B. Mayer | Fred Hutchinson Cancer Research Center (original) (raw)
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Papers by B. Mayer
Journal of The Royal Society Interface, 2011
The most commonly used dose -response models implicitly assume that accumulation of dose is a tim... more The most commonly used dose -response models implicitly assume that accumulation of dose is a time-independent process where each pathogen has a fixed risk of initiating infection. Immune particle neutralization of pathogens, however, may create strong time dependence; i.e. temporally clustered pathogens have a better chance of overwhelming the immune particles than pathogen exposures that occur at lower levels for longer periods of time. In environmental transmission systems, we expect different routes of transmission to elicit different dose-timing patterns and thus potentially different realizations of risk. We present a dose -response model that captures time dependence in a manner that incorporates the dynamics of initial immune response. We then demonstrate the parameter estimation of our model in a dose -response survival analysis using empirical time-series data of inhalational anthrax in monkeys in which we find slight dose-timing effects. Future dose-response experiments should include varying the time pattern of exposure in addition to varying the total doses delivered. Ultimately, the dynamic dose-response paradigm presented here will improve modelling of environmental transmission systems where different systems have different time patterns of exposure.
American Journal of Epidemiology, 2013
Polio eradication is on the cusp of success, with only a few regions still maintaining transmissi... more Polio eradication is on the cusp of success, with only a few regions still maintaining transmission. Improving our understanding of why some regions have been successful and others have not will help with both global eradication of polio and development of more effective vaccination strategies for other pathogens. To examine the past 25 years of eradication efforts, we constructed a transmission model for wild poliovirus that incorporates waning immunity (which affects both infection risk and transmissibility of any resulting infection), age-mediated vaccination rates, and transmission of oral polio vaccine. The model produces results consistent with the 4 country categories defined by the Global Polio Eradication Program: elimination with no subsequent outbreaks; elimination with subsequent transient outbreaks; elimination with subsequent outbreaks and transmission detected for more than 12 months; and endemic polio transmission. Analysis of waning immunity rates and oral polio vaccine transmissibility reveals that higher waning immunity rates make eradication more difficult because of increasing numbers of infectious adults, and that higher oral polio vaccine transmission rates make eradication easier as adults become reimmunized. Given these dynamic properties, attention should be given to intervention strategies that complement childhood vaccination. For example, improvement in sanitation can reduce the reproduction number in problematic regions, and adult vaccination can lower adult transmission.
Journal of The Royal Society Interface, 2011
The most commonly used dose -response models implicitly assume that accumulation of dose is a tim... more The most commonly used dose -response models implicitly assume that accumulation of dose is a time-independent process where each pathogen has a fixed risk of initiating infection. Immune particle neutralization of pathogens, however, may create strong time dependence; i.e. temporally clustered pathogens have a better chance of overwhelming the immune particles than pathogen exposures that occur at lower levels for longer periods of time. In environmental transmission systems, we expect different routes of transmission to elicit different dose-timing patterns and thus potentially different realizations of risk. We present a dose -response model that captures time dependence in a manner that incorporates the dynamics of initial immune response. We then demonstrate the parameter estimation of our model in a dose -response survival analysis using empirical time-series data of inhalational anthrax in monkeys in which we find slight dose-timing effects. Future dose-response experiments should include varying the time pattern of exposure in addition to varying the total doses delivered. Ultimately, the dynamic dose-response paradigm presented here will improve modelling of environmental transmission systems where different systems have different time patterns of exposure.
American Journal of Epidemiology, 2013
Polio eradication is on the cusp of success, with only a few regions still maintaining transmissi... more Polio eradication is on the cusp of success, with only a few regions still maintaining transmission. Improving our understanding of why some regions have been successful and others have not will help with both global eradication of polio and development of more effective vaccination strategies for other pathogens. To examine the past 25 years of eradication efforts, we constructed a transmission model for wild poliovirus that incorporates waning immunity (which affects both infection risk and transmissibility of any resulting infection), age-mediated vaccination rates, and transmission of oral polio vaccine. The model produces results consistent with the 4 country categories defined by the Global Polio Eradication Program: elimination with no subsequent outbreaks; elimination with subsequent transient outbreaks; elimination with subsequent outbreaks and transmission detected for more than 12 months; and endemic polio transmission. Analysis of waning immunity rates and oral polio vaccine transmissibility reveals that higher waning immunity rates make eradication more difficult because of increasing numbers of infectious adults, and that higher oral polio vaccine transmission rates make eradication easier as adults become reimmunized. Given these dynamic properties, attention should be given to intervention strategies that complement childhood vaccination. For example, improvement in sanitation can reduce the reproduction number in problematic regions, and adult vaccination can lower adult transmission.