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Abstract: This study describes the epidemiological impact of meningococcal C conjugate vaccine on age groups targeted by this vaccination programme in Spain, and estimates high short-term vaccine effectiveness values under field conditions in the 4 years following its introduction. Meningococcal C conjugate vaccine has led to a substantial reduction in incidence of meningococcal serogroup C disease in Spain among age groups targeted for intervention nationwide. Disease surveillance in the 4 years since the vaccine was introduced has enabled vaccine effectiveness (VE) to be estimated. The vaccine registered high short-term VE values but there has been some loss of VE with time. Four years after vaccination, vaccine protection levels exceeded 94% in cohorts immunised during the campaign. Among children vaccinated in routine childhood immunisation programmes, however, long-term VE loss was greater. Accordingly, there is a need for ongoing re-evaluation of VE and ascertainment of long-term vaccine protection. The findings reported would allow to decide on the advisability of revising current vaccination guidelines. [Copyright &y& Elsevier]

This study sought to describe influenza vaccination coverages for different Spanish population subgroups, stressing the analysis of vaccination-related factors in subjects aged 50–64 years and estimating the possible beneficial effect of extending universal vaccination to this age group.A total of 6400 surveys, targeting subjects over the age of 16 years and drawn from the 1997 Spanish National Health Survey, were used for study purposes.Influenza coverage was observed to rise significantly with age, and the reason cited by most subjects for seeking vaccination was medical indication. Coverage of the 50–64 age group was 21.6% (95% CI 19.4–23.8) and the variables associated with a greater probability of being vaccination were: residence in towns or cities with <10,000 inhabitants (OR 1.45); monthly income of less than €600 (OR 1.71); and presence of associated chronic disease (OR 3.07.) It is estimated that in Spain, 524,514 (40.7%) persons aged 50–64 years with associated chronic disease receive and 764,218 persons aged 50–64 years with associated chronic disease do not receive influenza vaccine.We conclude that the extremely high number of subjects in the 50–64 age range susceptible to influenza-related complications each year constitutes good grounds for universal vaccination being extended to said age group. [Copyright &y& Elsevier]

Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022–23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates. We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0–14, 15–64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one). We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations. Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022–23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons. [ABSTRACT FROM AUTHOR]

Background: Data from the sentinel surveillance system of severe acute respiratory infections in Spain were used to estimate the impact of administration of nirsevimab to children born from 1 April 2023 onwards. Methods: Estimated RSV hospitalisations in < 1‐year‐olds during weeks 40, 2023, to 8, 2024, were compared to the number that would be expected after accounting for the background change in RSV circulation in the 2023/24 season, compared to 2022/23. Results: We estimated 9364–9875 RSV hospitalisations less than expected, corresponding to a 74%–75% reduction. [ABSTRACT FROM AUTHOR]

Introduction: Epidemiological models have proven to be crucial in supporting the decision-making of health authorities during the COVID-19 pandemic as well as raising awareness among the general public of the different measures adopted by authorities (social distancing, mask usage, vaccination, etc.). Objectives: This work describes the methodology to integrate different data sources to generate a single time series that provides real incidence rates of COVID-19 in Spain. Methodology: This series considers both reported and non-notified cases, that is, those that have not been registered by health authorities. Results: This work also describes how the information generated in this project has been treated and stored, it presents the estimated real incidence data obtained, as well as the organizations and research teams that use it, and the different communication channels that have been used to disseminate it (webpage, sharing results with health authorities, and repository). Conclusion: This work integrates information from multiple data sources for the analysis and prediction of the incidence of COVID-19. Through a multidisciplinary approach, it has been possible to propose a response to the problem of estimating the real incidence of COVID-19 cases. [ABSTRACT FROM AUTHOR]

Background: All aged individuals with a chronic condition and those with 65 and more years are at increased risk of severe influenza post-infection complications. There is limited research on cases averted by the yearly vaccination programs in high-risk individuals. The objective was to estimate the impact of trivalent seasonal influenza vaccination on averted hospitalizations and death among the high-risk population in Portugal.Methods: The impact of trivalent seasonal influenza vaccination was estimated using vaccine coverage, vaccine effectiveness and the number of influenza-related hospitalizations and deaths. The number of averted events (NAE), prevented fraction (PF) and number needed to vaccinate (NVN) were estimated for seasons 2014/15 to 2016/17.Results: The vaccination strategy averted on average approximately 1833 hospitalizations and 383 deaths per season. Highest NAE was observed in the ≥65 years population (85% of hospitalizations and 95% deaths) and in the 2016/17 season (1957 hospitalizations and 439 deaths). On average, seasonal vaccination prevented 21% of hospitalizations in the population aged 65 and more, and 18.5% in the population with chronic conditions. The vaccination also prevented 29% and 19.5% of deaths in each group of the high-risk population. It would be needed to vaccinate 3360 high-risk individuals, to prevent one hospitalization and 60,471 high-risk individuals to prevent one death.Conclusion: The yearly influenza vaccination campaigns had a sustained positive benefit for the high-risk population, reducing hospitalizations and deaths. These results can support public health plans toward increased vaccine coverage in high-risk groups. [ABSTRACT FROM AUTHOR]

Background: Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent. Objectives: To explore previous influenza vaccination effects on current season VE among population targeted for vaccination. Methods: We used 2011/2012 to 2016/2017 I‐MOVE primary care multicentre test‐negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only. Results: We included 941, 2645 and 959 influenza‐like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were −68%, −21% and −19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%). Conclusions: We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects. [ABSTRACT FROM AUTHOR]

Background: Estimating the national burden of influenza disease is challenging. We aimed to estimate the disease burden of seasonal influenza in Spain, at the primary care and hospital level, over the 6 influenza seasons after 2009 pandemic. Methods: We used data from the Spanish Influenza Sentinel Surveillance System to estimate weekly influenza rates and the number of influenza‐like illness (ILI) and mild confirmed influenza cases (MCIC). From the surveillance of severe hospitalized confirmed influenza cases (SHCIC), we obtained hospitalization rates and total number of SHCIC, intensive care unit (ICU) admissions and deaths in influenza hospitalized patients. We estimated both mild and severe influenza cases, overall, and by age‐group (<5, 5‐14, 15‐64, and ≥65 years). Results: The highest cumulative rates of MCIC were observed in <15 years (1395‐3155 cases/100 000 population in 5‐14 years) and the lowest in ≥65 years (141‐608 cases/100 000 population). SHCIC rates revealed a characteristic U‐shaped distribution, with annual average hospitalization rates of 16.5 and 18.9 SHCIC/100, 000 p in 0‐4 years, and ≥65 years, respectively. We estimated an annual average of 866 868 cases of ILI attended in primary care (55% were MCIC), 3616 SHCIC, 1232 ICU admissions, and 437 deaths in SHCIC. The percentage of ICU admission among SHCIC was highest at 15‐64 years (42%), while the hospitalization fatality rate ranged from 1% in 0‐4 years to 18% in ≥65 years. Conclusions: The ongoing Spanish Influenza Surveillance System allowed obtaining crucial information regarding the impact of mild and severe influenza in Spain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Single-dose vaccination was widely recommended in the pre-Omicron era for persons with previous SARS-CoV-2 infection. The effectiveness of a second vaccine dose in this group in the Omicron era is unknown. Methods We linked nationwide population registries in Spain to identify community-dwelling individuals aged 18–64, with a positive SARS-CoV-2 test before single-dose mRNA vaccination (mRNA-1273 or BNT162b2). Every day between 3 January and 6 February 2022 we matched 1:1 individuals receiving a second mRNA vaccine dose and controls on sex, age, province, first dose type and time, month of primary infection, and number of previous tests. We then estimated Kaplan–Meier risks of confirmed SARS-CoV-2 reinfection. We performed a similar analysis in a Delta-dominant period, between 19 July and 30 November 2021. Results In the Omicron period, estimated effectiveness (95% CI) of a second dose was 62.2% (58.2–66.4%) 7–34 days after administration, similar across groups defined by age, sex, type of first vaccine, and time since the first dose. Estimated effectiveness was 65.4% (61.1–69.9%) for mRNA-1273 and 52.0% (41.8–63.1%) for BNT162b2. Estimated effectiveness was 78.5% (67.4–89.9%), 66.1% (54.9–77.5%), and 60.2% (55.5–64.8%) when primary infection had occurred in the Delta, Alpha, and pre-Alpha periods, respectively. In the Delta period, the estimated effectiveness of a second dose was 8.8% (−55.3% to 81.1%). Conclusions Our results suggest that, over 1 month after administration, a second dose of mRNA vaccine increases protection against SARS-CoV-2 reinfection with the Omicron variant among individuals with single-dose vaccination and previously infected with another variant. [ABSTRACT FROM AUTHOR]

Background: The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster.Methods: In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR.Findings: Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2-52·4). Estimated effectiveness was 52·5% (51·3-53·7) for an mRNA-1273 booster and 46·2% (43·5-48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5-61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford-AstraZeneca), 55·3% (52·3-58·2) with mRNA-1273 (Moderna), 49·7% (48·3-51·1) with BNT162b2 (Pfizer-BioNTech), and 48·0% (42·5-53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0-47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0-53·3) if administered more than 180 days after primary scheduled completion.Interpretation: Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster.Funding: None. [ABSTRACT FROM AUTHOR]

Background: Seasonal influenza‐associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic. Method: For Denmark, Spain, and the United States, we estimated age‐stratified excess mortality for (i) all‐cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time‐series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017. Results: The respective periods of weekly excess mortality for all‐cause and cause‐specific deaths were similar in their chronological patterns. Seasonal all‐cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3–6.1) and 14.3 (13.0–15.6) per 100,000 population, for the United States; 20.3 (15.8–25.0) and 24.0 (19.3–28.7) per 100,000 population for Denmark; and 22.9 (18.9–26.9) and 52.9 (49.1–56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all‐cause estimates. Discussion We observed fewer influenza‐associated deaths when we examined cause‐specific death categories compared with all‐cause deaths and observed the same trends in peaks in deaths with all death causes. Because all‐cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies. [ABSTRACT FROM AUTHOR]

Introduction The agreement between interim and final influenza vaccine effectiveness (VE) estimates would support the use of interim assessments as a proxy for final VE results to guide health authorities in influenza prevention. We aimed to compare interim/final VE estimates in Spain. Methods We used a test-negative case-control study (cycEVA) for 2010/11–2013/14 seasons. Sensitivity analyses were carried out by type/subtype of influenza virus and by target groups for vaccination. Results In general, interim estimates were higher compared to end-season estimates. Interim and final VE differences were higher for the target groups compared to all population. Subtype-specific interim/final VE estimates showed greater concordance (3–13%) than for any virus (7–24%). Conclusion In Spain, interim influenza VE estimates over 2010–2014 were a good proxy of the final protection of the vaccine. Interim and final estimates showed greater concordance for all population and if performed subtype-specific. [ABSTRACT FROM AUTHOR]

When responding to infectious disease outbreaks, rapid and accurate estimation of the epidemic trajectory is critical. However, two common data collection problems affect the reliability of the epidemiological data in real time: missing information on the time of first symptoms, and retrospective revision of historical information, including right censoring. Here, we propose an approach to construct epidemic curves in near real time that addresses these two challenges by 1) imputation of dates of symptom onset for reported cases using a dynamically-estimated "backward" reporting delay conditional distribution, and 2) adjustment for right censoring using the NobBS software package to nowcast cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020. We evaluate how these real-time estimates compare with more complete epidemiological data that became available later. We explore the impact of the different assumptions on the estimates, and compare our estimates with those obtained from commonly used surveillance approaches. Our framework can help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health systems in other locations. Author summary: When surveillance systems cannot be repurposed quickly enough for novel infectious agents, missing information becomes a major challenge in monitoring the outbreak in real time. We propose a statistical approach that uses available data to construct the epidemic curves, which describe the number of individuals infected over time. We apply our 3-step approach to estimate these real-time epidemic curves during the early SARS-CoV-2 outbreak in Spain. We demonstrate that our approach, combined with the understanding of its limitations, can (a) provide useful information earlier and more reliably than conventional surveillance approaches, and (b) aid in the decision-making process towards outbreak mitigation in real-time. [ABSTRACT FROM AUTHOR]

• Seasonal influenza vaccine programmes usually target at-risk and older individuals. • We used an age-structured dynamic-transmission model for eight European settings. • Older people benefit from adjuvanted or high-dose trivalent or quadrivalent vaccines. • Adopting mass paediatric influenza vaccination is also likely to be cost-effective. • Results rest on vaccine costs, willingness to vaccinate and unknown long-term effects. Despite seasonal influenza vaccination programmes in most countries targeting individuals aged ≥ 65 (or ≥ 55) years and high risk-groups, significant disease burden remains. We explored the impact and cost-effectiveness of 27 vaccination programmes targeting the elderly and/or children in eight European settings (n = 205.8 million). We used an age-structured dynamic-transmission model to infer age- and (sub-)type-specific seasonal influenza virus infections calibrated to England, France, Ireland, Navarra, The Netherlands, Portugal, Scotland, and Spain between 2010/11 and 2017/18. The base-case vaccination scenario consisted of non-adjuvanted, non-high dose trivalent vaccines (TV) and no universal paediatric vaccination. We explored i) moving the elderly to "improved" (i.e., adjuvanted or high-dose) trivalent vaccines (iTV) or non-adjuvanted non-high-dose quadrivalent vaccines (QV); ii) adopting mass paediatric vaccination with TV or QV; and iii) combining the elderly and paediatric strategies. We estimated setting-specific costs and quality-adjusted life years (QALYs) gained from the healthcare perspective, and discounted QALYs at 3.0%. In the elderly, the estimated numbers of infection per 100,000 population are reduced by a median of 261.5 (range across settings: 154.4, 475.7) when moving the elderly to iTV and by 150.8 (77.6, 262.3) when moving them to QV. Through indirect protection, adopting mass paediatric programmes with 25% uptake achieves similar reductions in the elderly of 233.6 using TV (range: 58.9, 425.6) or 266.5 using QV (65.7, 477.9), with substantial health gains from averted infections across ages. At €35,000/QALY gained, moving the elderly to iTV plus adopting mass paediatric QV programmes provides the highest mean net benefits and probabilities of being cost-effective in all settings and paediatric coverage levels. Given the direct and indirect protection, and depending on the vaccine prices, model results support a combination of having moved the elderly to an improved vaccine and adopting universal paediatric vaccination programmes across the European settings. [ABSTRACT FROM AUTHOR]

This study intended to identify and quantify the social ecological model (SEM) levels associated to seasonal IV uptake in the Portuguese elderly population. Data from the 2014 National Health Survey was restricted to individuals aged 65+ years (n = 5669). Twenty-three independent variables were allocated to the SEM levels: individual, interpersonal, organizational, community and policy. Sex stratified and age adjusted analysis using Poisson regression were performed for each level and for a fitted full model. Relative reduction in pseudo R magnitude measured marginal contribution of each level. For men and women, older groups (85+ vs. 65–69; men, PR = 1.59 and women, PR = 1.56); having 3+ chronic conditions (men, PR = 1.39 and women, PR = 1.35); previous 4 weeks GP and outpatient visits were associated to higher IV uptake. For men, only 2 SEM levels were associated (individual and organizational) while for women the community level was also relevant. Main marginal contribution came from individual (17.9% and 16.3%) and organizational (30.7% and 22.7%) levels. This study highlights the importance of individual characteristics, access and use of health care services for the IV uptake and the sex differential behaviour. [ABSTRACT FROM AUTHOR]

Background: Influenza A(H3N2), A(H1N1)pdm09 and B viruses co‐circulated in Europe in 2017‐18, predominated by influenza B. WHO‐recommended, trivalent vaccine components were lineage‐mismatched for B. The I‐MOVE hospital network measured 2017‐18 seasonal influenza vaccine effectiveness (IVE) against influenza A(H3N2) and B among hospitalised patients (≥65 years) in Europe. Methods: Following the same generic protocol for test‐negative design, hospital teams in nine countries swabbed patients ≥65 years with recent onset (≤7 days) severe acute respiratory infection (SARI), collecting information on demographics, vaccination status and underlying conditions. Cases were RT‐PCR positive for influenza A(H3N2) or B; controls: negative for any influenza. "Vaccinated" patients had SARI onset >14 days after vaccination. We measured pooled IVE against influenza, adjusted for study site, age, sex, onset date and chronic conditions. Results: We included 3483 patients: 376 influenza A(H3N2) and 928 B cases, and 2028 controls. Most (>99%) vaccinated patients received the B lineage‐mismatched trivalent vaccine. IVE against influenza A(H3N2) was 24% (95% CI: 2 to 40); 35% (95% CI: 6 to 55) in 65‐ to 79‐year‐olds and 14% (95% CI: −22 to 39) in ≥80‐year‐olds. Against influenza B, IVE was 30% (95% CI: 16 to 41); 37% (95% CI: 19 to 51) in 65‐ to 79‐year‐olds and 19% (95% CI: −7 to 38) in ≥80‐year‐olds. Conclusions: IVE against influenza B was similar to A(H3N2) in hospitalised older adults, despite trivalent vaccine and circulating B lineage mismatch, suggesting some cross‐protection. IVE was lower in those ≥80 than 65‐79 years. We reinforce the importance of influenza vaccination in older adults as, even with a poorly matched vaccine, it still protects one in three to four of this population from severe influenza. [ABSTRACT FROM AUTHOR]

Background: Predicting the details of how an epidemic evolves is highly valuable as health institutions need to better plan towards limiting the infection propagation effects and optimizing their prediction and response capabilities. Simulation is a cost- and time-effective way of predicting the evolution of the infection as the joint influence of many different factors: interaction patterns, personal characteristics, travel patterns, meteorological conditions, previous vaccination, etc. The work presented in this paper extends EpiGraph, our influenza epidemic simulator, by introducing a meteorological model as a modular component that interacts with the rest of EpiGraph's modules to refine our previous simulation results. Our goal is to estimate the effects of changes in temperature and relative humidity on the patterns of epidemic influenza based on data provided by the Spanish Influenza Sentinel Surveillance System (SISSS) and the Spanish Meteorological Agency (AEMET).Methods: Our meteorological model is based on the regression model developed by AB and JS, and it is tuned with influenza surveillance data obtained from SISSS. After pre-processing this data to clean it and reconstruct missing samples, we obtain new values for the reproduction number of each urban region in Spain, every 10 minutes during 2011. We simulate the propagation of the influenza by setting the date of the epidemic onset and the initial influenza-illness rates for each urban region.Results: We show that the simulation results have the same propagation shape as the weekly influenza rates as recorded by SISSS. We perform experiments for a realistic scenario based on actual meteorological data from 2010-2011, and for synthetic values assumed under simplified predicted climate change conditions. Results show that a diminishing relative humidity of 10% produces an increment of about 1.6% in the final infection rate. The effect of temperature changes on the infection spread is also noticeable, with a decrease of 1.1% per extra degree.Conclusions: Using a tool like ours could help predict the shape of developing epidemics and its peaks, and would permit to quickly run scenarios to determine the evolution of the epidemic under different conditions. We make EpiGraph source code and epidemic data publicly available. [ABSTRACT FROM AUTHOR]

We conducted a retrospective cohort study to assess the effect of influenza virus type and subtype on disease severity among hospitalized influenza patients in Spain. We analyzed the cases of 8,985 laboratory-confirmed case-patients hospitalized for severe influenza by using data from a national surveillance system for the period 2010-2017. Hospitalized patients with influenza A(H1N1)pdm09 virus were significantly younger, more frequently had class III obesity, and had a higher risk for pneumonia or acute respiratory distress syndrome than patients infected with influenza A(H3N2) or B (p<0.05). Hospitalized patients with influenza A(H1N1)pdm09 also had a higher risk for intensive care unit admission, death, or both than patients with influenza A(H3N2) or B, independent of other factors. Determining the patterns of influenza-associated severity and how they might differ by virus type and subtype can help guide planning and implementation of adequate control and preventive measures during influenza epidemics. [ABSTRACT FROM AUTHOR]

Based on previous observations during pandemics and seasonal epidemics, pregnant women are considered at risk of developing severe influenza outcomes after influenza infection. With the aim of preventing severe influenza illness, the World Health Organization (WHO) includes pregnant women as a target group for seasonal influenza vaccination. However, influenza vaccine uptake during pregnancy remains low in many countries, including Spain. The objectives of this study were to increase the evidence of pregnancy as a risk factor for severe influenza illness and to study the potential role of seasonal influenza vaccination in the prevention of severe outcomes in infected pregnant women. Using information from the surveillance of Severe Hospitalized Confirmed Influenza Cases (SHCIC) in Spain, from seasons 2010/11 to 2015/16, we estimated that pregnant women in our study had a relative risk of hospitalization with severe influenza nearly 7.8 times higher than non-pregnant women of reproductive age. Only 5 out of 167 pregnant women with known vaccination status in our study had been vaccinated (3.6%). Such extremely low vaccination coverage only allowed obtaining crude estimates suggesting a protective effect of the vaccine against influenza complications (ICU admission or death). Our overall results support that pregnant women could benefit from seasonal influenza vaccination, in line with national and international recommendations. [ABSTRACT FROM AUTHOR]

Background: During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. Methods: We used the test‐negative design in a multicentre case‐control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza‐like illness (ILI) laboratory‐confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza‐positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. Results: We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5‐46.7). Among those aged 0‐14, 15‐64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: −32.3 to 65.0), 41.4% (95% CI: 20.5‐56.7) and 13.2% (95% CI: −38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: −4.1 to 56.7). Among those aged 0‐14, 15‐64 and ≥65 years, VE against influenza B was −47.6% (95% CI: −124.9 to 3.1), 27.3% (95% CI: −4.6 to 49.4) and 9.3% (95% CI: −44.1 to 42.9), respectively. Conclusions: Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010–2011 season to the 2015–2016 season in Spain. Methods: We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. Results: We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Conclusion: Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus. [ABSTRACT FROM AUTHOR]

Introduction The 2014/15 influenza season in Spain was dominated by the circulation of drifted A(H3N2) and co-circulation of B viruses. We present the final estimates of influenza vaccine effectiveness (IVE) against confirmed influenza A(H3N2) and B its evolution along the season and with time since vaccination. Methods We used data collected on influenza like illness patients (ILI), systematically swabbed for the presence of influenza viruses within the Spanish Influenza Sentinel Surveillance System (SISS) and a restricted observational study (cycEVA). We used a test negative case–control design to compare influenza confirmed cases with negative controls. We estimated the IVE through a logistic regression model adjusting for potential confounders. The evolution of IVE was studied in early and late stages of the epidemic, and in different time intervals between receiving influenza vaccination and the onset of symptoms. Results At the end of the season we have found low and moderate IVE point estimates against influenza A(H3N2) and B, respectively, in all ages and target groups for vaccination. An IVE decreased from an early value of 37% to a late of −76% against influenza A(H3N2), and similarly, 84% vs −4% against Influenza B. When the onset of symptoms occurred more than three months after vaccination, the decrease of IVE was slower and milder against influenza B than against influenza A(H3N2). No significant change in the percentage of circulating drifted influenza A(H3N2) strains belonging to the 3c.2a and 3c.3a clades could be identified through the season. Conclusions In a season dominated by drifted A(H3N2) circulating virus, the vaccine offered little or no protection against A(H3N2) infection but had a moderate protective effect against influenza B. Efforts should be put in developing influenza vaccines that maintain their protective capabilities throughout the season and could stimulate a potentially broad immune response against diverse influenza strains. [ABSTRACT FROM AUTHOR]

Objectives Although influenza-like illnesses ( ILI) and acute respiratory illnesses ( ARI) surveillance are well established in Europe, the comparability of intensity among countries and seasons remains an unresolved challenge. The objective is to compare the intensity of ILI and ARI in some European countries. Design and setting Weekly ILI and ARI incidence rates and proportion of primary care consultations were modeled in 28 countries for the 1996/1997-2013/2014 seasons using the moving epidemic method ( MEM). We calculated the epidemic threshold and three intensity thresholds, which delimit five intensity levels: baseline, low, medium, high, and very high. The intensity of 2013/2014 season is described and compared by country. Results The lowest ILI epidemic thresholds appeared in Sweden and Estonia (below 10 cases per 100 000) and the highest in Belgium, Denmark, Hungary, Poland, Serbia, and Slovakia (above 100 per 100 000). The 2009/2010 season was the most intense, with 35% of the countries showing high or very high intensity levels. The European epidemic period in season 2013/2014 started in January 2014 in Spain, Poland, and Greece. The intensity was between low and medium and only Greece reached the high intensity level, in weeks 7 to 9/2014. Some countries remained at the baseline level throughout the entire surveillance period. Conclusions Epidemic and intensity thresholds varied by country. Influenza-like illnesses and ARI levels normalized by MEM in 2013/2014 showed that the intensity of the season in Europe was between low and medium in most of the countries. Comparing intensity among seasons or countries is essential for understanding patterns in seasonal epidemics. An automated standardized model for comparison should be implemented at national and international levels. [ABSTRACT FROM AUTHOR]

Background: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. Results: The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0-69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ⩾ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. [ABSTRACT FROM AUTHOR]

Measuring mortality has been a challenge during the COVID-19 pandemic. Here, we compared the results from the Spanish daily mortality surveillance system (MoMo) of excess mortality estimates, using a time series analysis, with those obtained for the confirmed COVID-19 deaths reported to the National Epidemiological Surveillance Network (RENAVE). The excess mortality estimated at the beginning of March 2020 was much greater than what has been observed in previous years, and clustered in a very short time. The cumulated excess mortality increased with age. In the first epidemic wave, the excess mortality estimated by MoMo was 1.5 times higher than the confirmed COVID-19 deaths reported to RENAVE, but both estimates were similar in the following pandemic waves. Estimated excess mortality and confirmed COVID-19 mortality rates were geographically distributed in a very heterogeneous way. The greatest increase in mortality that has taken place in Spain in recent years was detected early by MoMo, coinciding with the spread of the COVID-19 pandemic. MoMo is able to identify risk situations for public health in a timely manner, relying on mortality in general as an indirect indicator of various important public health problems. [ABSTRACT FROM AUTHOR]

Background In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Methods Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination. Results We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B. Conclusions Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pandemic influenza A (H1N1) 2009 virus appeared in Spain on April 25, 2009 for the first time. This new virus was adamantane-resistant but it was sensitive to neuraminidase (NA) inhibitors oseltamivir and zanamivir. Objectives: To detect oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses by the Spanish Influenza Surveillance System (SISS) and a possible spread of oseltamivir-resistant viruses in Spain since starting of the pandemic situation. Study design: A total of 1229 respiratory samples taken from 413 severe and 766 non-severe patients with confirmed viral detection of pandemic influenza A (H1N1) 2009 viruses from different Spanish regions were analyzed for the specific detection of the H275Y mutation in NA between April 2009 and May 2010. Results: H275Y NA substitution was found in 8 patients infected with pandemic influenza A (H1N1) 2009 viruses collected in November and December 2009 and in January 2010. All oseltamivir-resistant viruses were detected in severe patients (8/413, 1.93%) who previously received treatment with oseltamivir. Six of these patients were immunocompromised. Conclusion: In Spain, the number of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses is until now very low. No evidence for any spread of oseltamivir-resistant H1N1 viruses is achieved in our Country. [Copyright &y& Elsevier]

The European Paediatric Influenza Analysis (EPIA) project is a multi-country project that was created to collect, analyse and present data regarding the paediatric influenza burden in European countries, with the purpose of providing the necessary information to make evidence-based decisions regarding influenza immunisation recommendations for children. The initial approach taken is based on existing weekly virological and age-specific influenza-like illness (ILI) data from surveillance networks across Europe. We use a multiple regression model guided by longitudinal weekly patterns of influenza virus to attribute the weekly ILI consultation incidence pattern to each influenza (sub)type, while controlling for the effect of respiratory syncytial virus (RSV) epidemics. Modelling the ILI consultation incidence during 2002/2003–2008 revealed that influenza infections that presented for medical attention as ILI affected between 0.3% and 9.8% of children aged 0–4 and 5–14 years in England, Italy, The Netherlands and Spain in an average season. With the exception of Spain, these rates were always higher in children aged 0–4 years. Across the six seasons analysed (five seasons were analysed from the Italian data), the model attributed 47–83% of the ILI burden in primary care to influenza virus infection in the various countries, with the A(H3N2) virus playing the most important role, followed by influenza viruses B and A(H1N1). National season averages from the four countries studied indicated that between 0.4% and 18% of children consulted a physician for ILI, with the percentage depending on the country and health care system. Influenza virus infections explained the majority of paediatric ILI consultations in all countries. The next step will be to apply the EPIA modelling approach to severe outcomes indicators (i.e. hospitalisations and mortality data) to generate a complete range of mild and severe influenza burden estimates needed for decision making concerning paediatric influenza vaccination. [ABSTRACT FROM AUTHOR]

Abstract: We conducted a case–control and screening method studies to estimate influenza vaccine effectiveness (IVE) in the age group ≥65 years, based on the Spanish Influenza Sentinel Surveillance System (SISSS). Cases (influenza laboratory-confirmed) were compared to influenza-negative ILI patients (test-negative) and patients without ILI since the beginning of the season (non-ILI). For the screening method, cases’ vaccination coverage was compared to the vaccination coverage of the GPs’ catchment population. The results suggested a protective effect of the vaccine against laboratory-confirmed influenza in elderly in 2008–2009. The screening method and the test-negative control designs enable estimating IVE using exclusively SISSS data. [Copyright &y& Elsevier]

Background: Seasonal flu epidemics in the European region cause high numbers of cases and deaths. Flu-associated mortality has been estimated but morbidity studies are necessary to understand the burden of disease in the population. Our objective was to estimate the excess hospital admissions in Spain of diseases associated with influenza during four epidemic influenza periods (2000 - 2004). Methods: Hospital discharge registers containing pneumonia, chronic bronchitis, heart failure and flu from all public hospitals in Spain were reviewed for the years 2000 to 2004. Epidemic periods were defined by data from the Sentinel Surveillance System. Excess hospitalisations were calculated as the difference between the average number of weekly hospitalisations/100,000 in epidemic and non-epidemic periods. Flu epidemics were defined for seasons 2001/2002, 2002/2003, 2003/2004. Results: A(H3N2) was the dominant circulating serotype in 2001/2002 and 2003/2004. Negligible excess hospitalisations were observed during the 2002/2003 epidemic where A(H1N1) was circulating. During 2000/2001, flu activity remained below threshold levels and therefore no epidemic period was defined. In two epidemic periods studied a delay between the peak of the influenza epidemic and the peak of hospitalisations was observed. During flu epidemics with A(H3N2), excess hospitalisations were higher in men and in persons <5 and >64 years higher than 10 per 100,000. Pneumonia accounted for 70% of all flu associated hospitalisations followed by chronic bronchitis. No excess flu-specific hospitalisations were recorded during all seasons. Conclusion: Flu epidemics have an impact on hospital morbidity in Spain. Further studies that include other variables, such as temperature and humidity, are necessary and will deepen our understanding of the role of each factor during flu epidemics and their relation with morbidity. [ABSTRACT FROM AUTHOR]

Between 1999 and 2004, the European Union Invasive Bacterial Infections Surveillance Network (EU-IBIS) received c. 50 000 reports of meningococcal disease from 27 participating countries. Analysis has demonstrated a major decline in the incidence of invasive disease in those countries that have introduced routine vaccination against serogroup C infection. The establishment of rapid reporting of W135 and B2a/B2b strains has been able to provide early reassurance that these strains are not emerging as major public health problems in Europe. Between September 2001 and February 2005, the EU-MenNet project offered further opportunities for enhancing this data resource. Collaborative projects included: improving the EU-IBIS website; reviewing case ascertainment in Europe; reviewing cost-effectiveness studies for meningococcal serogroup C conjugate (MCC) vaccination; international comparisons of MCC vaccine efficacy; and mathematical modelling studies. In addition, linking of data from the European Meningococcal Multi-locus Sequence Type Centre to epidemiological data was performed. Particular clonal complexes were found to be preferentially associated with certain serogroups. Case fatality was also found to vary with clonal complex, suggesting that genotype can be a marker for hypervirulence. The importance of close collaboration between networks of epidemiologists, microbiologists, and the wider scientific and public health community is demonstrated. [ABSTRACT FROM AUTHOR]

Mosquito borne diseases are a group of infections that affect humans. Emerging or reemerging diseases are those that (re)occur in regions, groups or hosts that were previously free from these diseases: dengue virus; chikungunya virus; Zika virus; West Nile fever and malaria. In Europe, these infections are mostly imported; however, due to the presence of competent mosquitoes and the number of trips both to and from endemic areas, these pathogens are potentially emergent or re-emergent. Present and future climatic conditions, as well as meteorological, environmental and demographic aspects are risk factors for the distribution of different vectors and/or diseases. This review aimed to identify and analyze the existing literature on the transmission of mosquito borne diseases and those factors potentially affecting their transmission risk of them in six southern European countries with similar environmental conditions: Croatia, France, Greece, Italy, Portugal and Spain. In addition, we would identify those factors potentially affecting the (re)introduction or spread of mosquito vectors. This task has been undertaken with a focus on the environmental and climatic factors, including the effects of climate change. We undertook a systematic review of the vectors, diseases and their associations with climactic and environmental factors in European countries of the Mediterranean region. We followed the PRISMA guidelines and used explicit and systematic methods to identify, select and critically evaluate the studies which were relevant to the topic. We identified 1302 articles in the first search of the databases. Of those, 160 were selected for full-text review. The final data set included 61 articles published between 2000 and 2017.39.3% of the papers were related with dengue, chikungunya and Zika virus or their vectors. Temperature, precipitation and population density were key factors among others. 32.8% studied West Nile virus and its vectors, being temperature, precipitation and NDVI the most frequently used variables. Malaria have been studied in 23% of the articles, with temperature, precipitation and presence of water indexes as the most used variables. The number of publications focused on mosquito borne diseases is increasing in recent years, reflecting the increased interest in that diseases in southern European countries. Climatic and environmental variables are key factors on mosquitoes' distribution and to show the risk of emergence and/or spread of emergent diseases and to study the spatial changes in that distributions. [ABSTRACT FROM AUTHOR]

Background Morbidity, severity, and mortality associated with annual influenza epidemics are of public health concern. We analyzed surveillance data on hospitalized laboratory-confirmed influenza cases admitted to intensive care units to identify common determinants for fatal outcome and inform and target public health prevention strategies, including risk communication. Methods We performed a descriptive analysis and used Poisson regression models with robust variance to estimate the association of age, sex, virus (sub)type, and underlying medical condition with fatal outcome using European Union data from 2009 to 2017. Results Of 13 368 cases included in the basic dataset, 2806 (21%) were fatal. Age ≥40 years and infection with influenza A virus were associated with fatal outcome. Of 5886 cases with known underlying medical conditions and virus A subtype included in a more detailed analysis, 1349 (23%) were fatal. Influenza virus A(H1N1)pdm09 or A(H3N2) infection, age ≥60 years, cancer, human immunodeficiency virus infection and/or other immune deficiency, and heart, kidney, and liver disease were associated with fatal outcome; the risk of death was lower for patients with chronic lung disease and for pregnant women. Conclusions This study re-emphasises the importance of preventing influenza in the elderly and tailoring strategies to risk groups with underlying medical conditions. [ABSTRACT FROM AUTHOR]

Background: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination.Methods: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset.Results: The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0-69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval.Conclusions: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. [ABSTRACT FROM AUTHOR]