ABSTRACT The global reemergence of measles in 2018–2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

ABSTRACT The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

ABSTRACT Healthcare workers, the elderly and other vulnerable populations were the first to receive COVID-19 vaccines in public health programs. There were few vaccine safety data available on the elderly. This observational study aimed to evaluate the inactivated vaccine (CoronaVac) safety in the elderly, at the beginning of the vaccination program, in Sao Paulo city, Brazil. The elderly people that received CoronaVac at the Reference Center for Special Immunobiologicals (CRIE) or at home, administered by the Interdisciplinary Home Care Team (NADI) of the Hospital das Clinicas were invited to participate in this phase 4 observational study. The vaccination schedule included two CoronaVac doses 28 days apart. The information on solicited and unsolicited adverse events following immunization were collected by phone calls on days 4 and 8 after each vaccine dose. We enrolled 158 adults aged 65 to 101 years (mean of 84.1 years); 63.9% were females and 95.6% had chronic conditions, 21.5% had moderate or severe impairment in daily living activities; 34.2% were pre-frail and 19.6% were frail. We were able to contact 95.6% and 91.6% of the vaccinated people, after the first and second doses, respectively; 31.8% and 23.4% of the contacted participants reported some adverse events (AE) following the first and second doses, respectively. Pain at the injection site, fatigue, myalgia and headaches were the most frequent solicited AE. Most AE were mild to moderate. There were eight severe adverse events, but none of them were considered related to the vaccine. The CoronaVac was safe and well tolerated by these adults of advanced age with frailty and comorbidities.

ABSTRACT The article describes a strategy to facilitate access to pneumococcal conjugate vaccine 13 (PCV-13) for people living with HIV/AIDS (PLHIV) during the COVID-19 pandemic. Method: report on the experience regarding the organization of a care service for PLHIV in the city of São Paulo to facilitate access to PCV-13 in the framework of the 2020 influenza vaccination campaign during the COVID-19 pandemic. Results: through the integration between a PLHIV care service and an Immunization Center (CRIE in Portuguese), it was possible to offer PCV-13 to PLHIV at the point of care, reducing physical barriers to access to immunization. Thus, of the 1,906 PLHIV who passed through the service during the period March 23-July 31, 2020, 84.4% (1,609) received the influenza vaccine, PCV-13 or both. Of the 1609 vaccinated, 50.6% (814) were eligible and received PCV-13. Conclusion: offering the vaccine at the point of care and orienting PLHIV on the importance of vaccination as a disease prevention strategy, identifying those eligible to receive it, was an important action carried out by the institution together with the nursing team, as a strategy to facilitate access to vaccination.

RESUMEN El artículo describe una estrategia para facilitar el acceso a la vacuna neumocócica conjugada 13 (PCV-13) a las personas que viven con VIH/SIDA (PVVS) durante la pandemia de COVID-19. Método: relato de experiencia sobre la organización de un servicio de atención a las PVVS en la ciudad de São Paulo, para facilitar el acceso a la PCV-13 en el marco de la campaña de vacunación contra la gripe de 2020, durante la pandemia de COVID-19. Resultados: a través de la integración entre un servicio de atención a las PVVS y un Centro de Inmunización (CRIE), fue posible ofrecer la PCV-13 a las PVVS en su punto de atención, reduciendo las barreras físicas para el acceso a la inmunización. Así, de las 1.906 PVVS que pasaron por el servicio durante el periodo comprendido entre el 23 de marzo y el 31 de julio de 2020, el 84,4% (1.609) recibieron la vacuna de la gripe, la PCV-13 o ambas. De los 1609 vacunados, el 50,6% (814) eran elegibles y recibieron la PCV-13. Conclusión: ofrecer la vacuna en el lugar de atención y orientar a las PVVS sobre la importancia de la vacunación como estrategia de prevención de enfermedades, identificando a las personas elegibles para recibirlas, fue una acción importante realizada por la institución junto con el equipo de enfermería, como estrategia para facilitar el acceso a la vacunación.

RESUMO Descrever uma estratégia para facilitar o acesso à vacina conjugada pneumocócica 13-valente (PCV-13) para pessoas vivendo com HIV (PVHIV), durante a pandemia de COVID-19. Método: relato de experiência sobre a organização de um serviço de atendimento para PVHIV na cidade de São Paulo, para facilitar o acesso à PCV-13 no decorrer da campanha de vacinação de influenza de 2020, durante a pandemia de COVID-19. Resultados: por meio da integração entre um serviço de atendimento para PVHIV e um Centro de Imunizações (CRIE) foi possível oferecer a PCV-13 para as PVHIV em seu local de atendimento, diminuindo barreiras físicas de acesso à imunização. Dessa forma, das 1906 PVHIV que passaram pelo serviço durante o período de 23 de março a 31 de julho de 2020, 84,4% (1609) receberam a vacina influenza, PCV-13 ou ambas. Dos 1609 vacinados, 50,6% (814) foram elegíveis e receberam a PCV-13. Conclusão: oferecer a vacina em seu local de tratamento e orientar as PVHIV sobre a importância da vacinação como estratégia de prevenção de doenças, identificando os elegíveis a recebê-las, foi uma importante ação realizada pela instituição em conjunto com a equipe de enfermagem, como estratégia de facilitar o acesso à vacinação.

ABSTRACT This observational retrospective study conducted during an yellow fever (YF) outbreak in Sao Paulo, Brazil, in 2017-2018, describes adverse events (AE) following YF vaccination of immunocompromised persons. Risks and benefits of vaccination were individually evaluated by physicians. AE were assessed by phone call or electronic mail, 14 to 90 days after vaccination. Three hundred and eighty one immunocompromised persons received a full-dose of YF vaccine. Their age ranged from 1.4 to 89.3 years (median 50.8 years); 53% were women; 178 (46.7%) had chronic kidney disease, 78 (20.5%) had immune-mediated inflammatory diseases; 94 (24.7%) were using or had recently used immunosuppressive/ immunomodulatory drugs. All of them denied previous YF vaccination. We were able to contact 341 (89.5%) vaccinees: 233 (68.3%) of them received the YF vaccine from BioManguinhos and 108 (31.7%) received the vaccine from Sanofi-Pasteur; 130 (38.1%) vaccinees received other vaccines (up to 4) simultaneously with the the YF vaccine, mostly hepatitis B (59 vaccinees), pneumococcal polysaccharide 23-valent (46), influenza (43) and diphtheria-tetanus (dT, 41). One hundred and eleven vaccinees (32.6%) reported at least one AE: 79 (23.2%) presented systemic AE, 44 (12.9%) had local AE and 12 had both, local and systemic AE. The most common AE was pain at the injection site (41 persons, 12%), myalgia (34; 10%), fever (25; 7.3%) and headache (16; 4.7%). There was no statistically significant difference on the AE frequency according to the vaccine producer. There were four severe AE: one hospitalization and three deaths, considered not related to the YF vaccine.

Abstract Introduction: Vaccination with tetanus-diphtheria-acellular pertussis (Tdap) has been recommended for healthcare workers (HCWs) by Brazilian Ministry of Health since November 2014. Objective: To describe the strategies implemented to improve Tdap uptake, cumulative vaccine coverage after each intervention, variables associated to Tdap vaccination, and reasons for non-vaccination among HCWs of the main building of a quaternary hospital attached to the Sao Paulo University Medical School. Methods: A list of HCWs eligible for pertussis vaccination was generated. From April to December 2015, the following interventions were implemented: note on intern journal reminding the importance of pertussis vaccination; email to the head nurses strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians of Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. Vaccine coverage was accessed at the end of each month. Multivariate Poisson regression model with a robust error variance was used to evaluate variables associated with Tdap vaccination. Reasons for non-vaccination were evaluated from January to May 2017 through phone calls for HCWs who had not received Tdap. Results: The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.8% to 41.2%. In the multivariate analysis, occupation (physician), working place (obstetrics or anesthesiology) and influenza vaccination in 2015 were independently associated to Tdap vaccination. The main reason for non-vaccination was unawareness of Tdap recommendations. Conclusions: Tdap uptake among HCWs was low in our hospital. Providing vaccination at convenient places/times for HCW seems to be the most efficient strategy to increase vaccine uptake.

ABSTRACT OBJECTIVE To analyze the pneumococcal meningitis incidence rates in the State of São Paulo, Brazil, by age group, municipalities and micro-regions, as well as the spatial distribution of pneumococcal meningitis incidence rates among children under 5 years old in the pre- (2005–2009) and post-vaccination (2011–2013) periods and its associations with socioeconomic variables and vaccination coverage. METHODS The data source was the Brazilian Notifiable Diseases Information System. For the pre- and post-vaccination periods, thematic maps were built for pneumococcal meningitis incidence in under-5 children, by São Paulo state micro-regions, vaccination coverage and socioeconomic variables, using QGIS 2.6.1 software. Scan statistics performed by the SatScan 9.2 software were used to analyze spatial and spatiotemporal clusters in São Paulo municipalities and micro-regions. A Bayesian inference for latent Gaussian model with zero-inflated Poisson model through the integrated nested Laplace approximation was used in the spatial analysis to evaluate associations between pneumococcal meningitis incidence rates and socioeconomic variables of interest in São Paulo micro-regions. RESULTS From 2005 to 2013, 3,963 pneumococcal meningitis cases were reported in São Paulo. Under-5 children were the most affected in the whole period. In the post-vaccination period, pneumococcal meningitis incidence rates decreased among this population, particularly among infants (from 4.17/100,000 in 2005 to 2.54/100,000 in 2013). Two clusters were found in pre-vaccination – one of low risk for pneumococcal meningitis, in the northwest of the state (OR = 0.45, p = 0.0003); and another of high risk in the southeast (OR = 1.62, p = 0.0000). In the post-vaccination period, only a high-risk cluster remained, in the southeast (RR = 1.97, p = 0.0570). In Bayesian analysis, wealth was the only variable positively associated to pneumococcal meningitis (RR = 1.026, 95%CI 1.002–1.052). CONCLUSIONS Pneumococcal meningitis is probably underdiagnosed and underreported in São Paulo. Differentiated rates of pneumococcal meningitis diagnosis and reporting in each microregion, according to the São Paulo Index of Social Responsibility, might explain our results.

ABSTRACT OBJECTIVE To analyze the pneumococcal meningitis incidence rates in the State of São Paulo, Brazil, by age group, municipalities and micro-regions, as well as the spatial distribution of pneumococcal meningitis incidence rates among children under 5 years old in the pre- (2005–2009) and post-vaccination (2011–2013) periods and its associations with socioeconomic variables and vaccination coverage. METHODS The data source was the Brazilian Notifiable Diseases Information System. For the pre- and post-vaccination periods, thematic maps were built for pneumococcal meningitis incidence in under-5 children, by São Paulo state micro-regions, vaccination coverage and socioeconomic variables, using QGIS 2.6.1 software. Scan statistics performed by the SatScan 9.2 software were used to analyze spatial and spatiotemporal clusters in São Paulo municipalities and micro-regions. A Bayesian inference for latent Gaussian model with zero-inflated Poisson model through the integrated nested Laplace approximation was used in the spatial analysis to evaluate associations between pneumococcal meningitis incidence rates and socioeconomic variables of interest in São Paulo micro-regions. RESULTS From 2005 to 2013, 3,963 pneumococcal meningitis cases were reported in São Paulo. Under-5 children were the most affected in the whole period. In the post-vaccination period, pneumococcal meningitis incidence rates decreased among this population, particularly among infants (from 4.17/100,000 in 2005 to 2.54/100,000 in 2013). Two clusters were found in pre-vaccination – one of low risk for pneumococcal meningitis, in the northwest of the state (OR = 0.45, p = 0.0003); and another of high risk in the southeast (OR = 1.62, p = 0.0000). In the post-vaccination period, only a high-risk cluster remained, in the southeast (RR = 1.97, p = 0.0570). In Bayesian analysis, wealth was the only variable positively associated to pneumococcal meningitis (RR = 1.026, 95%CI 1.002–1.052). CONCLUSIONS Pneumococcal meningitis is probably underdiagnosed and underreported in São Paulo. Differentiated rates of pneumococcal meningitis diagnosis and reporting in each microregion, according to the São Paulo Index of Social Responsibility, might explain our results.

Abstract INTRODUCTION: This study describes cases of syphilis in pregnancy (SiP) and congenital syphilis (CS) and identifies factors associated with mother-to-child transmission in patients in Itapeva from January 1, 2010 to December 31, 2014. METHODS: Using SiP and CS notification forms and medical records, a cross-sectional study involving 149 pregnant women was conducted. RESULTS: Annual SiP detection rates ranged from 16.3-31.4/1000 live births. Most women had prenatal care started at the first trimester of pregnancy with ≥6 visits. Mother-to-child transmission rate was 69.7%. CS incidence rates varied from 9.1-22.3/1000 live births. CONCLUSIONS: The results suggest low quality of prenatal care.

ABSTRACT Annual vaccination is the most effective way to prevent seasonal influenza illness. Instituto Butantan (IB) performed clinical studies with its 2013, 2014 and 2015 seasonal trivalent influenza vaccines (inactivated split-virion). Prospective cohort studies were carried out to describe the safety and immunogenicity of Instituto Butantan influenza vaccines, in healthy adults and elderly, from 2013 to 2015. Immediately after the informed consent was signed, participants underwent blood collection followed by vaccination. On study days 1, 2 and 3 post-vaccination participants were contacted by the staff to evaluate the occurrence of solicited (local and systemic) and non-solicited adverse reactions. On study day 21 (+7) subjects returned to the clinical site for final safety assessments and blood collection to evaluate post-vaccination immunogenicity. The immunogenicity analyses were performed by means of hemagglutination inhibition (HI) assay. The immunogenicity endpoints were: seroprotection (SPR) and seroconversion (SCR) rates and the geometric mean HI antibody titer ratio (GMTR). The 2013 study was conducted at the Centro de Referência para Imunobiológicos Especiais (CRIE) and at the Centro de Pesquisa Clínica do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo while the 2014 and 2015 studies were conducted at CRIE. The vaccine composition followed the WHO recommendation for the Southern hemisphere seasonal influenza vaccine. Forty-seven healthy adults and 13 elderly participated in the 2013 study, 60 healthy adults and 60 elderly in the 2014 study, and 62 healthy adults and 57 elderly in the 2015 study. In the 2013, 2014 and 2015 studies, pain was the most frequent local adverse reaction and headache the most frequent systemic adverse reaction. All observed adverse reactions were classified as mild or moderate and none as severe. SPR >70% and SPR >60% were observed in adults and elderly, respectively, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. SCR >40% was observed in adults, for the three vaccine viruses, only in the 2014 study and SCR >30% was observed in the elderly, for the three vaccine viruses, only in the 2013 and 2014 studies. GMTR >2.5 among adults, for the three vaccine viruses was only observed in the 2013 study and GMTR >2.0 was observed among elderly, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. The 2013, 2014 and 2015 seasonal influenza vaccines produced by Instituto Butantan were safe and immunogenic according to the immunogenicity criteria defined by the European Medicines Agency (EMA).

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

ABSTRACT Introduction: The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged ≥ 60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. Methods: previously vaccinated healthy persons aged ≥ 18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. Results: 46 persons aged ≥ 60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. Conclusions: the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

Resumo OBJETIVO: avaliar capacidade da rede de frio (RF), conhecimento dos profissionais e práticas de conservação de imunobiológicos em unidades básicas de saúde (UBS) do município de São Paulo. MÉTODOS: estudo descritivo envolvendo amostra randômica de 24 UBS das regiões Sul e Centro-Oeste do município; de dezembro de 2011 a julho de 2012, foram entrevistados profissionais quanto ao conhecimento/prática em conservação de vacinas e observou-se a infraestrutura local, utilizando-se formulário desenvolvido para o projeto, sobre cujos itens atribuíram-se pontos e classificou-se cada UBS - suficiente, regular e insuficiente. RESULTADOS: a maioria das 24 UBS avaliadas era administrada por organizações sociais; todas possuíam câmaras de vacinas, cinco referiram utilizar sua capacidade máxima de armazenamento, nove UBS foram classificadas como de conhecimento/prática suficiente e 15 como de conhecimento/prática regular. CONCLUSÃO: a utilização da RF nessas UBS estava próxima da capacidade máxima; muitos profissionais não tinham conhecimentos básicos sobre conservação de vacinas.

Abstract OBJECTIVE: to assess the cold chain capacity, health workers' immunobiological product conservation knowledge and practices in Primary Healthcare Centers (PHC) in São Paulo city, Brazil. METHODS: this descriptive study included 24 randomly selected PHC in the South and Midwest regions of the city; between December 2011 and July 2012, we interviewed the health workers on their vaccine conservation knowledge/practice and observed the local infrastructure, using a form developed for this project; we assigned points to items of the form and classified each PHC as sufficient, regular or insufficient. RESULTS: most of the 24 PHC evaluated were administered by Social Organizations; all of them had vaccine storage chambers; 5 PHC reported using their maximum storage capacity; 9 PHC were classified as having sufficient knowledge/practice and 15 as having regular knowledge/practice. CONCLUSION: in these PHC, cold chain utilization was close to its maximum capacity; many health workers did not have basic knowledge about vaccine conservation.

Resumen OBJETIVO: evaluar la cadena de frío (CF), el conocimiento de los profesionales y las prácticas de conservación de vacunas en unidades básicas de salud (UBS) de São Paulo-SP, Brasil. MÉTODOS: estudio descriptivo de una muestra aleatoria de 24 UBS en las regiones Sur y Centro-Oeste del municipio; de diciembre del 2011 a julio del 2012, fueron entrevistados profesionales con respecto a sus conocimientos y prácticas en la conservación de vacunas, concomitantementese observó la infraestructura, utilizando un formulario desarrollado para el proyecto; atribuyéndose un puntaje específico para cada ítem, clasificamos las UBS como suficientes, regulares o insuficientes. RESULTADOS: la mayoría de las 24 UBS eran administradas por organizaciones sociales; todos tenían cámaras de vacunas; cinco informaron usar su capacidad máxima de almacenamiento; 9 UBS fueron clasificadas como suficientes y 15 como regulares. CONCLUSIÓN: la utilización de la CF en estas UBS estaba próxima al máximo; muchos profesionales no tenían conocimientos básicos acerca de conservación de vacunas.