Reconstructing unseen transmission events to infer dengue dynamics from viral sequences

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that reconstructs transmission across spatial scales and apply it to geocoded dengue virus sequences from Thailand (N=726 over 18 years). We find infected individuals spend 96% of their daytime hours in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining transmission. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable across pathogens.