Acanthamoeba: Dose Response Experiments (Cornea)

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] [1]. Considering these infections, some exposure routes of concern for Acanthamoeba spp. are the corneal and intranasal exposure routes.

Dean et al. (2020)^[2] 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

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.
Dean, K., Tamrakar S., Huang Y., Rose J., & Mitchell J. (2021). Modeling the Dose Response Relationship of Waterborne Acanthamoeba. Risk Analysis. 41,

ID	Exposure Route	# of Doses	Agent Strain	Dose Units	Host type	Μodel	LD50/ID50	Optimized parameters	Response type	Reference
Acanth_Cornea1	eyes-cornea	4	Acanthamoeba Ac118	no of trophozoites	rat	exponential	6,886	k = 1.01E-04	infection	Badenoch, P R., et al. "Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea." Archives of Ophthalmology. 108 (1990): 1.
Acanth_Cornea2	eyes-cornea	4	Acanthamoeba Ac118	no of trophozoites	rat	exponential	1.91E+03	k = 3.63E-04	infection	Badenoch, P R., et al. "Pathogenicity of Acanthamoeba and Corynebacterium in the Rat Cornea." Archives of Ophthalmology. 108 (1990): 1.

Experiment ID:

Acanth_Cornea1

# of Doses:

Agent Strain:

Acanthamoeba Ac118

Dose Units:

no of trophozoites

Host type:

rat

Μodel:

exponential

Optimized parameters:
k = 1.01E-04
LD₅₀/ID₅₀ = 6,886

Reference:

Badenoch et al. (1990)^[1] 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)^[1].

The exponential model provided the best fit to the data.

Acanth_Cornea1.png

Plot of 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

Acanth_Cornea1_Boot.png

Figure 2: Histogram of the 10,000 bootstrap replicates of k for the best fitting exponential model fit to Experiment 1