dose Response Experiments

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Overview

Giardia is a flagellated protozoan parasite of vertebrates. It attaches noninvasively to the small intestinal wall and absorbs nutrients (Miliotis & Bier 2003). Cysts are intermittently excreted in the stools of infected people; they are infectious immediately.

ID Exposure Route # of Doses Agent Strain Dose Units Host type Μodel LD50/ID50 Optimized parameters Response type Reference
46 oral 8.00 From an infected human Cysts human exponential 3.48E+01 k = 1.99E-02 infection
Rendtorff, R. C. (1954). The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules. American Journal of Hygiene, 59, 2. Retrieved from https://academic.oup.com/aje/article-abstract/59/2/196/89318?redirectedFrom=PDF
47 oral 4.00 From infected humans Cysts beaver beta-Poisson 1.46E+04 a = 1.37E-01 N50 = 1.46E+04 infection
Erlandsen, S. L., Sherlock, L. A., Januschka, M. ., Schupp, D. G., Schaefer, F. W., Jakubowski, W. ., & Bemrick, W. J. (1988). Cross-species transmission of Giardia spp.: inoculation of beavers and muskrats with cysts of human, beaver, mouse, and muskrat origin. Applied and Environmental Microbiology, 54, 11. Retrieved from http://aem.asm.org/content/54/11/2777.abstract
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Exposure Route:
oral
# of Doses:
8.00
Agent Strain:
From an infected human
Dose Units:
Cysts
Host type:
human
Μodel:
exponential
LD50/ID50:
3.48E+01
Optimized parameters: k = 1.99E-02
Response type:
infection
Reference:
The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules
Dose response data 
Dose Infected Non-infected Total
1 0 5 5
10 2 0 2
25 6 14 20
100 2 0 2
1E+04 3 0 3
1E+05 3 0 3
3E+05 3 0 3
1E+06 2 0 2

 

Goodness of fit and model selection
Model Deviance Δ Degrees 
of freedom		 χ20.95,1 
p-value 		χ20.95,m-k 
p-value
Exponential 8.37 -0.000469 7 3.84 
1 		14.1 
0.301
Beta Poisson 8.37 6 12.6 
0.212
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 1.99E-02 8.50E-03 1.05E-02 1.26E-02 2.92E-02 3.29E-02 3.71E-02
ID50/LD50/ETC* 3.48E+01 1.87E+01 2.11E+01 2.38E+01 5.49E+01 6.60E+01 8.15E+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

Exposure Route:
oral
# of Doses:
4.00
Agent Strain:
From infected humans
Dose Units:
Cysts
Host type:
beaver
Μodel:
beta-Poisson
LD50/ID50:
1.46E+04
Optimized parameters: a = 1.37E-01 N50 = 1.46E+04
Response type:
infection
Reference:
Cross-species transmission of Giardia spp.: inoculation of beavers and muskrats with cysts of human, beaver, mouse, and muskrat origin
Dose response data 
Dose Infected Non-infected Total
48 0 6 6
454 2 4 6
4460 1 2 3
550000 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 22.5 21.3 3 3.84 
3.97e-06 		7.81 
5.14e-05
Beta Poisson 1.22 2 5.99 
0.544
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 1.37E-01 1.34E-02 2.24E-02 4.22E-02 3.39E+00 2.21E+02 2.14E+03
N50 1.46E+04 5.09E+02 8.20E+02 1.06E+03 1.71E+08 8.25E+11 1.62E+18

 

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
Dose response data 
Dose Infected Non-infected Total
30 0 8 8
300 0 7 7
3E+04 0 6 6
125000 2 1 3
5E+05 4 1 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 2.49 0.0417 4 3.84 
0.838 		9.49 
0.646
Beta Poisson 2.45 3 7.81 
0.484
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 3.68E-06 1.13E-06 1.35E-06 1.88E-06 9.60E-06 9.60E-06 9.60E-06
ID50/LD50/ETC* 1.89E+05 7.22E+04 7.22E+04 7.22E+04 3.68E+05 5.14E+05 6.14E+05
*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
exponential
LD50/ID50
1.89E+05
Dose Units
Cysts
Response
infection
Exposure Route
stomach tube
Contains Preferred Model
k
3.68E-06
Agent Strain
From infected humans
Experiment ID
48
Host type
muskrat
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