Epidemic dynamics of pathogenic human enteroviruses. (360G-Wellcome-106073_Z_14_Z)

I aim to identify the mechanisms determining the epidemic dynamics of serotype-specific human enterovirus (HEV). I will use mathematical and statistical models to examine epidemiological and microbiological data collected since 2003 as part of ongoing enterovirus surveillance in the UK and the US. In particular, I will assess the importance of birth rates, serotype-specific population immunity, cross-immunity between serotypes, and climatic and environmental factors. I will use time-series an alysis to test relationships between climatic and environmental factors and HEV disease incidence, and correlation in the incidence of different serotypes over time and space. I will then develop mathematical models representing alternative hypotheses that can explain the patterns of disease occurrence. Mechanisms likely to result in the observed dynamics, such as serotype-specific and heterotypic immunity and seasonal determinants of transmission efficiency will be included. I will fit these models to HEV disease incidence using recently developed statistical methods, and estimate model parameters, including the degree and duration of homotypic and heterotypic immunity. Finally, I will examine whether available viral sequence data is consistent with patterns of diversity predicted by these mathematical models and use phylodynamic methods to see whether these data allow more accurate estimation of model parameters.