Description of vaccination coverage and hesitancy obtained by epidemiological survey of children born in 2017-2018, in Belo Horizonte and Sete Lagoas, Minas Gerais, Brazil.

OBJECTIVE: To describe vaccination coverage and hesitation for the basic children's schedule in Belo Horizonte and Sete Lagoas, Minas Gerais state, Brazil. METHODS: Population-based epidemiological surveys performed from 2020 to 2022, which estimated vaccine coverage by type of immunobiological product and full schedule (valid and ministered doses), according to socioeconomic strata; and reasons for vaccination hesitancy. RESULTS: Overall coverage with valid doses and vaccination hesitancy for at least one vaccine were, respectively, 50.2% (95%CI 44.1;56.2) and 1.6% (95%CI 0.9;2.7), in Belo Horizonte (n = 1,866), and 64.9% (95%CI 56.9;72.1) and 1.0% (95%CI 0.3;2.8), in Sete Lagoas (n = 451), with differences between socioeconomic strata. Fear of severe reactions was the main reason for vaccination hesitancy. CONCLUSION: Coverage was identified as being below recommended levels for most vaccines. Disinformation should be combated in order to avoid vaccination hesitancy. There is a pressing need to recover coverages, considering public health service access and socioeconomic disparities. MAIN RESULTS: Vaccination coverage of children up to 4 years old was 50.2% in Belo Horizonte, and 64.9% in Sete Lagoas. Fear of severe reactions and believing that vaccination against eradicated diseases is unnecessary were the main reasons for vaccination hesitancy. IMPLICATIONS FOR SERVICES: Recovery of high vaccination coverage among children, considering public health service access conditions and socioeconomic inequities. Acting on reasons for hesitancy that can assist in targeting actions. PERSPECTIVES: The multifactorial context of vaccination hesitancy demands the development of health education strategies to raise awareness about child immunization.

Efficacy and safety of Butantan-DV in participants aged 2-59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil.

BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

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.

Serotype Distribution and Antimicrobial Susceptibility Pattern of Streptococcus pneumoniae in COVID-19 Pandemic Era in Brazil.

Despite the introduction of the pneumococcal vaccine, Streptococcus pneumoniae remains a cause of invasive diseases in Brazil. This study provides the distribution of serotypes and antimicrobial susceptibility patterns for pneumococcal isolates before and during the years of the COVID-19 pandemic in two age groups, <5 and ≥50 years. This is a national laboratory-based surveillance study that uses data from the Brazilian national laboratory for invasive S. pneumoniae from the pre-COVID-19 (January 2016 to January 2020) and COVID-19 (February 2020 to May 2022) periods. Antimicrobial resistance was evaluated by disk diffusion and minimum inhibitory concentration. The year 2020 was marked by a 44.6% reduction in isolates received and was followed by an upward trend from 2021 onwards, which became evident in 2022. No differences were observed in serotypes distribution between the studied periods. The COVID-19 period was marked by the high prevalence of serotypes 19A, 3, and 6C in both age groups. Serotypes 19A and 6C were related to non-antimicrobial susceptibility. We observed a reduction in S. pneumoniae, without changes in serotypes distribution and epidemiological capsular switch during the COVID-19 period. We observed elevated resistance rates, mainly to penicillin and ceftriaxone for non-meningitis cases in children under 5 years of age.

Description of vaccination coverage and hesitancy obtained by epidemiological survey of children born in 2017-2018, in Belo Horizonte and Sete Lagoas, Minas Gerais, Brazil / Descripción de la cobertura de vacuna y de las vacunaciones obtenidas por la encuesta epidemiológica de niños nacidos en 2017-2018, en Belo Horizonte y Sete Lagoas, Minas Gerais / Descrição da cobertura e da hesitação vacinal obtida por inquérito epidemiológico de crianças nascidas em 2017-2018, em Belo Horizonte e Sete Lagoas, Minas Gerais

ABSTRACT Objective To describe vaccination coverage and hesitation for the basic children's schedule in Belo Horizonte and Sete Lagoas, Minas Gerais state, Brazil. Methods Population-based epidemiological surveys performed from 2020 to 2022, which estimated vaccine coverage by type of immunobiological product and full schedule (valid and ministered doses), according to socioeconomic strata; and reasons for vaccination hesitancy. Results Overall coverage with valid doses and vaccination hesitancy for at least one vaccine were, respectively, 50.2% (95%CI 44.1;56.2) and 1.6% (95%CI 0.9;2.7), in Belo Horizonte (n = 1,866), and 64.9% (95%CI 56.9;72.1) and 1.0% (95%CI 0.3;2.8), in Sete Lagoas (n = 451), with differences between socioeconomic strata. Fear of severe reactions was the main reason for vaccination hesitancy. Conclusion Coverage was identified as being below recommended levels for most vaccines. Disinformation should be combated in order to avoid vaccination hesitancy. There is a pressing need to recover coverages, considering public health service access and socioeconomic disparities.

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RESUMO Objetivo Descrever as coberturas e hesitação das vacinas do calendário básico infantil em Belo Horizonte e Sete Lagoas, Minas Gerais. Métodos Inquéritos epidemiológicos de base populacional realizados de 2020 a 2022, para estimar coberturas vacinais por tipo de imunobiológico e esquema completo (doses válidas e aplicadas) segundo estratos socioeconômicos, e os motivos de hesitação vacinal. Resultados A cobertura global com doses válidas e a hesitação vacinal de pelo menos uma vacina foram, respectivamente, de 50,2% (IC95% 44,1;56,2) e 1,6% (IC95% 0,9;2,7), em Belo Horizonte (n = 1.866), e de 64,9% (IC95% 56,9;72,1) e 1,0% (IC95% 0,3;2,8), em Sete Lagoas (n = 451), com diferenças entre os estratos. O receio de reações graves foi o principal motivo de hesitação vacinal. Conclusão Identificou-se coberturas abaixo do preconizado para a maioria das vacinas. A desinformação deve ser combatida, evitando-se a hesitação vacinal. Há necessidade premente de recuperar as coberturas, considerando acesso ao SUS e disparidades socioeconômicas.

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 / Desigualdades raciales en la vacunación infantil y obstáculos para la vacunación en Brazil entre nacidos vivos en 2017 y 2018: análisis de uma cohorte retrospectiva de los dos primeros años de vida / Desigualdades raciais na vacinação infantil e nos obstáculos à vacinação no Brasil entre nascidos vivos em 2017 e 2018: análise de uma coorte retrospectiva dos dois primeiros anos de vida

ABSTRACT 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.

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RESUMO Objetivo Descrever a completude vacinal em tempo oportuno nos primeiros 24 meses de vida no Brasil e os obstáculos para vacinação, testando-se associações com raça/cor da pele materna. Métodos Fez-se coleta de informações sobre os nascidos em 2017 e 2018, constantes no Inquérito Nacional de Cobertura Vacinal. Foram calculados prevalência e intervalos de confiança de 95% de obstáculos à vacinação e completude vacinal em tempo oportuno aos 5 meses, primeiro e segundo ano, segundo raça/cor da pele materna. Empregou-se regressão logística para análise de associações. Resultados Analisaram-se dados de 37.801 crianças. Do total, 7,2% (IC95% 6,3;8,2) dos responsáveis enfrentaram dificuldades para levar seus filhos para vacinação e 23,4% (IC95% 21,7;25,1) das crianças não foram vacinadas, mesmo sendo levadas. Essas proporções foram 75% (IC95% 1,25;2,45) e 97% (IC95% 1,57;2,48) mais elevadas, respectivamente, entre pretas; e 49,9% (IC95% 47,8;51,9) e 61,1% (IC95% 59,2;63,0) das crianças tiveram atraso em alguma vacina até os 5 meses e o primeiro ano, respectivamente. Tais valores foram maiores entre pardas/pretas. Conclusão Há desigualdades raciais nos obstáculos enfrentados e na vacinação no Brasil.

Risks of low vaccination coverage and strategies to prevent the resurgence of vaccine-preventable diseases in infants in the COVID-19 pandemic scenario: recommendations for Latin America and the Caribbean by the group of experts on infant immunization for Latin America.

INTRODUCTION: The WHO 2030 Immunization Agenda (IA-2030) harmonizes immunization activity plans at community, national, regional and global levels. Additionally, medical societies play an important role. The Latin American Group of Experts on Infant Immunization, established in 2018, advises on the harmonization, update, and optimization of infant vaccination programs in Latin America and the Caribbean (LAC). In September 2021, 41 such experts from 13 LAC countries met to develop recommendations for increasing regional vaccination coverage to avoid the reemergence of vaccine-preventable diseases and/or the occurrence of outbreaks. AREAS COVERED: The following items were evaluated: (i) immunization challenges before and during the COVID-19 pandemic; (ii) the status of current immunization programs, particularly infant pertussis and polio vaccination; (iii) possible solutions for overcoming vaccination challenges and achieving regional vaccination coverage targets. EXPERT OPINION/COMMENTARY: Medical societies provide valuable recommendations to guide and update vaccination schedules. In the LAC region, possible strategies to achieve target vaccination rates include the use of combination vaccines, strengthening surveillance systems, improving school attendance, advancing vaccine education and confidence, striving for vaccination equity, widening operational capacity, creating strategic alliances, and strengthening the role of medical groups. It is hoped that these recommendations will be implemented in the LAC region.

National Vaccine Coverage Survey 2020: methods and operational aspects.

OBJECTIVE: The national vaccination coverage survey on full vaccination at 12 and 24 months of age was carried out to investigate drops in coverage as of 2016. METHODS: A sample of 37,836 live births from the 2017 or 2018 cohorts living in capital cities, the Federal District, and 12 inner cities with 100 thousand inhabitants were followed for the first 24 months through vaccine record cards. Census tracts stratified according to socioeconomic levels had the same number of children included in each stratum. Coverage for each vaccine, full vaccination at 12 and 24 months and number of doses administered, valid and timely, were calculated. Family, maternal and child factors associated with coverage were surveyed. The reasons for not vaccinating analyzed were: medical contraindications, access difficulties, problems with the program, and vaccine hesitancy. RESULTS: Preliminary results showed that less than 1% of children were not vaccinated, full coverage was less than 75% at all capitals and the Federal District, vaccines requiring more than one dose progressively lost coverage, and there were inequalities among socioeconomic strata, favorable to the highest level in some cities and to the lowest in others. CONCLUSION: There was an actual reduction in full vaccination in all capitals and the Federal District for children born in 2017 and 2018, showing a deteriorating implementation of the National Immunization Program from 2017 to 2019. The survey did not measure the impacts of the COVID-19 pandemic, which may have further reduced vaccination coverage.

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.

Prevalence, Risk Factors and Vaccine Response against Hepatitis B in People Aged 50 Years or Older.

Universal immunization against hepatitis B has contributed to reducing incidence of the disease, but older individuals remain susceptible to acquiring the hepatitis B virus worldwide. Thus, this study aimed to investigate the epidemiology of HBV infection in individuals aged 50 years and over in central Brazil and to evaluate the immunogenicity of the monovalent vaccine against hepatitis B in this age group using two vaccine regimens. METHOD: Initially, a cross-sectional and analytical study was carried out to investigate the epidemiology of hepatitis B. Then, individuals without proof of vaccination for hepatitis B were recruited for a phase IV randomized and controlled clinical trial using two vaccine regimens: Intervention Regimen (IR) (three doses of 40 µg at months 0, 1 and 6) vs. Comparison Regimen (CR) (three doses of 20 µg at months 0, 1 and 6). RESULTS: The overall prevalence of exposure to HBV was 16.6% (95% CI: 14.0%-9.5%). In the clinical trial, statistical differences in protective titers were observed (p = 0.007; IR 96% vs. CR 86%) and the geometric mean of anti-HBs titers was higher in individuals who received the IR (518.2 mIU/mL vs. 260.2 mIU/mL). In addition, the proportion of high responders was higher among those who received the IR (65.3%). CONCLUSION: reinforced doses should be used in individuals aged 50 years or older to overcome the lower efficacy of the vaccine against hepatitis B.

Characteristics and clinical outcomes of COVID-19 in children: a hospital-based surveillance study in Latin America's hardest-hit city.

Background: In 2020, Brazil became the epicentre of the coronavirus disease (COVID-19) pandemic in Latin America, resulting in an unparalleled health catastrophe. Nevertheless, comprehensive clinical reports in Brazilian children are not available. Methods: This retrospective, hospital-based, active surveillance study was performed to identify paediatric patients with COVID-19 who presented at a private academic medical centre in a large urban area between March 2020 and March 2021. Clinical and demographic information was analysed for those requiring hospitalization, those with severe illness and those with clinical syndromes. Results: In total, 964 symptomatic cases were evaluated; of these, 17.7% required hospitalization, and 27.5% of hospitalized cases were classified as severe/critical. Acute bronchiolitis and pneumonia were the most common causes of hospitalization among the severe cases. Twenty-seven hospitalized children fulfilled the diagnostic criteria for multi-system inflammatory syndrome (median age 29 months; 85.2% cases were non-severe). A significant co-existing condition was present in 29% of hospitalized children. The risk of hospitalization was higher in children with at least one comorbidity, children aged <2 years and obese children. Increased risk of severe disease was described among those with leukopenia, leukocytosis or any significant comorbidity. No deaths occurred among the study population. Conclusion: Although most children with COVID-19 experienced mild disease, and no deaths occurred among the study population, a significant proportion of cases required hospitalization and developed severe illness. Obesity, young age, underlying comorbidity, leukopenia and leukocytosis were risk factors for hospitalization or severe disease.

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.

National Vaccine Coverage Survey 2020: methods and operational aspects / Inquérito Nacional de Cobertura Vacinal 2020: métodos e aspectos operacionais

ABSTRACT Objective: The national vaccination coverage survey on full vaccination at 12 and 24 months of age was carried out to investigate drops in coverage as of 2016. Methods: A sample of 37,836 live births from the 2017 or 2018 cohorts living in capital cities, the Federal District, and 12 inner cities with 100 thousand inhabitants were followed for the first 24 months through vaccine record cards. Census tracts stratified according to socioeconomic levels had the same number of children included in each stratum. Coverage for each vaccine, full vaccination at 12 and 24 months and number of doses administered, valid and timely, were calculated. Family, maternal and child factors associated with coverage were surveyed. The reasons for not vaccinating analyzed were: medical contraindications, access difficulties, problems with the program, and vaccine hesitancy. Results: Preliminary results showed that less than 1% of children were not vaccinated, full coverage was less than 75% at all capitals and the Federal District, vaccines requiring more than one dose progressively lost coverage, and there were inequalities among socioeconomic strata, favorable to the highest level in some cities and to the lowest in others. Conclusion: There was an actual reduction in full vaccination in all capitals and the Federal District for children born in 2017 and 2018, showing a deteriorating implementation of the National Immunization Program from 2017 to 2019. The survey did not measure the impacts of the COVID-19 pandemic, which may have further reduced vaccination coverage.

RESUMO Objetivo: Inquérito nacional de cobertura vacinal aos 12 e 24 meses de idade foi realizado para investigar as quedas nas coberturas a partir de 2016. Métodos: Amostra de 37.836 nascidos vivos das coortes de 2017 e 2018 residentes nas capitais, Distrito Federal (DF) e 12 cidades com mais de 100 mil habitantes, acompanhados nos primeiros 24 meses por registros nas cadernetas de vacinação. Setores censitários foram estratificados segundo condições socioeconômicas, e o mesmo número de crianças foi incluído para cada estrato. Calcularem-se coberturas vacinais de cada vacina e coberturas completas aos 12 e 24 meses, doses aplicadas, válidas e oportunas. Fatores familiares, maternos e da criança associados à cobertura foram pesquisados. Os motivos para não vacinar analisados foram: contraindicações médicas, dificuldades de acesso, problemas no funcionamento do programa e hesitação vacinal. Resultados: Os resultados preliminares mostram que menos de 1% das crianças não foram vacinadas, as coberturas pelo esquema completo são menores que 75% em todas as capitais e no DF, as vacinas com mais de uma dose perdem cobertura progressivamente, há diferenças entre os estratos socioeconômicos, favoráveis aos estratos mais altos em algumas cidades e aos estratos mais baixos em outras. Conclusão: Houve realmente redução da cobertura vacinal em todas as capitais e no DF para as crianças nascidas em 2017 e 2018, denotando piora na execução do Programa Nacional de Imunizações durante os anos de 2017 a 2019. O inquérito realizado não mensurou os impactos da pandemia de COVID-19 que podem ter reduzido ainda mais as coberturas vacinais.

Assessing the best time interval between doses in a two-dose vaccination regimen to reduce the number of deaths in an ongoing epidemic of SARS-CoV-2.

The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals. Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. By maintaining the minimum stock of vaccines under a given production rate, we evaluate the dose interval that minimizes the number of deaths. We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to vaccinate the second dose as soon as possible, while for high first-dose efficacy, the best strategy of time window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the best window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.

Emergence of Neisseria meningitidis W South American sublineage strain variant in Brazil: disease and carriage.

Introduction. Invasive meningococcal disease is a major health problem, impacting morbidity and mortality worldwide. Exploratory genomics has revealed insights into adaptation, transmissibility and virulence to elucidate endemic, outbreaks or epidemics caused by Neisseria meningitidis serogroup W (MenW) strains.Gap Statement. Limited information on the genomics of Neisseria meningitis serogroup W ST11/cc11 is available from emerging countries, especially in contemporary isolates.Aim. To (i) describe the antigenic diversity and distribution of genetic lineages of N. meningitidis serogroup W circulating in Brazil; (ii) study the carriage prevalence of hypervirulent clones in adolescents students and (iii) analyse the potential risk factors for meningococcal carriage.Methodology. Using whole-genome sequencing, we analysed the genomic diversity of 92 invasive N. meningitidis serogroup W isolates circulating in Brazil from 2016 to 2019. A cross-sectional survey of meningococcal carriage was conducted in 2019, in the city of Florianópolis, Brazil, among a representative sample of 538 students.Results. A predominance (58.5 %, 41/82) of ST11/cc11 presenting PorB2-144, PorA VR1-5, VR2-2, FetA 1-1, and a novel fHbp peptide 1241 was found on invasive N. meningitidis W isolates, on the other hand, a high diversity of clonal complexes was found among carriage isolates. The overall carriage rate was 7.5 % (40/538). A total of 28 of 538 swab samples collected were culture positive for N. meningitidis, including four serogroup/genogroup B isolates (14.8 %;4/27), 1 serogroup/genogroup Y isolate (3.7 %;1/27), 22 (81.5 %; 22/27) non-groupable isolates. No MenW isolate was identified among carriages isolates.Conclusion. This report describes the emergence of the new MenW ST11/cc11 South America sublineage variant, named here, 2016 strain, carrying a novel fHbp peptide 1241, but its emergence, was not associated with an increased MenW carriage prevalence. Continuous surveillance is necessary to ascertain the role of this sublineage diversification and how its emergence can impact transmission.

A case-control study to determine the effectiveness of a tetravalent dengue vaccine in the state of Paraná, Brazil.

Background: The Brazilian state of Paraná conducted a mass vaccination campaign against dengue with the tetravalent attenuated vaccine CYD-TDV. The campaign targeted thirty endemic municipalities. The objective of this study was to assess the effectiveness of CYD-TDV in preventing symptomatic virologically confirmed dengue cases according to specific age groups in five of the municipalities. Methods: A case-control study was carried out in the five most populous municipalities targeted by the vaccination, with a vaccine uptake of 25%. Symptomatic dengue cases were identified by the municipal health departments. The age groups targeted were 15-18 and 19-27 in four municipalities and 9-14 and 28-44 in one municipality. All cases were confirmed by real time reverse transcription quantitative polymerase chain reaction (RT-qPCR). For each case, two controls were selected: a neighbourhood control and a workplace or school/college control, matched by age group. A conditional logistic regression model was used to determine the odds ratio for vaccination and the vaccine effectiveness. Findings: Study participants included 618 RT-qPCR-confirmed dengue cases and 1,236 matched controls (with a non-reactive dengue IgM serologic test). Vaccine effectiveness against dengue due to any serotype was 11·1% (95% CI: -19·0%; 33·6%). Effectiveness against DENV-1 was 33·3% (95% CI: -5·0%; 57·6%) and against DENV-2 was -56·7% (95% CI: -142·2%; -5·0%). No DENV-3 was detected. The vaccine was significantly effective in the prevention of DENV-4 cases (VE = 93·3%; 95% CI: 47·7%; 99·2%). Interpretation: CYD-TDV was effective in the prevention of symptomatic cases due to DENV-4, but not due to any serotype. The low dengue seroprevalence in the target population could possibly be related to these results. Funding: This study was supported through a grant to the Sabin Vaccine Institute from Sanofi-Pasteur. Sanofi-Pasteur had no role in the study design, protocol development, data collection, analysis, or publication of results.

PREVALENCE OF NEUTRALIZING ANTIBODIES AGAINST POLIOVIRUS 1, 2, AND 3 IN HEALTHCARE PROFESSIONALS AGED 20-50 YEARS.

OBJECTIVE: To describe the prevalence of neutralizing antibodies against poliovirus (PV1, PV2, and PV3) in blood samples of healthcare professionals aged 20 to 50 years. METHODS: Health professionals who serve children at Darcy Vargas Children's Hospital and the Department of Pediatrics of Irmandade da Santa Casa de São Paulo. The sample size was calculated at 323 participants. The Mantel-Haenszel chi-square was used to verify differences between groups. The neutralization reaction detected human poliovirus antibodies. For susceptible individuals, vaccination with the inactivated+triple acellular polio vaccine was performed, and neutralizing antibodies were re-dosed after one week. RESULTS: 333 professionals were studied - 92.8% were immune to poliovirus 1, 86.5% to poliovirus 2, and 63.3% to poliovirus 3; 37% had titers less than 1:8 for any serotype, 5;1% had titers below 1:8 for all three. Vaccination with inactivated polio vaccine was performed for susceptible participants, and neutralizing antibodies were dosed after one week, showing increased titers for all polioviruses. CONCLUSIONS: Despite the detection of a significant percentage of individuals with low poliovirus antibody titer, the challenge with vaccination demonstrated immune response compatible with poliovirus immunity.

Topical Oxygen Jet Therapy (TOJT) for treating infected chronic surgical wounds.

OBJECTIVES: To evaluate the effectiveness of Topical Oxygen Jet Therapy (TOJT) in the treatment of surgical wounds in adult patients who has clinical signs of infection for over 30 days; and to identify the pathogens causing complicated skin and soft tissue infections. METHOD: Parallel, randomized clinical trials randomly divided into "Control Group" (CG) and "Treatment Group" (TG), which were followed up for 10 consecutive days. Venous antibiotics and dressings were used in both groups. In addition, TOJT were used on the wounds in the TG. The outcome criteria were based on clinical indicators: Pressure Ulcer Scale for Healing (PUSH) and Visual Analog Scale Pain (VAS). The paired t-test or Wilcoxon, chi-squared or Fisher's exact test, and Student's t-test or Mann-Whitney tests were used with a significance level of 5%. RESULTS: 73 inpatients were included and followed up: 39 in TG and 34, CG. There were no significant differences in socio-demographic variables or of initial laboratory tests, except for blood glucose that was higher in TG than in CG (p = 0.044). Ten days into treatment, both the area of PUSH wounds (p < 0.001) and the pain scale (p = 0.029) were significantly reduced in TG. Staphylococcus aureus was the most prevalent pathogen (40%) with no significant difference between the two groups. DISCUSSION: Although the follow-up time was of only ten days, a significant improvement was observed in TG. As a limitation of the study, the small sample size precluded the comparison of S. aureus infections between the two groups. CONCLUSION: TOJT accelerated the healing process, reduced pain and contributed to an improvement in the clinical status of the wounds when compared to CG. These findings demonstrate the effectiveness and relevance of the employed technique. It can be easily incorporated as a routine procedure in hospitals without extra investment.

Topical Oxygen Jet Therapy (TOJT) for treating infected chronic surgical wounds

ABSTRACT Objectives: To evaluate the effectiveness of Topical Oxygen Jet Therapy (TOJT) in the treatment of surgical wounds in adult patients who has clinical signs of infection for over 30 days; and to identify the pathogens causing complicated skin and soft tissue infections. Method: Parallel, randomized clinical trials randomly divided into "Control Group" (CG) and "Treatment Group" (TG), which were followed up for 10 consecutive days. Venous antibiotics and dressings were used in both groups. In addition, TOJT were used on the wounds in the TG. The outcome criteria were based on clinical indicators: Pressure Ulcer Scale for Healing (PUSH) and Visual Analog Scale Pain (VAS). The paired t-test or Wilcoxon, chi-squared or Fisher's exact test, and Student's t-test or Mann-Whitney tests were used with a significance level of 5%. Results: 73 inpatients were included and followed up: 39 in TG and 34, CG. There were no significant differences in socio-demographic variables or of initial laboratory tests, except for blood glucose that was higher in TG than in CG (p = 0.044). Ten days into treatment, both the area of PUSH wounds (p < 0.001) and the pain scale (p = 0.029) were significantly reduced in TG. Staphylococcus aureus was the most prevalent pathogen (40%) with no significant difference between the two groups. Discussion: Although the follow-up time was of only ten days, a significant improvement was observed in TG. As a limitation of the study, the small sample size precluded the comparison of S. aureus infections between the two groups. Conclusion: TOJT accelerated the healing process, reduced pain and contributed to an improvement in the clinical status of the wounds when compared to CG. These findings demonstrate the effectiveness and relevance of the employed technique. It can be easily incorporated as a routine procedure in hospitals without extra investment.

Prevalence of neutralizing antibodies against poliovirus 1, 2, and 3 in healthcare professionals aged 20-50 years / Prevalência de anticorpos neutralizantes contra poliovírus 1, 2 e 3 em profissionais de saúde de 20 a 50 anos de idade

ABSTRACT Objective: To describe the prevalence of neutralizing antibodies against poliovirus (PV1, PV2, and PV3) in blood samples of healthcare professionals aged 20 to 50 years. Methods: Health professionals who serve children at Darcy Vargas Children's Hospital and the Department of Pediatrics of Irmandade da Santa Casa de São Paulo. The sample size was calculated at 323 participants. The Mantel-Haenszel chi-square was used to verify differences between groups. The neutralization reaction detected human poliovirus antibodies. For susceptible individuals, vaccination with the inactivated+triple acellular polio vaccine was performed, and neutralizing antibodies were re-dosed after one week. Results: 333 professionals were studied - 92.8% were immune to poliovirus 1, 86.5% to poliovirus 2, and 63.3% to poliovirus 3; 37% had titers less than 1:8 for any serotype, 5;1% had titers below 1:8 for all three. Vaccination with inactivated polio vaccine was performed for susceptible participants, and neutralizing antibodies were dosed after one week, showing increased titers for all polioviruses. Conclusions: Despite the detection of a significant percentage of individuals with low poliovirus antibody titer, the challenge with vaccination demonstrated immune response compatible with poliovirus immunity.

RESUMO Objetivo: Descrever a prevalência de anticorpos neutralizantes contra poliovírus (tipos 1, 2 e 3) em amostra de sangue de profissionais de saúde com idade de 20 a 50 anos. Métodos: Profissionais de saúde que atendem crianças do Hospital Infantil Darcy Vargas e do Departamento de Pediatria da Irmandade da Santa Casa de São Paulo. O tamanho da amostra foi de 323 participantes. Os anticorpos contra poliovírus humanos foram detectados pela reação de neutralização. Para os indivíduos suscetíveis, foram administradas vacina para poliomielite inativada+tríplice e nova dosagem de anticorpos neutralizantes após uma semana. Utilizou-se o teste do qui-quadrado de Mantel-Haenszel para verificar as diferenças entre os grupos. Resultados: Foram estudados 333 profissionais - 92,8% eram imunes ao poliovírus 1; 86,5%, ao poliovírus 2; 63,57%, ao poliovírus 3; 37% apresentaram títulos inferiores a 1:8 para qualquer sorotipo; 5,1% tinham títulos abaixo de 1:8 para os três. Após a vacinação dos suscetíveis, houve elevação dos títulos para todos os poliovírus. Conclusões: Apesar da detecção de percentual significativo de indivíduos com baixo título de anticorpos para poliovírus, o desafio da vacinação demonstrou resposta imune robusta compatível.