LANDSCAPES OF IMMUNITY: FROM EPIDEMIOLOGICAL APPLICATIONS TO ECOLOGICAL DRIVERS

Abstract

Infectious diseases present unique scientific challenges that are also of huge societal importance; in particular, control measures are strengthened by a better understanding of transmission dynamics. Despite much research, there are still considerable knowledge gaps regarding the ecological and evolutionary interactions between pathogens and host immunity, across scales ranging from the molecular to the global. The over-arching theme of this dissertation is clarifying 'landscapes of immunity' – or, who’s protected from infection and who isn’t – with a focus on the two acute viral pathogen systems of measles and non-polio enteroviruses.

For measles, the availability of a safe and effective vaccine has led to the disease being a target for global elimination. However, measles continues to circulate in many countries and remains one of the leading killers of children globally. This is due to the efficiency with which the pathogen spreads, necessitating high levels of population immunity to interrupt transmission. Here, we develop models to identify spatial heterogeneities in susceptibility to measles, examining the interplay between epidemiology, demography, and geography (Chapter 1). We also deploy statistical methods to characterize the health system repercussions of the recent West African Ebola crisis, on increased susceptibility to measles and other childhood infections (Chapter 2).

The well-characterized epidemiology and transmission dynamics of measles has laid the foundational framework to study the epidemic clockwork of other childhood infections. In particular, the non-polio enteroviruses are a group of relatively recently emerged pathogens (close relatives of the polioviruses) that have been implicated in large outbreaks of hand, foot, and mouth disease among children in the Asia-Pacific region. Here, we elucidate key epidemiological parameters for two of the causative enterovirus serotypes, and explore ecological drivers of their disease dynamics using mechanistic transmission models. We link the modeling to incidence time series data from China (Chapter 3) and from Japan (Chapter 4), and characterize the extent to which observed epidemic patterns may be predictable.

Overall, this dissertation aims to elucidate landscapes of immunity through case studies, with relevance for guiding public health policy on vaccine-preventable diseases as well as for gaining novel insights into the biological mechanisms shaping multi-serotype pathogen dynamics.