Salmonella serotype newport: Dose Response Models

Salmonella Newport

Author: Sushil Tamrakar

General overview of Salmonella and Salmonellosis

Salmonella, a genus of rod-shaped, gram-negative, non-spore forming, predominantly motile enterobacteria, causes more than 10⁴ cases of infections per year in United States. Salmonellosis is an important medical problem, as while infection with non-typhoid Salmonella often causes mild self-limited illness, severe sequelae including death may occur, particularly in immunocompromised hosts. It has been reported that the incidence of salmonellosis is higher in developing than in developed countries, where food handlers may be a reservoir for further transmission of infection (Chalker and Blaser 1988).

Salmonella enterica serotype Newport is a gram-negative intracellular bacterium of considerable animal and public health concern. It causes significant clinical disease in livestock, particularly cattle, in humans, and in other animal species. Multiple antimicrobial resistant strains of S. newport have been recorded in the U.S. and Canada (Huston, Wittum et al. 2002).

---

Summary Data

McCullough and Eisele orally inoculated human volunteers with S. Newport in 1951 (McCullough and Eisele 1951).

Experiment serial number Reference Host type Agent strain Route # of doses Dose units Response Best fit model Optimized parameter(s) LD50/ID50 235* human Salmonella newport oral 3 CFU infection exponential k = 3.97E-06 1.74E+05 *This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.

---

Optimization Output for experiment 235

Human/Salmonella newport model data Dose Infected Non-infected Total 152000 3 3 6 385000 6 2 8 1350000 6 0 6

Goodness of fit and model selection Model Deviance Δ Degrees of freedom χ20.95,1 p-value χ20.95,m-k p-value Exponential 0.16 -3.32e-05 2 3.84 1 5.99 0.923 Beta Poisson 0.16 1 3.84 0.689 Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.

Optimized k parameter for the exponential model, from 10000 bootstrap iterations Parameter MLE estimate Percentiles 0.5% 2.5% 5% 95% 97.5% 99.5% k 3.97E-06 1.75E-06 2.16E-06 2.32E-06 7.36E-06 9.04E-06 1.27E-05 ID50/LD50/ETC* 1.74E+05 5.45E+04 7.67E+04 9.41E+04 2.98E+05 3.20E+05 3.97E+05 *Not a parameter of the exponential model; however, it facilitates comparison with other models.

Parameter histogram for exponential model (uncertainty of the parameter)

Exponential model plot, with confidence bounds around optimized model

---

Summary

Although both Beta-Poisson and Exponential models were acceptable fit to the available data set. Exponential was the best fit model because it has less parameters.

---

References

Huston CL, Wittum TE, et al. (2002) Persistent fecal Salmonella shedding in five dairy herds. Journal of the American Veterinary Medical Association 220(5): 605-655.

McCullough NB, Eisele CW (1951) Experimental Human Salmonellosis: III. Pathogenicity of Strains of Salmonella newport, Salmonella derby, and Salmonella bareilly Obtained from Spray-Dried Whole Egg. The Journal of Infectious Diseases 89(3): 209-213.