Jemma L. Geoghegan, Aldo F. Saavedra, Sebastián Duchêne, Sheena Sullivan, Ian Barr, Edward C. Holmes

The factors that determine the pattern and rate of spread of influenza virus at a continental-scale are uncertain. Although recent work suggests that influenza epidemics in the United States exhibit a strong geographical correlation, the spatiotemporal dynamics of influenza in Australia, a country and continent of approximately similar size and climate complexity but with a far smaller population, are not known. Using a unique combination of large-scale laboratory-confirmed influenza surveillance comprising >450,000 entries and genomic sequence data we determined the local-level spatial diffusion of this important human pathogen nationwide in Australia. We used laboratory-confirmed influenza data to characterize the spread of influenza virus across Australia during 2007-2016. The onset of established epidemics varied across seasons, with highly synchronized epidemics coinciding with the emergence of antigenically distinct viruses, particularly during the 2009 A/H1N1 pandemic. The onset of epidemics was largely synchronized between the most populous cities, even those separated by distances of >3000 km and those that experience vastly diverse climates. In addition, by analyzing global phylogeographic patterns we show that the synchronized dissemination of influenza across Australian cities involved multiple introductions from the global influenza population, coupled with strong domestic connectivity, rather than through the distinct radial patterns of geographic dispersal that are driven by work-flow transmission as observed in the United States. In addition, by comparing the spatial structure of influenza A and B, we found that these viruses tended to occupy different geographic regions, and peak in different seasons, perhaps indicative of moderate cross-protective immunity or viral interference effects. The highly synchronized outbreaks of influenza virus at a continental-scale revealed here highlight the importance of coordinated public health responses in the event of the emergence of a novel, human-to-human transmissible, virus.