Thursday, October 12, 2017

Eurosurveillance: Low 2016/17 Vaccine Effectiveness (VE) Among Elderly Hospitalized H3N2 Cases


It is not exactly `news' that last year's H3N2 vaccine component - particularly among elderly recipients - under performed. Here in the United States, we only saw a modest level of protection (34%) against H3N2, according to the CDC's MMWR report of June 30th.
2016–17 Influenza Vaccine Effectiveness
Data collected through the U.S. Influenza Vaccine Effectiveness Network during November 28, 2016–April 14, 2017, indicate that influenza vaccination this season reduced the overall risk for influenza-associated medical visits by 42% (95% CI = 35%–48%).
Vaccine effectiveness against the predominant influenza A(H3N2) viruses was 34% (95% CI = 24%–42%) and vaccine effectiv
eness against influenza B viruses was 56% (95% CI = 47%–64%).
Similarly, last February a Eurosurveillance report  Interim estimates of 2016/17 vaccine effectiveness against influenza A(H3N2), Canada, January 2017 DM Skowronski  et al. found an adjusted VE of 42%.
But at the same time we've been seeing reports of much lower VE - particularly among those over 65 - who were infected with some recently emerging variants of the H3N2 virus (see Changes in genetically drifted H3N2 influenza A viruses and vaccine effectiveness in adults 65 years and older during the 2016/17 season in Denmark),
A week ago, in ECDC: H3N2 Flu Vaccine Component Likely `Suboptimal', we looked at expectations of another lackluster performance - based on recent outbreaks in Hong Kong and Australia, and an announced change in next year's Southern Hemisphere H3N2 component by the WHO (see WHO: Recommended Composition of The 2018 Southern Hemisphere Flu Vaccine).
Today the Eurosurveillance Journal has published a cautionary report on last year's H3N2 Influenza Vaccine Effectiveness (IVE), and what it may portend for the upcomming flu season. 
While the numbers (17% protection for those over 65, 10% for those over 80) are disappointing, receipt of the vaccine did reduce hospitalizations and save lives.
I've only included some excerpts, follow the link to read the report in its entirety.

Rapid communication Open Access

Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2) among elderly: awareness warranted for 2017/18 season

Marc Rondy1, Alin Gherasim2,3, Itziar Casado3,4, Odile Launay5,6, Caterina Rizzo7, Daniela Pitigoi8, Aukse Mickiene9, Sierk D Marbus10, Ausenda Machado11, Ritva K Syrjänen12, Iva Pem-Novose13, Judith Krisztina Horváth14, Amparo Larrauri2,3, Jesús Castilla3,4, Philippe Vanhems5,15,16, Valeria Alfonsi7, Alina E Ivanciuc17, Monika Kuliese9, Rianne van Gageldonk-Lafeber10, Veronica Gomez11, Niina Ikonen18, Zvjezdana Lovric13, Annamária Ferenczi14, I-MOVE+ hospital working group19, Alain Moren1
In 2016/17, the influenza season in Europe was characterised by an early start (week 46, 2016) and a predominance of A(H3N2) viruses. Overall, 89% of strains reported to the European Centre for Disease Prevention and Control (ECDC) were A(H3N2) viruses [1]. High hospitalisation rates and case fatality ratios were reported among persons aged 65 years and above [2]. The I-MOVE + (Integrated Monitoring of Vaccines in Europe plus) hospital network early estimates, suggested a low 2016/17 seasonal influenza vaccine effectiveness (IVE) against hospitalisation with influenza A(H3N2) among persons aged 65 years and above in the European Union (EU) [3].

Since the A(H3N2) vaccine component has not changed in 2017/18, we present the final 2016/17 season IVE against hospitalisation with influenza A(H3N2) among persons aged 65 years and above in Europe, to inform on the level of IVE that can be expected against A(H3N2) in the upcoming 2017/18 season.

Vaccine effectiveness against influenza A(H3N2) in 2016/17

 We included 1,073 influenza A(H3N2) cases, nine A(H1N1)pdm09 cases, 13 cases of influenza B and 1,541 controls between week 47, 2016 and week 14, 2017. Due to the small number of cases, we were not able to measure IVE against influenza A(H1N1)pdm09 and B. We excluded these 22 records from all analyses.

The median age of A(H3N2) cases was 81 years (range: 65−102 years) while that of controls was 80 (range: 65−102 years). Ninety-four percent of cases and 95% of controls had at least one underlying condition (p = 0.14). Controls were more likely than cases to have underlying lung disease (44 vs 37%, p < 0.05), rheumatologic disease (22 vs 15%, p < 0.05) and cancer (24 vs 19%, p < 0.05), to have been hospitalised in the past 12 months (44 vs 33%, p < 0.05) and to be current smokers (26 vs 20%, p < 0.05) (Table 1).

The one-stage pooled adjusted IVE was 17% (95% confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among patients aged 65–79 years and 10% (95 %CI: −15 to 30) among those aged 80 years and above. Among patients with specific underlying conditions, IVE ranged between 19% (95% CI: −1 to 35) among patients with heart disease and 35% (95% CI: 14 to 51) among patients with lung disease (Table 2).

The 2016/17 seasonal IVE was −2% (95% CI: −44 to 28) among patients who had received 2015/16 seasonal influenza vaccine and 39% (95 %CI: −3 to 59) among patients not vaccinated in 2015/16 (Table 2). Taking as a reference patients unvaccinated in 2015/16 and 2016/17, IVE for those vaccinated in 2015/16 only was 19% (95% CI: −15 to 42) and IVE when vaccinated both in 2015/16 and 2016/17 was 15% (95 %CI: −3 to 30) (Table 3).


In the 2016/17 influenza season, A(H3N2) viruses largely predominated. IVE against hospitalisation with influenza A(H3N2) virus infection among persons aged 65 years and above was low at 17%. The IVE point estimate was even lower (10%) among patients aged 80 years and above. IVE was similar among patients with heart disease, diabetes mellitus and cancer. The IVE point estimate was higher among patients with lung disease. While 95% CIs were largely overlapping, the 2016/17 IVE point estimate was lower (IVE: −2%) among patients vaccinated also in 2015/16 than among those unvaccinated in 2015/16 (IVE: 39%).

Low IVE against influenza A(H3N2) among persons aged 65 years and above has been previously observed in hospital settings [6-8]. A recent meta-analysis measured that the pooled IVE against hospitalisation with influenza A(H3N2) in seasons when circulating and vaccine strains were antigenically different was 14% (95% CI: −3 to 30) among persons aged 65 years and above [9]. It was 43% (95% CI: 33 to 53) in seasons when circulating and vaccine A(H3N2) strains were antigenically similar; 48% (95% CI: 37 to 59) against influenza A(H1N1)pdm09 and 38% (95% CI: 25 to 53) against influenza B [9].

Based on specimens received from week 40/2016 to week 5/2017, available antigenic data from the World Health Organization (WHO) European Region indicated that most circulating viruses that could be analysed were considered as antigenically similar to the 2016/17 vaccine component [10]. Consequently, European data supported the WHO recommendation to maintain the same vaccine component A/Hong Kong/4801/2014 (clade 3C.2a) for influenza A(H3N2) in the 2017/18 season vaccine for the northern hemisphere [11]. However, one third of viruses isolated during the above-mentioned period could not be assigned to an antigenic reporting category, reflecting technical challenges or antigenic changes in circulating viruses. Genetic data from Europe centralised at the ECDC suggested that circulating A(H3N2) viruses had undergone considerable genetic diversification during the above-mentioned period, with the emergence of subclusters within clade 3C.2a and subclade 3C.2a1 [10].

In September 2017, WHO updated the A(H3N2) component to A/Singapore/INFIMH-16-0019/2016 (subclade 3C.2a1) in the 2018 seasonal vaccine for the southern hemisphere [12]. The latest WHO update on 2 October 2017, reported that influenza A(H3N2) viruses were still predominating worldwide in September 2017. Further genetic information was not provided at this stage [13].

Our results taking patients unvaccinated in both 2015/16 and 2016/17 seasons as a reference suggested that influenza vaccination in 2015/16 and/or 2016/17 reduced the risk of influenza-associated hospitalisation among vaccinated patients. Our stratified results suggested that 2015/16 vaccination modified the 2016/17 IVE. Although too imprecise to be conclusive, our results could suggest that patients vaccinated in both seasons benefited from a residual protection from the 2015/16 vaccine, with no additional effect of the 2016/17 vaccine uptake.


Our results suggest a low IVE against hospitalised influenza A(H3N2) among persons aged 65 years and above, particularly among patients aged 80 years and above. They also suggest a modifying effect of 2015/16 influenza vaccination on 2016/17 IVE. 

The A(H3N2) virus component included in the 2017/18 vaccine will remain the same as in the 2016/17 season. The latest WHO influenza surveillance report suggests that influenza A(H3N2) viruses were predominating worldwide in August 2017. Low IVE may be expected during the 2017/18 season in case of predominant circulation of A(H3N2) viruses.

However, IVE against influenza A(H1N1)pdm09 and B are usually reported to be higher. Close monitoring of virological surveillance data will be required to prompt early promotion of complementary measures such as the use of antivirals or non-pharmaceutical interventions.

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