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General overview

Acanthamoeba spp. are free-living amoeba (FLA) that have been commonly found in freshwater, tap water, and recreational water. Acanthamoeba spp. are capable of causing a variety of infections, including Acanthamoeba keratitis, an eye infection that has been associated with contect lens usage and cornea damage, and Granulomatous Amebic Encephalitis (GAE), a serious central nervous system infection that primarily affects immunocompromised individuals (Marciano-Cabral & Cabral, 2003; Visvesvara, Moura, & Schuster, 2007)[2] . Considering these infections, some exposure routes of concern for Acanthamoeba spp. are the corneal and intranasal exposure routes. 

 

Dean et al. (2020) fit dose response models to data from previously conducted animal studies for Acanthamoeba spp. and the corneal and instranasal exposure routes. These models are an important step towards characterizing the risk associated with FLA like Acanthamoeba for drinking water-relevant exposure scenarios. More detailed descriptions of the datasets, fitting methods, model evaluation, and results can be found in the published article: http://dx.doi.org/10.1111/risa.13603

Recommended Model

For the corneal exposure route, two dose response models are provided for consideration. 

 

Marciano-Cabral, F., & Cabral, G. (2003). Acanthamoeba spp. as agents of disease in humans. Clinical Microbiology Reviews. https://doi.org/10.1128/CMR.16.2.273-307.2003

 

ID Exposure Route # of Doses Agent Strain Dose Units Host type Μodel LD50/ID50 Optimized parameters Response type Reference
Acanth_Cornea1 eyes-cornea 4.00 Acanthamoeba Ac118 no of trophozoites rat exponential 6,886 k = 1.01E-04 infection
Badenoch, P. R., Johnson, A. M., Christy, P. E., & Coster, D. J. (1990). Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea. Archives of Ophthalmology, 108, 1. Retrieved from https://jamanetwork.com/journals/jamaophthalmology/article-abstract/638228
Acanth_Cornea2 eyes-cornea 4.00 Acanthamoeba Ac118 no of trophozoites rat exponential 1.91E+03 k = 3.63E-04 infection
Badenoch, P. R., Johnson, A. M., Christy, P. E., & Coster, D. J. (1990). Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea. Archives of Ophthalmology, 108, 1. Retrieved from https://jamanetwork.com/journals/jamaophthalmology/article-abstract/638228
Exposure Route:
eyes-cornea
# of Doses:
4.00
Agent Strain:
Acanthamoeba Ac118
Dose Units:
no of trophozoites
Host type:
rat
Μodel:
exponential
LD50/ID50:
6,886
Optimized parameters: k = 1.01E-04
Response type:
infection
Reference:
Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea

Badenoch et al. (1990) studied the combined effect of Acanthamoeba Ac118 (a group III isolate) and the bacterium Corynebacterium xerosis on the corneas of female Porton rats. A constant dose of 104 C. xerosis with increasing doses of Acanthamoeba spp. were injected into incisions in the rat corneas using a microsyringe (Badenoch et al. 1990).

The exponential model provided the best fit to the data. 

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

 

Exposure Route:
eyes-cornea
# of Doses:
4.00
Agent Strain:
Acanthamoeba Ac118
Dose Units:
no of trophozoites
Host type:
rat
Μodel:
exponential
LD50/ID50:
1.91E+03
Optimized parameters: k = 3.63E-04
Response type:
infection
Reference:
Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea

Badenoch et al. (1990) studied the combined effect of Acanthamoeba Ac118 (a group III isolate) and the bacterium Corynebacterium xerosis on the corneas of female Portion rats. A constant dose of 106 C. xerosis with increasing doses of Acanthamoeba spp. were injected into incisions in the rat corneas using a microsyringe.

The exponential model provided the best fit to the data.

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

References

  • Visvesvara, G. S., Moura, H. ., & Schuster, F. L. (2007). Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunology & Medical Microbiology, 50, 1–26. https://doi.org/10.1111/j.1574-695X.2007.00232.x
  • Dean, K. ., Tamrakar, S. ., Huang, Y. ., Rose, J. ., & Mitchell, J. . (2021). Modeling the Dose Response Relationship of Waterborne Acanthamoeba. Risk Analysis, 41. https://doi.org/10.1111/risa.13603
  • Badenoch, P. R., Johnson, A. M., Christy, P. E., & Coster, D. J. (1990). Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea. Archives of Ophthalmology, 108, 1. Retrieved from https://jamanetwork.com/journals/jamaophthalmology/article-abstract/638228