Incorporating time postinoculation into a dose-response model of Yersinia pestis in mice

Aims: To develop a time-dependent dose-response model for describing the survival of animals exposed to Yersinia pestis. Methods and Results: Candidate time-dependent dose-response models were fitted to a survival data set for mice intraperitoneally exposed to graded doses of Y. pestis using the maximum likelihood estimation method. An exponential dose-response model with the model parameter modified by an inverse-power dependency of time postinoculation provided a statistically adequate fit to the experimental survival data. This modified model was verified by comparison with prior studies. Conclusions: The incorporated time dependency quantifies the expected temporal effect of in vivo bacteria growth in the dose-response relationship. The modified model describes the development of animal infectious response over time and represents observed responses accurately. Significance and Impact of the Study: This is the first study to incorporate time in a dose-response model for Y. pestis infection. The outcome may be used for the improved understanding of in vivo bacterial dynamics, improved postexposure decision making or as a component to better assist epidemiological investigations.