Influenza vaccine effectiveness in Italy: Age,subtype-specific and vaccine type estimates 2014/15 season

The 2014/15 influenza season in Europe was characterised by the circulation of influenza A(H3N2) viruses with an antigenic and genetic mismatch from the vaccine strain A/Texas/50/2012(H3N2) recommended for the Northern hemisphere for the 2014/15 season. Italy, differently from other EU countries where most of the subtyped influenza A viruses were H3N2, experienced a 2014/15 season characterized by an extended circulation of two influenza viruses: A(H1N1)pdm09 and A(H3N2), that both contributed substantially to morbidity.Within the context of the existing National sentinel influenza surveillance system (InfluNet) a test-negative case-control study was established in order to produce vaccine effectiveness (VE) estimates. The point estimates VE were adjusted by age group (<5; 5–15; 15–64; 65+ years), the presence of at least one chronic condition, target group for vaccination and need help for walking or bathing. In Italy, adjusted estimates of the 2014/15 seasonal influenza VE against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza for all age groups were 6.0% (95%CI: −36.5 to 35.2%), 43.6% (95%CI: −3.7 to 69.3%), −84.5% (95%CI: (−190.4 to −17.2%) and 50.7% (95% CI: −2.5 to 76.3%) against any influenza virus, A(H1N1)pdm09, A(H3N2) and B, respectively. These results suggest evidence of good VE against A(H1N1)pdm09 and B viruses in Italy and evidence of lack of VE against A(H3N2) virus due to antigenic and genetic mismatch between circulating A(H3N2) and the respective 2014/15 vaccine strain.     

Influenza vaccine effectiveness against laboratory-confirmed influenza in a vaccine-mismatched influenza B-dominant season

BackgroundThe 2017–2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season.MethodsEnd-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval.ResultsSpecimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9–89.2%) observed in children 0.5–14 years old, while all ages VE was 46.6% (95%CI 10.4–68.2%). All ages VE against influenza B was 23.2% (95%CI −10.1–46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017–2018 season.ConclusionsThe moderate-high 2017–2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.     

Seasonal influenza vaccines induced high levels of neutralizing cross-reactive antibody responses against different genetic group influenza A(H1N1)pdm09 viruses

Influenza A(H1N1)pdm09 viruses have been circulating throughout the world since the 2009 pandemic. A/California/07/2009 (H1N1) virus was included in seasonal influenza vaccines for seven years altogether, providing a great opportunity to analyse vaccine-induced immunity in relation to the postpandemic evolution of the A(H1N1)pdm09 virus. Serum antibodies against various epidemic strains of influenza A(H1N1)pdm09 viruses were measured among health care workers (HCWs) by haemagglutination inhibition and microneutralization tests before and after 2010 and 2012 seasonal influenza vaccinations. We detected high responses of vaccine-induced neutralizing antibodies to six distinct genetic groups. Our results indicate antigenic similarity between vaccine and circulating A(H1N1)pdm09 strains, and substantial vaccine-induced immunity against circulating epidemic viruses.     

Influenza vaccine effectiveness estimates for Western Australia during a period of vaccine and virus strain stability, 2010 to 2012

During 2010–2012 the strain composition of the influenza vaccine in the Southern Hemisphere did not change, but the circulating virus type/subtype did. We pooled data for these years from the Western Australian sentinel medical practice surveillance system for influenza to estimate vaccine effectiveness (VE) by influenza virus type and subtype. A case test-negative design was used with VE estimated as (1-odds ratio) × 100%. There were 2182 patients included in the analysis across the 3 years studied. The predominant subtype was A/H1pdm09 in 2010 and 2011, and A/H3 in 2012. The overall adjusted VE estimate against all influenza for 2010–2012 was 51% (95% CI: 36, 63). Estimates were highest against A/H1pdm09 at 74% (95% CI: 47, 87), followed by 56% (95% CI: 33, 71) for influenza B and lowest against A/H3 at 39% (95% CI: 13, 57). When analyses were restricted to compare influenza-positive patients with patients who tested positive for a non-influenza virus, overall adjusted VE was 59% (95% CI: 39, 72). These results suggest moderate protection against influenza by vaccination in Western Australia over the period 2010–2012, and are consistent with findings from other settings.     

Influenza vaccine effectiveness against hospitalization with laboratory-confirmed influenza in Greece: A pooled analysis across six seasons, 2013–2014 to 2018–2019

BackgroundMonitoring seasonal influenza Vaccine Effectiveness (VE) is key to inform vaccination strategies and sustain uptake. Pooling data across multiple seasons increases precision and allows for subgroup analyses, providing more conclusive evidence. Our aim was to assess VE against hospitalization with laboratory-confirmed influenza in Greece over six seasons, from 2013 to 2014 to 2018–2019, using routinely collected surveillance data.MethodsSwab samples from hospitalized patients across the country were tested for influenza by RT-PCR. We used the test-negative design, with patients testing positive for influenza serving as cases and those testing negative serving as controls. VE was calculated as one minus the Odds Ratio (OR) for influenza vaccination, estimated by mixed-effects logistic regression and adjusted for age, sex, hospitalization type (being in intensive care or not), time from symptom onset to swabbing, and calendar time. Stratified estimates by age and hospitalization type were obtained, and also subgroup estimates by influenza type/subtype and season. Antigenic and genetic characterization of a subset of circulating influenza strains was performed.ResultsA total of 3,882 test-positive cases and 5,895 test-negative controls were analyzed. Across all seasons, adjusted VE was 45.5% (95% CI: 31.6–56.6) against all influenza, 62.8% against A(H1N1)pdm09 (95% CI: 40.7–76.7), 28.2% against A(H3N2) (95% CI: 12.0–41.3) and 45.5% against influenza B (95% CI: 29.1–58.1). VE was slightly lower for patients aged 60 years and over, and similar between patients hospitalized inside or outside intensive care. Circulating A(H1N1)pdm09 and B strains were antigenically similar to the vaccine strains, whereas A(H3N2) were not.ConclusionOur results confirm the public health benefits from seasonal influenza vaccination, despite the suboptimal effectiveness against A(H3N2) strains. Continued monitoring of VE is essential, and routinely collected surveillance data can be valuable in this regard.     

In silico prediction of influenza vaccine effectiveness by sequence analysis

The effectiveness of seasonal influenza vaccines varies with the matching of vaccine strains to circulating strains. Based on the genetic distance of hemagglutinin and neuraminidase gene of the influenza viruses to vaccine strains, we statistically quantified the relationship between the genetic mismatch and vaccine effectiveness (VE) for influenza A/H1N1pdm09, A/H3N2 and B. We also proposed a systematic approach to integrate multiple genes and influenza types for overall VE estimation. Evident linear relationships were identified and validated in independent data. The modelling framework may enable in silico prediction for VE on a real-time basis and inform the influenza vaccine selection strategy.     

Replication of live attenuated influenza vaccine viruses in human nasal epithelial cells is associated with H1N1 vaccine effectiveness

In the 2013–2014 and 2015–2016 influenza seasons, live attenuated influenza vaccine (LAIV) generated reduced vaccine effectiveness (VE) against circulating H1N1 strains. This reduced VE coincided with the introduction of pandemic 2009 H1N1 (A/H1N1pdm09) vaccine virus reassortants, in place of pre-2009 seasonal H1N1 strains. Here, we explored one specific hypothesis for reduced VE; decreased replicative fitness of A/H1N1pdm09 strains in humans. Two A/H1N1pdm09 strains with reduced VE, A/California/07/2009 (A/CA09) and A/Bolivia/559/2013 (A/BOL13), were compared to pre-2009 seasonal H1N1 strains, A/New Caledonia/20/1999 (A/NC99) and A/South Dakota/6/2007 (A/SD07). Initial results showed that A/H1N1pdm09 strains had reduced multi-cycle infectivity in Madin-Darby Canine Kidney (MDCK) cells, compared to their pre-2009 counterparts. The A/BOL13 viral titre was found to be 2.65 log₁₀/mL lower when measured by multi-cycle 50% tissue culture infectious dose (TCID₅₀) assay compared to single-cycle fluorescent focus assay (FFA). By contrast, clinically effective A/NC99 titres differed by only 0.54 log₁₀/mL. In human alveolar (A549) cells, A/H1N1pdm09 strains replicated less than pre-2009 strains, with A/CA09 and A/BOL13 generating lower peak viral titres over 5 days. This phenotype was corroborated in physiologically relevant, primary human nasal epithelial cells (hNECs). Here, peak titres for pre-2009 strains A/NC99 and A/SD07 were 8.43 log₁₀ TCID₅₀/mL and 8.52 log₁₀ TCID₅₀/mL, respectively, versus 6.89 log₁₀ TCID₅₀/mL and 6.06 log₁₀ TCID₅₀/mL for A/H1N1pdm09 strains A/CA09 and A/BOL13. This confirmed a reduced ability of A/H1N1pdm09 strains to sustain replication in human respiratory cells. Using this information, H1N1 candidate A/Slovenia/2903/2015 (A/SLOV15) was characterised for replacement of A/BOL13 in the 2017/18 LAIV. A/SLOV15 produced comparable single and multi-cycle infectivity titres (Δ 0.16 log₁₀/mL) and reached a peak titre 1.23 log₁₀ TCID₅₀/mL higher than that of A/BOL13 in hNEC cultures. Taken together, these data suggest a reduction in sustained multi-cycle replication in human cells as a plausible root cause for reduced A/H1N1pdm09 VE.     

Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States

PurposeThis analysis examined potential causes of the lack of vaccine effectiveness (VE) of live attenuated influenza vaccine (LAIV) against A/H1N1pdm09 viruses in the United States (US) during the 2013–2014 season. Laboratory studies have demonstrated reduced thermal stability of A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through 2013–2014.MethodsPost hoc analyses of a 2013–2014 test-negative case-control (TNCC) effectiveness study investigated associations between vaccine shipping conditions and LAIV lot effectiveness. Investigational sites provided the LAIV lot numbers administered to each LAIV recipient enrolled in the study, and the vaccine distributor used by the site for commercially purchased vaccine. Additionally, a review was conducted of 2009–2014 pediatric observational TNCC effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season, and geographic location.ResultsFrom the 2013 to 2014 TNCC study, the proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly higher among children who received a lot released between August 1 and September 15, 2013, compared with a lot shipped either earlier or later (21% versus 4%; P < 0.01). A linear relationship was observed between the proportion of subjects testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at distributors’ central locations. The review of LAIV VE studies showed that in the 2010–2011 and 2013–2014 influenza seasons, no significant effectiveness of LAIV against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations of LAIV in the US, respectively, in contrast to significant effectiveness against A/H3N2 and B strains during 2010–2014.ConclusionsThis study showed that the lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated with exposure of some LAIV lots to temperatures above recommended storage conditions during US distribution, and is likely explained by the increased susceptibility of the A/California/7/2009 (H1N1pdm09) LAIV strain to thermal degradation.Clinical trial registry: NCT01997450     

The 2015–2016 influenza epidemic in Beijing,China: Unlike elsewhere,circulation of influenza A(H3N2) with moderate vaccine effectiveness

BackgroundWhile the 2015–2016 influenza season in the northern hemisphere was dominated by A(H1N1)pdm09 and B/Victoria viruses, in Beijing, China, there was also significant circulation of influenza A(H3N2) virus. In this report we estimate vaccine effectiveness (VE) against influenza A(H3N2) and other circulating viruses, and describe further characteristics of the 2015–2016 influenza season in Beijing.MethodsWe estimated VE of the 2015–2016 trivalent inactivated vaccine (TIV) against laboratory-confirmed influenza virus infection using the test-negative study design. The effect of prior vaccination on current VE was also examined.ResultsOf 11,000 eligible patients included in the study, 2969 (27.0%) were influenza positive. Vaccination coverage was 4.2% in both cases and controls. Adjusted VE against all influenza was 8% (95% CI: −16% to 27%): 18% (95% CI: −38% to 52%) for influenza A(H1N1)pdm09, 54% (95% CI: 16% to 74%) for influenza A(H3N2), and −8% (95% CI: −40% to 18%) for influenza B/Victoria. The overall VE for receipt of 2015–2016 vaccination only, 2014–2015 vaccination only, and vaccinations in both seasons was −15% (95% CI: −63% to 19%), −25% (95% CI: −78% to 13%), and 18% (95% CI: −11% to 40%), respectively.ConclusionsOverall the 2015–2016 TIV was protective against influenza infection in Beijing, with higher VE against the A(H3N2) viruses compared to A(H1N1)pdm09 and B viruses.     

Haemagglutinin stability was not the primary cause of the reduced effectiveness of live attenuated influenza vaccine against A/H1N1pdm09 viruses in the 2013–2014 and 2015–2016 seasons

During the 2013–2014 influenza season, the quadrivalent live attenuated influenza vaccine (QLAIV), had lower than expected vaccine effectiveness (VE) against circulating A/H1N1pdm09 viruses in the USA. The underlying reason proposed for this was that the A/H1N1pdm09 vaccine strain, A/California/07/2009 (A/CA09), had a thermally unstable haemagglutinin (HA) protein. Consequently, a new A/H1N1pdm09 candidate strain, A/Bolivia/559/2013 (A/BOL13), was developed for inclusion in the 2015–2016 QLAIV. A key parameter for selection of A/BOL13 was its more thermostable HA phenotype compared with A/CA09. During the 2015–2016 season, QLAIV containing A/BOL13 was found in some studies to have improved, but still with suboptimal, VE against circulating A/H1N1pdm09 viruses and was not recommended for use by the CDC in the US market in the 2016–2017 influenza season. This suggested that improved HA thermostability had not entirely resolved the reduced VE observed. One hypothesis for this was that, by improving thermostability, the A/BOL13 HA protein had been over-stabilised, compromising its activation at the low endosomal pH required for successful viral entry. Here we demonstrate that, while the A/BOL13 HA protein is more stable than that of A/CA09, its thermal and pH stability were comparable with historically efficacious LAIV strains, suggesting that the HA had not been over-stabilised. Furthermore, studies simulating potential heat exposure during distribution by exposing QLAIV nasal sprayers to 33 °C for 4 h showed that, while remaining within product specification, A/CA09 viral potency was statistically decreased after 12 weeks at 2–8 °C. These data suggest that although unfavourable HA protein stability may have contributed to the reduced VE of A/CA09 in 2013–2014, it was unlikely to have affected A/BOL13 in 2015–2016. We conclude that HA stability was not the primary cause of the reduced effectiveness of LAIV against A/H1N1pdm09 viruses in the 2013–2014 and 2015–2016 seasons.     

Influenza vaccine effectiveness in preventing laboratory-confirmed influenza in outpatient settings: A test-negative case-control study in Beijing,China, 2016/17 season

BackgroundThe objective of this study was to estimate influenza vaccine effectiveness (VE) for the 2016/17 epidemic of co-circulating influenza A(H1N1)pdm09 and A(H3N2) viruses in Beijing, the capital of China.MethodsThe surveillance-based study included all swabbed patients through influenza virological surveillance, between November 2016 and April 2017. A test-negative case-control design was used to estimate influenza VE against medically-attended laboratory-confirmed influenza in outpatient settings. Cases were influenza-like illness (ILI) patients who tested positive for influenza, and controls were influenza negative patients.ResultsA total of 10,496 ILI patients were enrolled and swabbed. Among them, 735 tested positive for influenza A(H1N1)pdm09, 1851 for A(H3N2), and 40 for type B. Of the 45 randomly selected specimens out of 1851 influenza A(H3N2) viruses, 2(4.4%) belonged to the H3N2 3C.2a1 clade, and 43(95.6%) belonged to A/Hong Kong/4801/2014-like 3C.2a clade. Among the 43 viruses of the 3C.2a clade, 32 viruses clustered in one subgroup carrying T131K, R142K and R261Q substitutions. The adjusted VE against all influenza was low at 25% (95% confidence interval (CI): 0–43%), with 54% (95%CI: 22–73%) for influenza A(H1N1)pdm09, and 2% (95%CI: −35% to 29%) for influenza A(H3N2).ConclusionsOur study suggested a moderate VE against influenza A(H1N1)pdm09, but low VE against influenza A(H3N2) in Beijing, 2016/17 season. Amino acid substitutions in the hemagglutinin may contribute to the low VE against influenza A(H3N2) for this season.     

Influenza vaccine effectiveness against laboratory confirmed influenza in Greece during the 2013–2014 season: A test-negative study

BackgroundIn 2013–2014 Greece experienced a resurgence of severe influenza cases, coincidental with a shift to H1N1pdm09 predominance. We sought to estimate Vaccine Effectiveness (VE) for this season using available surveillance data from hospitals (including both inpatients and outpatients).MethodsSwab samples were sent by hospital physicians to one of three laboratories, covering the entire country, to be tested for influenza using RT-PCR. The test-negative design was employed, with patients testing positive serving as cases and those testing negative serving as controls. VE was estimated using logistic regression, adjusted for age group, sex, region and calendar time, with further adjustment for unknown vaccination status using inverse response propensity weights. Additional age group stratified estimates and subgroup estimates of VE against H1N1pdm09 and H3N2 were calculated.ResultsOut of 1310 patients with known vaccination status, 124 (9.5%) were vaccinated, and 543 patients (41.5%) tested positive for influenza. Adjusted VE was 34.5% (95% CI: 4.1–55.3%) against any influenza, and 56.7% (95% CI: 22.8–75.7%) against H1N1pdm09. VE estimates appeared to be higher for people aged 60 and older, while in those under 60 there was limited evidence of effectiveness. Isolated circulating strains were genetically close to the vaccine strain, with limited evidence of antigenic drift.ConclusionsThese results suggest a moderate protective effect of the 2013–2014 influenza vaccine, mainly against H1N1pdm09 and in people aged 60 and over. Vaccine coverage was very low in Greece, even among groups targeted for vaccination, and substantial efforts should be made to improve it. VE can and should be routinely monitored, and the results taken into account when deciding on influenza vaccine composition for next season.     

Antigenic and genetic characterization of influenza viruses circulating in Bulgaria during the 2015/2016 season

Influenza virological surveillance is an essential tool for early detection of novel genetic variants of epidemiologic and clinical significance. The aim of this study was to determine the antigenic and molecular characteristics of influenza viruses circulating in Bulgaria during the 2015/2016 season. The season was characterized by dominant circulation of A(H1N1)pdm09 viruses, accounting for 66% of detected influenza viruses, followed by B/Victoria-lineage viruses (24%) and A(H3N2) viruses (10%). All sequenced influenza A(H1N1)pdm09, A(H3N2) and B/Victoria-lineage viruses belonged to the 6B.1, 3C.2a and 1A genetic groups, respectively. Amino acid analysis of 57 A(H1N1)pdm09 isolates revealed the presence of 16 changes in hemagglutinin (HA) compared to the vaccine virus, five of which occurred in four antigenic sites, together with 16 changes in neuraminidase (NA) and a number of substitutions in proteins MP, NP, NS and PB2. Despite the many amino acid substitutions, A(H1N1)pdm09 viruses remained antigenically closely related to A/California/7/2009 vaccine virus. Bulgarian A(H3N2) strains (subclade 3C.2a) showed changes at 11 HA positions four of which were located in antigenic sites A and B, together with 6 positions in NA, compared to the subclade 3C.3a vaccine virus. They contained unique HA1 substitutions N171K, S312R and HA2 substitutions I77V and G155E compared to Bulgarian 3C.2a viruses of the previous season. All 20 B/Victoria-lineage viruses sequenced harboured two substitutions in the antigenic 120-loop region of HA, and 5 changes in NA, compared to the B/Brisbane/60/2008 vaccine virus. The results of this study reaffirm the continuous genetic variability of circulating seasonal influenza viruses and the need for continued systematic antigenic and molecular surveillance.     

End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19

2018/19 was the first season of introduction of a newly licensed adjuvanted influenza vaccine (aTIV) for adults aged 65 years and over and the sixth season in the roll-out of a childhood influenza vaccination programme with a quadrivalent live attenuated influenza vaccine (LAIV). The season saw mainly A(H1N1)pdm09 and latterly A(H3N2) circulation.End-of-season adjusted vaccine effectiveness (aVE) estimates against laboratory confirmed influenza infection in primary care were calculated using the test negative case control method adjusting for key confounders. End-of-season aVE was 44.3% (95% CI: 26.8, 57.7) against all laboratory-confirmed influenza; 45.7% (95% CI: 26.0, 60.1) against influenza A(H1N1)pdm09 and 35.1% (95% CI: −3.7,59.3) against A(H3N2). Overall aVE was 49.9% (95%CI: −13.7, 77.9) for all those ≥ 65 years of age and 62.0% (95% CI: 3.4, 85.0) for those who received aTIV. Overall aVE for 2–17 year olds receiving LAIV was 48.6% (95% CI: −4.4, 74.7). The paper provides evidence of overall significant influenza VE in 2018/19, most notably against influenza A(H1N1)pdm09, however, as seen in 2017/18, there was reduced, non-significant VE against A(H3N2). aTIV provided significant protection for those 65 years of age and over.     

Long term effectiveness of adjuvanted influenza A(H1N1)pdm09 vaccine in children

BackgroundImmunological studies have indicated that the effectiveness of AS03 adjuvanted monovalent influenza A(H1N1)pdm09 vaccine (Pandemrix^®) may be of longer duration than what is seen for non-adjuvanted seasonal influenza vaccines. Sixty-nine percent of children 6 months–18 years of age in Stockholm County received at least one dose of Pandemrix^® during the 2009 pandemic. We studied the effectiveness of the vaccine during the influenza seasons 2010–2011 and 2012–2013 in children hospitalized with virologically confirmed influenza. The season 2011–2012 was not included, since influenza A(H3N2) was the predominant circulating strain.MethodsIn a retrospective case-control study using a modified test-negative design we compared the percentage vaccinated with Pandemrix^® among children diagnosed with influenza A(H1N1)pdm09 (cases), with that of those diagnosed with influenza A(H3N2) or influenza B (controls) during the two seasons. We excluded children born after July 1, 2009, since only children who were 6 months of age or older received the pandemic vaccine in October–December 2009.ResultsDuring the 2010–2011 season, 3/16 (19%) of children diagnosed with influenza A(H1N1)pdm09, vs. 32/41 (78%) of those with influenza A(H3N2) or influenza B had been vaccinated with Pandemrix^® in 2009. The odds ratio, after adjustment for sex, age and underlying diseases, for becoming a case when vaccinated with Pandemrix^® was 0.083 (95%CI 0.014, 0.36), corresponding to a VE of 91.7%. During the season 2012–2013, there was no difference between the two groups; 59% of children diagnosed with influenza A(H3N2)/B and 60% of those with influenza A(H1N1)pdm09 had been vaccinated with Pandemrix^® in 2009.ConclusionThe AS03 adjuvanted monovalent influenza A(H1N1) pdm09 vaccine (Pandemrix^®) was effective in preventing hospital admission for influenza A(H1N1)pdm09 in children during at least two seasons.     

Understanding influenza vaccine protection in the community: An assessment of the 2013 influenza season in Victoria,Australia

BackgroundThe influenza virus undergoes frequent antigenic drift, necessitating annual review of the composition of the influenza vaccine. Vaccination is an important strategy for reducing the impact and burden of influenza, and estimating vaccine effectiveness (VE) each year informs surveillance and preventative measures. We aimed to describe the influenza season and to estimate the effectiveness of the influenza vaccine in Victoria, Australia, in 2013.MethodsRoutine laboratory notifications, general practitioner sentinel surveillance (including a medical deputising service) data, and sentinel hospital admission surveillance data for the influenza season (29 April to 27 October 2013) were collated in Victoria, Australia, to describe influenza-like illness or confirmed influenza during the season. General practitioner sentinel surveillance data were used to estimate VE against medically-attended laboratory confirmed influenza. VE was estimated using the case test negative design as 1 − adjusted odds ratio (odds of vaccination in cases compared with controls) × 100%. Cases tested positive for influenza while non-cases (controls) tested negative. Estimates were adjusted for age group, week of onset, time to swabbing and co-morbidities.ResultsThe 2013 influenza season was characterised by relatively low activity with a late peak. Influenza B circulation preceded that of influenza A(H1)pdm09, with very little influenza A(H3) circulation. Adjusted VE for all influenza was 55% (95%CI: −11, 82), for influenza A(H1)pdm09 was 43% (95%CI: −132, 86), and for influenza B was 56% (95%CI: −51, 87) Imputation of missing data raised the influenza VE point estimate to 64% (95%CI: 13, 85).ConclusionsClinicians can continue to promote a positive approach to influenza vaccination, understanding that inactivated influenza vaccines prevent at least 50% of laboratory-confirmed outcomes in hospitals and the community.     

Comparing influenza vaccine effectiveness between cell-derived and egg-derived vaccines, 2017–2018 influenza season

The Department of Defense Global Respiratory Pathogen Surveillance Program conducted a study to compare the differences in vaccine effectiveness (VE) of the cell-derived and egg-derived vaccines. DoD healthcare beneficiaries, excluding service members, that presented with influenza-like illness for the period of 1 October 2017 through 28 April 2018 were included in a test-negative case-control study examining laboratory confirmed influenza infections. Three VE analyses were performed (1) influenza infection among those vaccinated with cell-derived vaccines (2) influenza infection among those vaccinated with egg-derived vaccines and a (3) relative VE which directly compared the odds of influenza infection with cell-derived vaccine against those with egg-derived vaccines. The cell-derived and egg-derived vaccines were moderately protective against all influenza types with significant VE estimates for all dependents at 46% (95% confidence interval, 33, 56) and 53% (45, 60), respectively. Of the subtype analyses, influenza A(H1N1)pdm09 performed the best. In the cell-derived vaccine, the adult age group was moderate to high at 71% (44, 85) and children moderate at 56% (15, 75). In the egg-derived vaccine, the children age group was at a high 88% (80, 93) effectiveness and adults at 81% (56, 92). When comparing cell-derived vaccine directly to the egg-derived vaccine, the relative VE found significant results only for influenza A(H1N1)pdm09 which favored the egg-derived vaccine with odds ratios of 2.0 (1.1, 3.6) for all dependents and 2.9 (1.3, 6.3) for children. In the influenza A(H3N2) analysis, statistical significance was not gained; however, the odds favored the cell-derived vaccine.     

Repeated seasonal influenza vaccination among elderly in Europe: Effects on laboratory confirmed hospitalised influenza

In Europe, annual influenza vaccination is recommended to elderly. From 2011 to 2014 and in 2015–16, we conducted a multicentre test negative case control study in hospitals of 11 European countries to measure influenza vaccine effectiveness (IVE) against laboratory confirmed hospitalised influenza among people aged ≥65 years. We pooled four seasons data to measure IVE by past exposures to influenza vaccination.We swabbed patients admitted for clinical conditions related to influenza with onset of severe acute respiratory infection ≤7 days before admission. Cases were patients RT-PCR positive for influenza virus and controls those negative for any influenza virus. We documented seasonal vaccination status for the current season and the two previous seasons.We recruited 5295 patients over the four seasons, including 465A(H1N1)pdm09, 642A(H3N2), 278 B case-patients and 3910 controls. Among patients unvaccinated in both previous two seasons, current seasonal IVE (pooled across seasons) was 30% (95%CI: −35 to 64), 8% (95%CI: −94 to 56) and 33% (95%CI: −43 to 68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Among patients vaccinated in both previous seasons, current seasonal IVE (pooled across seasons) was −1% (95%CI: −80 to 43), 37% (95%CI: 7–57) and 43% (95%CI: 1–68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively.Our results suggest that, regardless of patients’ recent vaccination history, current seasonal vaccine conferred some protection to vaccinated patients against hospitalisation with influenza A(H3N2) and B. Vaccination of patients already vaccinated in both the past two seasons did not seem to be effective against A(H1N1)pdm09. To better understand the effect of repeated vaccination, engaging in large cohort studies documenting exposures to vaccine and natural infection is needed.