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

To develop a time-dependent dose-response model for describing the survival of animals exposed to Yersinia pestis. 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. 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. 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.