Artigos

INTRODUCTION
Influenza is an acute respiratory infection caused by the influenza virus, which belongs to the Orthomyxoviridae family and includes four main types: A, B, C, and D. The severity of the infection in humans is associated with the virus's replication in the lower respiratory tract, which is accompanied by severe inflammation due to the infiltration of immune cells. Seasonal outbreaks of the influenza virus occur in all regions of the world, typically during winter months when low humidity and low temperatures favor transmission1.
Worldwide, approximately one billion cases of seasonal flu occur annually, with three to five million of these cases being severe and resulting in approximately 290,000 to 650,000 deaths due to respiratory complications caused by influenza. The incidence of flu virus infections increases during pandemic years due to the lack of pre-existing immunity against the new virus, but the severity varies depending on the circulating strain2.
In Brazil, influenza is a national concern due to its repercussions for vulnerable groups and the burden it places on healthcare services3. In 2022, there were 37,815 hospitalizations due to influenza, with 12,944 of these occurring among older adults (60 years and older)4. When analyzing deaths, it was found that for the year 2022, 3,249 deaths were attributed to influenza as the underlying cause, with 2,577 of these occurring among older adults (79.31%)5. This scenario drives national strategies for the prevention and control of the disease, especially among priority groups3.
Brazil's demographic indicators signal the rapid growth of the older adults population, and their percentage has become increasingly significant within the population. In 2020, the older adults (aged 60 and over) reached a population of over 29.9 million people, accounting for 14.0% of the Brazilian population6. This population increase raises concerns regarding the urgent need to build actions and services capable of addressing the specificities of aging7.
As the older adults have a high mortality rate due to influenza (around 80.0% to 90.0%)8, the specific protection provided by the vaccine becomes a fundamental condition for health protection, minimizing the burden of the disease. In light of this, the National Immunization Program, aiming to meet a growing demand and an urgent health need, incorporated the influenza vaccine into the national vaccination schedule. The annual campaigns, which prioritize the older adults among other groups, aim to reduce viral circulation by expanding vaccination coverage3.
Influenza vaccination is therefore crucial to protect this age group. However, the effectiveness of this preventive measure depends on adequate adherence and vaccination coverage. Despite this vaccine being available free of charge in Brazil, national research has highlighted difficulties in the population's adherence to this immunogen9,10. A study conducted using data from the National Health Survey of 2019 found that the overall prevalence of influenza vaccination among the older adults in Brazil was 72.4%, a rate lower than the goal advocated by national campaigns (90.0%)9. This result underscored the need for constant monitoring of vaccination coverage to investigate the universal reach of influenza vaccination among the older adults in Brazil.
However, it is worth noting that despite the importance of this issue, no recent study has been identified that evaluated the temporal trend of influenza vaccination coverage among the older adults in the Brazilian context. Understanding the temporal trend is crucial for identifying behavioral patterns and possible gaps in the national vaccination strategy, allowing for the development of targeted interventions and the improvement of health policies and strategies in this segment.
In this regard, this study aimed to assess influenza vaccination coverage among older adults and its temporal trend in Brazil, regions and federative units from 2000 to 2019.

METHODS
This ecological time series study on the influenza vaccination coverage among older adults (60 years and older) in Brazil, regions, and their federative units. The vaccination coverage data analyzed originate from the National Immunization Program Information System (SI-PNI), covering the period from 2000 to 2019. The freely accessible database was made available by the Technical Information Management (GT/AINFO) of the Department of Immunization and Transmissible Diseases of the Ministry of Health (DEIDT/MS) under protocol 25072.027478/2022-88. It is noteworthy that the database for this study was obtained through active transparency, via a formal request submitted to the Ministry of Health.
The older adults population, which constitutes a priority group for the national influenza vaccination campaign, has been rapidly growing in Brazil, increasing from about 15,4 million people in 2000 to approximately 29 million in 20196. The estimation of the target audience eligible for influenza vaccination is established by the Ministry of Health, and the analysis of indicators considers the number of doses administered3.
For analysis purposes, the calculation of influenza vaccination coverage (VC) was estimated as the proportion of the target population effectively vaccinated, stratified by federative unit, administrative method following the methodology recommended by the Ministry of Health11. It is considered as the vaccinated population the older adults individuals who received one dose of influenza vaccine (single dose) each year of the study3. The proportion of VC among older adults was estimated by dividing the number of doses administered (numerator) by the target population (denominator), multiplied by 100.
The statistical information was obtained using Stata® software, version 18, and Microsoft Excel 2019. Initially, the proportion of VC was analyzed according to the year and study location, considering the target set by the Ministry of Health for the respective year (? 80.0% for the years 2000 to 2016 and ? 90.0% from 2017 onwards)3. Subsequently, temporal trends were estimated using the Prais-Winsten generalized linear regression model. To reduce the heterogeneity of the variance of residuals during regression analysis, a logarithmic transformation of the VC values was performed, a condition that facilitates the analysis of the annual percent variation (APV) of the time series. The APV and its respective 95% confidence intervals (CI95%) were estimated as recommended by Antunes and Cardoso12.
The data analysis considered time series with a p-value greater than 0.05 as non-significant, indicating a stationary trend. Time series with a p-value equal to or less than 0.05 and a positive regression coefficient were classified as significant with an increasing trend. Conversely, time series with a p-value equal to or less than 0.05 and a negative regression coefficient were considered significant with a decreasing trend. The spatial distribution of temporal trends observed was presented by federative units and was conducted using choropleth maps by the Quantum Geographic Information System (QGIS) software, version 3.34.2.
As this study utilizes secondary data from publicly available databases, submission of the project to an Ethics Committee for Research was not necessary.

RESULTS
During the period from 2000 to 2019, there was variation in influenza VC among older adults in Brazil and its regions. Figure 1 presents the historical series of influenza VC among older adults in Brazil and its regions, from 2000 to 2019. It was observed that the fluctuation in influenza VC among older adults varied by year and study location. Considering Brazil as the unit of analysis, influenza VC ranged from 72.53% in the year 2000 (lowest coverage) to 97.16% in 2018 (highest coverage). Regarding vaccine coverage in Brazilian regions, the Northeast, Southeast, and South regions had the lowest vaccine coverages in their historical series in the year 2000 (77.48%, 68.29%, and 70.50%, respectively). While the North and South regions had their highest vaccine coverage in 2019 (102.87% and 99.34%, respectively), and the Northeast and Midwest regions in 2018 (99.32% and 108.95%, respectively) (Figure 1).
When observing the regions of Brazil, it is noted that between 2000 and 2008, there was a correspondence in the fluctuations of VC among the regions. However, it is observed that the South region differentiated itself from the other regions starting from the year 2008, where it showed a sequence of increases in VC proportions, while the other regions continued to experience periods of decrease (Figure 1).
Table 1 presents the distribution of years in which vaccination goals were not achieved, categorized by study site. It is observed that Brazil, between 2000 and 2019, had six years of VC below the recommended target (2000, 2002, 2007, 2008, 2010, and 2019). Regarding the country's regions, the North region had the longest period of goals obtained, with only the year 2002 falling below the recommended level (CV=78.43%). On the other hand, the Southeast region failed to achieve the recommended targets for nine years (2000-2003, 2007-2010, and 2012). Regarding the federative units, it is noted that the states of Amapá and Maranhão stood out during the period with 100.00% compliance with the recommended targets (Table 1).
Table 2 presents the influenza VC among older adults and the APV in Brazil, its regions, and 27 federative units during the study period. It is observed that between 2000 and 2019, the average vaccination coverage (VCM) in Brazil was 84.07%, while the APV was 0.99% (p=0.001). Regarding the regions, the Southeast region had the lowest VCM (82.61%), yet it recorded the second highest APV (1.21%, p <0.001) during the same period (Table 2).
When analyzing the federative units, it is noted that the state of Amapá showed the highest VCM during the analyzed period (VCM=95.75%), while São Paulo recorded the lowest (VCM=79.48%). Considering the APV, the states of Santa Catarina and São Paulo stand out with the highest observed percentage variations between 2000 and 2019, 1.67% (p=0.001) and 1.57% (p<0.001), respectively (Table 2).
Figure 2 synthesizes the outcome observed for the trend of VC in the study period, according to the federation unit. The analysis reveals that, between 2000 and 2019, a growing trend of influenza VC among older adults was observed for 15 federative units (Amazonas, Amapá, Rondônia, Alagoas, Bahia, Maranhão, Paraíba, Pernambuco, Goiás, Mato Grosso do Sul, Minas Gerais, Rio de Janeiro, São Paulo, Santa Catarina and Rio Grande do Sul).

DISCUSSION
This study highlighted fluctuations in influenza VC among older adults in Brazil and its regions over a 20-year period of analysis. It was found that influenza VC in Brazil, between 2000 and 2019, reached more than half of the target population; however, the recommended target was not achieved for six years in the country. Regarding the regions, the North and Southeast regions stood out for having the longest and shortest periods, respectively, of VC in accordance with national targets. Concerning the federative units, Amapá and Maranhão excelled in meeting vaccination targets during the period, with Amapá showing the highest APV, while São Paulo had the lowest. Regarding temporal trends, there was an increasing trend in influenza VC among older adults in 15 federative units of the country.
The variation in influenza VC among older adults observed in this study corroborates findings from other research conducted in countries with national vaccination programs13-15. Studies conducted in Italy and Spain, analyzing the periods from 2000 to 2017 and 2006 to 2017, respectively, found that despite the availability of influenza vaccine for the older adults (65 years and older), VC fluctuates and fails to reach the recommended immunization targets in these countries (Italy: target of 75.0%; Spain: target of 65.0%)13,15. Despite the observed fluctuation in VC among Brazilian older adults and a failure to meet Ministry of Health targets for six years, it is important to highlight the significant coverage rates observed nationally. It should be noted that comparisons with the international scenario should take into account differences in the profile of the analyzed population as well as the age group considered, which can lead to significant differences in vaccine coverage.
In Brazil, the proportion of VC has shown a significant increase since the incorporation of the vaccine into the annual vaccination schedule. Additionally, the vaccination rates observed are quite representative when compared to other countries13-15, even considering the different age group analysis and the profile of the observed audience. However, it is important to emphasize that the fluctuation in VC observed during the study, even with high vaccination coverage rates, signals the existence of older adults who did not get vaccinated against influenza, a concerning condition considering the mortality rates of due to the disease (70.0% to 90.0% of influenza-related deaths)8. This situation reinforces the need to identify older adults who do not adhere to vaccination in order to prevent undesirable outcomes caused by the disease.
This study identified differences in VC across regions of Brazil over the study period. The North region stood out with the highest number of years achieving the recommended vaccination targets, while the Southeast region had the lowest. Regarding the federative units, it was observed that the states of Rio de Janeiro, São Paulo, and Rio Grande do Sul failed to meet vaccination targets for more than half of the study period. Analyzing the APV, it was noted that the Southeast and South regions showed the largest variations during the period. It is known that various factors influence adherence to vaccination campaigns16-18, which can help explain the territorial differences observed in Brazil.
Between individual and contextual factors, differences in sociodemographic profile (predominant age group and education level) and healthcare assistance (number of services/professionals and resources/supplies) are among the aspects related to vaccination coverage. In addition, factors such as vaccine knowledge and perception as preventive measures, along with management strategies, significantly impact vaccination rates and can provide explanations for regional disparities observed throughout Brazil. However, it is also important to note that the direct method of evaluating the coverage of vaccination used by the Ministry of Health, which calculates doses administered against the target population, can lead to inaccurate and potentially inflated coverage rates19. This situation emphasizes the need for careful analysis when evaluating vaccination rates in the Brazilian regions.
When examining APV, it was noticed that regions such as the Southeast and the South showed significant increases of the CV over the study period. This significant increase may be attributed to various factors, including encouragement through media campaigns, active seeking of health services, education on the importance of vaccination, reduction of vaccine hesitancy, as well as the consolidation of vaccines in the national schedule and provision of supplies20-22. A national study conducted with data from the three cycles of the National Program for Improvement of Access and Quality of Primary Care identified, between 2012 and 2018, a growing trend in the prevalence of vaccine availability in Brazil, with particular emphasis on the Southeast and South regions20, condition that may justify the highest percentage variations in these regions as observed by this study.
Lastly, when analyzing the temporal trend of VC, this study found a growing trend in most federative units of Brazil throughout the historical series. This result is relevant, reinforcing the effectiveness of Brazil's national immunization program, and highlighting the strategies for preventing morbidity and mortality from influenza among older adults. Brazil is a country experiencing accelerated population aging, which requires constant monitoring of VC to identify the most vulnerable groups considering the territorial context. Systematic monitoring of vaccination coverage allows for identifying vaccination trends among different target populations, measuring inequalities, and providing support for maintaining individual and collective health. Considering that annual influenza vaccination is an effective strategy for preventing new cases and reducing disease-related complications2, monitoring the results of vaccination campaigns becomes a fundamental condition for strategic health planning.
Although this study aimed to assess influenza VC among older adults and its temporal trend, limitations such as the use of secondary data from health information systems, which are subject to underreporting, incomplete data capture, and data entry errors, may affect its analyses. In addition, it is important to note that many changes have occurred in the national context due to the Covid-19 pandemic, which especially impacted vaccination, and since 2023, there has been a national process of reconquesting vaccine coverage. In this sense, it is recognized that, in fact, it is relevant that the impact aspect of Covid-19 pandemic is evaluated in a study outlined for this purpose. However, despite these limitations, the study provides valuable evidence for health monitoring and evaluation purposes.
In short, influenza VC among older adults in Brazil exhibited fluctuations over the 20-year study period and territorial analysis identified differences in VC in Brazil. Difficulties in meeting national targets were observed after a few years of study, however, a growing trend in VC was noted in most federative units of the country.
Vaccination against influenza in the older adults helps reduce the risks of complications and adverse outcomes associated with the disease. Therefore, ensuring universal vaccination coverage becomes essential for protecting the health of these individuals. The results observed in this study underscore the importance of monitoring and evaluating vaccination indicators for the implementation of effective strategies for capturing and vaccinating priority groups.

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