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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Climate zones and the location of the most populous cities within Australia.

The map was constructed using freely available data from the Bureau of Meteorology’s website (www.bom.gov.au) and utilizes their temperature/humidity classification system [25]. Population data was from the Australian Bureau of Statistics [26]. Latitude figures are freely available on Google Maps.

Fig 2. Patterns (event types) of inter-seasonal influenza transmission.

The black line represents the theoretical periodicity of influenza in a typical seasonal pattern, horizontal bars represent lengths of transmission events and are colored blue when falling inside the season and red when in the inter-seasonal period.

Fig 3. Phylogenetic trees showing a real data example of each event type.

Australian inter-seasonal sequences are shown in red, seasonal sequences are shown in blue, and global sequences are shown in black. Bootstrap support values (>70%) are shown for key nodes. (a) Importation event within influenza A/H1N1pdm. This imported lineage transmitted for at least two months during the 2010/2011 inter-seasonal period within Australia (earliest sample collected on 13 Jan 2011 and latest on 18 March 2011, both from Darwin), and spread to a temperate region (Perth). (b) Herald event within influenza B virus, with virus Sydney/2/2012 isolated on 27 February 2012 and then extending into the following influenza season in both Australia (Sydney and South Australia) and New Zealand. (c) Straggler event within influenza A/H1N1pdm, with viruses transmitting within the 2010 season into the 2010–2011 inter-seasonal period. Although the strongest evidence for this involves A/Victoria/662/2010 isolated on 17 November 2010 (bottom clade), a similar pattern may occur with A/Brisbane/32/2011 sampled on 4 February 2011 although with weak bootstrap support (top clade). (d) Persistent lineage of influenza B virus transmitting within the 2010 season, throughout the 2010/2011 inter-seasonal period, and into the 2011 season (i.e. for a total of 14 months). (e) A two-tailed A/H1N1pdm lineage transmitting from 18 February 2011 (2010/2011 inter-seasonal period) to 01 December 2011 (2011/2012 inter-seasonal period). All trees were rooted using the earliest non-Australian sequence shown to be an outgroup in the expansive phylogenetic trees shown in S1 Fig. The date of sampling is shown in the sequence label in the format year-month-day.

Fig 4. NNDSS influenza notifications in Australia.

Laboratory-confirmed influenza notifications throughout the seasonal and inter-seasonal period in Australia. The plot shows laboratory-confirmed diagnoses per 100,000 population from 2009–2014, with states and territories displayed separately. Data on laboratory confirmed cases of influenza in Australia was obtained from the Australian National Notifiable Diseases Surveillance Systems (NNDSS) website (http://www9.health.gov.au/cda/source/cda-index.cfm).