Hospitalizações por doença pneumocócica no Brasil, 2004 - 2006

OBJETIVO: Estimar las hospitalizaciones por enfermedad neumocócica con base en datos del Sistema de Informaciones Hospitalarias (SIH). MÉTODOS: Estudio descriptivo con base en datos del SIH de enero de 2004 a diciembre de 2006: números de hospitalizaciones y muertes por meningitis neumocócica, sepsis neumocócica, neumonía neumocócica y Streptococcus pneumoniae como causa de enfermedades ocurridas en Brasil. Datos de la Investigación Nacional por Muestras de Domicilios 2003 fueron utilizados para el sector privado. Casos y muertes por meningitis neumocócica notificados en el Sistema Nacional de Agravios de Notificación en el mismo período también fueron analizados. RESULTADOS: La enfermedad neumocócica fue responsable por 34.217 hospitalizaciones en el Sistema Único de Salud, (0,1% de todas las hospitalizaciones). Neumonía neumocócica fue responsable por 64,8% de tales hospitalizaciones. La distribución de las estimaciones de hospitalizaciones según grupo etáreo mostró curva en "U", con mayor frecuencia entre niños < 1 año (110-136,9/100.000 niños/año). La letalidad hospitalaria fue más alta entre ancianos, y entre casos de meningitis y sepsis. CONCLUSIONES: Enfermedad neumocócica es importante problema de salud pública en Brasil. Análisis basado en el SIH puede contribuir para la vigilancia epidemiológica de la enfermedad neumocócica y para la evaluación del impacto del programa de vacunación.OBJETIVO: Estimar as hospitalizações por doença pneumocócica com base em dados do Sistema de Informações Hospitalares (SIH). MÉTODOS: Estudo descritivo com base em dados do SIH de janeiro de 2004 a dezembro de 2006: números de hospitalizações e mortes por meningite pneumocócica, sepse pneumocócica, pneumonia pneumocócicca e Streptococcus pneumoniae como causa de doenças ocorridas no Brasil. Dados da Pesquisa Nacional por Amostras de Domicílios 2003 foram utilizados para o setor privado. Casos e mortes por meningite pneumocócica notificados no Sistema Nacional de Agravos de Notificação no mesmo período também foram analisados. RESULTADOS: A doença pneumocócica foi responsável por 34.217 hospitalizações no Sistema Único de Saúde (0,1% de todas as hospitalizações). Pneumonia pneumocócica foi responsável por 64,8% dessas hospitalizações. A distribuição das estimativas de hospitalizações segundo faixa etária mostrou curva em "U", com maior freqüência entre crianças < 1 ano (110-136,9/100.000 crianças/ano). A letalidade hospitalar foi mais alta entre idosos, e entre casos de meningite e sepse. CONCLUSÕES: Doença pneumocócica é importante problema de saúde pública no Brasil. Análise baseada no SIH pode contribuir para a vigilância epidemiológica da doença pneumocócica e para a avaliação do impacto do programa de vacinação.OBJECTIVE: To estimate hospitalization rates for pneumococcal disease based on the Brazilian Hospital Information System (SIH). METHODS: Descriptive study based on the Hospital Information System of Brazilian National Health System data from January 2004 to December 2006: number of hospitalizations and deaths for pneumococcal meningitis, pneumococcal sepsis, pneumococcal pneumonia and Streptococcus pneumoniae as the cause of diseases reported in Brazil. Data from the 2003 Brazilian National Household Survey were used to estimate events in the private sector. Pneumococcal meningitis cases and deaths reported to the Notifiable Diseases Information System during the study period were also analyzed. RESULTS: Pneumococcal disease accounted for 34,217 hospitalizations in the Brazilian National Health System (0.1% of all hospitalizations in the public sector). Pneumococcal pneumonia accounted for 64.8% of these hospitalizations. The age distribution of the estimated hospitalization rates for pneumococcal disease showed a "U"-shape curve with the highest rates seen in children under one (110 to 136.9 per 100,000 children annually). The highest hospital case-fatality rates were seen among the elderly, and for sepsis and meningitis. CONCLUSIONS: PD is a major public health problem in Brazil. The analysis based on the SIH can provide an important input to pneumococcal disease surveillance and the impact assessment of immunization programs

Avaliação da implantação dos Centros de Referência para Imunobiológicos Especiais

OBJETIVO Descrever os Centros de Referência para Imunobiológicos Especiais e avaliar sua implantação considerando as regulamentações formais. MÉTODOS Foi realizada uma avaliação de programa, tipo pesquisa avaliativa. De agosto de 2011 a janeiro de 2012, foi aplicado questionário aos responsáveis pelos 42 Centros de Referência para Imunobiológicos Especiais existentes no País, abordando as dimensões estrutura, recursos humanos e atividades desenvolvidas. Foi feita análise descritiva dos dados e utilizado agrupamento para dados binários com uso da distância euclidiana quadrática, pelo método do vizinho mais distante, para agregar serviços com características semelhantes. RESULTADOS Observou-se grande diversidade entre os serviços nas três dimensões. O agrupamento resultou em cinco perfis de serviços, denominados de acordo com suas características. 1) Melhor estrutura: 12 Centros de Referência para Imunobiológicos Especiais com a maior proporção de serviços com o mínimo de salas preconizado, câmaras de vacinas, manutenção preventiva da rede de frio e fonte de oxigênio. 2) Dispensador de imunobiológicos: seis Centros de Referência para Imunobiológicos Especiais que mais dispensavam do que aplicavam imunógenos; sem médico presente por mais da metade do expediente do serviço e sem câmara de vacinas. 3) Implantação incipiente: cinco Centros de Referência para Imunobiológicos Especiais com estrutura inadequada, como ausência de câmaras de vacinas, de manutenção preventiva da rede de frio e de fonte de oxigênio; nenhum possuía computador. 4) Sala de vacinas: 13 Centros de Referência para Imunobiológicos Especiais, todos faziam imunização de rotina, a maioria participava de campanhas de vacinação. 5) Ensino e pesquisa: seis serviços, todos inseridos em hospitais de ensino, desenvolviam pesquisas e recebiam estagiários; a maioria possuía médicos em mais da metade do expediente. CONCLUSÕES A avaliação de implantação dos Centros de Referência para Imunobiológicos Especiais baseou-se nos perfis encontrados e considerou as regulamentações oficiais: os serviços categorizados como “melhor estrutura” e “ensino e pesquisa” foram considerados implantados; os serviços “dispensador de imunobiológicos” e “sala de vacinas”, parcialmente implantados e os do perfil “implantação incipiente”, não implantados. Os resultados dessa avaliação podem contribuir para a reformulação dos serviços, considerando o contexto atual.OBJECTIVE To describe the Reference Centers for Special Immunobiologicals and evaluate their implementation considering formal regulations. METHODS We conducted a program evaluation, of evaluative research type. From August 2011 to January 2012, a questionnaire was applied to the 42 Reference Centers for Special Immunobiologicals existing in the Country, approaching the structure, human resources, and developed activities dimensions. We conducted a descriptive analysis of data and used a clustering for binary data with the squared Euclidean distance, by the farthest neighbor method, to aggregate services with similar features. RESULTS We observed great diversity among the services in the three dimensions. The clustering resulted in five service profiles, named according to their characteristics. 1) Best structure: 12 Reference Centers for Special Immunobiologicals with the highest proportion of services with the minimum of rooms recommended, purpose-built vaccine refrigerators, preventive maintenance of the cold chain, and oxygen source. 2) Immunobiologicals distributor: six Reference Centers for Special Immunobiologicals that distributed more than applied immunogens; no doctor present for more than half of the working hours and no purpose-built vaccine refrigerators . 3) Incipient implementation: five Reference Centers for Special Immunobiologicals with inadequate structure, such as absence of purpose-built vaccine refrigerators, preventive maintenance of the cold chain and oxygen source; none had computer. 4) Vaccination rooms: 13 Reference Centers for Special Immunobiologicals, everyone did routine immunization, most participated in vaccination campaigns. 5) Teaching and research: six services, all inserted into teaching hospitals, developed researches and received trainees; most had doctors in more than half of the working hours. CONCLUSIONS The evaluation of the Reference Centers for Special Immunobiologicals implementation was based on the profiles found and considered the official regulations: services categorized as “better structure” and “teaching and research” were considered implemented; “immunobiologicals distributor” and “vaccination room” services, partially implemented, and the ones with the “incipient implementation” profile, not implemented. The results of this evaluation can contribute to the reformulation of the services, considering the current context

Adverse events following yellow fever vaccination in immunocompromised persons

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

Spatial analysis of pneumococcal meningitis in São Paulo in the pre- and post-immunization era

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

Annual national direct and indirect cost estimates of the prevention and treatment of cervical cancer in Brazil

OBJECTIVE: To estimate the annual direct and indirect costs of the prevention and treatment of cervical cancer in Brazil. METHODS: This cost description study used a "gross-costing" methodology and adopted the health system and societal perspectives. The estimates were grouped into sets of procedures performed in phases of cervical cancer care: the screening, diagnosis and treatment of precancerous lesions and the treatment of cervical cancer. The costs were estimated for the public and private health systems, using data from national health information systems, population surveys, and literature reviews. The cost estimates are presented in 2006 USD. RESULTS: From the societal perspective, the estimated total costs of the prevention and treatment of cervical cancer amounted to USD $1,321,683,034, which was categorized as follows: procedures (USD$213,199,490), visits (USD $325,509,842), transportation (USD$106,521,537) and productivity losses (USD $676,452,166). Indirect costs represented 51% of the total costs, followed by direct medical costs (visits and procedures) at 41% and direct non-medical costs (transportation) at 8%. The public system represented 46% of the total costs, and the private system represented 54%. CONCLUSION: Our national cost estimates of cervical cancer prevention and treatment, indicating the economic importance of cervical cancer screening and care, will be useful in monitoring the effect of the HPV vaccine introduction and are of interest in research and health care management

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation

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

Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

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

Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults

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

Prospective cohort studies to evaluate the safety and immunogenicity of the 2013, 2014, and 2015 seasonal influenza vaccines produced by Instituto Butantan

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. Fortyseven 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 &gt;70% and SPR &gt;60% were observed in adults and elderly, respectively, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. SCR &gt;40% was observed in adults, for the three vaccine viruses, only in the 2014 study and SCR &gt;30% was observed in the elderly, for the three vaccine viruses, only in the 2013 and 2014 studies. GMTR &gt;2.5 among adults, for the three vaccine viruses was only observed in the 2013 study and GMTR &gt;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)

Adverse events following immunization of elderly with COVID-19 inactivated virus vaccine (CoronaVac) in Southeastern Brazil: an active surveillance study

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