We generally recommend a single dose-response model, and we justify the decision in terms of specific criteria. This decision is somewhat subjective, since dose response datasets seldom meet all of these criteria. If all available models are unsatisfactory, we choose a single model to ‘recommend with reservations’. Our recommended model will seldom (if ever) be the best model for all applications. The user should carefully choose the model that is most appropriate for their particular problem.
Criteria for Model Selection
We prefer dose-response models with the following criteria, in rough order of importance:
- Statistically acceptable fit (fail to reject goodness of fit, p > 0.05)
- Human subjects, or animal models that mimic human pathophysiology well
- Infection as the response, rather than disease, symptoms, or death
- Exposure route similar/identical to the exposure route of natural infection
- Pathogen strain is similar to strains causing natural infection
- Pooled model using data from 2 or more experiments, provided the data sets are statistically similar (fail to reject that datasets are from the same distribution, p > 0.05)
- Low ID50/LD50 (to obtain a conservative risk estimate)
Agent | Μodel | Optimized parameters | Host type | Agent Strain | Exposure Route | Response | # of Doses | Dose Units | Reference |
---|---|---|---|---|---|---|---|---|---|
Acanthamoeba Experiments |
beta-Poisson |
a = 0.245 N50 = 19357 (beta=1215) |
mice | A. castellanii HN-3 and A culbertsoni A1 | intranasal | death | 9 | no of trophozoites | |
Acanthamoeba Experiments |
beta-Poisson |
a = 0.245 N50 = 19357 (beta=1215) |
mice | A. castellanii HN-3 and A culbertsoni A1 | intranasal | death | 9 | no of trophozoites | |
Adenovirus Experiments |
exponential |
k = 6.07E-01 LD50/ID50 = 1.14E+00 |
human | type 4 | inhalation | infection | 4 | TCID50 | Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission. Bacteriological Reviews. 30, 3. | (1966).
Bacillus anthracis Experiments |
exponential |
k = 1.65E-05 LD50/ID50 = 4.2E+04 |
guinea pig | Vollum | inhalation | death | 4 | spores | Experiments in feeding adult volunteers with Escherichia coli 55, B5, a coliform organism associated with infant diarrhea. American Journal of Hygiene. 57(2), | (1953).
Burkholderia mallei Experiments |
beta-Poisson |
a = 3.28E-01 LD50/ID50 = 5.43E+03 N50 = 5.43E+03 |
C57BL/6 mice and diabetic rat | KHW,316c | death | 10 | CFU | Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates.. Infection and immunity. 64, 2824–2828. | (1996).|
Campylobacter coli Experiments |
beta-Poisson |
a = 1.44E-01 LD50/ID50 = 8.9E+02 N50 = 8.9E+02 |
human | strain A3249 | oral (in milk) | infection | 6 | CFU | Experimental Campylobacter jejuni Infection in Humans. Journal of Infectious Diseases. 157, 3. | (1988).
Campylobacter jejuni Experiments |
beta-Poisson |
a = 1.44E-01 LD50/ID50 = 8.9E+02 N50 = 8.9E+02 |
human | strain A3249 | oral (in milk) | infection | 6 | CFU | Experimental Campylobacter jejuni Infection in Humans. Journal of Infectious Diseases. 157, 3. | (1988).
Coxiella burnetii Experiments |
beta-Poisson |
a = 3.57E-01 LD50/ID50 = 4.93E+08 N50 = 4.93E+08 |
C57BL/1OScN mice | phase I Ohio | intraperitoneal | death | 10 | PFU | Biological and immunological properties of Coxiella burnetii vaccines in C57BL/10ScN endotoxin-nonresponder mice. Infection and Immunity. 35, 3. | (1982).
Cryptosporidium hominis Experiments |
exponential |
k = 5.72E-02 LD50/ID50 = 1.21E+01 |
human | TAMU isolate | oral | infection | 4 | oocysts | Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data. Water Research. 35, 16. | (2001).
Cryptosporidium parvum Experiments |
exponential |
k = 5.72E-02 LD50/ID50 = 1.21E+01 |
human | TAMU isolate | oral | infection | 4 | oocysts | Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data. Water Research. 35, 16. | (2001).
Echovirus Experiments |
beta-Poisson |
a = 1.06E+00 LD50/ID50 = 9.22E+02 N50 = 9.22E+02 |
human | strain 12 | oral | infection | 4 | PFU | Studies of echovirus-12 in volunteers: determination of minimal infectious dose and the effect of previous infection on infectious dose. The Journal of infectious diseases. 150, 6. | (1984).
Entamoeba coli Experiments |
beta-Poisson |
a = 1.01E-01 LD50/ID50 = 3.41E+02 N50 = 3.41E+02 |
human | From an infected human | oral | infection | 5 | Cysts | The experimental transmission of human intestinal protozoan parasites. I. Endamoeba coli cysts given in capsules. American journal of hygiene. 59, 2. | (1954).
Enterovirus Experiments |
exponential |
k = 3.74E-03 LD50/ID50 = 1.85E+02 |
pig | porcine, PE7-05i | oral | infection | 3 | PFU | Experimental infection by waterborne enteroviruses. Journal of Food Protection. 44, 861–865. | (1981).
Escherichia coli Experiments |
beta-Poisson |
a = 1.55E-01 LD50/ID50 = 2.11E+06 N50 = 2.11E+06 |
human | EIEC 1624 | oral (in milk) | positive stool isolation | 3 | CFU | Pathogenesis of Escherichia coli diarrhea. The New England journal of medicine. 285, 1. | (1971).
Francisella tularensis Experiments |
exponential |
k = 4.73E-02 LD50/ID50 = 1.46E+01 |
monkey | SCHU S-4 | inhalation | death | 4 | CFU | Infectivity of Tularemia Applied to Intact Skin and Ingested in Drinking Water. Science. 123, 942-943. | (1956).
Giardia duodenalis Experiments |
exponential |
k = 1.99E-02 LD50/ID50 = 3.48E+01 |
human | From an infected human | oral | infection | 8 | Cysts | The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules. American journal of hygiene. 59, 2. | (1954).
Influenza Experiments |
beta-Poisson |
a = 5.81E-01 LD50/ID50 = 9.45E+05 N50 = 9.45E+05 |
human | H1N1,A/California/10/78 attenuated strain,H3N2,A/Washington/897/80 attenuated strain | intranasal | infection | 9 | TCID50 | Dose Response of Cold-Adapted, Reassortant Influenza A/California/10/78 Virus (H1N1) in Adult Volunteers. Journal of Infectious Diseases. 149, 5. | (1984).
Lassa virus Experiments |
exponential |
k = 2.95E+00 LD50/ID50 = 2.35E-01 |
guinea pig | Josiah strain | subcutaneous | death | 6 | PFU | Pathogenesis of Lassa virus infection in guinea pigs. Infection and Immunity. 37, 2. | (1982).
Legionella pneumophila Experiments |
exponential |
k = 5.99E-02 LD50/ID50 = 1.16E+01 |
guinea pig | Philadelphia 1 | inhalation | infection | 4 | CFU | Aerosol infection of animals with strains of Legionella pneumophila of different virulence: comparison with intraperitoneal and intranasal routes of infection. Epidemiology & Infection. 90, | (1983).
Mycobacterium avium Experiments |
exponential |
k = 6.93E-04 LD50/ID50 = 1000 |
deer | sub sp. Paratuberculosis Bovine | oral | infection | 3 | CFU | Quantitative studies of Mycobacterium johnei in tissues of sheep. III. Intestinal histopathology. Journal of comparative pathology. 72, 80. | (1962).
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