Silvia Jiménez-Jorge

I-MOVE Multi-Centre Case Control Study 2010-11: Overall and Stratified Estimates of Influenza Vaccine Effectiveness in Europe

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.

Influenza vaccine effectiveness estimates in Europe in a season with three influenza type/subtypes circulating: the I-MOVE multicentre case–control study, influenza season 2012/13

In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case-control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels.

Effectiveness of the 2010–11 seasonal trivalent influenza vaccine in Spain: cycEVA study

BACKGROUND In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using an observational study (cycEVA) conducted in the frame of the Spanish Influenza Sentinel Surveillance System. We aimed to measure the effectiveness of the seasonal trivalent vaccine in preventing influenza like illness (ILI) laboratory-confirmed influenza infection at the end of the season 2010-11. METHODS We conducted a test-negative case-control study between weeks 50/2010 and 12/2011. Cases were ILI laboratory-confirmed influenza infection and controls were those testing negative. Sentinel physicians collected data on demographic and clinical characteristics, vaccination status, and on covariates related to confounding factors associating with influenza VE. We calculated adjusted odds ratios (OR), using logistic regression and computed influenza VE as (1-OR) × 100. RESULTS The adjusted influenza VE against A(H1N1)pdm09 infection was 46% (95% confidence interval (95%CI): 0; 72). In A(H1N1)pdm09 infected patients who had received both 2010-11 trivalent influenza seasonal and 2009 monovalent pandemic vaccines, influenza VE was 74% (95%CI: 13; 93). The adjusted influenza VE against B infection was 23% (95%CI: -180; 79). CONCLUSION The trivalent influenza vaccine 2010-11 showed a moderate VE for preventing ILI laboratory confirmed influenza infections. Influenza VE estimates were higher in patients who had received both 2010-11 seasonal trivalent and 2009 monovalent pandemic vaccines.

The European I-MOVE Multicentre 2013-2014 Case-Control Study. Homogeneous moderate influenza vaccine effectiveness against A(H1N1)pdm09 and heterogenous results by country against A(H3N2)

BACKGROUND In the first five I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe) influenza seasons vaccine effectiveness (VE) results were relatively homogenous among participating study sites. In 2013-2014, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in six European Union (EU) countries to measure 2013-2014 influenza VE against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Influenza A(H3N2) and A(H1N1)pdm09 viruses co-circulated during the season. METHODS Practitioners systematically selected ILI patients to swab within eight days of symptom onset. We compared cases (ILI positive to influenza A(H3N2) or A(H1N1)pdm09) to influenza negative patients. We calculated VE for the two influenza A subtypes and adjusted for potential confounders. We calculated heterogeneity between sites using the I(2) index and Cochranes Q test. If the I(2) was <50%, we estimated pooled VE as (1 minus the OR)×100 using a one-stage model with study site as a fixed effect. If the I(2) was >49% we used a two-stage random effects model. RESULTS We included in the A(H1N1)pdm09 analysis 531 cases and 1712 controls and in the A(H3N2) analysis 623 cases and 1920 controls. For A(H1N1)pdm09, the Q test (p=0.695) and the I(2) index (0%) suggested no heterogeneity of adjusted VE between study sites. Using a one-stage model, the overall pooled adjusted VE against influenza A(H1N1)pdm2009 was 47.5% (95% CI: 16.4-67.0). For A(H3N2), the I(2) was 51.5% (p=0.067). Using a two-stage model for the pooled analysis, the adjusted VE against A(H3N2) was 29.7 (95% CI: -34.4-63.2). CONCLUSIONS The results suggest a moderate 2013-2014 influenza VE against A(H1N1)pdm09 and a low VE against A(H3N2). The A(H3N2) estimates were heterogeneous among study sites. Larger sample sizes by study site are needed to prevent statistical heterogeneity, decrease variability and allow for two-stage pooled VE for all subgroup analyses.

Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study.

Adjusted early estimates of the 2013/14 influenza vaccine effectiveness (VE) in Spain for all age groups was 35% (95% CI: -9 to 62), 33% (95% CI: -33 to 67) and 28% (95% CI: -33 to 61) against any influenza virus type, A(H1N1)pdm09 and A(H3N2) viruses, respectively. For the population targeted for vaccination, the adjusted VE was 44% (95% CI: -11 to 72), 36% (95% CI: -64 to 75) and 42% (95% CI: -29 to 74), respectively. These preliminary results in Spain suggest a suboptimal protective effect of the vaccine against circulating influenza viruses.

Influenza-related mortality in Spain, 1999-2005

OBJECTIVE To estimate the excess deaths attributed to influenza in Spain, using age-specific generalized linear models (GLM) and the Serfling model for the period 1999-2005. METHOD We reviewed mortality from influenza and pneumonia and all-cause deaths. We used an additive GLM procedure, including the numbers of weekly deaths as a response variable and the number of influenza virus and respiratory syncytial virus weekly isolates, the population and two variables to adjust for annual fluctuations as covariates. Using the Serfling model, we removed the trend and applied a temporal regression model, excluding data from December to April to account for the expected baseline mortality in the absence of influenza activity. RESULTS Globally, the excess mortality attributable to influenza was 1.1 deaths per 100,000 for influenza and pneumonia and 11 all-cause deaths per 100,000 using the GLM model. The highest mortality rates were obtained with the Serfling model in adults older than 64 years, with an excess mortality attributable to influenza of 57 and 164 deaths per 100,000 for influenza and pneumonia and all-cause, respectively. CONCLUSIONS The GLM model, which takes viral activity into account, yields systematically lower estimates of excess mortality than the Serfling model. The GLM model provides independent estimates associated with the activity of different viruses and even with other factors, which is a significant advantage when trying to understand the impact of viral respiratory infections on mortality in the Spanish population.

Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010

BackgroundPhysicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study.MethodsWe conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100.ResultsWe included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected.ConclusionPoint estimates of the pandemic influenza vaccine effectiveness suggested a protective effect of the pandemic vaccine against laboratory-confirmed influenza A(H1N1)2009 in the season 2009-2010. Both studies were limited by the low vaccine coverage and the late start of the vaccination campaign. Routine influenza surveillance provides reliable estimates and could be used for influenza vaccine effectiveness studies in future seasons taken into account the surveillance system limitations.

Influenza-related mortality in Spain. 1999-2005

OBJECTIVE To estimate the excess deaths attributed to influenza in Spain, using age-specific generalized linear models (GLM) and the Serfling model for the period 1999-2005. METHOD We reviewed mortality from influenza and pneumonia and all-cause deaths. We used an additive GLM procedure, including the numbers of weekly deaths as a response variable and the number of influenza virus and respiratory syncytial virus weekly isolates, the population and two variables to adjust for annual fluctuations as covariates. Using the Serfling model, we removed the trend and applied a temporal regression model, excluding data from December to April to account for the expected baseline mortality in the absence of influenza activity. RESULTS Globally, the excess mortality attributable to influenza was 1.1 deaths per 100,000 for influenza and pneumonia and 11 all-cause deaths per 100,000 using the GLM model. The highest mortality rates were obtained with the Serfling model in adults older than 64 years, with an excess mortality attributable to influenza of 57 and 164 deaths per 100,000 for influenza and pneumonia and all-cause, respectively. CONCLUSIONS The GLM model, which takes viral activity into account, yields systematically lower estimates of excess mortality than the Serfling model. The GLM model provides independent estimates associated with the activity of different viruses and even with other factors, which is a significant advantage when trying to understand the impact of viral respiratory infections on mortality in the Spanish population.

Influenza pandemic (H1N1) 2009 activity during summer 2009: Effectiveness of the 2008-9 trivalent vaccine against pandemic influenza in Spain

INTRODUCTION The Spanish influenza surveillance system (SISS) maintained its activity during the summer of 2009 to monitor the influenza pandemic. OBJECTIVES To describe pandemic influenza activity from May to September 2009 and to estimate the effectiveness of the 2008-9 seasonal influenza vaccine against laboratory-confirmed pandemic (H1N1) 2009 influenza. METHODS Data from the SISS were used to identify the trend of pandemic (H1N1) 2009 influenza outside the influenza season. For the effectiveness study, we compared the vaccination status of notified cases [influenza-like illnesses (ILI) laboratory confirmed as pandemic influenza] with that of the test-negative controls. RESULTS The first laboratory-confirmed case of the pandemic virus was notified in the system in week 20/2009. The ILI rate increased gradually in the study period, exceeding basic activity in week 38. The proportion of pandemic (H1N1) 2009 influenza viruses detected by the system represented 14% in week 20/2009 and rapidly increased to 90% in week 34. The adjusted vaccine effectiveness of the 2008-9 seasonal vaccine against laboratory-confirmed pandemic influenza was 12% (-30; 41). CONCLUSIONS The SISS became an essential tool for pandemic monitoring in Spain. The improved SISS will provide more accurate information on influenza activity in future seasonal or pandemic waves. Using surveillance data, we could not demonstrate the effectiveness of the seasonal 2008-9 vaccine against laboratory-confirmed pandemic influenza.

Epidemiology of the 2009 influenza pandemic in Spain. The Spanish Influenza Surveillance System

In accordance with European Centre for Disease Prevention and Control recommendations, the Spanish Influenza Surveillance System (SISS) maintained its activity during the summer of 2009, and since July 2009 the pandemic virus activity was monitored by the SISS. In this paper, we describe the epidemiological and virological characteristics of the 2009 pandemic in the Spain through the SISS. Spain experienced a transmission of the new A(H1N1)pdm09 influenza virus during the summer of 2009, which gradually increased, resulting in the pandemic wave in early autumn of that year. The reproductive number R0, estimated during the growth phase of the pandemic wave (1.32; 95% confidence interval [95%CI], 1.29-1.36), showed a transmissibility comparable to preceding pandemics. There was an almost complete replacement of the previous seasonal A(H1N1) influenza virus by the pandemic virus A(H1N1)pdm09. The pandemic virus produced a greater burden of illness than seasonal influenza in children younger than 15 years old, while the incidence in those older than 64 years was lower compared with previous inter-pandemic seasons. Nevertheless, in Spain the 2009 pandemic was characterized as mild, considering the duration of the pandemic period and the influenza detection rate, both in the range of those observed in previous inter-pandemic seasons. Also, the case fatality ratio (CFR) was estimated at 0.58 deaths/1,000 confirmed ILI cases (95%CI, 0.52-0.64), in the range of the two previous pandemics of 1957 and 1968, with the highest CFR observed in the older than 64 years age group. In the 2009 pandemic there was a higher percentage of pandemic confirmed deaths in the younger ages, compared to seasonal influenza, since only 28% of the reported deaths occurred in persons aged 64 years and older.