Vaccination In Spain Research Articles

Hepatitis B Virus-Related Cirrhosis and Hepatocellular Carcinoma Hospital Discharge Rates from 2005 to 2021 in Spain: Impact of Universal Vaccination.

Background: The main consequences of chronic hepatitis B virus (HBV) infections are cirrhosis and hepatocellular carcinoma (HCC), both associated with frequent hospitalization. The aim of this study was to analyze the impact of universal HBV vaccination in Spain on chronic HBV-related hospital discharges from 2005 to 2021. Methods: Using data from the Minimum Basic Data Set of the Spanish National Health System, we calculated the hospital discharge rate ratio (HDRR) and 95% confidence interval (CI) values for chronic HBV-related discharges between 2005 and 2021. For comparative purposes, we calculated the HDRR and 95% confidence interval (CI) values for the early (2005-2013) and later (2014-2021) periods and the vaccinated compared with unvaccinated cohorts for the 20-39 age group. Results: The hospital discharge rate per 1,000,000 people was 3.08 in 2005 and 4.50 in 2021 for HCC, and 4.81 in 2005 and 1.92 in 2021 for cirrhosis. Comparing the early and later periods, values were higher for HCC (HDRR 1.13; 95% CI: 1.06-1.20) and lower for cirrhosis (HDRR 0.56; 95% CI: 0.51-0.60). The rate for the 20-39 age group was lower for the vaccinated compared with the unvaccinated cohorts overall (HDRR 0.53; 95% CI: 0.45-0.62), for HCC (HDRR 0.66; 95% CI: 0.53-0.82), and for cirrhosis (HDRR 0.41; 95% CI: 0.33-0.53). Conclusions: This study describes the important impact, after 25 years, of universal HBV vaccination in Spain: cirrhosis hospital discharge rate was reduced, and the vaccinated cohorts, compared with the unvaccinated cohorts in the 20-39 age group, had a lower hospital discharge rate of both HCC and cirrhosis.

Analyzing Changes in Attitudes and Behaviors towards Seasonal Influenza Vaccination in Spain’s Adult Population over Three Seasons

Background/Objectives: The experience of the COVID-19 pandemic has turned the spotlight on the importance of public health measures and disease prevention. Despite this, the acceptance of influenza vaccination has remained low in most countries (and far from the 75% target set by the World Health Organization). The objective of this study has been to investigate how attitudes and behaviors regarding influenza vaccination in the Spanish adult population have changed over the last three years (from 2021 to 2024) in order to analyze trends in influenza vaccination. Methods: To this end, a cross-sectional study was conducted through 2206 telephone interviews, and the results were compared with those obtained in previous campaigns. Results: The findings indicate a significant decline in overall vaccination intent. Healthcare professionals remain the most influential factor in encouraging vaccination, yet there is a notable increase in the lack of vaccine recommendations, contributing to the decision not to vaccinate. This study also reveals low awareness of the influenza vaccine campaign, emphasizing the need for improved public health communication. Conclusions: To counteract these trends, this study recommends intensifying awareness campaigns, strengthening the role of healthcare providers in vaccine advocacy, and tailoring communication strategies. These efforts are crucial to enhancing vaccination coverage and protecting vulnerable populations against influenza.

Effectiveness of influenza vaccines in children aged 6 to 59 months: a test-negative case-control study at primary care and hospital level, Spain 2023/24.

During 2023/24, all children aged 6 to 59 months were targeted for seasonal influenza vaccination in Spain nationally. Using a test-negative case-control design with sentinel surveillance data, we estimated adjusted influenza vaccine effectiveness (IVE) against any influenza type to be 70% (95% confidence interval (CI): 51 to 81%) for primary care patients with acute respiratory illness (ARI) and 77% (95% CI: 21 to 93%) for hospitalised patients with severe ARI. In primary care, where most subtyped viruses (61%; 145/237) were A(H1N1), adjusted IVE was 77% (95% CI: 56 to 88%) against A(H1N1)pdm09.

Updating and Refining of Economic Evaluation of Rotavirus Vaccination in Spain: A Cost-Utility and Budget Impact Analysis.

Two vaccines against rotavirus diseases, Rotarix® and RotaTeq®, are being marketed in Spain; but rotavirus is not presently among the diseases covered by universal vaccination in Spain. The aim of this study was to assess the efficiency of extending Spain's current targeted rotavirus vaccination strategy including only preterm babies, to a policy of universal vaccination. A de novo cohort-based Markov model was built to evaluate the efficiency of three compared rotavirus vaccination strategies in Spain: targeted, universal, and no vaccination. Using Rotarix® or RotaTeq®, we compared the cost-utility of these strategies from both a societal perspective and Spanish National Health System (SNHS) perspective. The model represents the most important clinical events conceivably linked to rotavirus infection. Efficacy, effectiveness, safety, costs, and utilities were identified by systematic reviews. Incremental cost-utility ratio (ICUR) is EUR 23,638/QALY (Quality-Adjusted Life Year) for targeted vaccination with Rotarix® compared with no vaccination. The ICUR for the rest of the strategies evaluated are above EUR 30,000/QALY. The sensitivity analysis shows price as the only parameter that could make the universal vaccination strategy efficient. Considering a threshold of EUR 25,000/QALY, only targeted vaccination with Rotarix® would be efficient from societal perspective. Price drops of 36.9% for Rotarix® and 44.6% for RotaTeq® would make universal vaccination efficient.

Impact of the Universal Implementation of Adolescent Hepatitis B Vaccination in Spain.

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; p < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; p = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; p < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.

Hospitalization burden associated with anus and penis neoplasm in Spain (2016-2020)

ABSTRACT In 2020, there were approximately 50,865 anal cancer cases and 36,068 penile cancer cases worldwide. HPV is considered the main causal agent for the development of anal cancer and one of the causal agents responsible for the development of penile cancer. The aim of this epidemiological, descriptive, retrospective study was to describe the burden of hospitalization associated with anal neoplasms in men and women and with penis neoplasms in men in Spain from 2016 to 2020. The National Hospital Data Surveillance System of the Ministry of Health, Conjunto Mínimo Básico de Datos, provided the discharge information used in this observational retrospective analysis. A total of 3,542 hospitalizations due to anal cancer and 4,270 hospitalizations due to penile cancer were found; For anal cancer, 57.4% of the hospitalizations occurred in men, and these hospitalizations were also associated with significantly younger mean age, longer hospital stays and greater costs than those in women. HIV was diagnosed in 11.19% of the patients with anal cancer and 1.74% of the patients with penile cancer. The hospitalization rate was 2.07 for men and 1.45 for women per 100,000 in anal cancer and of 4.38 per 100,000 men in penile cancer. The mortality rate was 0.21 for men and 0.12 for women per 100,000 in anal cancer and 0.31 per 100.000 men in penile cancer and the case-fatality rate was 10.07% in men and 8,26% in women for anal cancer and 7.04% in penile cancer. HIV diagnosis significantly increased the cost of hospitalization. For all the studied diagnoses, the median length of hospital stays and hospitalization cost increased with age. Our study offers relevant data on the burden of hospitalization for anal and penile cancer in Spain. This information can be useful for future assessment on the impact of preventive measures, such as screening or vaccination in Spain.

Reduced pertussis disease severity in infants following the introduction of pertussis vaccination of pregnant women in Spain, 2015–2019

BackgroundMaternal pertussis vaccination during the third trimester of pregnancy was implemented in 2015 in Spain, reaching a national coverage of 84% in 2019. In this ecological study, we investigated whether there was a change in the disease severity for pertussis in infants upon introduction of prenatal pertussis vaccination. MethodsWe performed a time-trend analysis of infant pertussis hospitalizations during 2005–2019 in Spain using national register data. Annual hospitalization rates per 100,000 population and the mean length of hospitalization were calculated for infants < 3 months of age (target group benefiting from the prenatal vaccination) and a reference group aged 3–11 months. We compared overall rates and annual percent changes of the above variables in both groups for the time period before (2005–2014) and after vaccination introduction (2015–2019), using segmented Poisson regression. ResultsDuring the pre-vaccination period, infants aged 0–2 months had a 5-times higher rate of pertussis hospitalization and spent on average 50 % longer in hospital than the reference group. After the maternal vaccination introduction, the hospitalization rate decreased more rapidly in infants aged 0–2 months than in infants aged 3–11 months: annual reduction of 34 % (95 % CI: 31–38) versus 26 % (95 % CI: 21–31) in the hospitalization rate and 13 % (95 % CI: 11–15) versus 6 % (95 % CI: 2–9) in the mean hospital stay, respectively. In 2019, the mean hospital stay for pertussis was about 4.5 days in both groups. ConclusionsMaternal pertussis vaccination in Spain led to a reduction in disease severity in the target group as compared to older infants, highlighting the need for increased efforts on educating healthcare professionals on the importance of maternal vaccinations.

Current perspective of vaccination in Spain for dogs and cats from a pharmaceutical approach.

Current perspective of vaccination in Spain for dogs and cats from a pharmaceutical approach.

A Profile of Adult Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia Patients According to Pneumococcal Vaccination Status.

Certain patient profile characteristics, such as preexisting medical conditions, can modify the risk of developing SARS-CoV-2 pneumonia among adults vaccinated and not vaccinated against pneumococcal disease. This retrospective cohort study aimed to quantify the risk of pneumonia caused by SARS-CoV-2 among individuals from 15 to 64 years old with and without pneumococcal vaccination in Spain during the 2020-2021 influenza season and establish a risk profile of patients more likely to develop SARS-CoV-2 pneumonia. Data (demographic information, patient medical history, and lifestyle habits) were gathered both directly from the patient via personal interview and by reviewing electronic medical records. In an adjusted analysis for pneumococcal vaccinated patients, visits to hospital outpatient clinics were protective while visits to primary health care services, being widowed, obese, and not using masks in outdoor open spaces were identified as risk factors. For patients who had not received a pneumococcal vaccine, visits to hospital outpatient clinics were protective, while being overweight or obese, alcohol consumption, and not using masks in outdoor open spaces were identified as risk factors. Concerning comorbidities, in the pneumococcal vaccinated group none were found to be protective but having diabetes or other respiratory diseases were identified as risk factors. In the unvaccinated group, undergoing immunosuppressive treatment and having metastatic tumors were protective factors, while cerebrovascular disease and obesity with a BMI ≥ 40 were risk factors. A similar risk profile for developing SARS-CoV-2 pneumonia in pneumococcal vaccinated and non-vaccinated individuals was found. Generally, vaccinated individuals had a lower risk of developing SARS-CoV-2. The findings suggest that vaccination against S. pneumoniae could prevent and reduce SARS-CoV-2 pneumonia. Additionally, this study has identified individuals with other medical conditions, such as obesity, underweight, diabetes, and a history of respiratory diseases, who are at an increased risk of developing SARS-CoV-2 pneumonia and could benefit from vaccination and supervision.

Attitudes towards COVID-19 vaccine in Spain: correlational and configurational analyses

This study explains attitude towards vaccination against COVID-19. It evaluates four cognitive, affective and normative (CAN) factors: fear of COVID-19 (FCOVID), fear of the vaccine (FVACC), efficacy (EFFICACY), and social influence (SOCINF) and three sociodemographic variables: gender, age, and income level. Ordered logistic regression showed a significant positive influence of FCOVID, EFFICACY and SOCINF and a negative impact of FVACC and income level (INCOME). Configurational analysis allowed observing that all evaluated factors are relevant for explaining the attitude towards vaccination and that the sign of the relationship in configurations between CAN factors and attitude is positive for FCOVID, EFFICACY and SOCINF and negative for FVACC. These variables symmetrically impact on willingness and unwillingness to use the vaccine. INCOME and regarding gender (GENDER) impact asymmetrically to induce acceptance and resistance to vaccination. The results in our paper have clear practical implications. Correlational analysis discovers the average strength of assessed factors on vaccine acceptation and so identifying the most relevant variables. On the other hand, configurational analysis identifies how factors combine to shape profiles of persons with willingness and unwillingness to get vaccinated. These last profiles are of special concern for health policy-makers since their resistance diminishes the effectivity of collective vaccination.

An Economic Comparison in the Elderly of Adjuvanted Quadrivalent Influenza Vaccine with Recombinant Quadrivalent Influenza Vaccine in Spain.

Influenza infections impose a high burden of morbidity and mortality among older adults, at great cost to individuals and society. Enhanced influenza vaccines, which contain either an immune adjuvant or higher than normal doses of influenza virus antigens, are recommended for older adults. We used a health economics model to evaluate the cost effectiveness in Spain of a recently licensed recombinant quadrivalent influenza vaccine (QIVr), which contains three times the standard dose of influenza virus hemagglutinin but no neuraminidase, compared with an MF59-adjuvanted quadrivalent influenza vaccine (aQIV). Based on current tender prices in Spain and a conservative assumption that QIVr is 10.7% relatively more effective than aQIV, the incremental cost-effectiveness ratio (ICER) for QIVr was EUR 101,612.41 per quality-adjusted life year (QALY) gained. To meet the Spanish willingness-to-pay threshold of EUR 25,000 per QALY gained, QIVr would need to be 34.1% relatively more effective than aQIV. In a probabilistic sensitivity analysis conducted to confirm the robustness of the analysis, 99.7% of simulations for QIVr were higher than the willingness-to-pay curve. These findings suggest that QIVr is not currently a cost-effective influenza vaccine option relative to aQIV for older persons living in Spain.

Universal childhood influenza vaccination in Spain: Has the time come?

Influenza vaccination is the most effective strategy to prevent influenza infection. The timehas come to include systematic influenza vaccination in the childhood and get over ourunfinished assignment with society. The debate is no longer about if we should vaccinatechildren or not, the consensus effort should be aimed in determining at which age rangeshould we implement vaccination and what types of flu vaccines we must use.

Cost-effectiveness and epidemiological impact of gender-neutral HPV vaccination in Spain

ABSTRACT All EU countries have introduced Human papilloma virus (HPV) vaccination for adolescent girls and many countries are expanding the strategy to include adolescent boys. There is uncertainty about the cost-effectiveness and epidemiological impact of a gender-neutral HPV vaccination strategy. Here we present the results of an economic model adapted for Spain. Five vaccination strategies were compared from the Spanish healthcare system perspective, combining two vaccines (4-valent and 9-valent) in a gender-neutral or girls-only programme in a dynamic population-based model with a discrete-time Markov approach. Costs and benefits were discounted at 3%. The benefits of immunization were measured with quality-adjusted life years (QALYs), which are achieved by reducing the incidence of diseases attributable to HPV. Incremental cost-effectiveness ratio (ICER) was compared with the willingness-to-pay threshold in Spain. The two most effective strategies were compared: gender-neutral 9-valent vaccination vs. girls-only 9-valent vaccination, resulting in an ICER of € 34,040/QALY, and an important number of prevented cases of invasive cancers and anogenital warts. The sensitivity analysis revealed that gender-neutral 9-valent vaccination would become cost-effective if protection against oropharyngeal and penile cancers was included or if the price per dose decreased from €45 to €28. The gender-neutral 9-valent HPV vaccination in Spain offers more benefits than any other modeled strategy, although in the conservative base case it is not cost-effective. However, certain plausible assumptions would turn it into an efficient strategy, which should be borne in mind by the decision makers together with equity and justice arguments.

Social Vulnerability and COVID-19 Vaccine in Spain.

Different analyses show that the design of vaccination policies should especially protect the most vulnerable social groups, since the level of acceptance is determined by the population's knowledge, attitude and concerns about the safety and efficacy of vaccines. The objective of this work will be to detect the most socially vulnerable groups with respect to COVID-19 and to analyze the factors that influence predisposition to vaccination. This is a cross-sectional study using data from the Centro de Investigaciones Sociológicas (CIS) on the Effects and Consequences of Coronavirus (Study 3346 of December 2021). Sociodemographic variables (sex, age, employment status, studies and subjective class identification) were extracted, as well as the answers to the questions indicating the attitude towards vaccination, corresponding to questions 7,8,10 and 11 of the study. The most vulnerable group was lower class women (self-perceived), under 45 years of age with lower educational level, unemployed or performing unpaid work in the home. Most of them are not predisposed to vaccinate only because of the obligation to do so, mainly due to lack of belief in the power and efficacy of vaccines, as well as fear of health risks/collateral side effects. The lower vaccine uptake in this vulnerable population group may be due to a lack of awareness and lower trust in the authorities, as well as the benefits of the vaccine, which could be related to a lack of policy targeting the most socially vulnerable populations.

Dynamics of B-Cell Responses after SARS-CoV-2 Vaccination in Spain.

The high mortality rate due to COVID-19 has necessitated the mass vaccination against SARS-CoV-2 to induce protective humoral and cellular immunity. (1) Objective: To study the dynamics of SARS-CoV-2-specific B cells after two doses of the Pfizer-BioNTech SARS-CoV-2 vaccine. (2) Methods: Immunophenotyping and cellular cultures were used to determine the kinetics of B-cell subpopulations and vaccine responses in volunteers before and seven days, three months and seven months after the second dose in Spain (n = 19). (3) Results: Seven days after immunisation, memory B cells and plasmablasts expressing receptors for factors implicated in the maturation of plasma cells were augmented in blood. Three months after vaccination, SARS-CoV-2 spike-specific plasmablasts disappeared from circulation while spike-specific memory-B cells circulated, with heterogeneous dynamics among individuals. (4) Conclusion: After vaccination, specific plasmablasts equipped with receptors for maturation factors were quickly generated and disappeared rapidly from the blood, while specific memory B cells circulated for at least seven months.

The relationship between income per capita and access to meningococcal serogroup B vaccination in Spain: an ecological correlation study

Background: Invasive meningococcal disease (IMD) remains a public health concern because of its serious consequences, which mainly affect infants and young children. In Spain, Neisseria meningitidis serotype B accounts for &gt;40% of IMD cases. The multicomponent meningococcal serogroup B vaccine (4CMenB) is available privately in the absence of national public funding in Spain. This study evaluates whether potential inequities in access to 4CMenB exist among families because of financial disparities. Methods: An ecological correlation study was carried out using aggregate birth data, average income per capita and average number of 4CMenB vaccine units dispensed at province and municipal levels, including municipalities with &gt;50,000 inhabitants. The base-case scenario used birth data from 2018, 4CMenB uptake from March 2018 to February 2019 and income per capita from 2017. The Spearman correlation test was used to compute bivariate correlation coefficients (rs) between the ratio of 4CMenB uptake per birth and income per capita. Sensitivity analyses were carried out to study the impact of observational period, territorial assignment and target population on base-case results. Results: At province level, no correlation between mean income per capita and 4CMenB units was observed. At municipality level, a statistically significant positive correlation was observed between 4CMenB uptake per birth and average income per capita (rs = 0.22; p = 0.007). The results were robust under sensitivity analyses. Conclusions: Despite the low level of granularity, these results suggest that access to the 4CMenB vaccine in Spain is associated with the income level of families at municipal level, producing inequities in the context of no national public funding. Keywords: Ecological correlation study, Meningococcal serogroup B vaccine, Vaccine uptake in Spain, Inequities in vaccine access, Financial impact.

Analysis of the best strategies to promote flu vaccination coverage among healthcare professionals

ObjectiveThe flu represents a major public health issue. The flu vaccination rate among healthcare professionals has traditionally been lower than recommended by national health authorities, and there is also regional heterogeneity. The objective of the Gripetool project was to identify the most effective initiatives to promote influenza vaccination in Spain among healthcare workers. Material and methodsInformation was obtained through an online survey conducted among members of the Spanish Society of Primary Care Physicians (SEMERGEN) between July and November 2020, which had been previously validated by a committee of experts. A multiple linear regression analysis was performed to analyse the possible relationship between the vaccination coverage of health professionals and the different promotion measures reported in the survey. ResultsAccording to respondents (n = 385), the publication of vaccination recommendations (18.6%), the use of media and social networks (14.4%), and the active recruitment through email/letters (10.6%) are the most effective measures to increase vaccination rates. According to the statistical analysis, there are 10 measures that have a positive impact on the vaccination rate, the most relevant include the distribution of posters in health centres (17 percentage points increase, pp), the publication of vaccination recommendations (14 pp), and the development of protocols and guidelines (13 pp). ConclusionsThe most effective strategies to increase influenza vaccination comprehend actions at macro-, meso-, and micro levels to promote vaccination and communicate its benefits, exploiting the potential of new technologies.

Análisis de las mejores estrategias para el fomento de las coberturas de vacunación antigripal entre los profesionales sanitarios

ObjectiveThe flu represents a major public health issue. The flu vaccination rate among healthcare professionals has traditionally been lower than recommended by national health authorities, and there is also regional heterogeneity. The objective of the Gripetool project was to identify the most effective initiatives to promote influenza vaccination in Spain among healthcare workers. Material and methodsInformation was obtained through an online survey conducted among members of the Spanish Society of Primary Care Physicians (SEMERGEN) between July and November 2020, which had been previously validated by a committee of experts. A multiple linear regression analysis was performed to analyse the possible relationship between the vaccination coverage of health professionals and the different promotion measures reported in the survey. ResultsAccording to respondents (n = 385), the publication of vaccination recommendations (18.6%), the use of media and social networks (14.4%) and the active recruitment through email/letters (10.6%) are the most effective measures to increase vaccination rates. According to the statistical analysis there are ten measures that have a positive impact on the vaccination rate, the most relevant include the distribution of posters in health centres (17 percentage points increase, pp), the publication of vaccination recommendations (14pp) and the development of protocols and guidelines (13pp). ConclusionsThe most effective strategies to increase influenza vaccination comprehend actions at macro, meso and micro levels to promote vaccination and communicate its benefits, exploiting the potential of new technologies.

Heterologous COVID-19 Vaccination in Spain: A Case Study of Individual Autonomy in the Real World

In Spain, 1.5 million essential < 60-year-old workers were vaccinated with a first AstraZeneca vaccine dose. After assessing the cases of thrombosis with thrombocytopenia associated to this vaccine, the European Medicines Agency (EMA) supported the administration of 2 doses of the AstraZeneca vaccine with no age restrictions. Nevertheless, Spain decided not to administer the second dose of this vaccine to < 60-year-olds. The government sponsored a clinical trial (CombiVacS) to assess the immunogenicity response to a Pfizer/BioNTech vaccine dose in adults primed with the AstraZeneca vaccine. The positive results backed the Public Health Commission and the Spanish Ministry of Health to offer the Pfizer/BioNTech vaccine as the booster. Nevertheless, regional public health authorities—responsible for administering vaccines—believed that, following the EMA’s decision, an AstraZeneca booster dose should be given. The public confrontation of these 2 positions forced the Spanish Health Ministry to request the signature of an informed consent form to those individuals willing to receive the AstraZeneca vaccine booster and rejecting the Pfizer/BioNTech vaccine dose. Eventually, it was decided that these essential workers could choose the vaccine but signing an informed consent form. All relevant information was posted on the Ministry of Health and regional health authorities’ websites and provided to potential vaccine recipients at vaccination sites. Most individuals (≥ 75%) chose the AstraZeneca vaccine: perhaps because they likely trusted the EMA more than the CombiVacS results. This unprecedented and massive exercise of individual autonomy about the choice of COVID-19 vaccines from 2 different platforms has shown that adequately informed persons can autonomously weigh their options, regardless of government decisions. Exercising individual autonomy may contribute to the success of future COVID-19 booster vaccination campaigns.

Updating and Refining the Economic Evaluation of Rotavirus Vaccination in Spain

Updating and Refining the Economic Evaluation of Rotavirus Vaccination in Spain