Dose response models for rotavirus

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Rotavirus infection in healthy 18-45 year old humans

Ward et al. (1986) administered rotavirus (unpassaged CJN strain) to human volunteers by the oral route. The dose units were FFU, and the response was infection. Slightly different model fit results were published in Haas, Rose, and Gerba (1999) and Haas et al. (1993).

  • N50 = 6.17, 95% CI 2.14 to 24.42
  • α = 0.25, 95% CI 0.15 to 0.66

The deviance of this model fit is 6.20 with 6 degrees of freedom.
The p-value for the null hypothesis of goodness of fit is 0.401.
The p-value for the null hypothesis that the beta-Poisson model fits no better than the exponential model is 0.000.
At a dose of 6.17, the expected percentage of hosts that would suffer the response would be 50%.

Scatter plot of α and N50
Dose response model with confidence intervals

Rotavirus (OSU strain) infection in piglets

Two experiments yielding significantly different dose response models are available concerning rotavirus dose-response in piglets.

Graham et al. (1987) administered rotavirus (OSU strain) to specific-pathogen-free, colostrum-deprived, caesarean-derived newborn piglets by the oral route. The dose units were PFU, and the response was infection. Bootstrapped confidence limits for the k parameter of the exponential model could not be obtained because dosing groups were either all positive or all negative.

  • k = 3.71, 95% CI 3.71 to 3.71

The deviance of this model fit is 0.471 with 3 degrees of freedom.
The p-value for the null hypothesis of goodness of fit is 0.93.
The p-value for the null hypothesis that the beta-Poisson model fits no better than the exponential model is 1.00.
At a dose of 0.19, the expected percentage of hosts that would suffer the response would be 50%.

Histogram of k
Dose response model with confidence intervals

Payment et al. (1990) administered rotavirus (OSU strain, ATCC VR892) to 4-5 day old colostrum-deprived newborn piglets by the intragastric inoculation route. The dose units were particles, and the response was infection.

  • k = 0.01734, 95% CI 0.00721 to 0.03282

The deviance of this model fit is 1.102 with 9 degrees of freedom.
The p-value for the null hypothesis of goodness of fit is 1.00.
The p-value for the null hypothesis that the beta-Poisson model fits no better than the exponential model is 1.00.
At a dose of 40.0, the expected percentage of hosts that would suffer the response would be 50%.

Histogram of k
Dose response model with confidence intervals

Rotavirus infection in newborn mice

Gouvea et al. (1986) administered rotavirus (MET strain, serotype 3, subgroup II) to newborn Swiss SW55 mice by the oral route. The dose units were TCID50, and the response was infection. The model fit poorly. Bootstrapped confidence limits for the k parameter of the exponential model could not be obtained because dosing groups were either all positive or all negative.

  • k = 0.000126, 95% CI 0.000126 to 0.000126

The deviance of this model fit is 29.73 with 8 degrees of freedom.
The p-value for the null hypothesis of goodness of fit is 0.00024.
The p-value for the null hypothesis that the beta-Poisson model fits no better than the exponential model is 1.00.
At a dose of 5501, the expected percentage of hosts that would suffer the response would be 50%.

Histogram of k
Dose response model with confidence intervals

References

Gouvea VS et al., 1986. Diarrhoea in mice infected with a human rotavirus. Journal of General Virology, 57:577-581. [1]

Graham DY, DuFour GR, Estes MK, 1987. Minimal infectious dose of rotavirus. Archives of Virology, 92:261-271. [2]

Haas, C.N. et al., 1993. Risk assessment of virus in drinking water. Risk Analysis: An Official Publication of the Society for Risk Analysis, 13(5), 545-552.

Haas CN, Rose JB, Gerba CP, 1999. Quantitative Microbial Risk Assessment. John Wiley & Sons, Inc., New York.

Payment P & Morin E, 1990. Minimal infective dose of the OSU strain of porcine rotavirus. Archives of Virology, 112:277-282. [3]

Ward RL et al., Nov. 1986. Human Rotavirus Studies in Volunteers: Determination of Infectious Dose and Serological Response to Infection. Journal of Infectious Diseases, 154(5):871-880. [4]