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: 

  1. Statistically acceptable fit (fail to reject goodness of fit, p > 0.05)
  2. Human subjects, or animal models that mimic human pathophysiology well
  3. Infection as the response, rather than disease, symptoms, or death
  4. Exposure route similar/identical to the exposure route of natural infection
  5. Pathogen strain is similar to strains causing natural infection
  6. 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)
  7. Low ID50/LD50 (to obtain a conservative risk estimate)
Agent Exposure Route Μodel Optimized parameters LD50/ID50 Host type Agent Strain Response type # of Doses Dose Units Reference
Acanthamoeba
intranasal beta-Poisson a = 0.245 N50 = 19357 mice A. castellanii HN-3 and A culbertsoni A1 death 9.00 no of trophozoites
Adenovirus
inhalation exponential k = 6.07E-01 1.14E+00 human type 4 infection 4.00 TCID50
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.
Bacillus anthracis
inhalation exponential k = 1.65E-05 4.2E+04 guinea pig Vollum death 4.00 spores
June, R. ., Ferguson, W. ., & Worfel, M. . (1953). Experiments in feeding adult volunteers with Escherichia coli 55, B5, a coliform organism associated with infant diarrhea. American Journal of Hygiene, 57(2). https://doi.org/10.1093/oxfordjournals.aje.a119570
Burkholderia mallei
beta-Poisson a = 3.28E-01 N50 = 5.43E+03 5.43E+03 C57BL/6 mice and diabetic rat KHW,316c death 10.00 CFU
Brett, P. J., & Woods, D. E. (1996). Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates. Infection and Immunity, 64, 2824–2828.
Campylobacter jejuni
oral beta-Poisson a = 1.44E-01 N50 = 8.9E+02 8.9E+02 human strain A3249 infection 6.00 CFU
Black, R. E., Levine, M. M., Clements, M. L., Hughes, T. P., & Blaser, M. J. (1988). Experimental Campylobacter jejuni Infection in Humans. Journal of Infectious Diseases, 157, 3. https://doi.org/10.1093/infdis/157.3.472
Coxiella burnetii
intraperitoneal beta-Poisson a = 3.57E-01 N50 = 4.93E+08 4.93E+08 C57BL/1OScN mice phase I Ohio death 10.00 PFU
Williams, J. C., & Cantrell, J. L. (1982). Biological and immunological properties of Coxiella burnetii vaccines in C57BL/10ScN endotoxin-nonresponder mice. Infection and Immunity, 35, 3.
Cryptosporidium hominis
oral exponential k = 5.72E-02 1.21E+01 human TAMU isolate infection 4.00 oocysts
Messner, M. J., Chappell, C. L., & Okhuysen, P. C. (2001). Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data. Water Research, 35, 16. Retrieved from https://www.sciencedirect.com/science/article/pii/S0043135401001191
Cryptosporidium parvum
oral exponential k = 5.72E-02 1.21E+01 human TAMU isolate infection 4.00 oocysts
Messner, M. J., Chappell, C. L., & Okhuysen, P. C. (2001). Risk Assessment for Cryptosporidium: A Hierarchical Bayesian Analysis of Human Dose Response Data. Water Research, 35, 16. Retrieved from https://www.sciencedirect.com/science/article/pii/S0043135401001191
Echovirus
oral beta-Poisson a = 1.06E+00 N50 = 9.22E+02 9.22E+02 human strain 12 infection 4.00 PFU
Schiff, G. M., Stefanović, G. M., Young, E. C., Sander, D. S., Pennekamp, J. K., & Ward, R. L. (1984). 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. Retrieved from https://academic.oup.com/jid/article-abstract/150/6/858/880281
Entamoeba coli
oral beta-Poisson a = 1.01E-01 N50 = 3.41E+02 3.41E+02 human From an infected human infection 5.00 Cysts
Rendtorff, R. C. (1954). The experimental transmission of human intestinal protozoan parasites. I. Endamoeba coli cysts given in capsules. American Journal of Hygiene, 59, 2. https://doi.org/https://doi.org/10.1093/oxfordjournals.aje.a119633
Enterovirus
oral exponential k = 3.74E-03 1.85E+02 pig porcine, PE7-05i infection 3.00 PFU
Cliver, D. O. (1981). Experimental infection by waterborne enteroviruses. Journal of Food Protection, 44, 861–865. Retrieved from http://www.jfoodprotection.org/doi/abs/10.4315/0362-028X-44.11.861?code=fopr-site
Escherichia coli
oral (in milk) beta-Poisson a = 1.55E-01 N50 = 2.11E+06 2.11E+06 human EIEC 1624 positive stool isolation 3.00 CFU
DuPont, H. L., Formal, S. B., Hornick, R. B., Snyder, M. J., Libonati, J. P., Sheahan, D. G., … Kalas, J. P. (1971). Pathogenesis of Escherichia coli diarrhea. The New England Journal of Medicine, 285, 1.
Francisella tularensis
inhalation exponential k = 4.73E-02 1.46E+01 monkey SCHU S-4 death 4.00 CFU
Quan, S. F., McManus, A. G., & von Fintel, H. . (1956). Infectivity of Tularemia Applied to Intact Skin and Ingested in Drinking Water. Science, 123, 942-943.
Giardia duodenalis
oral exponential k = 1.99E-02 3.48E+01 human From an infected human infection 8.00 Cysts
Rendtorff, R. C. (1954). The experimental transmission of human intestinal protozoan parasites. II. Giardia lamblia cysts given in capsules. American Journal of Hygiene, 59, 2. Retrieved from https://academic.oup.com/aje/article-abstract/59/2/196/89318?redirectedFrom=PDF
Influenza
intranasal beta-Poisson a = 5.81E-01 N50 = 9.45E+05 9.45E+05 human H1N1,A/California/10/78 attenuated strain,H3N2,A/Washington/897/80 attenuated strain infection 9.00 TCID50
Murphy, B. R., Clements, M. L., Madore, H. P., Steinberg, J. ., O’Donnell, S. ., Betts, R. ., … Maassab, H. F. (1984). Dose Response of Cold-Adapted, Reassortant Influenza A/California/10/78 Virus (H1N1) in Adult Volunteers. Journal of Infectious Diseases, 149, 5. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/6726007
Lassa virus
subcutaneous exponential k = 2.95E+00 2.35E-01 guinea pig Josiah strain death 6.00 PFU
Jahrling, P. B., Smith, S. ., Hesse, R. A., & Rhoderick, J. B. (1982). Pathogenesis of Lassa virus infection in guinea pigs. Infection and Immunity, 37, 2. Retrieved from http://iai.asm.org/content/37/2/771.abstract
Legionella pneumophila
inhalation exponential k = 5.99E-02 1.16E+01 guinea pig Philadelphia 1 infection 4.00 CFU
Fitzgeorge, R. B., Baskerville, A. ., Broster, M. ., Hambleton, P. ., & Dennis, P. J. (1983). Aerosol infection of animals with strains of Legionella pneumophila of different virulence: comparison with intraperitoneal and intranasal routes of infection. Epidemiology & Infection, 90.
Mycobacterium avium
oral exponential k = 6.93E-04 1000 deer sub sp. Paratuberculosis Bovine infection 3.00 CFU
Nisbet, D. I., Gilmour, N. J., & Brotherston, J. G. (1962). Quantitative studies of Mycobacterium johnei in tissues of sheep. III. Intestinal histopathology. Journal of Comparative Pathology, 72, 80.
Naegleria fowleri
intravenous exponential k = 3.42E-07 2.03E+06 mice LEE strain death 7.00 no of trophozoites
Adams, A. C., John, D. T., & Bradley, S. G. (1976). Modification of resistance of mice to Naegleria fowleri infections. Infection and Immunity, 13, 1387–1391. Retrieved from http://iai.asm.org/content/13/5/1387.full.pdf+html
Poliovirus
oral (capsule) exponential k = 4.91E-01 1.41E+00 human type 1,attenuated alimentary infection 3.00 PD50 (mouse paralytic doses)
Koprowski, H. . (1956). Immunization against Poliomyelitis with Living Attenuated Virus. The American Journal of Tropical Medicine and Hygiene, 5, 3.
Prion
oral beta-Poisson a = 1.76E+00 N50 = 1.04E+05 1.04E+05 hamsters scrapie strain 263k death 5.00 LD50 i.c.
Jacquemot, C. ., Cuche, C. ., Dormont, D. ., & Lazarini, F. . (2005). High Incidence of Scrapie Induced by Repeated Injections of Subinfectious Prion Doses. Journal of Virology, 79(14). https://doi.org/10.1128/JVI.79.14.8904-8908.2005
Pseudomonas aeruginosa
contact lens beta-Poisson a = 1.9E-01 N50 = 1.85E+04 1.85E+04 white rabbit corneal ulceration 10.00 CFU
Lawin-Brüssel, C. A., Refojo, M. F., Leong, F. L., Hanninen, L. ., & Kenyon, K. R. (1993). Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis. Cornea, 12, 1.
Pseudomonas aeruginosa
injected in eyelids exponential k = 1.05E-04 6.61E+03 Swiss webster mice (5day old) ATCC 19660 death 12.00 CFU
Hazlett, L. D., Rosen, D. D., & Berk, R. S. (1978). Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice. Infection and Immunity, 20, 1.
Rhinovirus
intranasal beta-Poisson a = 2.21E-01 N50 = 1.81E+00 1.81E+00 human type 39 infection 6.00 TCID50
Hendley, J. O., Edmondson, W. P., & Gwaltney, J. M. (1972). Relation between Naturally Acquired Immunity and Infectivity of Two Rhinoviruses in Volunteers. Journal of Infectious Diseases, 125, 3.
Rickettsia rickettsi
beta-Poisson a = 7.77E-01 N50 = 2.13E+01 2.13E+01 pooled R1 and Sheila Smith morbidity 27.00 CFU
Saslaw, S. ., & Carlisle, H. N. (1966). Aerosol infection of monkeys with Rickettsia rickettsii. Bacteriological Reviews, 30, 3.
Salmonella anatum
oral (with eggnog) beta-Poisson a = 3.18E-01 N50 = 3.71E+04 3.71E+04 human strain I positive stool culture 16.00 CFU
McCullough, N. ., & Elsele, C. . (1951). Experimental Human Salmonellosis: I. Pathogenicity of Strains of Salmonella Meleagridis and Salmonella Anatum Obtained from Spray-Dried Whole Egg. Oxford Journal of Infectious Diseases, 88(3). https://doi.org/https://doi.org/10.1093/infdis/88.3.278
Salmonella meleagridis
oral (with eggnog) beta-Poisson a = 3.89E-01 N50 = 1.68E+04 1.68E+04 human strain I infection 11.00 CFU
McCullough, N. ., & Elsele, C. . (1951). Experimental Human Salmonellosis: I. Pathogenicity of Strains of Salmonella Meleagridis and Salmonella Anatum Obtained from Spray-Dried Whole Egg. Oxford Journal of Infectious Diseases, 88(3). https://doi.org/https://doi.org/10.1093/infdis/88.3.278
Salmonella newport
oral exponential k = 3.97E-06 1.74E+05 human *Salmonella newport* infection 3.00 CFU
McCullough, N. ., & Elsele, C. . (1951). Experimental Human Salmonellosis: I. Pathogenicity of Strains of Salmonella Meleagridis and Salmonella Anatum Obtained from Spray-Dried Whole Egg. Oxford Journal of Infectious Diseases, 88(3). https://doi.org/https://doi.org/10.1093/infdis/88.3.278
Salmonella nontyphoid
intraperitoneal beta-Poisson a = 2.1E-01 N50 = 4.98E+01 4.98E+01 mice strain 216 and 219 death 10.00 CFU
Meynell, G. G., & Meynell, E. W. (1958). The growth of micro-organisms in vivo with particular reference to the relation between dose and latent period. The Journal of Hygiene, 56(3). https://doi.org/10.1017/s0022172400037827
Salmonella typhi
oral (in milk) beta-Poisson a = 1.75E-01 N50 = 1.11E+06 1.11E+06 human Quailes disease 8.00 CFU
Hornick, R. ., Woodward, T. ., McCrumb, F. ., Snyder, M. ., Dawkins, A. ., Bulkeley, J. ., … Corozza, F. . (1966). Study of induced typhoid fever in man. I. Evaluation of vaccine effectiveness. Transactions of the Association of American Physicians, 79, 361-367. Retrieved from https://pubmed.ncbi.nlm.nih.gov/5929469/
SARS
intranasal exponential k = 2.46E-03 2.82E+02 mice hACE-2 and A/J rSARS-CoV death 0.00 PFU
Shigella flexneri
oral (in milk) beta-Poisson a = 2.65E-01 N50 = 1.48E+03 1.48E+03 human 2a (strain 2457T) positive stool isolation 4.00 CFU
DuPont, H. L., Hornick, R. B., Snyder, M. J., Libonati, J. P., Formal, S. B., & Gangarosa, E. J. (1972). Immunity in Shigellosis. I. Response of Man to Attenuated Strains of Shigella. Journal of Infectious Diseases, 125, 1.
Staphylococcus aureus
subcutaneous exponential k = 7.64E-08 9.08E+06 human infection 6.00 CFU/cm2
Lawin-Brüssel, C. A., Refojo, M. F., Leong, F. L., Hanninen, L. ., & Kenyon, K. R. (1993). Effect of Pseudomonas aeruginosa concentration in experimental contact lens-related microbial keratitis. Cornea, 12, 1.
Vibrio cholerae
oral (with NaHCO3) beta-Poisson a = 2.50E-01 N50 = 2.43E+02 2.43E+02 human Inaba 569B infection 6.00 CFU
Diringer, H. ., Roehmel, J. ., & Beekes, M. . (1998). Effect of repeated oral infection of hamsters with scrapie. Journal of General Virology, 79. Retrieved from http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.541.3587&rep=rep1&type=pdf
Yersinia pestis
intranasal exponential k = 1.63E-03 4.26E+02 mice CO92 death 4.00 CFU
Lathem, W. W., Crosby, S. D., Miller, L. . , V, & Goldman, W. E. (2005). Progression of primary pneumonic plague: A mouse model of infection, pathology, and bacterial transcriptional activity. Proceedings of the National Academy of Sciences of the United States of America, 102, 17786-17791. https://doi.org/10.1073/pnas.0506840102