Strategies for expanding childhood vaccination in the Americas following the COVID-19 pandemic.

Objective: To provide an overview of the status of the childhood vaccination schedule in the Americas, outline program structures, and identify updated implementation strategies to improve vaccination coverage following the COVID-19 pandemic. Methods: A group of experts in pediatrics, epidemiology, vaccines, and global and public health discussed the current status of the childhood vaccination schedule in the Americas, describing the program structure and identifying new implementation strategies that have the potential to improve vaccination coverage in the post-pandemic context, after the challenges COVID-19 presented for more than two years. Results: The Americas currently face a high risk of resurgence of diseases that were previously controlled or eliminated. Therefore, it is important to find new strategies to educate citizens on the risks associated with lower vaccination rates, especially in children. Conclusions: New strategies along with strong mobilization of the population and advocacy by citizens are necessary to prevent antivaccination groups from gaining a stronger presence in the region and jeopardizing the credibility of the Expanded Program on Immunization.

[Analysis of the Vaccine Adverse Event Reporting System in Brazil, 2014 to 2016Análisis del Sistema de Información de Vigilancia de Eventos Adversos Posvacunación en Brasil, 2014 a 2016]. / Análise do Sistema de Informação da Vigilância de Eventos Adversos Pós-Vacinação no Brasil, 2014 a 2016.

OBJECTIVE: To describe the characteristics of vaccine adverse events (VAE) reports in the online VAE Reporting System (VAE-RS) after 2 years of operation. METHOD: A descriptive analysis of VAE reports entered into the VAE-RS between July 2014 and June 2016 was performed. RESULTS: During the study period, 24 732 VAE were reported. Of 5 570 Brazilian municipalities, 2 571 (46.2%) reported at least one VAE; however, only 1 622 (6.6%) reports had been completed/closed at the end of the study period. Of these, 89.9% referred to mild VAE. Among the completed reports, 19.7% did not provide information on "type of medical care provided," and 98.7% had no information regarding laboratory tests. Systemic neurological symptoms were the most frequent serious VAE among closed reports (59.5% of serious signs/symptoms). Concerning age, the highest VAE reporting coefficients were recorded for children aged ≤ 4 years. CONCLUSION: The VAE-RS is useful to monitor immunization safety. However, municipal services must increase adherence to the system and perform the required investigation and reporting of VAE, with timely and adequate completion of the VAE-RS form. Knowledge regarding VAE can be used in the daily routine of surveillance services, improving the safety of immunobiological agents.

OBJETIVO: Describir las características de las notificaciones de eventos adversos posvacunación (EAPV) en el Sistema de Información de Vigilancia de EAPV (SI-EAPV, un sistema en línea, durante los primeros 2 años de ejecución del sistema. MÉTODO: Se realizó un estudio descriptivo de los registros de EAPV notificados en el SI-EAPV entre julio de 2014 y junio de 2016. RESULTADOS: Durante el período del estudio, se registraron 24 732 notificaciones. De 5 570 municipios brasileños, 2 571 (46,2%) notificaron algún EAPV. Sin embargo, solamente 1 622 (6,6%) notificaciones estaban cerradas al momento del estudio; de ellas, el 89,9% no presentó gravedad. Respecto a las notificaciones cerradas, en el 19,7% no fue anotada la variable "atención médica" y el 98,7% no presentó registro de exámenes de laboratorio. Entre los eventos adversos graves cerrados, las manifestaciones clínicas sistémicas neurológicas fueron las más frecuentes, representado el 59,5% de los signos y síntomas. En cuanto a la edad, los mayores coeficientes de notificación se registraron entre los menores de 4 años. CONCLUSIÓN: El SI-EAPV es útil para el monitoreo de la seguridad de las vacunas. Sin embargo, los municipios necesitan ampliar la adhesión al sistema, así como realizar las investigaciones y notificaciones de los EAPV, llenando la ficha de notificación de forma adecuada y oportuna. El conocimiento sobre EAPV puede ser aplicado en la práctica de los servicios de vigilancia en salud, mejorando la seguridad en la utilización de los productos inmunobiológicos.

Introduction of sequential inactivated polio vaccine-oral polio vaccine schedule for routine infant immunization in Brazil's National Immunization Program.

In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule.

Racial inequalities in child vaccination and barriers to vaccination in Brazil among live births in 2017 and 2018: an analysis of a retrospective cohort of the first two years of life.

OBJECTIVE: To describe timely vaccination completion and obstacles in the first 24 months of life in Brazil, examining associations with maternal race/skin color. METHODS: Study participants were 37,801 children born in 2017 and 2018 included in the National Immunization Coverage Survey. We calculated prevalence and 95% confidence intervals for timely vaccine completeness and obstacles at 5, 12 and 24 months of life, according to maternal race/skin color. Associations were analyzed using logistic regression. RESULTS: 7.2% (95%CI 6.3;8.2) of mothers faced difficulties in taking their children to be vaccinated, and 23.4% (95%CI 21.7;25.1) were not vaccinated when taken. These proportions were 75% (95%CI 1.25;2.45) and 97% (95%CI 1.57;2.48) higher, respectively, among Black mothers. At least one vaccination was delayed among 49.9% (95%CI 47.8;51.9) and 61.1% (95%CI 59.2;63.0) of children by 5 and 12 months, respectively. These rates were higher among Black/mixed race mothers. CONCLUSION: There are racial inequalities in both the obstacles faced and in vaccination rates in Brazil. MAIN RESULTS: Marked racial inequalities were found in the obstacles to vaccination of children under 24 months in Brazil and to timely vaccination at 5 months and in the first year of life. IMPLICATIONS FOR SERVICES: Racial inequalities in the occurrence of vaccination shortcomings in health services, in the objective restrictions faced by families in taking their children to vaccination centers and in incomplete vaccination in a timely manner need to be addressed by the Brazilian National Health System. PERSPECTIVES: Equal public policies to address barriers to vaccination and qualification of health services need to be implemented. Studies need to deepen understanding of the structural determinants that lead to racial disparities.

Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults.

The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30-45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30-45) as compared to NV(D0) (532vs398). Moreover, PV(D30-45) exhibited increased levels of Terminal Effector (CD45RA+CCR7-) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30-45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

Immune response induced by standard and fractional doses of 17DD yellow fever vaccine.

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

Vaccination coverage in children in the period before and during the COVID-19 pandemic in Brazil: a time series analysis and literature review.

OBJECTIVE: To evaluate the behavior of VCR and VCH, per municipality and per vaccines offered at the NVC, to identify priority areas for intervention. METHODS: Descriptive study of a time series, using secondary data and accompanied by a narrative review of the literature evaluating VCR and VCH. Vaccines offered to children under one year and to those aged one year in the pre-pandemic period of COVID-19 (2015 to 2019) were selected and compared to those offered during the pandemic period (2020 and 2021). RESULTS AND DISCUSSIONS: The decrease in VCR and VCH is a process that precedes the COVID-19 pandemic but was intensified during this period. In 2021, the VCR was around 70% for most vaccines. This phenomenon encompasses the entire country; however, it is more intense in the states/municipalities located in the north and northeast regions, suggesting greater difficulty in accessing health services. CONCLUSIONS: Low and heterogeneous VCR requires the adoption of practices that were previously implemented, establishing partnerships with governmental and non-governmental institutions, with adequate communication, active search for non-compliance and non-adherence to the regular vaccination program, adopting intra- and extramural vaccination strategies, to reverse the current situation and reduce the risk of recurrence of diseases that have been already controlled and eliminated.

Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

[Changes in the pattern of COVID-19 hospitalizations and deaths after substantial vaccination of the elderly in Manaus, Amazonas State, Brazil]. / Mudanças no padrão de internações e óbitos por COVID-19 após substancial vacinação de idosos em Manaus, Amazonas, Brasil.

The impact of COVID-19 vaccination in the elderly has received relatively little attention, particularly in a scenario predominated by the gamma variant. The aim of this study was to assess vaccination coverage and its relationship to changes in the pattern of COVID-19 hospitalizations and deaths in the elderly in Manaus, Amazonas State, Brazil. This was an ecological study with Brazilian Ministry of Health data on hospitalizations and deaths, assessing vaccination coverage based on a two-dose regimen, in addition to two vaccination regimens associated with a significant protective effect, one partial (35 days or more after the first dose of the Oxford/AstraZeneca vaccine) and the other complete (14 days or more after the second dose of the Sinovac-CoronaVac vaccine). Based on the date of initial symptoms, patterns of COVID-19 hospitalizations and deaths were assessed comparatively in elderly 60-69 years and 70 years or more in two groups of Epidemiological Weeks (EW) in 2020 (unvaccinated) and 2021 (vaccinated). Hospitalization and death rates were estimated with Poisson regression. In the groups 60-69 and 70 years or more, vaccination coverage rates were 41.8% and 54.8%, as well as 53.5% and 90.1%, in the EW groups 18-20/2021 and 21-23/2021, respectively. Both EW groups in 2021 showed a substantial change in the patterns of COVID-19 hospitalizations and deaths, with an increase in the risk of hospitalization and death in unvaccinated younger individuals and an important reduction in vaccinated elderly, especially those 60-69 years of age, besides overall reductions of 62% (95%CI: 52-69) and 63% (95%CI: 43-75) in hospitalization and death rates, respectively. Our results emphasize the importance of mass vaccination, especially during an epidemic such as in Manaus, marked by high circulation of the gamma variant.

A avaliação do impacto da vacinação contra a COVID-19 em idosos é escassa, sobretudo em um cenário com predomínio da variante Gama. O objetivo deste estudo foi avaliar a cobertura vacinal e sua relação com mudanças no padrão de internações e óbitos por COVID-19 em idosos de Manaus, Amazonas, Brasil. Este é um estudo ecológico com dados de internações e óbitos do Ministério da Saúde que avaliou a cobertura vacinal, mediante esquema com duas doses, além de dois regimes de vacinação associados a significativo efeito protetor, um parcial (35 ou mais dias após a primeira dose da vacina Oxford/AstraZeneca) e outro completo (14 dias ou mais após a segunda dose da vacina Sinovac-CoronaVac). A partir da data dos primeiros sintomas, padrões de internação e óbito por COVID-19 foram avaliados, comparativamente, em idosos de 60-69 e de 70 anos ou mais, em dois grupos de Semanas Epidemiológicas (SE) de 2020 (não vacinados) e 2021 (vacinados). Taxas de internação e óbito foram estimadas pelo modelo Poisson. Entre 60-69 anos e naqueles com 70 anos ou mais, a cobertura por vacina foi 41,8% e 54,8%, bem como 53,5% e 90,1% nos grupos de SE 18-20/2021 e 21-23/2021, respectivamente. Em ambos os grupos de SE de 2021, observou-se substancial mudança nos padrões de internações e óbitos por COVID-19, com aumento no risco de internação e óbito nos mais jovens não vacinados, e importante redução no número de idosos vacinados, sobretudo naqueles com 60-69 anos, além de redução global de 62% (IC95%: 52-69) e 63% (IC95%: 43-75) nas taxas de internação e óbitos, respectivamente. Nossos resultados reforçam a importância da vacinação em massa, especialmente em contexto epidêmico como o de Manaus, marcado por elevada circulação da variante Gama.

La evaluación del impacto de la vacunación contra la COVID-19 en ancianos es escasa, sobre todo en un escenario con predominio de la variante Gamma. El objetivo de este estudio fue evaluar la cobertura de vacunación y su relación con cambios en el patrón de internamientos y óbitos por COVID-19 en ancianos de Manaos, Amazonas, Brasil. Este es un estudio ecológico con datos de internamientos y óbitos del Ministerio de Salud, que evaluó la cobertura de vacunación, mediante un esquema con dos dosis, además de dos regímenes de vacunación, asociados a un significativo efecto protector, uno parcial (35 o más días tras la primera dosis de la vacuna Oxford/AstraZeneca) y otro completo (14 días o más tras la segunda dosis de la vacuna Sinovac-CoronaVac). A partir de los datos de los primeros síntomas, se evaluaron patrones de internamiento y óbito por COVID-19, comparativamente, en ancianos de 60-69 y de 70 años o más, en dos grupos de Semanas Epidemiológicas (SE) de 2020 (no vacunados) y 2021 (vacunados). Se estimaron tasas de internamiento y óbito mediante el modelo Poisson. Entre 60-69 años y en aquellos con 70 años o más, la cobertura por vacuna fue 41,8% y 54,8%, así como 53,5% y 90,1% en los grupos de SE 18-20/2021 y 21-23/2021, respectivamente. En ambos grupos de SE de 2021, se observó un cambio sustancial en los patrones de internamiento y óbitos por COVID-19, con un aumento en el riesgo de internamiento y óbito en los más jóvenes no vacunados e importante reducción en los ancianos vacunados, sobre todo en aquellos con 60-69 años, además de una reducción global de 62% (IC95%: 52-69) y 63% (IC95%: 43-75) en las tasas de internamiento y óbitos, respectivamente. Nuestros resultados refuerzan la importancia de la vacunación en masa, especialmente en un contexto epidémico como el de Manaos, marcado por una elevada circulación de la variante Gamma.

Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project.

Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

Evaluation of the National Immunization Program Surveillance System - Vaccination Record Module, Brazil, 2017. / Avaliação do Sistema de Vigilância do Programa Nacional de Imunizações - Módulo Registro do Vacinado, Brasil, 2017.

OBJETIVO: To evaluate the National Immunization Program Immunization Surveillance System, based on its Vaccination Record module, for Brazil in 2017. METHODS: This was a descriptive study using the Guidelines for Evaluating Public Health Surveillance Systems, published by the Centers for Disease Control and Prevention (CDC/Atlanta/GA/United States) to evaluate the attributes of simplicity, flexibility, data quality, sensitivity, timeliness and usefulness of the system for six vaccines on the child immunization schedule. RESULTS: The Immunization Surveillance System was considered complex in its description; flexible to changes in the immunization schedule; of poor data quality for the DTP and rotavirus vaccines; regular acceptability; high sensitivity for the BCG vaccine; untimely for the hepatitis B vaccine and useful for the purposes of the National Immunization Program. CONCLUSION: The data quality, acceptability and timeliness results were not satisfactory, so that actions are needed to enhance the information system.

The Brazilian National Immunization Program: 46 years of achievements and challenges. / 46 anos do Programa Nacional de Imunizações: uma história repleta de conquistas e desafios a serem superados.

The Brazilian National Immunization Program (PNI, in Portuguese) is coordinated by the Ministry of Health in cooperation with state and municipal health departments. Since the program's creation in 1973, it has become one of the country's most relevant public health interventions, having produced important results such as certification of Brazil as free of wild poliovirus circulation, the elimination rubella virus circulation, and an important reduction in cases and deaths from vaccine-preventable diseases. Brazil is one of the countries that offers the most vaccines free of cost to the population, with 15 vaccines for children, 9 for adolescents, and 5 for adults and the elderly. The program's expansion and the maintenance of high vaccination coverage rates led to a rapid decrease in vaccine-preventable diseases, completely changing the epidemiological scenario of these diseases in Brazil in the last four decades. The country is currently witnessing an increasing share of the population without adequate vaccination. To the extent that these diseases are no longer circulating, precisely because of the high vaccination coverage rates, especially since the early 2000s, many of them are now unknown to the population. As a result, many people have no notion of the danger these diseases represent. We thus need to understand the multiple factors contributing to this decrease in coverage, which has created the risk of resurgence of serious diseases that had already been controlled or eliminated in Brazil.

O Programa Nacional de Imunizações (PNI), coordenado pelo Ministério da Saúde, de forma compartilhada com as secretarias estaduais e municipais de saúde, vem se consolidando como uma das principais e mais relevantes intervenções em saúde pública, com a conquista de resultados importantes, como a certificação de área livre da circulação do poliovírus selvagem, a eliminação da circulação do vírus da rubéola e pelo importante impacto na redução dos casos e mortes pelas doenças imunopreveníveis, a partir da sua criação em 1973. O Brasil é um dos países que oferece o maior número de vacinas, de forma gratuita, com 15 vacinas para crianças, 9 para os adolescentes, cinco para os adultos e idosos. A partir dessa expansão do programa e da manutenção de elevadas coberturas vacinais, foi possível observar o rápido impacto na diminuição das doenças imunopreveníveis, mudando completamente o cenário epidemiológico dessas doenças no país, ao longo destas últimas quatro décadas. Atualmente, o país vive um contexto em que aumenta a parcela da população sem vacinação adequada. Na medida em que as doenças passam a não circular mais, justamente porque se mantiveram elevadas coberturas vacinais principalmente a partir dos anos 2000, muitas doenças tornaram-se desconhecidas, fazendo com que algumas pessoas não tenham noção do perigo representado por elas. É necessário, portanto, entender os múltiplos fatores que estão contribuindo para essa diminuição, criando, dessa forma, o risco de ressurgimento de doenças graves já controladas ou eliminadas na população.

El Programa Nacional de Inmunizaciones de Brasil (PNI), coordinado por el Ministerio de la Salud, de forma compartida con Las secretarías estatales y municipales de salud, se ha consolidando como una de las principales y más relevantes intervenciones en salud pública, con la conquista de resultados importantes, como la certificación de área libre de la circulación del poliovirus salvaje, la eliminación de la circulación del virus de la rubeola, además de por el importante impacto en la reducción de los casos y muertes por enfermedades inmunoprevenibles, a partir de su creación en 1973. Brasil es uno de los países que ofrece el mayor número de vacunas, de forma gratuita, con 15 vacunas, 9 para adolescentes, 5 para adultos y ancianos. A partir de esta expansión del programa y del mantenimiento de elevadas coberturas de vacunación fue posible observar el rápido impacto en la disminución de las enfermedades inmunoprevenibles, cambiando completamente el escenario epidemiológico de esas enfermedades en el país, a lo largo de estas últimas cuatro décadas. Actualmente, el país vive un contexto en que aumenta la proporción de la población sin vacunación adecuada. A medida que las enfermedades pasan a no circular más, justamente porque se mantuvieron elevadas, principalmente a partir de la década del 2000, muchas enfermedades se convirtieron en desconocidas, provocando que algunas personas no tengan noción del peligro representado por ellas. Es necesario, por tanto, entender los múltiples factores que están contribuyendo a esta disminución, creando, de esta forma, el riesgo de resurgimiento de enfermedades graves ya controladas o eliminadas de la población.

Factors associated with severity of adverse events following yellow fever vaccination during the biggest outbreak of the disease recorded in Brazil, 2016-2017. / Fatores associados à gravidade dos eventos adversos pós-vacinação contra a febre amarela durante o maior surto da doença registrado no Brasil, 2016-2017.

OBJECTIVE: to analyze characteristics, incidence and factors associated with serious adverse events (SAEs) following yellow fever vaccination during an outbreak of the disease in Brazil (2016-2017). METHODS: this was a case-control study using data from the National Immunization Program Information System (SI-PNI); SAE were considered to be cases, and non-serious adverse events (NSAE) were considered to be controls. RESULTS: we analyzed 135 SAE cases and 1,058 controls; of the 135 SAE, 79 (58.5%) were males and median age was 28 years [09-49]; incidence in January 2017 reached 1.3 case per 100,000 vaccine doses administered; there was statistical association with males (Odds Ratio [OR]=1.73 - 95%CI 1.20;2.48), primary vaccination (OR=1.65 - 95%CI 1.01;2.71), and being 60 years of age or older taking as reference those aged under 5 (OR=4.4; p-value <0.02). CONCLUSION: SAE owing to yellow fever vaccine showed a greater chance of occurring in men, the elderly and primary vaccination.

Prevalence of human papillomavirus (HPV) in Brazil: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to estimate the prevalence of genital, anal and oral HPV infection in Brazil through systematic review and meta-analysis. METHODS: We searched EMBASE, LILACS, MEDLINE, Web of Science and SciELO from inception to December 2018. Original research articles that assessed the prevalence of genital (i.e., cervical, penile), anal and oral HPV infection in Brazil were selected in pairs by independent authors. No sex, age, HPV vaccination, language or date restrictions were applied. HPV prevalence was estimated and stratified according to risk factors population and by geographic area throughout the country. The study prevalence was pooled using a random effects model. Analysis was performed using R (version 3.5.2), packages meta version 4.9-4 and metaphor 2.0-0. This review is registered on PROSPERO under protocol number CRD42016032751. RESULTS: We identified 3,351 references. After the screening process, 139 of them were eligible for this systematic review (57,513 total participants). Prevalence of cervical HPV was 25.41% (95% CI 22.71-28.32). Additionally, prevalence was 36.21% (95% CI 23.40, 51.33) in the penile region, 25.68% (95%CI 14.64, 41.04) in the anal region, and 11.89% (95%CI 6.26, 21.43) in the oral region. Subgroup analysis showed prevalence in each anatomic site was higher in high-risk populations. CONCLUSION: The prevalence of HPV is high in the Brazilian population and varies by population risk and anatomic body site, with lower rates in the oral cavity compared to that in the cervical, penile and anal region. Studies on HPV have primarily been developed to evaluate infection and cancer in the cervical region. There is a profound lack of HPV data in many geographic regions of Brazil and for different anatomic sites.

Strategies for expanding childhood vaccination in the Americas following the COVID-19 pandemic / Estrategias para ampliar la vacunación infantil en la Región de las Américas después de la pandemia de COVID-19 / Estratégias para ampliar a vacinação infantil nas Américas depois da pandemia de COVID-19

[ABSTRACT]. Objective. To provide an overview of the status of the childhood vaccination schedule in the Americas, outline program structures, and identify updated implementation strategies to improve vaccination coverage following the COVID-19 pandemic. Methods. A group of experts in pediatrics, epidemiology, vaccines, and global and public health discussed the current status of the childhood vaccination schedule in the Americas, describing the program structure and identifying new implementation strategies that have the potential to improve vaccination coverage in the post-pandemic context, after the challenges COVID-19 presented for more than two years. Results. The Americas currently face a high risk of resurgence of diseases that were previously controlled or eliminated. Therefore, it is important to find new strategies to educate citizens on the risks associated with lower vaccination rates, especially in children. Conclusions. New strategies along with strong mobilization of the population and advocacy by citizens are necessary to prevent antivaccination groups from gaining a stronger presence in the region and jeopardizing the credibility of the Expanded Program on Immunization.

[RESUMEN]. Objetivo. Presentar un panorama general de la situación del calendario de vacunación infantil en la Región de las Américas, describir la estructura de los programas y encontrar estrategias actualizadas para su ejecución a fin de mejorar la cobertura de vacunación después de la pandemia de COVID-19. Métodos. Un grupo de expertos en pediatría, epidemiología, vacunas y salud pública y mundial analizó la situación actual del calendario de vacunación infantil en la Región de las Américas, mediante la descripción de la estructura de los programas y la búsqueda de nuevas estrategias de ejecución capaces de mejorar la cobertura de vacunación en el contexto posterior a la pandemia de COVID-19, una vez superados los desafíos planteados por esta durante más de dos años. Resultados. En este momento, en la Región de las Américas hay un riesgo alto de reaparición de enferme- dades previamente controladas o eliminadas. En consecuencia, es importante contar con nuevas estrategias para la educación de salud de la ciudadanía sobre los riesgos asociados a las tasas bajas de vacunación, especialmente en la población infantil. Conclusiones. Es necesario contar con nuevas estrategias, acompañadas de una fuerte movilización de la población y una promoción por parte de la ciudadanía, para evitar que los grupos que generan mensajes antivacunas aumenten su presencia en la Región y pongan en peligro la credibilidad del Programa Ampliado de Inmunización.

[RESUMO]. Objetivo. Apresentar um panorama da situação do calendário de vacinação infantil nas Américas, definir a estrutura do programa e identificar estratégias de implementação atualizadas para melhorar a cobertura vacinal depois da pandemia de COVID-19. Métodos. Um grupo de especialistas em pediatria, epidemiologia, vacinas e saúde pública e global discutiu a situação atual do calendário de vacinação infantil nas Américas, descrevendo a estrutura dos programas e identificando novas estratégias de implementação que poderiam melhorar a cobertura vacinal no contexto pós-pandemia, na sequência dos desafios impostos pela COVID-19 durante mais de dois anos. Resultados. Atualmente, as Américas enfrentam um grande risco de ressurgimento de doenças já controla- das ou eliminadas. Desse modo, é importante identificar novas estratégias para conscientizar os cidadãos sobre os riscos decorrentes da queda das taxas de vacinação, sobretudo em crianças. Conclusões. É necessário adotar novas estratégias, aliadas a uma forte mobilização da população e pro- moção da causa pelos cidadãos, a fim de impedir que os grupos antivacinas fortaleçam sua presença na região e coloquem em risco a credibilidade do Programa Ampliado de Imunização.

Strategies for expanding childhood vaccination in the Americas following the COVID-19 pandemic / Estrategias para ampliar la vacunación infantil en la Región de las Américas después de la pandemia de COVID-19 / Estratégias para ampliar a vacinação infantil nas Américas depois da pandemia de COVID-19

ABSTRACT Objective. To provide an overview of the status of the childhood vaccination schedule in the Americas, outline program structures, and identify updated implementation strategies to improve vaccination coverage following the COVID-19 pandemic. Methods. A group of experts in pediatrics, epidemiology, vaccines, and global and public health discussed the current status of the childhood vaccination schedule in the Americas, describing the program structure and identifying new implementation strategies that have the potential to improve vaccination coverage in the post-pandemic context, after the challenges COVID-19 presented for more than two years. Results. The Americas currently face a high risk of resurgence of diseases that were previously controlled or eliminated. Therefore, it is important to find new strategies to educate citizens on the risks associated with lower vaccination rates, especially in children. Conclusions. New strategies along with strong mobilization of the population and advocacy by citizens are necessary to prevent antivaccination groups from gaining a stronger presence in the region and jeopardizing the credibility of the Expanded Program on Immunization.

RESUMEN Objetivo. Presentar un panorama general de la situación del calendario de vacunación infantil en la Región de las Américas, describir la estructura de los programas y encontrar estrategias actualizadas para su ejecución a fin de mejorar la cobertura de vacunación después de la pandemia de COVID-19. Métodos. Un grupo de expertos en pediatría, epidemiología, vacunas y salud pública y mundial analizó la situación actual del calendario de vacunación infantil en la Región de las Américas, mediante la descripción de la estructura de los programas y la búsqueda de nuevas estrategias de ejecución capaces de mejorar la cobertura de vacunación en el contexto posterior a la pandemia de COVID-19, una vez superados los desafíos planteados por esta durante más de dos años. Resultados. En este momento, en la Región de las Américas hay un riesgo alto de reaparición de enfermedades previamente controladas o eliminadas. En consecuencia, es importante contar con nuevas estrategias para la educación de salud de la ciudadanía sobre los riesgos asociados a las tasas bajas de vacunación, especialmente en la población infantil. Conclusiones. Es necesario contar con nuevas estrategias, acompañadas de una fuerte movilización de la población y una promoción por parte de la ciudadanía, para evitar que los grupos que generan mensajes antivacunas aumenten su presencia en la Región y pongan en peligro la credibilidad del Programa Ampliado de Inmunización.

RESUMO Objetivo. Apresentar um panorama da situação do calendário de vacinação infantil nas Américas, definir a estrutura do programa e identificar estratégias de implementação atualizadas para melhorar a cobertura vacinal depois da pandemia de COVID-19. Métodos. Um grupo de especialistas em pediatria, epidemiologia, vacinas e saúde pública e global discutiu a situação atual do calendário de vacinação infantil nas Américas, descrevendo a estrutura dos programas e identificando novas estratégias de implementação que poderiam melhorar a cobertura vacinal no contexto pós-pandemia, na sequência dos desafios impostos pela COVID-19 durante mais de dois anos. Resultados. Atualmente, as Américas enfrentam um grande risco de ressurgimento de doenças já controladas ou eliminadas. Desse modo, é importante identificar novas estratégias para conscientizar os cidadãos sobre os riscos decorrentes da queda das taxas de vacinação, sobretudo em crianças. Conclusões. É necessário adotar novas estratégias, aliadas a uma forte mobilização da população e promoção da causa pelos cidadãos, a fim de impedir que os grupos antivacinas fortaleçam sua presença na região e coloquem em risco a credibilidade do Programa Ampliado de Imunização.

Trends and spatial distribution of MMR vaccine coverage in Brazil during 2007-2017.

We analyzed the time trends and spatial distribution of MMR vaccine coverage in Brazil during 2007-2017. In early 2018, a measles outbreak started in the North region of Brazil, reaching 11 of the 27 federal units by January 24, 2019. In this period, 10,302 cases were confirmed. Although the reintroduction of measles in Brazil is likely due to migration from Venezuela, the spread of the virus was made possible by the low levels of MMR coverage, as a result of significant decreases during the study period. Areas with high concentration of municipalities with low coverage are more susceptible to the spread of the virus, especially in the North and Northeast regions. Increasing vaccination coverage is essential to block the ongoing outbreak in Brazil. Vaccination strategies might target priority areas, especially those with a marked decrease in coverage. Moreover, it is essential to extend actions to travelers, migrants and refugees.

Vaccination coverage in children in the period before and during the COVID-19 pandemic in Brazil: a time series analysis and literature review

Abstract Objective: To evaluate the behavior of VCR and VCH, per municipality and per vaccines offered at the NVC, to identify priority areas for intervention. Methods: Descriptive study of a time series, using secondary data and accompanied by a narrative review of the literature evaluating VCR and VCH. Vaccines offered to children under one year and to those aged one year in the pre-pandemic period of COVID-19 (2015 to 2019) were selected and compared to those offered during the pandemic period (2020 and 2021 ). Results and discussions: The decrease in VCR and VCH is a process that precedes the COVID-19 pandemic but was intensified during this period. In 2021, the VCR was around 70% for most vaccines. This phenomenon encompasses the entire country; however, it is more intense in the states/municipalities located in the north and northeast regions, suggesting greater difficulty in accessing health services. Conclusion: Low and heterogeneous VCR requires the adoption of practices that were previously implemented, establishing partnerships with governmental and non-governmental institutions, with adequate communication, active search for non-compliance and non-adherence to the regular vaccination program, adopting intra- and extramural vaccination strategies, to reverse the current situation and reduce the risk of recurrence of diseases that have been already controlled and eliminated.

[Anaphylaxis related to measles, mumps, and rubella vaccine in Santa Catarina State, Brazil, 2014 and 2015]. / Anafilaxia relacionada à vacina sarampo, caxumba e rubéola, Santa Catarina, Brasil, 2014 e 2015.

The study aimed to describe cases and verify the frequency of anaphylaxis related to measles, mumps, and rubella (MMR) vaccine produced by manufacturer A and to assess associated risk factors. This was a case-control study (1:4) in Santa Catarina State, Brazil, from July 14, 2014, to January 12, 2015, in children from one year to less than five years of age, vaccinated with MMR and reported with anaphylaxis, while the controls were without anaphylaxis. The measure of association was odds ratio (OR) with 95% confidence interval (95%CI), using the chi-square and Fisher's exact tests. Anaphylaxis rates were calculated per doses distributed/administered. Fifteen cases and 60 controls were interviewed in 12 municipalities (counties). Anaphylaxis rates were 2.46 and 5.05 cases per 100,000 doses distributed and administered, respectively. Among the cases of anaphylaxis, eight (53.4%) were males, and among the controls, 36 (60%), with p = 0.64. The bivariate analysis of anaphylaxis and cow's milk protein allergy (CMPA) showed OR = 51.62, with p = 0.00002 and 95%CI: 5.59-476.11. The variables family food allergy, breastfeeding, previous post-vaccine adverse event (PVAE), and simultaneous vaccination were not statistically significant (p = 0.48; p = 1.00; p = 0.49; p = 0.61). Anaphylaxis rates per doses distributed/administered exceeded 1/100,000 doses administered (expected rate). Anaphylaxis and CMPA showed a statistically significant association. No statistically significant associations were found with simultaneous vaccination, breastfeeding, family food allergy, or history of PVAE. RECOMMENDATIONS: the manufacturer should specify the product's components in the package insert, and children with a history of CMPA should not be vaccinated with this vaccine.

Os objetivos consistiram em descrever os casos e verificar a frequência de anafilaxia relacionada à vacina sarampo, caxumba e rubéola (SCR) do produtor A, bem como avaliar os possíveis fatores de risco associados. Estudo de caso-controle (1:4), em Santa Catarina, Brasil, de 14 de julho de 2014 a 12 de janeiro de 2015, em crianças de um a menores de cinco anos, vacinadas com SCR e notificadas com anafilaxia, sendo os controles sem anafilaxia. Utilizou-se, como medida de associação, odds ratio (OR) com intervalo de 95% de confiança (IC95%) e os testes qui-quadrado e exato de Fisher. Calcularam-se taxas de anafilaxia por doses distribuídas/aplicadas. Entrevistaram-se 15 casos e 60 controles, em 12 municípios. As taxas de anafilaxia foram 2,46 e 5,05 por doses distribuídas e aplicadas, respectivamente. Dentre os casos de anafilaxia, oito (53,4%) eram do sexo masculino, e dentre os controles, 36 (60%), com p = 0,64. Na análise bivariada referente à anafilaxia e alergia à proteína do leite de vaca (APLV), verificou-se OR = 51,62, com p = 0,00002 e IC95%: 5,59-476,11. As variáveis alergia alimentar familiar, aleitamento materno, evento adverso pós-vacinação (EAPV) anterior e vacinação simultânea não foram estatisticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Taxas de anafilaxia por doses distribuídas/aplicadas ficaram acima de 1/100 mil doses aplicadas (taxa esperada). Anafilaxia e APLV apresentaram associação estatisticamente significativa. Não foram encontradas associações estatísticas referentes à vacinação simultânea, aleitamento materno, alergia alimentar familiar e EAPV anterior. Recomendou-se ao produtor informar na bula todos os componentes do produto e que crianças com história pregressa de APLV não sejam vacinadas com essa vacina.

Los objetivos consistieron en describir los casos y verificar la frecuencia de anafilaxia, relacionada con la vacuna del sarampión, paperas y rubeola (SCR) del productor A, así como evaluar los posibles factores de riesgo asociados. Estudio de caso-control (1:4), en Santa Catarina, Brasil, de 14 de julio de 2014 a 12 de enero de 2015, en niños de uno a menores de cinco años, vacunadas con SCR y notificadas con anafilaxia, siendo los controles sin anafilaxia. Se utilizó, como medida de asociación, odds ratio (OR) con un intervalo de 95% de confianza (IC95%) y los testes chi-cuadrado y exacto de Fisher. Se calcularon las tasas de anafilaxia por dosis distribuidas/aplicadas. Se entrevistaron 15 casos y 60 controles, en 12 municipios. Las tasas de anafilaxia fueron 2,46 y 5,05 por dosis distribuidas y aplicadas, respectivamente. Entre los casos de anafilaxia, ocho (53,4%) eran del sexo masculino, y entre los controles, 36 (60%), con p = 0,64. En el análisis bivariado referente a la anafilaxia y alergia a la proteína de leche de vaca (APLV), se verificó OR = 51,62, con p = 0,00002 e IC95%: 5,59-476,11. Las variables alergia alimentaria familiar, lactancia materna , evento adverso pos-vacunación (EAPV) anterior y vacunación simultánea no fueron estadísticamente significativas (p = 0,48; p = 1,00; p = 0,49; p = 0,61). Tasas de anafilaxia por dosis distribuidas/aplicadas se situaron encima de 1/100.000 dosis aplicadas (tasa esperada). Anafilaxia y APLV presentaron una asociación estadísticamente significativa. No fueron encontradas asociaciones estadísticas referentes a la vacunación simultánea, lactancia materna, alergia alimentaria familiar y EAPV anterior. Se recomendó al productor informar en el prospecto sobre todos los componentes del producto, y que los niños con historial anterior de APLV no sean vacunados con esa vacuna.

Mudanças no padrão de internações e óbitos por COVID-19 após substancial vacinação de idosos em Manaus, Amazonas, Brasil / Changes in the pattern of COVID-19 hospitalizations and deaths after substantial vaccination of the elderly in Manaus, Amazonas State, Brazil / Cambios en el patrón de internamientos y óbitos por COVID-19 tras una elevada vacunación de ancianos en Manaos, Amazonas, Brasil

A avaliação do impacto da vacinação contra a COVID-19 em idosos é escassa, sobretudo em um cenário com predomínio da variante Gama. O objetivo deste estudo foi avaliar a cobertura vacinal e sua relação com mudanças no padrão de internações e óbitos por COVID-19 em idosos de Manaus, Amazonas, Brasil. Este é um estudo ecológico com dados de internações e óbitos do Ministério da Saúde que avaliou a cobertura vacinal, mediante esquema com duas doses, além de dois regimes de vacinação associados a significativo efeito protetor, um parcial (35 ou mais dias após a primeira dose da vacina Oxford/AstraZeneca) e outro completo (14 dias ou mais após a segunda dose da vacina Sinovac-CoronaVac). A partir da data dos primeiros sintomas, padrões de internação e óbito por COVID-19 foram avaliados, comparativamente, em idosos de 60-69 e de 70 anos ou mais, em dois grupos de Semanas Epidemiológicas (SE) de 2020 (não vacinados) e 2021 (vacinados). Taxas de internação e óbito foram estimadas pelo modelo Poisson. Entre 60-69 anos e naqueles com 70 anos ou mais, a cobertura por vacina foi 41,8% e 54,8%, bem como 53,5% e 90,1% nos grupos de SE 18-20/2021 e 21-23/2021, respectivamente. Em ambos os grupos de SE de 2021, observou-se substancial mudança nos padrões de internações e óbitos por COVID-19, com aumento no risco de internação e óbito nos mais jovens não vacinados, e importante redução no número de idosos vacinados, sobretudo naqueles com 60-69 anos, além de redução global de 62% (IC95%: 52-69) e 63% (IC95%: 43-75) nas taxas de internação e óbitos, respectivamente. Nossos resultados reforçam a importância da vacinação em massa, especialmente em contexto epidêmico como o de Manaus, marcado por elevada circulação da variante Gama.

The impact of COVID-19 vaccination in the elderly has received relatively little attention, particularly in a scenario predominated by the gamma variant. The aim of this study was to assess vaccination coverage and its relationship to changes in the pattern of COVID-19 hospitalizations and deaths in the elderly in Manaus, Amazonas State, Brazil. This was an ecological study with Brazilian Ministry of Health data on hospitalizations and deaths, assessing vaccination coverage based on a two-dose regimen, in addition to two vaccination regimens associated with a significant protective effect, one partial (35 days or more after the first dose of the Oxford/AstraZeneca vaccine) and the other complete (14 days or more after the second dose of the Sinovac-CoronaVac vaccine). Based on the date of initial symptoms, patterns of COVID-19 hospitalizations and deaths were assessed comparatively in elderly 60-69 years and 70 years or more in two groups of Epidemiological Weeks (EW) in 2020 (unvaccinated) and 2021 (vaccinated). Hospitalization and death rates were estimated with Poisson regression. In the groups 60-69 and 70 years or more, vaccination coverage rates were 41.8% and 54.8%, as well as 53.5% and 90.1%, in the EW groups 18-20/2021 and 21-23/2021, respectively. Both EW groups in 2021 showed a substantial change in the patterns of COVID-19 hospitalizations and deaths, with an increase in the risk of hospitalization and death in unvaccinated younger individuals and an important reduction in vaccinated elderly, especially those 60-69 years of age, besides overall reductions of 62% (95%CI: 52-69) and 63% (95%CI: 43-75) in hospitalization and death rates, respectively. Our results emphasize the importance of mass vaccination, especially during an epidemic such as in Manaus, marked by high circulation of the gamma variant.

La evaluación del impacto de la vacunación contra la COVID-19 en ancianos es escasa, sobre todo en un escenario con predominio de la variante Gamma. El objetivo de este estudio fue evaluar la cobertura de vacunación y su relación con cambios en el patrón de internamientos y óbitos por COVID-19 en ancianos de Manaos, Amazonas, Brasil. Este es un estudio ecológico con datos de internamientos y óbitos del Ministerio de Salud, que evaluó la cobertura de vacunación, mediante un esquema con dos dosis, además de dos regímenes de vacunación, asociados a un significativo efecto protector, uno parcial (35 o más días tras la primera dosis de la vacuna Oxford/AstraZeneca) y otro completo (14 días o más tras la segunda dosis de la vacuna Sinovac-CoronaVac). A partir de los datos de los primeros síntomas, se evaluaron patrones de internamiento y óbito por COVID-19, comparativamente, en ancianos de 60-69 y de 70 años o más, en dos grupos de Semanas Epidemiológicas (SE) de 2020 (no vacunados) y 2021 (vacunados). Se estimaron tasas de internamiento y óbito mediante el modelo Poisson. Entre 60-69 años y en aquellos con 70 años o más, la cobertura por vacuna fue 41,8% y 54,8%, así como 53,5% y 90,1% en los grupos de SE 18-20/2021 y 21-23/2021, respectivamente. En ambos grupos de SE de 2021, se observó un cambio sustancial en los patrones de internamiento y óbitos por COVID-19, con un aumento en el riesgo de internamiento y óbito en los más jóvenes no vacunados e importante reducción en los ancianos vacunados, sobre todo en aquellos con 60-69 años, además de una reducción global de 62% (IC95%: 52-69) y 63% (IC95%: 43-75) en las tasas de internamiento y óbitos, respectivamente. Nuestros resultados refuerzan la importancia de la vacunación en masa, especialmente en un contexto epidémico como el de Manaos, marcado por una elevada circulación de la variante Gamma.