Effectiveness of one and two doses of acellular pertussis vaccines against laboratory-confirmed pertussis requiring hospitalisation in infants: Results of the PERTINENT sentinel surveillance system in six EU/EEA countries, December 2015 - December 2019.

BACKGROUND: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. METHODS: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). RESULTS: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. CONCLUSIONS: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study.

BACKGROUND: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). METHODS: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. RESULTS: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. CONCLUSIONS: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.

Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011-2014 but increased during 2015-2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5-64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies. METHODS: For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011-2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 - IRR)*100. RESULTS: After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI -4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI -8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20-29% and 32-53% of IPD cases in PCV13 and PCV10 sites, respectively. CONCLUSION: Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.

Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study.

BACKGROUND: The Streptococcus pneumoniae Invasive Disease network (SpIDnet) actively monitors populations in nine sites in seven European countries for invasive pneumococcal disease. Five sites use 13-valent pneumococcal conjugate vaccine (PCV13) alone and four use the ten-valent PCV (PCV10) and PCV13. Vaccination uptake is greater than 90% in six sites and 67-78% in three sites. We measured the effects of introducing high-valency PCVs on the incidence of invasive pneumococcal disease in children younger than 5 years. METHODS: We compared the incidence of invasive pneumococcal disease in each of the 4 years after the introduction of PCV13 alone or PCV10 and PCV13 with the average incidence during the preceding period of heptavalent PCV (PCV7) use, overall and by serotype category. We calculated incidence rate ratios (IRRs) and 95% CIs for each year and pooled the values for all sites in a random effects meta-analysis. FINDINGS: 4 years after the introduction of PCV13 alone or PCV10 and PCV13, the pooled IRR was 0·53 (95% CI 0·43-0·65) for invasive pneumococcal disease in children younger than 5 years caused by any serotype, 0·16 (0·07-0·40) for disease caused by PCV7 serotypes, 0·17 (0·07-0·42) for disease caused by 1, 5, and 7F serotypes, and 0·41 (0·25-0·69) for that caused by 3, 6A and 19A serotypes. We saw a similar pattern when we restricted the analysis to sites where only PCV13 was used. The pooled IRR for invasive pneumococcal disease caused by non-PCV13 serotypes was 1·62 (1·09-2·42). INTERPRETATION: The incidence of invasive pneumococcal disease caused by all serotypes decreased due to a decline in the incidence of vaccine serotypes. By contrast, that of invasive pneumococcal disease caused by non-PCV13 serotypes increased, which suggests serotype replacement. Long-term surveillance will be crucial to monitor the further effects of PCV10 and PCV13 vaccination programmes in young children. FUNDING: European Centre for Disease Prevention and Control, Czech National Institute of Public Health, French National Agency for Public Health, Irish Health Services Executive, Norwegian Institute of Public Health, Public Health Agency of Catalonia, Public Health Department of Community of Madrid, Navarra Hospital Complex, Public Health Institute of Navarra, CIBER Epidemiology and Public Health, Institute of Health Carlos III, Public Health Agency of Sweden, and NHS Scotland.

[cycEVA study: case control study measuring influenza vaccine effectiveness in Spain, 2008-2013]. / Estudio cycEVA: casos y controles para la estimación de la efectividad de la vacuna antigripal en España, 2008-2013.

BACKGROUND: In Spain, influenza vaccine effectiveness (EV) is estimated since 2008-09 season through the cycEVA case-control study, the Spanish component of the European I-MOVE (Monitoring Influenza Vaccine Effectiveness in the EU/EEA) network. We aimed at describing cycEVA performance in its five consolidated editions 2008/09 -; 2012/13. METHODS: During the study period the following indicators were analysed: 1) the participation of sentinel general practitioners and pediatricians (MP), 2) the population studied and the study period, 3) the data quality and 4) the dissemination of the cycEVA results. Trend analysis of the indicators was done using the Cochran-Armitage test to compute the Annual Percentage Change (PCA). RESULTS: The number of participating MP increased from 164 in 2008-09 to 246 in the following editions. The percentage of MP recruiting at least one patient increased significantly annually (PCA = 15.33%). The percentage of recruited patients included into the analysis increased (PCA=5.91%) from 77% in 2008-09 to more than 95% in the following editions. The percentage of cycEVA patients contributing to the I-MOVE study ranged between 23% and 30% in the pilot and 2011-12 editions respectively.. Final results were disseminated in quartile 2 peer-reviewed journals and 2010-11 and 2011-12 preliminary EV estimates were published in quartile 1 journals. cycEVA publications received 97 citations. CONCLUSION: cycEVA study achieved more quality information, timely EV estimates and a higher impact of the results.

Estudio cycEVA: caos y controles para la estimación de la efectividad de la vacuna antigripal en España, 2008-2013 / cycEVA study: case control study Measuring influenza vaccine effectiveness in Spain, 2008-2013

Fundamentos: Desde 2008-09 la efectividad de la vacuna (EV) antigripal en España se estima con el estudio de casos y controles para la evaluación de la EV antigripal (cycEVA), componente español de la red europea (Influenza- Monitoring Vaccine Effectiveness (I-MOVE). El objetivo es describir la evolución del estudio cycEVAdurante las cinco temporadas del período 2008/09-2012/13. Métodos: Se analizaron los siguientes indicadores: 1) participación de los médicos/pediatras centinela (MP); 2) población y periodo de estudio, 3) calidad de los datos y 4) difusión de los resultados mediantes publicaciones. Se calculó el porcentaje anual de cambio constante de los indicadores analizándose su tendencia mediante el test de Cochran-Armitage. Resultados: El número de MP participantes aumentó de 164 en 2008-09 hasta 246 en ediciones posteriores. El porcentaje de médicos que reclutaron al menos un paciente experimentó un cambio anual significativo (PCA) del 15,33%. El porcentaje de pacientes reclutados incluidos en el análisis aumentó del 77% en 2008-09 a más del 95% en las siguientes ediciones (PCA=5,91%). El porcentaje de casos y controles participantes en cycEVA sobre el total de pacientes que contribuyeron al estudio europeo I-MOVE osciló entre el 23% en la edición piloto y 30% en la temporada 2011-12. Los resultados finales se difundieron en revistas científicas con un factor de impacto situado en el cuartil 2 y en 2010-11 y 2011-12 se publicaron resultados preliminares en revistas con un factor de impacto situado en el cuartil 1 (97 citas). Conclusiones: La experiencia del estudio cycEVA se reflejó en una mejora en la oportunidad e impacto de sus resultados, cruciales para orientar las recomendaciones anuales de vacunación antigripal (AU)

Background: In Spain, influenza vaccine effectiveness (EV) is estimated since 2008-09 season through the cycEVAcase-control study, the Spanish component of the European I-MOVE (Monitoring Influenza Vaccine Effectiveness in the EU/EEA) network.We aimed at describing cycEVAperformance in its five consolidated editions 2008/09 - 2012/13. Methods: During the study period the following indicators were analysed: 1) the participation of sentinel general practitioners and pediatricians (MP), 2) the population studied and the study period, 3) the data quality and 4) the dissemination of the cycEVA results. Trend analysis of the indicators was done using the Cochran-Armitage test to compute theAnnual Percentage Change (PCA). Results: The number of participatingMP increased from 164 in 2008-09 to 246 in the following editions. The percentage of MP recruiting at least one patient increased significantly annually (PCA = 15.33%). The percentage of recruited patients included into the analysis increased (PCA=5.91%) from 77% in 2008-09 to more than 95% in the following editions. The percentage of cycEVA patients contributing to the I-MOVE study ranged between 23% and 30% in the pilot and 2011-12 editions respectively.. Final results were disseminated in quartile 2 peer-reviewed journals and 2010-11 and 2011-12 preliminary EV estimates were published in quartile 1 journals. cycEVA publications received 97 citations. Conclusion: cycEVA study achieved more quality information, timely EV estimates and a higher impact of the results (AU)

Higher vaccine effectiveness in seasons with predominant circulation of seasonal influenza A(H1N1) than in A(H3N2) seasons: test-negative case-control studies using surveillance data, Spain, 2003-2011.

BACKGROUND: We used data provided by the Spanish influenza surveillance system to measure seasonal influenza vaccine effectiveness (VE) against medically attended cases, laboratory confirmed with the predominately circulating influenza virus over eight seasons (2003-2011). METHODS: Using the test-negative case-control design, we compared the vaccination status of swabbed influenza-like illnesses (ILI) patients who were laboratory confirmed with predominantly circulating influenza strain in the season (cases) to that of ILI patients testing negative for any influenza (controls). Data on age, sex, vaccination status and laboratory results were available for all seasons. We used logistic regression to calculate adjusted influenza VE for age, week of swabbing, Spanish region and season. We calculated the influenza VE by each season and pooling the seasons with the same predominant type/subtype. RESULTS: Overall influenza VE against infection with A(H3N2) subtype (four seasons) was 31 (95% confidence interval (CI):10; 48). For seasonal influenza A(H1N1) (two seasons), the effectiveness was 86% (95% CI: 65; 94). Against B infection (three seasons), influenza VE was 47% (95% CI: 27; 62). CONCLUSIONS: The Spanish influenza surveillance system allowed estimating influenza VE in the studied seasons for the predominant strain. Strengthening the influenza surveillance will result in more precise VE estimates for decision making.

Trends in infectious disease mortality rates, Spain, 1980-2011.

Using mortality data from National Institute of Statistics in Spain, we analyzed trends of infectious disease mortality rates in Spain during 1980-2011 to provide information on surveillance and control of infectious diseases. During the study period, 628,673 infectious disease-related deaths occurred, the annual change in the mortality rate was -1.6%, and the average infectious disease mortality rate was 48.5 deaths/100,000 population. Although the beginning of HIV/AIDS epidemic led to an increased mortality rate, a decreased rate was observed by the end of the twentieth century. By codes from the International Classification of Diseases, 9th revision, the most frequent underlying cause of death was pneumonia. Emergence and reemergence of infectious diseases continue to be public health problems despite reduced mortality rates produced by various interventions. Therefore, surveillance and control systems should be reinforced with a goal of providing reliable data for useful decision making.

Influenza-related mortality in Spain, 1999-2005

Objetivo Estimar los excesos de mortalidad atribuible a la gripe en España por grupos de edad, usando modelos lineales generalizados (MLG) y modelos Serfling, para el periodo 1999-2005.MétodoSe revisó la mortalidad por gripe y neumonía y por todas las causas. En el MLG aditivo se incluyó como variable respuesta el número de defunciones semanales, y como covariables el número de aislamientos semanales de virus de la gripe y de virus respiratorio sincitial, la población y dos variables que corrigen las fluctuaciones anuales. En el modelo Serfling se eliminó previamente la tendencia y se aplicó un modelo de regresión cíclica, excluyendo los valores desde diciembre hasta abril, para cuantificar la mortalidad esperada en ausencia de actividad gripal. Resultados El exceso de mortalidad atribuible a la gripe fue de 1,1 defunciones por 100.000 habitantes por gripe y neumonía, y de 11 defunciones por todas las causas usando el MLG. Las tasas de mortalidad más altas se observaron con el modelo Serfling en los mayores de 64 años, con un exceso de mortalidad de 57 y 164 defunciones por 100.000 habitantes por gripe y neumonía y por todas las causas, respectivamente. Conclusiones El MLG tiene en cuenta la actividad viral y produce de forma sistemática estimaciones de exceso de mortalidad más bajas que el modelo Serfling. El MLG tiene la ventaja de dar estimaciones independientes asociadas a la actividad de diferentes virus y otros factores, lo cual representa un paso importante cuando intentamos entender el impacto de las infecciones virales respiratorias en la mortalidad de nuestra población (AU)

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.MethodWe 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 (AU)

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.

BACKGROUND: Physicians 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. METHODS: We 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. RESULTS: We 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. CONCLUSION: Point 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.

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.

Estimates of pandemic influenza vaccine effectiveness in Europe, 2009-2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study.

BACKGROUND: A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009-2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1). METHODS AND FINDINGS: Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6-85.5) overall; 78.4% (95% CI 54.4-89.8) in patients <65 years; and 72.9% (95% CI 39.8-87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9-84.8), 71.3% (95% CI 29.1-88.4), and 70.2% (95% CI 19.4-89.0), respectively. The adjusted PIVE was 66.0% (95% CI -69.9 to 93.2) if vaccinated 8-14 days before ILI onset. The adjusted 2009-2010 seasonal influenza VE was 9.9% (95% CI -65.2 to 50.9). CONCLUSIONS: Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009-2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010-2011 season, when vaccination will occur before the influenza season starts.

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.

Incidencia y factores de riesgo de gastroenteritis en los peregrinos del Camino de Santiago durante el verano de 2008 en el camino francés / Incidence and risk factors for acute gastroenteritis among pilgrims following the French way to Santiago de Compostela (Spain) in summer 2008

Objetivos Conocer la incidencia de gastroenteritis aguda en los peregrinos del Camino de Santiago, los factores de riesgo asociados y su caracterización microbiológica. Métodos Se diseñaron dos estudios simultáneos, uno transversal mediante encuestas autocumplimentadas de peregrinos llegados a Santiago y otro de casos y controles a los peregrinos en el camino. Se hizo un análisis multivariado mediante regresión logística. Resultados En el estudio transversal la densidad de incidencia fue de 23,5 episodios de gastroenteritis aguda por 1.000 peregrinos-día (intervalo de confianza del 95% [IC95%]: 18,9–29,4/103). En el estudio de casos y controles los factores de mayor riesgo fueron la edad <20 años (odds ratio [OR]=4,72; IC95%: 2,16–10,28), viajar en grupo (tres personas o más) (OR=1,49; IC95%: 0,98–2,28) y consumir agua no embotellada (OR=2,09; IC95%: 0,91–4,82). Norovirus fue el microorganismo aislado con más frecuencia (56%).Conclusiones Ser peregrino menor de 20 años, realizar el camino en grupo y consumir agua no embotellada se asocian con un mayor riesgo de presentar gastroenteritis aguda (AU)

Objectives To determine the incidence of acute gastroenteritis in pilgrims on St. James’ Way, as well as associated risk factors and microbiological characteristics. Methods Two studies were designed simultaneously: a cross-sectional study through self-completed questionnaires among pilgrims reaching Santiago, and a case-control study of pilgrims traveling along the Way. Multivariate analysis was performed using logistic regression. Results In the cross-sectional study, the incidence rate was 23.5 episodes of acute gastroenteritis/103 pilgrims-day (95% CI: 18.9–2.4/103). In the case-control study, the major risk factors were age <20 years (OR=4.72; 95% CI: 2.16–10.28), traveling in groups (three or more) (OR=1.49; 95% CI: 0.98–2.28), and drinking unbottled water (OR=2.09; 95% CI: 0.91–4.82). The most frequent etiologic agent was norovirus (56%).Conclusions Age less than 20 years, traveling in groups and drinking unbottled water were important risk factors for acute gastroenteritis (AU)

[Incidence and risk factors for acute gastroenteritis among pilgrims following the French way to Santiago de Compostela (Spain) in 2008]. / Incidencia y factores de riesgo de gastroenteritis en los peregrinos del Camino de Santiago durante el verano de 2008 en el camino francés.

OBJECTIVES: To determine the incidence of acute gastroenteritis in pilgrims on St. James' Way, as well as associated risk factors and microbiological characteristics. METHODS: Two studies were designed simultaneously: a cross-sectional study through self-completed questionnaires among pilgrims reaching Santiago, and a case-control study of pilgrims traveling along the Way. Multivariate analysis was performed using logistic regression. RESULTS: In the cross-sectional study, the incidence rate was 23.5 episodes of acute gastroenteritis/10³ pilgrims-day (95% CI: 18.9-2.4/10³. In the case-control study, the major risk factors were age <20 years (OR=4.72; 95% CI: 2.16-10.28), traveling in groups (three or more) (OR=1.49; 95% CI: 0.98-2.28), and drinking unbottled water (OR=2.09; 95% CI: 0.91-4.82). The most frequent etiologic agent was norovirus (56%). CONCLUSIONS: Age less than 20 years, traveling in groups and drinking unbottled water were important risk factors for acute gastroenteritis.

Estimating the influenza vaccine effectiveness in elderly on a yearly basis using the Spanish influenza surveillance network--pilot case-control studies using different control groups, 2008-2009 season, Spain.

We conducted a case-control and screening method studies to estimate influenza vaccine effectiveness (IVE) in the age group >or=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.

[Efficiency of seasonal influenza vaccine in persons older than 65 in Romania. Pilot case-control study I-MOVE, 2008-2009]. / Eficacitatea vaccinului gripal sezonier la persoanele cu vârsta peste 65 de ani din România. Studiul pilot caz-martor I-MOVE, 2008-2009.

Cantacuzino Institute conducted between September 2008 and June 2009, a pilot case-control study to monitor the influenza vaccine effectiveness on people over 65 years of age from Romania. This study is part of the I-MOVE project "Monitoring the vaccine effectiveness during seasonal and pandemic influenza in EU/EEA member states, 2008-2009", coordinated by EpiConcept, France and financed by European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. Forty seven family doctors and epidemiologists from Bucharest and seven influenza sentinel districts were selected to participate in this project, based on epidemiological and geographical criteria. Family doctors swabbed all people over 65-years-old consulting for influenza like illness (ILI). Influenza confirmed cases (classified as cases) were compared to influenza negative controls. Influenza vaccine effectiveness (IVE) was obtained using the formula: 1 - odds ratio, with 95% confidence interval (CI). One hundred and three ILI patients were enrolled in the study. Ninety nine from them (96.1%) were swabbed in the first 7 days after the onset, met the inclusion criteria and case definition and were included in analysis. Thirty (30.3%) were ILI flu positive and were classified as cases, sixty nine (69.7%) were ILI flu negative and classified as controls. Influenza vaccine effectiveness adjusted for the predefined set of confounders (age, sex, chronic diseases, smoking, previous influenza vaccination, functional status) was 86.8% (95% CI, 38.0, 97.2); influenza vaccine coverage in people older than 65 years was 49.4%. The result of the study showed a high influenza vaccine effectiveness in the elderly. In order to achieve a greater precision, the national and also the European samples should be extended for the next season.

Echocardiographic predictors of embolic events in infective endocarditis.

BACKGROUND: Systemic embolisation occurs in 22% to 50% of patients with infective endocarditis (IE). Up to 65% of embolic events (EE) involve the central nervous system which increases the mortality rate. Several echocardiographic studies have demonstrated higher embolic rates with the increase of vegetation (VEG) dimensions and mobility. AIM: To define echocardiographic parameters which can help in identifying patients with a high risk of EE and to assess the value of transesophageal echocardiography (TEE) in predicting EE in patients with IE. METHODS: 236 patients (58% male, mean age 47.8+/-6) diagnosed with IE according to Duke criteria were followed for 3 years or until cardiac surgery. Echocardiographic parameters measured on VEG included the maximum length, thickness, the narrowest diameter, neck and mobility. RESULTS: The rate of EE was 51.27% without any significant differences with respect to gender, age, fever, anaemia, VEG site or the presence of a significant regurgitation murmur. The univariate analysis showed a significant correlation between EE and IE caused by staphylococcus, IE of the right heart, and the length as well as mobility of VEG. The only independent predictors of EE were the maximum VEG length >15 mm and the increased mobility of VEG with a maximal displacement angle >60.7 degrees. In 23% of patients EE occurred after the initiation of antibiotic treatment. VEG in this group were big and very mobile (length >15 mm, maximal angle of displacement >65 degrees). CONCLUSIONS: 1. Vegetation dimension and mobility determined by TEE are important predictors of the embolic risk. 2. Significant echocardiographic predictors of embolic events included vegetation length >15 mm, neck/thickness ratio >0.69, and maximal angle of displacement of vegetation during cardiac cycle >60.7 degrees. 3. During antibiotic treatment, the embolic risk depends only on vegetation mobility and dimension.