Examining the Effect of Immunity on Infection Dynamics at the Host, Population, and Multi-Population Levels.

Abstract

Dynamic modeling is an important tool for informing public health decisions. In this dissertation, we explored the role of host immunity in infection transmission models at the host, population, and multi-population level. We applied these models to two pathogen systems: 1) anthrax infection at the host level and 2) polio transmission at the population and multi-population level. At the host level, dose-response models are used to characterize the risk of infection given a pathogen exposure and are one of the primary tools for risk assessments. These models are generally static assuming invariant risk over time. We developed a dose-response model that incorporates the immune response to pathogen exposures and thereby allows risk calculations to be dependent on exposure patterns that vary over time. An analysis of an anthrax disease system indicated that the risk of anthrax is invariant to exposure patterns. Although the anthrax data set did not reveal a dose-timing pattern of risk, more variable exposure data is needed to fully evaluate this process. At the population level, transmission models elucidate dynamic infection processes and provide a framework to analyze intervention effectiveness. We developed a model of polio transmission that incorporates vaccine strain transmission and waning immunity to assess the successes and failures of the polio eradication campaign. We demonstrated that long-term success might be difficult due to reinfection transmission dynamics attributable to waning immunity. Increased vaccine strain transmission mitigates the influence of reinfection by boosting immunity but cannot be relied upon due to risk of disease caused by circulating vaccine. Therefore additional interventions may be appropriate such as adult boosters or improved sanitary conditions. We then extended the polio transmission model to the multi-population level to assess the effect of vaccination policies across population groups through migration. Our analysis demonstrated that if vaccination coverage lapses in one population, it is detrimental to the vaccination programs in neighboring populations. This is exemplified when migration comes from high transmission populations. Thus, eradication campaign success might be greatly aided by interventions focusing on mobile populations.