title: Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence.
abstract: The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May - 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including "stragglers" from the preceding season and "heralds" of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality.
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences, and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Patterson Ross
authors.affiliation: World Health Organisation Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute, Melbourne, Victoria, Australia.
authors.forename: Naomi
authors.initials: N
authors.lastname: Komadina
authors.affiliation: World Health Organisation Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute, Melbourne, Victoria, Australia.
authors.forename: Yi-Mo
authors.initials: YM
authors.lastname: Deng
authors.affiliation: World Health Organisation Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute, Melbourne, Victoria, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Spirason
authors.affiliation: VIDRL, Peter Doherty Institute, Melbourne, Victoria, Australia; National Centre for Epidemiology and Population Health, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Heath A
authors.initials: HA
authors.lastname: Kelly
authors.affiliation: World Health Organisation Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute, Melbourne, Victoria, Australia.
authors.forename: Sheena G
authors.initials: SG
authors.lastname: Sullivan
authors.affiliation: World Health Organisation Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute, Melbourne, Victoria, Australia; VIDRL, Peter Doherty Institute, Melbourne, Victoria, Australia.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Barr
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences, and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
mesh_terms: D001315:Australia; D002980:Climate; D004196:Disease Outbreaks; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000302:isolation & purification; D009981:Influenza B virus / Q000235:genetics / Q000302:isolation & purification*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D012621:Seasons; D017422:Sequence Analysis, DNA / Q000379:methods