Acanthamoeba: Dose Response Experiments (Intranasal)
General overview
Acanthamoeba spp. are free-living amoeba (FLA) that have been commonly found in freshwater, tap water, and recreational water. Acanthamoeba spp.
ID | Exposure Route | # of Doses | Agent Strain | Dose Units | Host type | Μodel | LD50/ID50 | Optimized parameters | Response type | Reference |
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Acanth_Intranasal1 | intranasal | 6.00 | A. culbertsoni (A1) | no of trophozoites | mice | beta-Poisson | a = 0.161 N50 = 14,690 or 14,538 | death | ||
Acanth_Intranasal2 | intranasal | 3.00 | A. castellanii HN-3 | no of trophozoites | mice | exponential | 5.28E+03 | k = 1.31E-04 | death |
Culbertson, C. ., Ensminger, P. ., & Overton, W. . (1966). Hartmannella (acanthamoeba). Experimental chronic, granulomatous brain infections produced by new isolates of low virulence. American Journal of Clinical Pathology, 46, 305–314. |
Acanth_Intranasal3 | intranasal | 3.00 | A. castellanii HN-3 | no of trophozoites | mice | exponential | 749 | k = 9.26E-04 | brain invasion |
Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (acanthamoeba). Experimental chronic, granulomatous brain infections produced by new isolates of low virulence. American Journal of Clinical Pathology, 46, 305-314. |
Acanth_Intranasal4 | intranasal | 3.00 | A. castellanii HN-3 | no of trophozoites | mice | exponential | 2.67E+03 | k = 2.60E-04 | acute meningoencephalitis |
Culbertson, C. ., Ensminger, P. ., & Overton, W. . (1966). Hartmannella (acanthamoeba). Experimental chronic, granulomatous brain infections produced by new isolates of low virulence. American Journal of Clinical Pathology, 46, 305–314. |
Acanth_Intranasal_Pooled | intranasal | 9.00 | A. castellanii HN-3 and A culbertsoni A1 | no of trophozoites | mice | beta-Poisson | a = 0.245 N50 = 19357 | death |
Červa (1967a,b) studied white mice of the Czechoslovak H-strain weighing 13-15 grams inoculated intranasally by placing 0.02 mL of the A1 strain of Acanthamoeba over the nares of the ethyl-ether anesthetized mice (Cerva, 1967b).
The beta-Poisson model provided the best fit to the data.
Cerva, L. (1967b). Intranasal, Intrapulmonary, and Intracardial Inoculation of Experimental Animals with Hartmanella castellanii. Folia Parasitologica (Praha), 14, 207–215.
Culbertson et al. (1966) studied the pathogenicity of the HN-3 strain of A. castellanii (Culbertson et al., 1966; Marciano-Cabral & Cabral, 2003) on ether-anesthetized-specific-pathogen-free (SPF) mice. Cultures of amebae were grown in trypticase soy broth and diluted so that 0.03 mL of a concentrated suspension could be instilled intranasally into the mice by placing fluid over the nares (Culbertson et al., 1966; Culbertson, Ensminger, & Overton, 1965a; Culbertson, Ensminger, & Overton, 1965b).
The exponential model provided the best fit to the data.
Culbertson, C. G., Holmes, D. H., & Overton, W. M. (1965b). Hartmanella castellani (Acanthamoeba sp.). The American Journal of Clinical Pathology, 43(4), 361–364.
Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.
Culbertson et al. (1966) studied the pathogenicity of the HN-3 strain of A. castellanii (Culbertson et al., 1966; Marciano-Cabral & Cabral, 2003) on ether-anesthetized-specific-pathogen-free (SPF) mice. Cultures of amebae were grown in trypticase soy broth and diluted so that 0.03 mL of a concentrated suspension could be instilled intranasally into the mice by placing fluid over the nares (Culbertson et al., 1966; Culbertson, Ensminger, & Overton, 1965a; Culbertson, Ensminger, & Overton, 1965b).
The exponential model provided the best fit to the data.
Culbertson, C. G., Holmes, D. H., & Overton, W. M. (1965b). Hartmanella castellani (Acanthamoeba sp.). The American Journal of Clinical Pathology, 43(4), 361–364.
Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.
Culbertson et al. (1966) studied the pathogenicity of the HN-3 strain of A. castellanii (Culbertson et al., 1966; Marciano-Cabral & Cabral, 2003) on ether-anesthetized-specific-pathogen-free (SPF) mice. Cultures of amebae were grown in trypticase soy broth and diluted so that 0.03 mL of a concentrated suspension could be instilled intranasally into the mice by placing fluid over the nares (Culbertson et al., 1966; Culbertson, Ensminger, & Overton, 1965a; Culbertson, Ensminger, & Overton, 1965b).
The exponential model provided the best fit to the data.
Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.
The same exposure route and endpoint was evaluated for Experiments 3 and 4 (Cerva, 1967b; Culbertson et al. 1966)[6] [5]. A pooling analysis was attempted and successful. The beta-Poisson model provided a good fit to the pooled data and is shown below in Figure 1. Note: both the exact and approximate beta-Poisson models were fit to the data. The figures shown below and the csv file of bootstrapped parameter replicates are for the best fitting parameters of the exact beta-Poisson model. The successful pooling of multiple datasets generally increases the confidence in the estimated model parameters.
[6] Cerva, L. (1967b). Intranasal, Intrapulmonary, and Intracardial Inoculation of Experimental Animals with Hartmanella castellanii. Folia Parasitologica (Praha), 14, 207–215.
[5] Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.
The same exposure route and endpoint was evaluated for Experiments 3 and 4 (Cerva, 1967b; Culbertson et al. 1966)[6] [5]. A pooling analysis was attempted and successful. The beta-Poisson model provided a good fit to the pooled data and is shown below in Figure 1. Note: both the exact and approximate beta-Poisson models were fit to the data. The figures shown below and the csv file of bootstrapped parameter replicates are for the best fitting parameters of the exact beta-Poisson model. The successful pooling of multiple datasets generally increases the confidence in the estimated model parameters.
[6] Cerva, L. (1967b). Intranasal, Intrapulmonary, and Intracardial Inoculation of Experimental Animals with Hartmanella castellanii. Folia Parasitologica (Praha), 14, 207–215.
[5] Culbertson, C. G., Ensminger, P. W., & Overton, W. M. (1966). Hartmannella (Acanthamoeba): Experimental Chronic, Granulomatous Brain Infections Produced by New Isolates of Low Virulence. The American Journal of Clinical Pathology, 46(3), 305–314.
SARS: Dose Response Experiments
General Overview
Coronaviruses cause acute and chronic respiratory, enteric, and central nervous system (CNS) diseases in humans and many species of animals. Coronaviruses are divided into three groups based on the genome sequences, including SARS-CoV (a member of group II) as well as murine hepatitis virus (MHV), bovine coronavirus, porcine hemagglutinating encephalomyelitis virus (HEV), equine coronavirus, and human coronavirues OC43 and NL63, which also cause respiratory infections.
ID | Exposure Route | # of Doses | Agent Strain | Dose Units | Host type | Μodel | LD50/ID50 | Optimized parameters | Response type | Reference |
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260 | intranasal | 4.00 | rSARS-CoV | PFU | mice hACE-2 | exponential | 2.33E+02 | k = 2.97E-03 | death |
Albuquerque, N. D., Baig, E. ., Ma, X. ., Zhang, J. ., He, W. ., Rowe, A. ., … Levy, G. A. (2006). Murine Hepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A/J Mice. Journal of Virology, 80, 21. https://doi.org/10.1128/JVI.00747-06 |
260, 261 | intranasal | 0.00 | rSARS-CoV | PFU | mice hACE-2 and A/J | exponential | 2.82E+02 | k = 2.46E-03 | death | |
261 | intranasal | 4.00 | MHV-1 | PFU | A/J mice | exponential | 3.24E+02 | k = 2.14E-03 | death |
Albuquerque, N. D., Baig, E. ., Ma, X. ., Zhang, J. ., He, W. ., Rowe, A. ., … Levy, G. A. (2006). Murine Hepatitis Virus Strain 1 Produces a Clinically Relevant Model of Severe Acute Respiratory Syndrome in A/J Mice. Journal of Virology, 80, 21. https://doi.org/10.1128/JVI.00747-06 |
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Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
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Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
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Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
Adenovirus: Dose Response Experiments
ID | Exposure Route | # of Doses | Agent Strain | Dose Units | Host type | Μodel | LD50/ID50 | Optimized parameters | Response type | Reference |
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31 | inhalation | 4.00 | type 4 | TCID50 | human | exponential | 1.14E+00 | k = 6.07E-01 | infection |
Couch, R. B., Cate, T. R., Douglas, R. G., Gerone, P. J., & . (1966). Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission. Bacteriological Reviews, 30, 3. |
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Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model
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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
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