Co-circulation of influenza A(H1N1)pdm09 and influenza A(H3N2) viruses, World Health Organization (WHO) European Region, October 2018 to February 2019

In the World Health Organization European Region, the 2018/19 influenza season started in week 49 2018, crossing 10% virus-positivity in sentinel surveillance specimens. At week 5 2019, activity remained elevated with positivity rates at 55%. Both A(H1N1)pdm09 and A(H3N2) viruses circulated widely and detection levels in primary care and hospital settings were similar to past seasons. Hospitalisation data may suggest an increased susceptibility to A(H1N1)pdm09 virus in older age groups.

In the World Health Organization European Region, the 2018/19 influenza season started in week 49 2018, crossing 10% virus-positivity in sentinel surveillance specimens. At week 5 2019, activity remained elevated with positivity rates at 55%. Both A(H1N1)pdm09 and A(H3N2) viruses circulated widely and detection levels in primary care and hospital settings were similar to past seasons. Hospitalisation data may suggest an increased susceptibility to A(H1N1)pdm09 virus in older age groups.
The influenza season in 2018/19 in the World Health Organization European Region has been elevated for 9 weeks, with both influenza A viruses circulating, but the distribution of viruses differs greatly by country. Severity seems similar to past years that have had cocirculating influenza A viruses. Preliminary analyses of data from hospitalised influenza cases may suggest some increase in susceptibility to A(H1N1)pdm09 virus in older age groups.

Influenza surveillance in the European Region
Every week, 50 of 53 Member States (MS) of the World Health Organization (WHO) European Region and Kosovo*report epidemiological and virological influenza surveillance data to the European Surveillance System (TESSy), hosted by the European Centre for Disease Prevention and Control (ECDC). Analyses of these data during the influenza season (weeks 20 to 40) are published jointly with the WHO Regional Office for Europe in a weekly influenza update, FluNewsEurope [1]. Influenza surveillance is primarily based on primary care sentinel sites collecting specimens from patients with acute respiratory infection (ARI) and/or influenza like illness (ILI) [2]. A subset of countries conducts surveillance of hospitalised influenza or respiratory infections. Here, we present data from week 40 (starting 1 October 2018) through week 5 (ending 3 February 2019). Data analysis of detected viruses, hospitalised cases and severe acute respiratory infection (SARI) includes cases reported to TESSy as at 11 February 2019; genetic and antigenic characterisation and antiviral resistance data are provided as at 7 February 2019.

Start of the 2018/19 influenza season and activity as at 3 February
Influenza activity started to increase in early December (week 49 2018) and has continued into early February (week 5 2019); during these 9 weeks, more than 10% of the sentinel ARI/ILI specimens were positive for influenza (i.e. 10% threshold).
In the 2018/19 season, the 10% threshold was crossed 1 week later than in the B-dominated 2017/18 influenza season, 3 weeks later than the A(H3N2)-dominated 2016/17 season and 2 weeks before the previous influenza A(H1N1)pdm09-dominated season of 2015/16. In addition, percent specimen positivity in week 5 2019 was 55%, comparable to what was observed during the past two seasons ( Figure 1) [3,4].
The increase in influenza activity was first reported in the eastern part of the Region, with Georgia, Kyrgyzstan and Ukraine reporting medium influenza intensity by week 49 2018. These increases coincided with a steep rise in influenza virus detections from hospitalised SARI cases, with all three countries reporting over 50% percent positivity in week 50 2018. In Georgia and Kyrgyzstan detections were almost all influenza A(H1N1)pdm09, but in Ukraine A(H3N2).
Influenza activity has continued to intensify across the Region. In week 5 2019, the median positivity of sentinel specimens by MS was 57% with several countries, particularly in the southern and eastern part of the Region, reporting it as an intense influenza season. Turkey and Israel (countries where influenza A(H3N2) viruses circulated predominantly), reported weekly consultation rates for ILI exceeding those of the previous two seasons (2016/17 and 2017/18). Georgia and Albania, who had influenza A(H1N1)pdm09 viruses circulating predominantly, observed more SARI cases and higher percent positivity for influenza than in previous seasons. While in most countries reported activity was increasing or levelling off in week 5 2019, some countries in the southern and eastern European Region reported decreasing activity.

Virology Influenza A
As at week 5 2019, 58% of all 7,437 subtyped influenza A viruses were influenza A(H1N1)pdm09 and 42% were influenza A(H3N2) among influenza cases detected though general practitioner sentinel systems; distribution of circulating influenza A subtypes varied by country ( Figure 2). Influenza A(H1N1)pdm09 and A(H3N2) co-infections were reported and a seasonal reassortant influenza A(H1N2) virus was detected in Sweden [5]. Genetically, 81% (n = 432) belonged to clade 3C.2a and of these, the majority (83% n = 358) were in the 3C.2a1b group. Viruses belonging to clade 3C.3a were reported by some countries.

Influenza B
Given the low prevalence, few influenza B viruses were genetically or antigenically characterised. All four B/ Yamagata viruses antigenically characterised were similar to the quadrivalent vaccine virus and assigned to clade B/Phuket/3072/2013 of the quadrivalent vaccine virus. Three of four antigenically characterised B/

Discussion and conclusions
This is the tenth influenza season with circulation of A(H1N1)pdm09 virus since its initial appearance during the 2009 pandemic. Influenza A(H1N1)pdm09 seasons affect younger adults more severely; an estimated 65% of deaths from the first 12 months of the pandemic were in persons 18-64 [6]. In contrast, A(H3N2) affects adults 65 years and older more; about 80-90% of deaths from A(H3N2) occur in this age group [7,8]. As expected, among hospitalised patients in ICUs, we saw these age differences between influenza A(H1N1) pdm09 and influenza A(H3N2) cases. Persons aged 75 years and older accounted for a higher proportion of influenza A(H3N2) ICU admissions compared with A(H1N1)pdm09. However, when comparing ICU admissions from the 2014/15 season to the current season, we saw the relative proportion of adults aged 25-44 and 65-74 years increase among A(H1N1)pdm09related ICU admissions and the proportion of those aged 45-64 years increase among cases with influenza A(H3N2). This changing age-distribution by subtype may, in part, reflect the ageing population of those with pre-pandemic exposure to the 1918-like A(H1N1) virus, who may have some residual immunologic protection [9]. This might explain the increased proportion of adults aged 65-74 years among A(H1N1)pdm09 detections in the current season, although this subset of data from 12 countries may not be generalisable and these early observations will require further, more rigorous, examination at the end of the season.
The relative proportion of circulating influenza A(H1N1) pdm09 and influenza A(H3N2) viruses varied by country and region this season. Recent interim vaccine effectiveness (VE) estimates indicate that the current vaccine is effective at preventing influenza virus infection, particularly by A(H1N1)pdm09 viruses, in children [10][11][12]. In recent years, the vaccine was less effective against influenza A(H3N2) viruses [13]. VE may vary across the Region based on the mix of circulating influenza subtypes and variation within the antigenic likeness of circulating A(H3N2) viruses with the eggpropagated A(H3N2) vaccine component. Despite its limitations, vaccination remains the most effective way to prevent influenza. Circulating influenza viruses during 2018/19 were largely susceptible to the antiviral drugs oseltamivir and zanamivir and these should be used as indicated by national guidelines.

Note
* For the purposes of this publication, all references, including in the bibliography, to 'Kosovo' should be understood/ read as 'Kosovo (in accordance with Security Council resolution 1244 (1999))'. This designation is without prejudice to positions on status, and is in line with UNSCR 1244/1999 and the ICJ Opinion on the Kosovo declaration of independence. Penttinen and SJ Olsen: surveillance strategy, critical review of the manuscript; surveillance network: collection and analysis of country data, critical review of the manuscript.