@article {1799, title = {{A} {data} {simulation} {method} to {optimize} a {mechanistic} {dose-response} {model} for {viral} {loads} of {hepatitis} {A}}, journal = {Microbial Risk Analysis}, year = {2019}, pages = {100102}, abstract = {

Driven by the quantitative estimate of risk via the dose-response models, quantitative microbial risk assessment has been used successfully for public health interventions. The dose-response models are derived starting from an average exposed dose of infectious particles, this dictates the dose data units required. Then dose-response data from animal model experiments are used to optimize these mechanistic dose-response models. For hepatitis A (Hep-A), the only available dose-response data use grams of feces for dose units. Therefore, to develop a dose-response model for Hep-A a method of converting these doses in grams of feces into infectious particles, while accounting for the uncertainty of this conversion is needed. This research develops a method to couple data simulation with the likelihood estimation method for model optimization to accomplish this. This adapted method uses data simulation to model the doses as viruses while accounting for the within-group variability of this simulation. Then these simulated doses, coupled with the original dose-response data, are used to optimize the mechanistic dose-response models. This method results in a more computationally rigorous means of modeling these types of dose-response data. The resulting dose-response model for Hep-A is also more appropriate to use than the current option for Hep-A risk models.

}, keywords = {Data simulation, Dose-response, Hepatitis A, QMRA}, issn = {2352-3522}, doi = {10.1016/j.mran.2019.100102}, url = {http://www.sciencedirect.com/science/article/pii/S2352352219300222}, author = {Weir, Mark H.} } @article {1949, title = {Development of a dose{\textendash}response model for Naegleria fowleri}, journal = {Journal of Water and Health}, volume = {17}, year = {2018}, month = {10}, pages = {63-71}, abstract = {

{This study develops novel dose{\textendash}response models for Naegleria fowleri from selected peer-reviewed experiments on the virulence based on the intranasal exposure pathway. One data set measured the response of mice intranasally inoculated with the amebae and the other study addressed the response of mice swimming in N. fowleri infected water. The measured response for both studies was death. All experimental data were best fit by the beta-Poisson dose{\textendash}response model. The three swimming experiments could be pooled, and this is the final recommended model with an LD50 of 13,257 amebae. The results of this study provide a better estimate of the probability of the risk to N. fowleri exposure than the previous models developed based on an intravenous exposure. An accurate dose{\textendash}response model is the first step in quantifying the risk of free-living amebae like N. fowleri, which pose risks in recreational environments and have been detected in drinking water and premise plumbing systems. A better understanding of this risk will allow for risk management that limits the ability for pathogen growth, proliferation, and exposure.}

}, issn = {1477-8920}, doi = {10.2166/wh.2018.181}, url = {https://doi.org/10.2166/wh.2018.181}, author = {Dean, Kara and Weir, Mark H. and Mitchell, Jade} } @article {1820, title = {Quantification of the {Effects} of {Age} on the {Dose} {Response} of {{Variola} major in {Suckling} {Mice}}, journal = {Human and Ecological Risk Assessment: An International Journal}, volume = {15}, year = {2009}, pages = {1245{\textendash}1256}, abstract = {

Dose-response data for Variola major (V. major), the causative agent of smallpox, were obtained from the open literature, summarized, and fitted with three doseresponse models. It is known from prior outbreak experience that there is generally a difference in infectivity of the agent and its subsequent mortality depending on the age of the patient. A source of animal dose-response data were found with age delineation for the exposure group (suckling mice, intraperitoneal exposure). This delineation was used to adapt current dose-response models to include an age dependency parameter. The degree of the models{\textquoteright} fit to the data was ascertained using maximum likelihood estimation (MLE). The effect of host age could be described quantitatively using modifications to the beta Poisson and exponential dose-response models. The modifications improvement in the accuracy of risk prediction by 72\% for the beta Poisson model and 7\% for the exponential model, compared to the original (unmodified) models.

}, issn = {1080-7039, 1549-7860}, doi = {10.1080/10807030903304906}, url = {http://www.tandfonline.com/doi/full/10.1080/10807030903304906}, author = {Weir, Mark H. and Haas, Charles N.} }