Acanthamoeba Keratitis: Dose Response Models

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Acanthamoeba Keratitis

Author: Sushil Tamrakar


General overview of Acanthamoeba Keratitis

Acanthamoeba keratitis is a rare but serious infection of the eye that can result in permanent visual damage or even causes blindness. This infection is caused by free-living amoeba Acanthamoeba. Acanthamoeba causes the disease when it infects the cornea. Acanthamoebae are very common in nature and can be found in water and soil [1].



Summary Data

Badenoch et al (1990) experimented with Acanthamoeba and Corynabacteruim in rats to study the effect of pathogens in the cornea. In that study, the authors inoculated Acanthamoeba (Ac 118) and Corynebacterium organisms into rat corneas. No effect was observed for groups of rats dosed with graded doses of Acanthamoeba alone, while in combination with Corynebacterium, there were some responses at higher doses.


Experiment serial number Reference Host type Agent strain Route # of doses Dose units Response Best fit model Optimized parameter(s) LD50/ID50
264 [2] rat Ac118 eyes -cornea 4 no of trophozoites infection exponential k = 1.01E-04 6.89E+03
265 [2] rat Ac119 eyes -cornea 4 no of trophozoites infection exponential k = 3.63E-04 1.91E+03
*This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.


Exponential and betapoisson model.jpg

Optimization Output for experiment 264

Dose response data [2]
Dose Infected Non-infected Total
10 0 8 8
100 0 16 16
1000 2 16 18
1E+04 5 3 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 0.388 0.00767 3 3.84
0.93
7.81
0.943
Beta Poisson 0.381 2 5.99
0.827
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 1.01E-04 2.24E-05 3.58E-05 4.82E-05 1.90E-04 2.16E-04 2.59E-04
ID50/LD50/ETC* 6.89E+03 2.68E+03 3.21E+03 3.65E+03 1.44E+04 1.94E+04 3.10E+04
*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


Optimization Output for experiment 265

Dose response data [2]
Dose Infected Non-infected Total
10 0 8 8
100 0 16 16
1000 7 17 24
1E+04 10 0 10


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 1.78 -0.000219 3 3.84
1
7.81
0.62
Beta Poisson 1.78 2 5.99
0.411
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 3.63E-04 2.04E-04 2.30E-04 2.59E-04 5.69E-04 5.69E-04 7.09E-04
ID50/LD50/ETC* 1.91E+03 9.78E+02 1.22E+03 1.22E+03 2.68E+03 3.01E+03 3.39E+03
*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



Summary

There was no effect of Acanthamoeba without Corynebacterium.



References

  1. CDC. (2012). "Parasites- Acanthamoeba." Retrieved 03/30/2012, 2012, from http://www.cdc.gov/parasites/acanthamoeba/.
  2. 2.0 2.1 2.2 2.3 Badenoch, P. R., A. M. Johnson, et al. (1990). "Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea." Archives of Ophthalmology 108: 107-112.