key: cord-0735262-aztqzktw
authors: Césare, Náthaly; Mota, Tiago F.; Lopes, Fernanda F.L.; Lima, Ana Claudia M.; Luzardo, Ricardo; Quintanilha, Luiz Fernando; Andrade, Bruno B.; Queiroz, Artur T.L.; Fukutani, Kiyoshi F.
title: Longitudinal Profiling of the Vaccination Coverage in Brazil Reveals a Recent Change in the Patterns Hallmarked by Differential Reduction Across Regions
date: 2020-06-30
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.06.092
sha: 71c008f7e5cdf97526b4643853f25c8c6420c85d
doc_id: 735262
cord_uid: aztqzktw

Abstract Objective Vaccination coverage is decreasing worldwide, favoring potential reemergence of vaccine-preventable disease. Here, we performed a longitudinal characterization of the vaccination coverage in Brazil and compared the profiles between the distinct regions in the country to test whether there has been a substantial change over the last five years. Methods We retrieved de-identified data publicly available from the repository of the Brazilian Ministry of Health, comprising detailed information on vaccination coverage, in all age groups, between 1994 and 2019. We examined the vaccination coverage from the whole country and each Brazilian region, by year, and performed a time-series pattern analysis. Results A significant decrease in overall vaccination coverage across the country regions was observed between 2017 and 2019, especially in childhood immunization. BCG, Hepatitis B, influenza and rotavirus vaccines displayed a reduction in coverage. Conversely, vaccines against measles, mumps, rubella, varicella, and meningococcus had an increase in coverage. Region-specific changes in vaccination patterns within the study period were observed. Conclusions Substantial reduction in vaccination coverage was detected in Brazil, a country already highly susceptible to emergency of epidemic infectious diseases. Recursively evaluation of the immunization program actions may help to improve vaccination coverage and prevent new epidemics.

In the last decades, humanity has experienced control and eradication of several diseases due to the development of vaccines (Hotez et al. 2020) . Some generations have never experienced an epidemic situation of some diseases such as measles and polio (Greenlee and Newton 2018) . Recently, nevertheless, the world has been through the SARS-Cov-2 pandemic, and the absence of an effective vaccination against such virus has caused so far devastating impact on public health, with millions of casualties (Luan et al. 2020; Velavan and Meyer 2020) , reinforcing the importance of vaccines. Unfortunately, vaccination coverage has been decreasing worldwide and this reduction could be a potential risk of reemergence of vaccine-preventable disease (VPDs), jeopardizing the overall population health (Siani 2019) . The Brazilian National Immunization Program (Programa Nacional de Imunizações, PNI) and the Unified Health System (Sistema Único de Saúde, SUS) have been providing free vaccines for several diseases to people from all age groups, reaching a national coverage higher than 90% (Sato 2018) . Notwithstanding, the government efforts with the vaccination campaigns, Brazil's vaccination coverage has been dropping since 2013 and an increased level of vaccine refusal has been detected in the country (Brown et al. 2018 ). These phenomena have been strongly associated with the "scientific proofed disadvantages of vaccines" rapidly spread through social media. This misinformation campaign leads the population hesitancy to be vaccinated and has become a big challenge for the PNI in recent years . Despite the regular challenges to vaccinate the population, all these new issues have a harmful impact on the coverage with a potential increase in the number of preventable deaths (Sato 2018) . The comprehension of the dynamics of the vaccination coverage in Brazil can be accessed using the PNI's vaccination data. This approach helps to identify the behavior of the population and potential risks for reintroduction of VPDs in the country.

The present study was aimed at evaluating the PNI's vaccination data from the whole country and its dynamics over the years in different regions, to understand the vaccination coverage profiles and potentially identify which vaccines have been decreased in Brazil. In the analysis of the whole country, a seasonal pattern was observed starting in 2004; such pattern was lost in 2011 ( Figure 4B ). In order to confirm the seasonal pattern, a lag plot analysis was performed. The lag plots showed an absence of autocorrelation within the timeseries, suggesting a random structure across the data by the months ( Figure 4C ). To predict the vaccination coverage pattern for the next 5 years, the exponential smoothing state space model was employed using ARIMA (see Methods for details). The prediction model revealed a maintenance of random pattern in vaccination coverage for the next 5 years ( Figure 4D ).

The same approach was performed in each Brazilian region and revealed that the change from seasonal to random as well as the prediction for the next 5 years were reproduced in all regions (Supplementary Figure 1) . This observation is of extreme concern, because of this age group's increased susceptibility to new infections due to less mature immune system. Furthermore, successfully controlled VPDs would be ready to return, potentially causing new epidemics, raising challenges for new physicians without experience with these diseases (Greenlee and Newton 2018) . Since 2016, the vaccination coverage has been dropping in children under 10 years about 10% to 20% in Brazil (Hussain et al. 2018 ). This reduction was associated with reduction in funding dedicated to the SUS, aside from the increasing people's distrust in vaccines and vaccination hesitancy (Sato 2018) . However, in the present study, we observed a peak of overall immunization in 2017, due to yellow fever vaccine shots especially in the southeastern region, which was the epicenter of a yellow fever outbreak in that year (Goldani 2017 ). This peak was followed by a continuous decrease in the absolute number of vaccinations in the following two years. The ARIMA time-series model was used here to predict the vaccination coverage profile for the next 5 years in the whole country and in each region. This model has been used to predict mortality incidence of pneumonia and influenza (Choi and Thacker 1981) , infectious diseases (Allard 1998) pointed out as challenges for the Brazilian national immunization program (Hotez et al. 2020) . A study conducted in São Paulo has highlighted the psychological element as an important factor in delaying vaccination schedules due to parents' anxiety, pitying their children from getting vaccine shots (Silveira et al. 2020) . Such aspects combined with antivaccination groups activism in social media and distrust in medical science expose the complexity of contending the reduction of vaccination coverage (Smith 2017; Silveira et al. 2020 ). Therefore, a multifaceted strategy is necessary to avert recurrence of VPDs and to eradicate once again such diseases. Although our findings led us to speculate that there is a relation between anti-vaccination movement and immunization coverage in Brazil, additional prospective investigations systematically collecting primary data on both anti-vaccination movement and vaccination hesitancy are still warranted to directly test hypotheses.

People tend to avoid vaccination when they perceive it as unnecessary due to the lack of illness threat perceptions. They pay more attention to vaccine minor side effects such as mild fever, muscle, and joint aches, headache and pain where the shot was given (Nour 2019 ). This behavior is reinforced by anti-vaccination propaganda, spread in social media, which highlights those side effects together with unproven "facts" (e.g. MMR vaccine associated with autism (Kolff et al. 2018) ) over the individual and community benefits of vaccines. Therefore, to counteract this bad propaganda against vaccines, the physicians, scientific community and health agencies should be more active in the internet and social media remembering how dangerous these VPDs are and guiding people to maintain better health behaviors (Smith 2017) . A social-ecological model can suggest where vaccination campaigns should go to promote increased coverage taking into account strategies in individual, interpersonal, organizational, community and society levels (Kolff et al. 2018) . Not only social media should be aimed at, but blogs and apps delivering surveillance data and health education material may also contribute to stimulating healthy behaviors. It is important to note that to battle such a complex health problem, all strategies should be performed together and for a long-term solution it is essential to educate future generations about scientific methodology and evidence-based medicine and health, leading them to critically evaluate the veracity of the information they get from social media (Hopf et al. 2019) .

The findings from the present study corroborate with the idea that there is a tendency of lower vaccination coverage in the last years in Brazil, especially in vaccines indicated for childhood immunization. Thus, it is extremely important for physicians, the scientific community and health agencies to take countermeasures and avoid the recurrence of once eradicated VPDs. The reduction in the last 3 years and the random pattern of vaccination coverage detected and predicted by the analyses presented here are an alert to Brazilian authorities and strategies must be developed to improve the vaccine coverage and reduce the vaccine hesitancy, primarily in the pediatric vaccines.

J o u r n a l P r e -p r o o f Ethical approval: This study used de-identified publicly available data and did not require approval by the Institutional Review Board.

The authors declare that they have no conflicts of interest. year. Colors represent different vaccines tested using the Pearson's chi-square test. The "*"

in the label represents a statistically significant difference (p<0.05).

J o u r n a l P r e -p r o o f 

Use of time-series analysis in infectious disease surveillance

Adverse events of vaccines and the consequences of non-vaccination: a critical review

Vaccine confidence and hesitancy in Brazil

An evaluation of influenza mortality surveillance, 1962-1979. I. Time series forecasts of expected pneumonia and influenza deaths

Yellow fever outbreak in Brazil

A Review of Traditional Vaccine-Preventable Diseases and the Potential Impact on the Otolaryngologist

Fake science and the knowledge crisis: ignorance can be fatal

Combating vaccine hesitancy and other 21st century social determinants in the global fight against measles. Curr Opin Virol

The Anti-vaccination Movement: A Regression in Modern Medicine. Cureus

The use of technology to promote vaccination: A social ecological model based framework

Sichuan Da Xue Xue Bao Yi Xue Ban

A Systematic Review of Methods to Improve Attitudes Towards Childhood Vaccinations

Resurgence of Vaccine-Preventable Diseases in Venezuela as a Regional Public Health Threat in the Americas

R Development Core Team. The R Reference Manual: Base Package

What is the importance of vaccine hesitancy in the drop of vaccination coverage in Brazil?

Measles outbreaks in Italy: A paradigm of the re-emergence of vaccine-preventable developed countries

The emergence of vaccine hesitancy among upper-class Brazilians: Results from four birth cohorts

Vaccine Rejection and Hesitancy: A Review and Call to Action. Open Forum Infect Dis

Stochastic modeling of empirical time series of childhood infectious diseases data before and after mass vaccination

The COVID-19 epidemic

Immunization in the United States: Recommendations, Barriers, and Measures to Improve Compliance: Part 1: Childhood Vaccinations

The authors would like to thank Mrs. ElzeLeite for administrative support.

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.J o u r n a l P r e -p r o o f