Cobertura e abandono vacinal em menores de dois anos no Brasil: um estudo de séries temporais

Rev Paul Pediatr rpp Revista Paulista de Pediatria Rev. paul. pediatr. 0103-0582 1984-0462 Sociedade de Pediatria de São Paulo RESUMO Objetivo: Analisar a tendência das taxas de cobertura e abandono vacinal em menores de dois anos no Brasil, no período de 2015 a 2021. Métodos: Estudo ecológico de séries temporais. As variáveis dependentes da pesquisa foram a cobertura vacinal e a taxa de abandono, avaliadas por região brasileira. Os dados foram extraídos do Sistema de Informação do Programa Nacional de Imunizações em julho de 2022. Para a análise de tendência, empregou-se a técnica de Prais-Winsten com o auxílio do software STATA 16.0. Resultados: Identificou-se que a média de cobertura vacinal no Brasil foi de 76,96%, com tendência decrescente no período (variação percentual anual=-5,12; intervalo de confiança de 95% — IC95% -7,81; -2,34). Em 2015 a taxa foi de 88,85%, caindo para 62,35% em 2021. A taxa geral de abandono, por sua vez, foi de 24,00% em 2015 para 9,01% em 2021, sendo a taxa média de 10,48% e a tendência estacionária (variação percentual anual=-9,54; IC95% -22,92; 6,12). Em 2021, todas as vacinas tiveram cobertura abaixo de 74,00% no país. Conclusões: A tendência da taxa de cobertura vacinal de crianças menores de dois anos mostrou-se estacionária ou decrescente para todos os imunobiológicos em todas as regiões brasileiras, com exceção da febre amarela nas Regiões Sul e Sudeste. Houve aumento da tendência da taxa de abandono da vacina Meningo C no país e, especificamente em relação às regiões, para BCG no norte, nordeste e centro-oeste e Meningo C no norte e nordeste. INTRODUCTION The World Health Organization (WHO) highlights childhood vaccination as one of the best investments in health, as it is estimated that, thanks to compliance with the basic childhood vaccination scheme, approximately 2.5 million deaths are prevented every year.1 It is noteworthy that, since 1975, Brazil has adopted the National Immunization Program (Programa Nacional de Imunização— PNI) as a public health strategy with the purpose of coordinating vaccination actions and ensuring the quality of life of the population with prevention of diseases, based on free vaccination of children, adults and aged people.2 Currently, the basic vaccination schedule for Brazilian children includes 17 different immunobiologicals, routinely offered in the country's health services.3 However, incomplete vaccination schedules can represent a serious public health problem, as it is necessary to achieve high vaccination coverage (VC) to reduce or prevent circulation of a specific infectious agent.4,5 Thus, the VC indicators, which show the number of doses administered and the abandonment rate, which estimates the population's adherence when considering the number of individuals that started and did not complete the regime, represent important instruments for monitoring diseases that are of interest for public health.6,7 Nonetheless, in recent years, several countries presented reductions in infant VC rates, such as Mexico, Colombia, Paraguay, Venezuela, Jordan and also Brazil, which may directly reflect on the increase in morbidity and mortality, as children's vulnerability is increased, especially in those under two years old.7-14 The decrease in vaccination coverage is a process that preceded the COVID-19 pandemic, but has intensified during this period throughout the country. However, it is also influenced by access to vaccination services and by availability of products.4 The United Nations Children's Fund (UNICEF) and the WHO point out that disinformation is behind the continuous reduction in childhood vaccinations over the last three decades, accentuated by the COVID-19 pandemic. Thus, the percentage of children in the world that received all three doses of the Diphtheria, Tetanus and Poliomyelitis (DTP) vaccine, for example, dropped from 86.00% in 2019 to 81.00% in 2021. It is noted that the DTP vaccine is used as a key indicator of global immunization coverage.15 Despite all the achievements of the Brazilian PNI, several challenges have limited the scope and maintenance of high vaccination coverage, such as fake news, vaccine hesitancy, organization and opening hours of services, fear of adverse events, and efficacy and safety of the vaccines.5 In view of this, there is lack of information on the serial vaccination behavior among children under two years of age. All vaccines offered to children have an indication for doses up to two years of age, according to the country's Childhood Vaccination Schedule, and only two of them are indicated at four years of age as a second vaccine booster, namely: the Diphtheria and Tetanus vaccine (dT) and the Poliomyelitis vaccine (PV).3 Therefore, this study aimed at analyzing the trend in vaccination coverage and abandonment rates among children under two years of age in Brazil, from 2015 to 2021. These results allow us to know about the situation of childhood immunization and how its indicators have behaved in recent years, especially among infants, a priority group of the Brazilian PNI. It is known that surveilling vaccine coverage and monitoring vaccine abandonment are powerful instruments to target and devise actions aimed at controlling vaccine-preventable diseases in childhood. METHOD This is an ecological study with a time-series design (trend study)16 of the vaccination coverage and abandonment rates in Brazil and its regions, between 2015 and 2021. The dependent variables of the research were the following PNI health indicators: VC and abandonment rates,17 both assessed by Brazilian region. The Brazilian territory is politically and administratively organized by the grouping of all 27 Federation Units into five regions: North, Northeast, Midwest, Southeast and South.18 The years (from 2015 to 2021) were considered as an independent variable (time). This period of time was chosen because it is not recommended to analyze series with less than seven points, as the trends tend to be non-significant and the small statistical power of the regression analysis tends to make it difficult to identify a significant trend, either increasing or decreasing.19 The data were extracted in July 2022 from the Information System of the National Immunization Program (Sistema de Informação do Programa Nacional de Imunização — SI-PNI) on the website of the Informatics Department belonging to the Unified Health System (DATASUS) [http://datasus.saude.gov.br/], considering the national calendar recommended for children under two years of age in Brazil (Table 1). Information was obtained about the VC corresponding to each immunobiological agent by region and according to year, as well as about the doses of each vaccine administered by region, according to year. Table 1 Vaccination schedule of children under two years of age according to vaccine, age and recommended scheme, Brazil, 2023.3 Vaccine Recommended scheme Age and recommended scheme Basic scheme Booster Bacillus Calmette and Guérin (BCG) 1 dose - At birth (months) Hepatitis B (HEPB) 4 doses - At birth–dose 1 2–dose 2 (PENTA) 4–dose 3 (PENTA) 6–dose 4 (PENTA) Pentavalent (PENTA) 3 doses 2 doses with the Measles, Mumps and Rubella (MMR) vaccine (DTP)* 2–dose 1 4–dose 2 6–dose 3 15–booster 1 (DPT-R1) 4 years old–booster 2 (DTP-R2)* Poliomyelitis (POLIO) 3 doses with the Injectable Poliomyelitis Vaccine (IPV) 2 doses with the Oral Poliomyelitis Vaccine (OPV) 2–dose 1 4–dose 2 6–dose 3 15–booster 1 (POLIO-R1) 4 years old–booster 2 (POLIO-R2)* 10-valent pneumococcal (PNEUMO-10) 2 doses 1 dose 2–dose 1 4–dose 2 12–booster (PNEUMO-R1) Oral Human Rotavirus Vaccine (OHRV) 2 doses - 2–dose 1 4–dose 2 Conjugate Meningococcal C (MENINGO-C) 2 doses 1 dose 3–dose 1 5–dose 2 12–ooster (MENINGO-R1) Yellow Fever (YF) 1 dose 1 dose 9–dose 1 Triple viral (SCR) 1 dose - 12–dose 1 (SCR) Tetra Viral (SCRV) 1 dose - 15–dose 1 Hepatitis A (HEPA) 1 dose - 15–dose 1 * Dose applied after 2 years. The coverage rates are already provided as calculated by SI-PNI. The formula for calculating coverage is the number of doses applied of the indicated dose (1st, 2nd and 3rd dose, single dose or booster dose, according to the recommended schedule for each vaccine) divided by the target population, and multiplied by 100. In the case of the Measles, Mumps and Rubella (MMR) vaccine, as the second dose can be applied with the tetra viral or MMR, the calculation is provided per dose. The abandonment rates (referring to multidose vaccines in children under one year old) were calculated by dividing the difference between the number of first doses and the number of last doses administered in the vaccination schedule by the total number of first doses, multiplying the result of the division by 100. Low (<5.00%), average (≥5.00% and <10.00%) and high (≥10.00%) abandonment rates were considered.6 Prais-Winsten regression was used for the trend analysis of the rates, as described by researchers Antunes and Cardoso,19 which foresees first-order autocorrelation correction. The dependent variable was the logarithm of the rates and the independent variable was the years from the historical series. The Annual Percent Change (APC) was calculated by means of the following expression: APC= [– 1 + 10b] * 100%. The following was used to calculate the confidence intervals (CIs): 95%CI [-1 +10b±t*se.] * 100%, where "b" corresponds to the annual increase rate and "se" to the standard error, both extracted from the regression analysis, and the "t" value is provided by the Student's t distribution table. An increasing trend was considered when the rate was positive; decreasing when negative; and stationary when there was no significant difference between its value and zero in the CI.19 This analysis was performed with the aid of the STATA 16.0 software. The study is exempt from submission to a Research Ethics Committee because it evaluates data in the public domain. RESULTS Between 2015 and 2021, the mean overall coverage rate for the immunobiological agents among children under two years old in Brazil was 76.96%, whereas in 2015 it was 88.85% and, in 2021, 62.35%, with a decreasing trend during the period (APC=-5.12; CI95% -7.81; -2.34). In turn, the mean overall abandonment rate was 10.48%: 24.00% in 2015 and 9.01% in 2021, representing a stationary trend (APC=-9.54; CI95% -22.92; 6.12), as highlighted in Figure 1. Figure 1 Time series corresponding to the overall coverage and abandonment rate of the immunobiological agents among children under two years old in Brazil (2015–2021). Tables 2 and 3 present the time series corresponding to the VC rate by immunobiological agent (%) among children under two years old in Brazil and by regions, from 2015 to 2021. A decreasing VC trend was observed in Brazil for the following immunobiological agents: BCG, HEPB, PENTA, PNEUMO-10, POLIO, OHRV, MENINGO-C, Triple Viral Dose 1 (SCR-D1), Tetra Viral (SCRV), Pneumococcal Booster 1 (PNEUMO-B1), Meningococcal Booster 1 (MENINGO-B1) and Poliomyelitis Booster 1 (POLIO-B1); and a stationary trend for the others, namely: Yellow Fever (YF), SCR Dose 2 (SCR-D2), HEPA and triple bacterial Booster 1 (DTP-B1). Therefore, no immunobiological agent presented VC values with an increasing trend in the country. An increasing trend in relation to YF was only observed in the Brazilian Southeast and South regions. The other immunobiological agents showed a decreasing or stationary trend in all the Brazilian regions across the years analyzed. Table 2 Time series corresponding to the vaccination coverage rate by immunobiological agent (%) in children under two years old. Brazil, Regions, from 2015 to 2021. Region Rate 2015 Rate 2021 Rate Mean APC 95%CI Trend BCG North 103.72 74.85 89.76 -4.84 -7.83; -1.75 Decreasing Northeast 105.52 66.59 88.75 -7.15 -11.56; -2.51 Decreasing Southeast 104.76 65.94 89.23 -7.42 -12.43; -2.12 Decreasing South 106.00 74.61 90.91 -4.49 -5.79; -3.18 Decreasing Midwest 105.44 74.57 93.78 -5.65 -8.97; -2.21 Decreasing Total 105.08 69.01 89.76 -6.54 -10.44; -2.47 Decreasing HEPB North 89.43 69.99 80.05 -2.33 -6.57; 2.10 Stationary Northeast 90.88 64.09 80.14 -5.09 -10.20; 0.30 Stationary Southeast 90.83 56.63 77.39 -8.20 -13.81; -2.23 Decreasing South 89.86 61.48 74.67 -4.78 -6.91; -2.60 Decreasing Midwest 95.38 69.64 85.86 -5.02 -9.86; 0.07 Stationary Total 90.93 61.97 78.79 -6.04 -10.66; -1.19 Decreasing PENTA North 85.08 61.31 71.80 -4.83 -6.00; -3.64 Decreasing Northeast 95.93 67.69 80.16 -5.70 -7.62; -3.73 Decreasing Southeast 99.13 70.91 84.80 -4.90 -6.85; -2.91 Decreasing South 98.40 80.03 87.11 -2.95 -4.86; -1.01 Decreasing Midwest 95.17 73.65 84.41 -5.11 -7.05; -3.12 Decreasing Total 96.30 70.41 82.38 -4.67 -6.08; -3.25 Decreasing PNEUMO-10 North 75.00 68.11 80.51 -1.88 -7.53; 4.10 Stationary Northeast 93.29 70.30 87.21 -4.32 -8.68; 0.26 Stationary Southeast 99.01 72.85 89.99 -5.08 -8.26; -1.78 Decreasing South 98.44 83.03 92.62 -2.04 -3.03; -1.03 Decreasing Midwest 92.76 78.28 91.11 -3.45 -4.81; -2.06 Decreasing Total 94.23 73.45 88.64 -3.68 -6.72; -0.53 Decreasing POLIO North 88.16 61.27 74.17 -4.43 -8.13; -0.58 Decreasing Northeast 100.44 66.69 82.19 -5.16 -8.99; -1.17 Decreasing Southeast 100.52 70.67 85.72 -4.65 -7.65; -1.55 Decreasing South 95.57 79.23 88.18 -1.72 -3.20; -0.21 Decreasing Midwest 97.88 73.50 86.57 -4.10 -5.34; -2.84 Decreasing Total 98.29 69.91 83.89 -4.68 -7.73; -1.54 Decreasing OHRV North 83.09 62.65 75.00 -3.75 -7.45; 0.09 Stationary Northeast 94.25 66.84 82.64 -4.44 -7.92; -0.82 Decreasing Southeast 98.52 70.83 86.73 -4.86 -7.58; -2.07 Decreasing South 98.23 80.53 90.11 -2.34 -4.16; -0.47 Decreasing Midwest 95.27 74.87 87.52 -3.78 -5.33; -2.20 Decreasing Total 95.35 70.46 84.84 -4.29 -6.95; -1.55 Decreasing MENINGO-C North 87.19 64.90 77.40 -3.65 -6.35; -0.86 Decreasing Northeast 97.40 67.29 84.39 -5.34 -8.88; -1.66 Decreasing Southeast 100.81 70.82 87.22 -5.14 -7.62; -2.60 Decreasing South 101.48 80.63 91.38 -2.87 -4.66; -1.05 Decreasing Midwest 97.35 75.35 89.19 -3.99 -5.45; -2.51 Decreasing Total 98.19 70.89 86.09 -2.51 -7.24; -2.08 Decreasing YF North 75.34 51.01 65.84 -6.05 -9.56; -2.40 Decreasing Northeast 38.90 43.24 36.36 0.92 -3.37; 5.39 Stationary Southeast 31.17 63.65 52.56 15.18 1.50; 30.71 Increasing South 58.05 69.38 64.75 4.59 0.37; 8.98 Increasing Midwest 87.17 66.81 79.50 -5.26 -6.76; -3.73 Decreasing Total 46.31 57.66 53.59 4.72 -0.34; 10.04 Stationary APC: Annual Percentage Change; CI: Confidence Interval; BCG: Bacillus Calmette and Guérin; HEPB: Hepatitis B; PENTA: Pentavalent; PNEUMO-10: 10-valent pneumococcal; POLIO: Poliomyelitis; OHRV: Oral Human Rotavirus Vaccine; MENINGO-C: Conjugate Meningococcal C; YF: Yellow Fever. Table 3 Time series corresponding to the vaccination coverage rate by immunobiological agent (%) in children under two years old. Brazil, Regions, from 2015 to 2021. Region Rate 2015 Rate 2021 Rate Mean APC 95%CI Trend SCR-D1 North 85.60 67.80 78.84 -3.05 -7.53; 1.66 Stationary Northeast 95.31 69.16 87.99 -4.74 -9.17; -0.09 Decreasing Southeast 99.92 73.93 90.18 -4.35 -7.30; -1.31 Decreasing South 96.12 82.73 89.59 -1.83 -3.38; -0.25 Decreasing Midwest 93.73 78.56 88.02 -3.13 -5.02; -1.20 Decreasing Total 96.07 73.49 88.09 -3.75 -6.82; -0.57 Decreasing SCR-D2 North 62.76 34.76 61.75 -7.94 -19.14; 4.81 Stationary Northeast 80.35 45.54 64.89 -6.72 -13.90; 1.05 Stationary Southeast 86.97 58.55 75.83 -5.62 -10.02; -1.01 Decreasing South 76.54 62.76 80.84 -2.47 -7.89; 3.27 Stationary Midwest 72.57 44.71 74.31 -6.68 -15.14; 2.62 Stationary Total 79.94 51.62 71.80 -6.11 -12.79; 1.07 Stationary SCRV North 58.01 1.64 50.48 -32.85 -59.55; 11.46 Stationary Northeast 77.05 4.88 27.71 -43.67 -53.14; -32.29 Decreasing Southeast 86.98 4.73 34.09 -42.31 -48.33; -35.59 Decreasing South 70.69 13.46 64.57 -17.78 -35.37; 4.60 Stationary Midwest 68.23 5.61 61.49 -24.50 -46.17; 5.91 Stationary Total 77.37 5.74 40.83 -30.18 -40.11; -18.60 Decreasing HEPA North 86.67 57.23 71.02 -3.78 -9.04; 1.77 Stationary Northeast 94.35 60.93 76.56 -4.38 -9.22; 0.71 Stationary Southeast 101.02 69.88 81.45 -2.37 -7.19; 2.70 Stationary South 101.63 76.46 85.90 -1.44 -5.52; 2.82 Stationary Midwest 93.56 70.09 82.22 -3.06 -6.23; 0.22 Stationary Total 97.07 66.87 79.61 -2.62 -7.02; 2.00 Stationary PNEUMO-B1 North 72.13 60.69 70.61 -2.03 -6.51; 2.66 Stationary Northeast 86.40 63.12 76.90 -4.48 -8.21; -0.59 Decreasing Southeast 92.90 64.59 79.85 -5.01 -8.09; -1.83 Decreasing South 92.51 72.05 83.35 -3.33 -6.07; -0.52 Decreasing Midwest 87.73 71.85 82.42 -2.49 -5.10; 0.20 Stationary Total 88.35 65.36 78.72 -4.02 -7.06; -0.88 Decreasing MENINGO-B1 North 72.06 62.51 73.28 -2.49 -5.81; 0.95 Stationary Northeast 86.25 64.27 79.96 -4.51 -7.37; -1.56 Decreasing Southeast 93.07 68.11 81.99 -4.37 -6.87; -1.80 Decreasing South 90.23 76.71 87.16 -2.68 -5.20; -0.10 Decreasing Midwest 85.06 72.91 85.34 -3.94 -6.80; -0.98 Decreasing Total 87.85 67.98 81.46 -3.79 -6.11; -1.42 Decreasing DTP-B1 North 71.62 52.87 60.42 -1.80 -4.11; 0.57 Stationary Northeast 86.18 57.23 68.63 -3.96 -6.30; -1.55 Decreasing Southeast 90.23 65.71 72.28 -1.83 -6.00; 2.53 Stationary South 84.41 73.43 75.07 1.53 -1.70; 4.87 Stationary Midwest 83.68 65.93 71.42 -3.48 -8.37; 1.68 Stationary Total 85.78 62.97 70.29 -1.95 -5.05; 1.24 Stationary POLIO-B1 North 71.68 51.93 60.75 -2.72 -6.89; 1.65 Stationary Northeast 86.53 52.77 68.85 -5.65 -9.07; -2.11 Decreasing Southeast 88.50 63.01 75.66 -4.18 -6.08; -2.25 Decreasing South 80.10 69.52 78.74 -1.39 -3.18; 0.43 Stationary Midwest 83.42 63.97 76.09 -3.22 -5.01; -1.39 Decreasing Total 84.52 59.86 72.60 -3.95 -6.24; -1.60 Decreasing APC: Annual Percentage Change; CI: Confidence Interval; SCR-D1: Triple Viral Dose 1; SCR-D2: Triple Viral Dose 2; SCRV: Tetra Viral; HEPA: Hepatitis A; PNEUMO-B1: Pneumococcal Booster 1; MENINGO-B1: Meningococcal Booster 1; DTP-R1: Triple Bacterial Booster 1; POLIO-R1: Poliomyelitis Booster 1. Table 4 presents the time series corresponding to the vaccination abandonment rate by multidose immunobiological agent (%) among children under two years old in Brazil, both in the entire country and according to its regions between 2015 and 2016. In the country, a decreasing trend was identified in the abandonment rates for the POLIO and OHRV vaccines, stationary for the PENTA, PNEUMO-10 and triple viral (SCR) vaccines, and increasing for MENINGO-C. The increasing trends in the abandonment rate in the regions of the following immunobiologicals stand out: BCG in the North, Northeast and Midwest; and MENINGO-C in the North and Northeast. In addition to that, many immunobiological agents maintained the stationary trend of this rate in the regions throughout the years under study. Table 4 Time series corresponding to the vaccination abandonment rate by immunobiological agent (%) in children under two years old. Brazil, Regions, from 2015 to 2021. Region Rate 2015 Rate 2021 Rate Mean APC 95%CI Trend PENTA North 14.87 19.10 19.55 9.11 2.38; 16.28 Increasing Northeast 9.31 7.62 11.80 8.01 0.09; 16.57 Increasing Southeast 5.25 4.01 6.55 -2.76 -18.72; 6.35 Stationary South 6.83 3.80 7.13 3.56 -6.33; 14.49 Stationary Midwest 6.73 6.69 9.16 11.43 0.79; 23.19 Increasing Total 7.75 6.91 9.73 5.93 -3.21; 15.92 Stationary PNEUMO-10 North 12.95 8.52 7.48 1.08 -10.21; 13.80 Stationary Northeast 8.40 1.84 3.37 -18.59 -26.39; -9.98 Decreasing Southeast 4.18 1.32 1.79 -6.77 -39.84; 44.48 Stationary South 6.34 1.27 2.05 -16.05 -34.55; 7.67 Stationary Midwest 7.27 1.69 2.60 -9.40 -25.84; 10.68 Stationary Total 6.81 2.27 2.93 -10.24 -23.15; 4.83 Stationary POLIO North 99.70 18.91 30.83 -17.44 -36.61; 7.52 Stationary Northeast 99.06 8.43 24.07 -25.94 -44.17; -1.77 Decreasing Southeast 96.83 4.59 19.75 -34.58 -53.58; -7.79 Decreasing South 99.59 4.96 19.90 -33.90 -55.84; -1.07 Decreasing Midwest 99.73 6.99 22.08 -29.47 -49.46; -1.58 Decreasing Total 98.83 7.52 22.43 -28.11 -47.51; -1.54 Decreasing OHRV North 9.69 8.62 8.31 9.50 -4.50; 25.56 Stationary Northeast 10.20 2.61 6.40 -20.00 -26.97; -12.37 Decreasing Southeast 6.48 1.88 3.55 -14.84 -29.47; 2.82 Stationary South 5.18 1.70 2.94 -11.63 -23.84; 2.55 Stationary Midwest 4.62 2.40 3.72 -6.57 -20.49; 9.79 Stationary Total 7.55 2.81 4.77 -12.36 -21.92; -1.63 Decreasing MENINGO-C North 7.87 10.67 9.05 10.37 0.35; 21.40 Increasing Northeast 3.17 6.06 5.13 14.59 5.01; 25.04 Increasing Southeast 0.48 2.70 1.56 7.75 -57.53; 173.39 Stationary South 1.96 2.99 2.10 17.52 -15.95; 64.31 Stationary Midwest 2.10 4.08 2.77 27.83 -0.86; 64.82 Stationary Total 2.32 4.68 3.53 18.33 1.35; 38.16 Increasing SCR North 32.45 48.82 23.13 8.72 -11.84; 34.08 Stationary Northeast 20.09 34.26 27.40 2.13 -7.71; 13.01 Stationary Southeast 14.66 21.02 16.43 5.09 -6.79; 18.49 Stationary South 27.73 24.40 10.81 4.53 -29.53; 55.04 Stationary Midwest 29.04 43.19 17.05 10.55 -19.39; 51.61 Stationary Total 20.77 29.89 19.48 4.34 -11.55; 23.08 Stationary APC: Annual Percentage Change; CI: Confidence Interval; PENTA: Pentavalent; PNEUMO-10: 10-valent pneumococcal; POLIO: Poliomyelitis; OHRV: Oral Human Rotavirus Vaccine; MENINGO-C: Conjugate Meningococcal C; SCR: Triple Viral. DISCUSSION The study results pointed out important aspects related to the vaccination of children under two years old in Brazil, highlighting the decreasing VC rate and the stationary abandonment rate during the period analyzed. This indicates a considerable deterioration in recent years in the vaccination status of this population group in the country, as immunobiologicals in the basic vaccination schedule such as SCRV (77.37%), SCR-D2 (79.94%) and YF (46.31%) did not achieve desirable coverage rates as early as 2015. Furthermore, there has been a significant drop in VC since then, falling short of what is recommended by the Brazilian Ministry of Health, with most vaccines presenting VC values below 70%. In the population group analyzed, vaccination coverage is considered adequate when it reaches values equal to or greater than: 90.00% for BCG and HRV; and 95.00% for the POLIO, PENTA, HEPB, MENINGO-C, PNEUMO-10, YF and HEPA vaccines.17,20,21 Therefore, from the results it can be seen that none of the vaccines reached an adequate VC in 2021 when we consider the total. Regarding the regions, the results indicate that, in general, the lowest VC values are in the North and Northeast regions; this is possibly due to difficulties accessing vaccination services, to availability of products and, not least, to geographic access difficulties in both regions.4 It is evident that, throughout its history, the Brazilian PNI has become increasingly complex with the inclusion of new vaccines in the basic schedule routinely offered in health services, which resulted in a favorable change in the epidemiological scenario of vaccine-preventable childhood diseases in the country.2,5 However, in view of these results, the number of children that have not completed the vaccination schedule is still significant, even though these vaccines are available in the Brazilian health system free of charge. This is because vaccination success goes beyond availability and supply of vaccines, being influenced by lack of confidence and acceptance of the vaccines, by the services operating at inappropriate times for the population and by fear of adverse events after vaccination, among others.5 A study that analyzed VC for HEPA, CVS and Varicella among children aged 15 months old in the Brazilian state of Minas Gerais also showed low VC in 2020.13 In São Paulo, another Brazilian state, a number of researchers investigated VC specifically for measles, an infectious disease included in the country's basic vaccination schedule, and identified low VC between 2015 and 2020, with a greater reduction for the second dose of the vaccine against the disease.14 Also in this regard, a research study that evaluated VC for agents that cause respiratory tract infections and the prevalence of childhood hospitalizations for these conditions in Brazil from 2015 to 2020 also found low VC and a significant increase in hospitalizations due to measles during the same period.22 Regarding the trend of VC rates by each immunobiological specifically, a decreasing or stationary trend was observed in all regions, with the exception of the YF vaccine, which was increasing in the South and Southeast regions. This points to certain risk for the reintroduction or resurgence of controlled or eradicated diseases in the country, a phenomenon observed worldwide, especially since 2016.6 In this way, children under the age of two become more vulnerable to contracting serious and life-threatening diseases such as severe forms of tuberculosis, hepatitis b, diphtheria, tetanus, pertussis, poliomyelitis, rotavirus diarrhea, pneumonia, meningitis, yellow fever, measles, mumps, pertussis, hepatitis a, varicella and rubella. Because of this scenario, the emergence of diseases that had already been eliminated has been observed, such as measles, eradicated in the country in 2016. In this sense, according to the epidemiological bulletin of the Brazilian Ministry of Health, the last measles cases in the country were reported in 2015 and, in 2016, the country received a certification corresponding to elimination of the virus. Consequently, in 2016 and 2017, no measles cases were confirmed in the country. However, in 2018, 10,346 cases of the disease were reported. In 2019, after a year of free circulation of the virus and the confirmation of 20,901 cases of the disease, Brazil lost the "measles-free country" certification.23 This scenario put health authorities in Brazil and the Americas on alert, as other diseases had already been controlled or even eradicated, as was the case with smallpox, poliomyelitis, rubella and congenital rubella,5,24,25 making it necessary to intensify actions aimed at achieving the VC rate for all immunobiological agents in the basic vaccination schedule. Over the years, many studies have shown the positive impact of vaccination on hospital admissions and infant mortality. Thus, it is estimated that, worldwide, approximately 2.5 million deaths are prevented every year thanks to compliance with the basic vaccination schedule for children under five years old. However, at least 20.00% of the children born each year do not receive the benefits of vaccination and are exposed to the risks of becoming ill and dying before the age of five.26 A study that described the impact of introducing the SCRV vaccine in the Brazilian PNI in 2013 for 15-month-old children showed that vaccination significantly reduced the mortality and hospitalization rates associated with varicella in Brazil. In addition, the country presented a 57.00% drop in the mortality rate among infants and a 49.00% reduction in children aged from one to four years old. In terms of hospitalizations, the reductions were 40.00 and 47.00%, respectively.27 However, when comparing the findings of this research with the global infant VC rates, according to a report published in 2022 by the WHO in partnership with UNICEF, it is observed that the global VC dropped from 86.00% in 2019 to 81.00% in 2021; in other words, the number of non-vaccinated children increased by 5 million from 2019 to 2021. Thus, it is estimated that, worldwide, 25 million children under one year old did not receive the vaccines in the basic schedule, the highest number since 2009.15 It is also noteworthy that the 62.30% VC among children under two years of age in Brazil in 2021 was below the global rate (81.00%). This highlights the weakness of the PNI in the country which, despite currently offering the largest number of vaccines free of charge (17 immunobiologicals for children under two years of age in the basic calendar), is among the ten worst nations in the world in terms of vaccination.3 Another result that was highlighted in the current study refers to the vaccine abandonment rate among children under two years old in Brazil, which proved to be stationary and growing for most immunobiologicals during the period analyzed, especially with the increasing BCG abandonment rate in the North, Northeast and Midwest regions, and MENINGO-C also in the North and Northeast regions. Also regarding this aspect, there was an increase in the overall abandonment rate during the last three years analyzed, from 6.40% in 2019 to 9.00% in 2021. In this sense, a recent study that analyzed the MMR vaccine abandonment rate in Brazil according to regions of the country, from 2014 to 2021, corroborated the results found in the current research since, during the period investigated, the abandonment rate varied among the Federation Units that make up the Brazilian regions, ranging from 22.20% in 2014 to 37.40% in 2021.7 Therefore, the abandonment rate is considered average, and investments are required to reduce it in the country.6 Some studies have pointed out the factors that contribute to the decrease in VC and the increase in the abandonment rate, such as fear of a post-vaccination reaction, lack of knowledge on the part of parents about the importance of vaccination and about the severity of vaccine-preventable diseases, the socioeconomic conditions and geographic characteristics of the population, the working conditions of the nursing professionals who work in vaccination rooms, dissemination of fake news about vaccines, an increase in anti-vaccination movements and false contraindications.9,28 It is evident that the advent of the infection caused by SARS-CoV-2, considered a pandemic by the WHO in March 2020,29 also emerged as an important factor that negatively influenced the VC and vaccine abandonment rates among children under two years old in Brazil and in the world. In 2020 and 2021, Brazil faced the worst moment of the COVID-19 pandemic, which strongly modified how health services were resorted to, in which face-to-face attendance dropped dramatically even for childhood vaccinations, due to social distancing measures implemented in order to reduce transmission of the virus, in addition to the parents’ fear of contracting COVID-19 when taking their children to be vaccinated.30 A study carried out in Jordan corroborates these findings, as a decline in the VC of Jordanian children was identified during the COVID-19 pandemic in 2020, highlighting the importance of formulating future strategies to promote vaccination and avoid setbacks in the vaccination rates during new waves of the COVID-19 or other pandemics. The researchers also signal the need to improve the health services, alleviate the caregivers’ concerns about the coronavirus contamination risk and organize vaccination campaigns outside health centers.11 Regarding strategies to improve the vaccination rates, in the international scenario, research studies carried out in Mexico, Colombia, Paraguay and Venezuela point to initiatives to reduce vaccine abandonment and achieve VC in children. Among them, an active search for newborns to adhere to the vaccination program, as well as their follow-up until conclusion of the recommended schedule, taking advantage of all contacts with health services to vaccinate them and also discussing false contraindications for children, as the mothers’ knowledge about vaccines was pointed out as a decisive aspect for acceptance of the immunobiologicals.8-10 It is also noteworthy that the results indicate that there are different behaviors between vaccines that should be carried out at the same time, such as the first DTP booster and the poliomyelitis booster, recommended at 15 months of age. This distinction may be due to unavailability of certain immunobiologicals in the services or to specific vaccine hesitancy.12 Thus, the importance of monitoring the VC and abandonment rates in all Brazilian regions is reinforced, in order to support the development of strategies to achieve the recommended VC and reduce vaccine abandonment, protecting children against countless serious preventable diseases. Health professionals need to engage as health educators to discuss with the population the role of immunobiologicals in disease prevention, as well as to update the vaccination schedule whenever appropriate. Access to secondary databases as an information source stands out as a study limitation since, despite being an official source from the Brazilian Ministry of Health, it may present inconsistencies in relation to data feeding and updating. Some atypical extreme values are common in municipalities with a small population (less than one hundred children), where the quality of state data may be compromised, as any variation in the birth rate and/or registration of the dose applied alters the behavior of the target indicator performance, with rates higher than 100.00%.4 Therefore, such overestimated or underestimated values at the levels at which these indices are found are questionable and it was not possible to include them in the context of adequate VC; therefore, despite being a good indicator to suggest "population immunity", they should be viewed with caution. In conclusion, the study results show a worrisome scenario in Brazil, with a stationary or decreasing vaccination coverage rate trend in children under two years old for all the immunobiologicals in all Brazilian regions, with the exception of YF in the South and Southeast regions. There was an increase in the abandonment rate trend for the Meningococcal C vaccine in the country. In relation to the regions, there was an increase in the abandonment rate for BCG in the North, Northeast and Midwest and for Meningococcal C in the North and Northeast. Finally, new studies must be carried out in order to understand the individual and subjective aspects involved in children's vaccination behavior, including their parents’/guardians’ perspective, in order to target and devise strategies for monitoring and increasing the VC rate and reducing the abandonment rate. Funding This study did not receive any funding. Declaration The database that originated the article is available with the corresponding author. REFERENCES 1 World Health Organization [homepage on the Internet] Ten threats to global health in 2019 cited 2023 Jan 31 Available from: https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 1 World Health Organization [homepage on the Internet]. Ten threats to global health in 2019 [cited 2023 Jan 31]. Available from: https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 2 Brazil. Ministério da Saúde [homepage on the Internet] Programa Nacional de Imunizações – Vacinação cited 2023 Jan 12 Available from: https://www.gov.br/saude/pt-br/acesso-a-informacao/acoes-e-programas/programa-nacional-de-imunizacoes-vacinacao/programa-nacional-de-imunizacoes-vacinacao 2 Brazil. Ministério da Saúde [homepage on the Internet]. Programa Nacional de Imunizações – Vacinação [cited 2023 Jan 12]. Available from: https://www.gov.br/saude/pt-br/acesso-a-informacao/acoes-e-programas/programa-nacional-de-imunizacoes-vacinacao/programa-nacional-de-imunizacoes-vacinacao 3 Brazil. Ministério da Saúde [homepage on the Internet] Calendário de vacinação cited 2023 Nov 28 Available from: https://www.gov.br/saude/pt-br/vacinacao/calendario 3 Brazil. Ministério da Saúde [homepage on the Internet]. Calendário de vacinação [cited 2023 Nov 28]. Available from: https://www.gov.br/saude/pt-br/vacinacao/calendario 4 Domingues CM Teixeira AM Moraes JC Vaccination coverage in children in the period before and during the COVID-19 pandemic in Brazil: a time series analysis and literature review J Pediatr (Rio J) 2023 Supp 1 S12 S21 https://doi.org/10.1016/j.jped.2022.11.004 4 Domingues CM, Teixeira AM, Moraes JC. Vaccination coverage in children in the period before and during the COVID-19 pandemic in Brazil: a time series analysis and literature review. J Pediatr (Rio J). 2023;(Supp 1):S12-21. https://doi.org/10.1016/j.jped.2022.11.004 5 Domingues CM Maranhão AG Teixeira AM Fantinato FF Domingues RA The Brazilian National Immunization Program: 46 years of achievements and challenges Cad Saúde Pública 2020 36 Suppl 2 e00222919 https://doi.org/10.1590/0102-311X00222919 5 Domingues CM, Maranhão AG, Teixeira AM, Fantinato FF, Domingues RA. The Brazilian National Immunization Program: 46 years of achievements and challenges. Cad Saúde Pública. 2020;36(Suppl 2):e00222919. https://doi.org/10.1590/0102-311X00222919 6 Brazil. Ministério da Saúde Secretaria de Vigilância em Saúde. Coberturas vacinais no Brasil. Período: 2010–2014 Brasília Ministério da Saúde 2015 6 Brazil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Coberturas vacinais no Brasil. Período: 2010–2014. Brasília: Ministério da Saúde; 2015. 7 Moura LL Neto M Souza-Santos R Temporal trend of the dropout rate and vaccination coverage of the triple viral vaccine in Brazil, 2014-2021 Epidemiol Serv Saúde 2023 32 e2023117 https://doi.org/10.1590/s2237-96222023000300004.EN 7 Moura LL, Neto M, Souza-Santos R. Temporal trend of the dropout rate and vaccination coverage of the triple viral vaccine in Brazil, 2014-2021. Epidemiol Serv Saúde. 2023;32:e2023117. https://doi.org/10.1590/s2237-96222023000300004.EN 8 Díaz-Ortega JL Cruz-Hervert LP Ferreira-Guerrero E Ferreyra-Reyes LD Delgado-Sánchez G García-García ML Vaccination coverage and proportion of incomplete vaccination schedule in children under seven years of age in Mexico Salud Publica Mex 2018 60 338 346 https://doi.org/10.21149/8812 8 Díaz-Ortega JL, Cruz-Hervert LP, Ferreira-Guerrero E, Ferreyra-Reyes LD, Delgado-Sánchez G, García-García ML. Vaccination coverage and proportion of incomplete vaccination schedule in children under seven years of age in Mexico. Salud Publica Mex. 2018;60:338-46. https://doi.org/10.21149/8812 9 Escobar-Díaz F Osorio-Merchán MB De la Hoz-Restrepo F Reasons some children under 5 do not get vaccinated in four Colombian cities Rev Panam Salud Publica 2017 41 e123 https://doi.org/10.26633/RPSP.2017.123 9 Escobar-Díaz F, Osorio-Merchán MB, De la Hoz-Restrepo F. Reasons some children under 5 do not get vaccinated in four Colombian cities. Rev Panam Salud Publica. 2017;41:e123. https://doi.org/10.26633/RPSP.2017.123 10 Muyulema R Guerrero Guerrero E Melendres I Conocimiento vaccinal en madres con hijos menores de 5 años Revista Digital de Postgrado 2020 9 e197 https://doi.org/10.37910/RDP.2020.9.1.e197 10 Muyulema R, Guerrero Guerrero E, Melendres I. Conocimiento vaccinal en madres con hijos menores de 5 años. Revista Digital de Postgrado. 2020;9:e197. https://doi.org/10.37910/RDP.2020.9.1.e197 11 Abu-Rish EY Bustanji Y Abusal K Nationwide routine childhood vaccination coverage during the COVID-19 pandemic in Jordan: current situation, reasons, and predictors of vaccination Int J Clin Pract 2022 7918604 7918604 https://doi.org/10.1155/2022/7918604 11 Abu-Rish EY, Bustanji Y, Abusal K. Nationwide routine childhood vaccination coverage during the COVID-19 pandemic in Jordan: current situation, reasons, and predictors of vaccination. Int J Clin Pract. 2022;7918604. https://doi.org/10.1155/2022/7918604 12 Sato AP What is the importance of vaccine hesitancy in the drop of vaccination coverage in Brazil? Rev Saúde Pública 2018 52 96 96 https://doi.org/10.11606/S1518-8787.2018052001199 12 Sato AP. What is the importance of vaccine hesitancy in the drop of vaccination coverage in Brazil? Rev Saúde Pública. 2018;52:96. https://doi.org/10.11606/S1518-8787.2018052001199 13 Oliveira GC Arroyo LH Vimieiro AM Gusmão JD Oliveira VC Guimarães EA Spatial behavior of hepatitis A, MMR, and varicella vaccination coverage in the state of Minas Gerais, 2020 Rev Bras Epidemiol 2023 26 e230030 https://doi.org/10.1590/1980-549720230030 13 Oliveira GC, Arroyo LH, Vimieiro AM, Gusmão JD, Oliveira VC, Guimarães EA. Spatial behavior of hepatitis A, MMR, and varicella vaccination coverage in the state of Minas Gerais, 2020. Rev Bras Epidemiol. 2023;26:e230030. https://doi.org/10.1590/1980-549720230030 14 Pamplona YA Nascimento AM Olinda RA Barbieri CL Braga AL Martins LC Spatial analysis of measles vaccination coverage in the State of São Paulo BMC Public Health 2023 23 29 29 https://doi.org/10.1186/s12889-022-14797-z 14 Pamplona YA, Nascimento AM, Olinda RA, Barbieri CL, Braga AL, Martins LC. Spatial analysis of measles vaccination coverage in the State of São Paulo. BMC Public Health. 2023;23:29. https://doi.org/10.1186/s12889-022-14797-z 15 United Nations Children's Fund. World Health Organization [homepage on the Internet] Pandemia de covid-19 alimenta o maior retrocesso contínuo nas vacinações em três décadas cited 2023 Jan 31 Available from: https://www.unicef.org/brazil/comunicados-de-imprensa/pandemia-de-covid-19-alimenta-o-maior-retrocesso-continuo-nas-vacinacoes-em-tres-decadas 15 United Nations Children's Fund. World Health Organization [homepage on the Internet]. Pandemia de covid-19 alimenta o maior retrocesso contínuo nas vacinações em três décadas [cited 2023 Jan 31]. Available from: https://www.unicef.org/brazil/comunicados-de-imprensa/pandemia-de-covid-19-alimenta-o-maior-retrocesso-continuo-nas-vacinacoes-em-tres-decadas 16 Gordis L Epidemiologia 5a ed Rio de Janeiro Thieme Revinter 2017 16 Gordis L. Epidemiologia. 5a ed. Rio de Janeiro: Thieme Revinter; 2017. 17 Brazil. Ministério da Saúde Secretaria de Vigilância em Saúde. Departamento de Vigilância das Doenças Transmissíveis Geografia [homepage on the Internet] Manual de normas e procedimentos para vacinação Brasília Ministério da Saúde 2014 cited 2023 Oct 14 Available from: https://bvsms.saude.gov.br/bvs/publicacoes/manual_procedimentos_vacinacao.pdf 17 Brazil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância das Doenças Transmissíveis Geografia [homepage on the Internet]. Manual de normas e procedimentos para vacinação. Brasília: Ministério da Saúde; 2014 [cited 2023 Oct 14]. Available from: https://bvsms.saude.gov.br/bvs/publicacoes/manual_procedimentos_vacinacao.pdf 18 Brazil. Instituto Brasileiro de Geografia e Estatística Coordenação de Geografia [homepage on the Internet] Divisão regional do Brasil em regiões geográficas imediatas e regiões geográficas intermediárias: 2017 Rio de Janeiro Instituto Brasileiro de Geografia e Estatística 2017 cited 2023 Nov 25 Available from: https://biblioteca.ibge.gov.br/visualizacao/livros/liv100600.pdf 18 Brazil. Instituto Brasileiro de Geografia e Estatística. Coordenação de Geografia [homepage on the Internet]. Divisão regional do Brasil em regiões geográficas imediatas e regiões geográficas intermediárias: 2017. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2017 [cited 2023 Nov 25]. Available from: https://biblioteca.ibge.gov.br/visualizacao/livros/liv100600.pdf 19 Antunes JL Cardoso MR Uso da análise de séries temporais em estudos epidemiológicos Epidemiol Serv Saúde 2015 24 565 576 https://doi.org/10.5123/S1679-49742015000300024 19 Antunes JL, Cardoso MR. Uso da análise de séries temporais em estudos epidemiológicos. Epidemiol Serv Saúde. 2015;24:565-76. https://doi.org/10.5123/S1679-49742015000300024 20 Brito WI Souto FJ Universal hepatitis A vaccination in Brazil: analysis of vaccination coverage and incidence five years after program implementation Rev Bras Epidemiol 2020 23 e200073 https://doi.org/10.1590/1980-549720200073 20 Brito WI, Souto FJ. Universal hepatitis A vaccination in Brazil: analysis of vaccination coverage and incidence five years after program implementation. Rev Bras Epidemiol. 2020;23:e200073. https://doi.org/10.1590/1980-549720200073 21 Organização Pan-Americana da Saúde Organização Mundial da Saúde [homepage on the Internet] Alerta epidemiológico febre amarela cited 2023 Nov 25 Available from: https://www.paho.org/pt/documentos/alerta-epidemiologico-febre-amarela-31-agosto-2022 21 Organização Pan-Americana da Saúde. Organização Mundial da Saúde [homepage on the Internet]. Alerta epidemiológico febre amarela [cited 2023 Nov 25]. Available from: https://www.paho.org/pt/documentos/alerta-epidemiologico-febre-amarela-31-agosto-2022 22 Muniz AE Lopes GS Sousa LS Hasselmann MC Cafezeiro ML Brasil MQ Análise da cobertura vacinal e a prevalência de internações por doenças do trato respiratório por agentes imunopreveníveis no período de janeiro de 2015 a julho de 2020 Rev Ciênc Méd Biol (Impr) 2022 20 520 525 https://doi.org/10.9771/cmbio.v20i4.43715 22 Muniz AE, Lopes GS, Sousa LS, Hasselmann MC, Cafezeiro ML, Brasil MQ. Análise da cobertura vacinal e a prevalência de internações por doenças do trato respiratório por agentes imunopreveníveis no período de janeiro de 2015 a julho de 2020. Rev Ciênc Méd Biol (Impr). 2022;20:520-5. https://doi.org/10.9771/cmbio.v20i4.43715 23 Brazil. Ministério da Saúde Secretaria de Vigilância em Saúde [homepage on the Internet]. Vigilância epidemiológica do sarampo no Brasil – semanas epidemiológicas 1 a 52 de 2021 Boletim Epidemiológico 2022 53 cited 2023 May 03 Available from: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/edicoes/2022/boletim-epidemiologico-vol-53-no03.pdf 23 Brazil. Ministério da Saúde. Secretaria de Vigilância em Saúde [homepage on the Internet]. Vigilância epidemiológica do sarampo no Brasil – semanas epidemiológicas 1 a 52 de 2021. Boletim Epidemiológico; 2022(53) [cited 2023 May 03]. Available from: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/edicoes/2022/boletim-epidemiologico-vol-53-no03.pdf 24 Brazil. Ministério da Saúde Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiol[ogica [homepage on the Internet] Programa Nacional de Imunizações (PNI) : 40 anos Brasília Ministério da Saúde 2013 cited 2023 Apr 13 Available from: https://bvsms.saude.gov.br/bvs/publicacoes/programa_nacional_imunizacoes_pni40.pdf 24 Brazil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiol[ogica [homepage on the Internet]. Programa Nacional de Imunizações (PNI) : 40 anos. Brasília: Ministério da Saúde; 2013 [cited 2023 Apr 13]. Available from: https://bvsms.saude.gov.br/bvs/publicacoes/programa_nacional_imunizacoes_pni40.pdf 25 Brazil. Ministério da Saúde Secretaria de Atenção à Saúde. Departamento de Ações Programáticas e Estratégicas [homepage on the Internet] Política Nacional de Atenção Integral à Saúde da Criança: orientações para implementação Brasília Ministério da Saúde 2018 cited 2023 May 25 Available from: https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/pnaisc/ 25 Brazil. Ministério da Saúde. Secretaria de Atenção à Saúde. Departamento de Ações Programáticas e Estratégicas [homepage on the Internet]. Política Nacional de Atenção Integral à Saúde da Criança: orientações para implementação. Brasília: Ministério da Saúde; 2018 [cited 2023 May 25]. Available from: https://portaldeboaspraticas.iff.fiocruz.br/biblioteca/pnaisc/ 26 World Health Organization [homepage on the Internet] The global vaccine action plan 2011-2020: review and lessons learned: strategic advisory group of experts on immunization cited 2023 Jan 31 Available from: https://www.who.int/publications-detail-redirect/the-global-vaccine-action-plan-2011-2020-review-and-lessons-learned-strategic-advisory-group-of-experts-on-immunization 26 World Health Organization [homepage on the Internet]. The global vaccine action plan 2011-2020: review and lessons learned: strategic advisory group of experts on immunization [cited 2023 Jan 31]. Available from: https://www.who.int/publications-detail-redirect/the-global-vaccine-action-plan-2011-2020-review-and-lessons-learned-strategic-advisory-group-of-experts-on-immunization 27 Ribeiro MZ Kupek E Ribeiro PV Pinheiro CE Impact of the tetra viral vaccine introduction on varicella morbidity and mortality in the Brazilian macro regions J Pediatr (Rio J) 2020 96 702 709 https://doi.org/10.1016/j.jped.2019.10.009 27 Ribeiro MZ, Kupek E, Ribeiro PV, Pinheiro CE. Impact of the tetra viral vaccine introduction on varicella morbidity and mortality in the Brazilian macro regions. J Pediatr (Rio J). 2020;96:702-9. https://doi.org/10.1016/j.jped.2019.10.009 28 Frugoli AG Prado RS Silva TM Matozinhos FP Trapé CA Lachtim SA Vaccine fake news: an analysis under the World Health Organization's 3Cs model Rev Esc Enferm USP 2021 55 e03736 https://doi.org/10.1590/S1980-220X2020028303736 28 Frugoli AG, Prado RS, Silva TM, Matozinhos FP, Trapé CA, Lachtim SA. Vaccine fake news: an analysis under the World Health Organization's 3Cs model. Rev Esc Enferm USP. 2021;55:e03736. https://doi.org/10.1590/S1980-220X2020028303736 29 Singh S Sharma BB Severe acute respiratory syndrome-coronavirus 2 and novel coronavirus disease 2019: an extraordinary pandemic Lung India 2020 37 268 271 https://doi.org/10.4103/lungindia.lungindia_170_20 29 Singh S, Sharma BB. Severe acute respiratory syndrome-coronavirus 2 and novel coronavirus disease 2019: an extraordinary pandemic. Lung India. 2020;37:268-71. https://doi.org/10.4103/lungindia.lungindia_170_20 30 Sato AP Pandemic and vaccine coverage: challenges of returning to schools Rev Saude Publica 2020 54 115 115 https://doi.org/10.11606/s1518-8787.2020054003142 30 Sato AP. Pandemic and vaccine coverage: challenges of returning to schools. Rev Saude Publica. 2020;54:115. https://doi.org/10.11606/s1518-8787.2020054003142