Unifying the epidemiological, ecological and evolutionary dynamics of Dengue

In under 6 decades dengue has emerged from South East Asia to become the most widespread arbovirus affecting human populations. Recent dramatic increases in epidemic dengue fever have mainly been attributed to factors such as vector expansion and ongoing ecological, climate and socio-demographic changes. The failure to control the virus in endemic regions and prevent global spread of its mosquito vectors and genetic variants, underlines the urgency to reassess previous research methods, hypotheses and empirical observations. This thesis comprises a set of studies that integrate currently neglected and emerging epidemiological, ecological and evolutionary factors into unified mathematical frameworks, in order to better understand the contemporary population biology of the dengue virus. The observed epidemiological dynamics of dengue are believed to be driven by selective forces emerging from within-host cross-immune reactions during sequential, heterologous infections. However, this hypothesis is mainly supported by modelling approaches that presume all hosts to contribute equally and significantly to the selective effects of cross-immunity both in time and space. In the research presented in this thesis it is shown that the previously proposed effects of cross-immunological reactions are weakened in agent-based modelling approaches, which relax the common deterministic and homogeneous mixing assumptions in host-host and host-pathogen interactions. Crucially, it is shown that within these more detailed models, previously reported universal signatures of dengue's epidemiology and population genetics can be reproduced by demographic and natural stochastic processes alone. While this contrasts with the proposed role of cross-immunity, it presents demographic stochasticity as a parsimonious mechanism that integrates, for the first time, multi-scale features of dengue's population biology. The implications of this research are applicable to many other pathogens, involving challenging new ways of determining the underlying causes of the complex phylodynamics of antigenically diverse pathogens.EThOS - Electronic Theses Online ServiceFundação para a Ciência e Tecnologia (Portugal)GBUnited Kingdo