Amparo Larrauri

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.

Impact of the meningococcal C conjugate vaccine in Spain: an epidemiological and microbiological decision.

The new meningococcal C conjugate vaccine became available in Spain and was included in the infant vaccination schedule in 2000. A catch-up campaign was carried out in children under six years of age. As a consequence, the incidence of meningococcal disease caused by serogroup C has fallen sharply during the last three epidemiological years in Spain. The risk of contracting serogroup C disease in 2002/2003 fell by 58% when compared with the season before the conjugate vaccine was introduced. There was also an important decrease in mortality. Three deaths due to serogroup C occurred in the age groups targeted for vaccination in 2002/2003, compared with 30 deaths in the same age groups in the season before the launch of the vaccine campaign. In the catch-up campaign the vaccine coverage reached values above 92%. For the 2001, 2002 and 2003 routine childhood immunisation programme coverage values ranged from 90% to 95%. During the past three years a total of 111 cases of serogroup C disease have been reported in patients in the vaccine target group. Most of the vaccination failures occurred during the epidemiological year 2002/2003. Eight (53%) vaccine failures occurred in children who had been routinely immunised in infancy, and could be related to a lost of protection with time since vaccination. The isolation of several B:2a:P1.5 strains (ST-11 lineage) is noteworthy. These may have their origin in C:2a:P1.5 strains which, after undergoing genetic recombination at the capsular operon level, express serogroup B. These strains could have relevant epidemic potential.

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.

Excess mortality among the elderly in European countries, December 2014 to February 2015.

Since December 2014 and up to February 2015, the weekly number of excess deaths from all-causes among individuals ≥ 65 years of age in 14 European countries have been significantly higher than in the four previous winter seasons. The rise in unspecified excess mortality coincides with increased proportion of influenza detection in the European influenza surveillance schemes with a main predominance of influenza A (H3N2) viruses seen throughout Europe in the current season, though cold snaps and other respiratory infections may also have had an effect.

Influenza coverages in Spain and vaccination-related factors in the subgroup aged 50-64 years.

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 6,400 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.

I-MOVE multicentre case–control study 2010/11 to 2014/15 : is there within-season waning of influenza type/subtype vaccine effectiveness with increasing time since vaccination?

Since the 2008/9 influenza season, the I-MOVE multicentre case-control study measures influenza vaccine effectiveness (VE) against medically-attended influenza-like-illness (ILI) laboratory confirmed as influenza. In 2011/12, European studies reported a decline in VE against influenza A(H3N2) within the season. Using combined I-MOVE data from 2010/11 to 2014/15 we studied the effects of time since vaccination on influenza type/subtype-specific VE. We modelled influenza type/subtype-specific VE by time since vaccination using a restricted cubic spline, controlling for potential confounders (age, sex, time of onset, chronic conditions). Over 10,000 ILI cases were included in each analysis of influenza A(H3N2), A(H1N1)pdm09 and B; with 4,759, 3,152 and 3,617 influenza positive cases respectively. VE against influenza A(H3N2) reached 50.6% (95% CI: 30.0-65.1) 38 days after vaccination, declined to 0% (95% CI: -18.1-15.2) from 111 days onwards. At day 54 VE against influenza A(H1N1)pdm09 reached 55.3% (95% CI: 37.9-67.9) and remained between this value and 50.3% (95% CI: 34.8-62.1) until season end. VE against influenza B declined from 70.7% (95% CI: 51.3-82.4) 44 days after vaccination to 21.4% (95% CI: -57.4-60.8) at season end. To assess if vaccination campaign strategies need revising more evidence on VE by time since vaccination is urgently needed.

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.

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.

La vigilancia de la gripe: nuevas soluciones a un viejo problema

The pandemic potential of influenza has made this disease the principal target of both national and international surveillance systems. The intrinsic characteristics of sentinel networks enable them to integrate epidemiological and virological information of a high incidence disease such as influenza, so helping in the early detection and characterization of the circulating influenza viruses and in evaluating their spread capacity in the population. A sentinel network, which covers 75% of the population, was created in Spain more than ten years ago. This provides a new approach to human influenza surveillance based on the individualized reporting of each case and the linkage of clinical, epidemiological and virological data. This system has contributed to a more accurate evaluation of influenza activity in Spain. In spite of the limitations of this sentinel system, which mainly derive from the lack of representativeness that any surveillance system based on population samples can encounter, it provides data which have proved useful for the follow-up and control of influenza. Rapid information transmission is one of the main advantages of the system, allowing its integration in the international disease surveillance networks and improving the timeliness of both information spread and formulation of recommendations.