The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis

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.

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

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.

Facilitating access to pneumococcal vaccine for people living with HIV: an experience report / Como facilitar el acceso a la vacuna neumocócica a las personas que viven con el VIH: informe de una experiencia / Facilitando o acesso à vacina pneumocócica para pessoas vivendo com HIV: relato de experiência

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.

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

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.

Low tetanus-diphtheria-acellular pertussis (Tdap) vaccine coverage among healthcare workers in a quaternary university hospital in São Paulo, Brazil: need for continuous surveillance and implementation of active strategies

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.

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

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.

Syphilis in pregnancy, congenital syphilis, and factors associated with mother-to-child transmission in Itapeva, São Paulo, 2010 to 2014

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.

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

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.

Avaliação da rede de frio para conservação de vacinas em unidades básicas de saúde das regiões Sul e Centro-Oeste do município de São Paulo em 2011-2012 / Evaluation of the cold chain for vaccine conservation in primary healthcare centers in the South and Midwest regions of São Paulo city, Brazil, in 2011-2012 / Evaluación de la cadena de frío para la conservación de vacunas en Unidades Básicas de Salud de las regiones Sur y Medio-Oeste de São Paulo en 2011-2012

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.

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.

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.

Evaluation of Reference Centers for Special Immunobiologicals implementation / Avaliação da implantação dos Centros de Referência para Imunobiológicos Especiais

ABSTRACT 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.

RESUMO 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.

Healthcare resource utilization and costs of outpatient follow-up after liver transplantation in a university hospital in São Paulo, Brazil: cost description study / Utilização de recursos em saúde e custos do acompanhamento ambulatorial pós-transplante de fígado em um hospital universitário em São Paulo, Brasil: estudo de descrição de custos

CONTEXT AND OBJECTIVE: Data on the costs of outpatient follow-up after liver transplantation are scarce in Brazil. The purpose of the present study was to estimate the direct medical costs of the outpatient follow-up after liver transplantation, from the first outpatient visit after transplantation to five years after transplantation. DESIGN AND SETTING: Cost description study conducted in a university hospital in São Paulo, Brazil. METHODS: Cost data were available for 20 adults who underwent liver transplantation due to acute liver failure (ALF) from 2005 to 2009. The data were retrospectively retrieved from medical records and the hospital accounting information system from December 2010 to January 2011. RESULTS: Mean cost per patient/year was R$ 13,569 (US$ 5,824). The first year of follow-up was the most expensive (R$ 32,546 or US$ 13,968), and medication was the main driver of total costs, accounting for 85% of the total costs over the five-year period and 71.9% of the first-year total costs. In the second year after transplantation, the mean total costs were about half of the amount of the first-year costs (R$ 15,165 or US$ 6,509). Medication was the largest contributor to the costs followed by hospitalization, over the five-year period. In the fourth year, the costs of diagnostic tests exceeded the hospitalization costs. CONCLUSION: This analysis provides significant insight into the costs of outpatient follow-up after liver transplantation due to ALF and the participation of each cost component in the Brazilian setting. .

CONTEXTO E OBJETIVO: Dados sobre os custos do seguimento ambulatorial pós-transplante de fígado são escassos no Brasil. O objetivo do presente estudo foi estimar os custos diretos médicos do seguimento ambulatorial pós-transplante de fígado a partir da primeira visita ambulatorial pós-transplante até cinco anos após o transplante. TIPO DE ESTUDO E LOCAL: Estudo de descrição de custos realizado em um hospital universitário em São Paulo, Brasil. MÉTODOS: Dados de custos estavam disponíveis para 20 adultos que foram submetidos a transplante de fígado devido a insuficiência hepática aguda (IHA) de 2005 a 2009. Os dados foram retrospectivamente obtidos em prontuários médicos e no sistema de informação contábil hospitalar de dezembro de 2010 a janeiro de 2011. RESULTADOS: A média de custo por paciente/ano foi de R$ 13.569 (US$ 5.824). O primeiro ano de acompanhamento foi o mais caro, R$ 32.546 (US$ 13,968), e medicação foi o principal impulsionador dos custos totais, respondendo por 85% dos custos totais no período de cinco anos e 71,9% dos custos totais do primeiro ano. No segundo ano pós-transplante, os custos médios totais foram cerca da metade do montante de custos do primeiro ano (R$ 15.165 ou US$ 6,509). Medicação foi o maior contribuinte para os custos seguido da internação, no período de cinco anos. No quarto ano, os custos dos testes diagnósticos superam os custos de internação. CONCLUSÃO: Esta análise proporciona uma compreensão significativa dos custos do seguimento ambulatorial pós-transplante de fígado por IHA e a participação de cada componente de custo no cenário brasileiro. .

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. .

Methods and challenges for the health impact assessment of vaccination programs in Latin America / Métodos e desafios da avaliação do impacto na saúde de programas de vacinação na América Latina

ABSTRACT OBJECTIVE To describe methods and challenges faced in the health impact assessment of vaccination programs, focusing on the pneumococcal conjugate and rotavirus vaccines in Latin America and the Caribbean. METHODS For this narrative review, we searched for the terms "rotavirus", "pneumococcal", "conjugate vaccine", "vaccination", "program", and "impact" in the databases Medline and LILACS. The search was extended to the grey literature in Google Scholar. No limits were defined for publication year. Original articles on the health impact assessment of pneumococcal and rotavirus vaccination programs in Latin America and the Caribbean in English, Spanish or Portuguese were included. RESULTS We identified 207 articles. After removing duplicates and assessing eligibility, we reviewed 33 studies, 25 focusing on rotavirus and eight on pneumococcal vaccination programs. The most frequent studies were ecological, with time series analysis or comparing pre- and post-vaccination periods. The main data sources were: health information systems; population-, sentinel- or laboratory-based surveillance systems; statistics reports; and medical records from one or few health care services. Few studies used primary data. Hospitalization and death were the main outcomes assessed. CONCLUSIONS Over the last years, a significant number of health impact assessments of pneumococcal and rotavirus vaccination programs have been conducted in Latin America and the Caribbean. These studies were carried out few years after the programs were implemented, meet the basic methodological requirements and suggest positive health impact. Future assessments should consider methodological issues and challenges arisen in these first studies conducted in the region.

RESUMO OBJETIVO Descrever métodos e desafios enfrentados na avaliação do impacto de programas de vacinação, com foco nas vacinas pneumocócica conjugada e de rotavírus nos países da América Latina e Caribe. MÉTODOS Para esta revisão narrativa, foi realizada busca nas bases de dados Medline e Lilacs, usando os termos "rotavirus", "pneumococcal", "conjugate vaccine", "vaccination", "program", e "impact". A busca foi estendida à literatura cinza no Google Acadêmico. Não houve limitação por ano de publicação. Foram incluídos estudos originais de avaliação do impacto dos programas de vacinação de pneumococo e rotavírus na América Latina e Caribe, publicados em inglês, espanhol ou português. RESULTADOS Foram identificados 207 artigos. Após remover duplicatas e avaliar elegibilidade, 33 estudos foram revisados, 25 sobre programas de vacinação de rotavírus e oito de pneumococo. Estudos ecológicos, com análise de série temporal ou comparação de períodos antes e após a vacinação, foram mais frequentes. As principais fontes de dados foram: sistemas de informação em saúde; sistemas de vigilância de base populacional, sentinela ou laboratorial; relatórios estatísticos; e prontuários médicos de um ou poucos serviços de saúde. Poucos estudos utilizaram dados primários. Hospitalizações e mortes foram os principais desfechos avaliados. CONCLUSÕES Nos últimos anos, número significativo de avaliações do impacto dos programas de vacinação de pneumococo e rotavírus foram realizados nos países da América Latina e Caribe. Esses estudos foram conduzidos poucos anos após a implementação dos programas, preenchem os requisitos metodológicos básicos e sugerem impacto positivo dos programas. Futuras avaliações devem considerar questões metodológicas e desafios que surgiram nesses primeiros estudos conduzidos na região.

Polio inactivated vaccine costs into routine childhood immunization in Brazil / Custos da vacina inativada de pólio na imunização infantil de rotina no Brasil

OBJECTIVE To analyze the costs of vaccination regimens for introducing inactivated polio vaccine in routine immunization in Brazil. METHODS A cost analysis was conducted for vaccines in five vaccination regimens, including inactivated polio vaccine, compared with the oral polio vaccine-only regimen. The costs of the vaccines were estimated for routine use and for the “National Immunization Days”, during when the oral polio vaccine is administered to children aged less than five years, independent of their vaccine status, and the strategic stock of inactivated polio vaccine. The presented estimated costs are of 2011. RESULTS The annual costs of the oral vaccine-only program (routine and two National Immunization Days) were estimated at US$19,873,170. The incremental costs of inclusion of the inactivated vaccine depended on the number of vaccine doses, presentation of the vaccine (bottles with single dose or ten doses), and number of “National Immunization Days” carried out. The cost of the regimen adopted with two doses of inactivated vaccine followed by three doses of oral vaccine and one “National Immunization Day” was estimated at US$29,653,539. The concomitant replacement of the DTPw/Hib and HepB vaccines with the pentavalent vaccine enabled the introduction of the inactivated polio without increasing the number of injections or number of visits needed to complete the vaccination. CONCLUSIONS The introduction of the inactivated vaccine increased the annual costs of the polio vaccines by 49.2% compared with the oral vaccine-only regimen. This increase represented 1.13% of the expenditure of the National Immunization Program on the purchase of vaccines in 2011. .

OBJETIVO Analisar os custos de esquemas de vacinação para a introdução da vacina inativada de pólio na imunização de rotina no Brasil. MÉTODOS Foi realizada análise de custos das vacinas de cinco esquemas de vacinação, incluindo vacina pólio inativada, comparados ao esquema apenas-vacina oral de pólio. Foram estimados custos das vacinas para rotina, para os “Dias Nacionais de Imunização”, quando a vacina de pólio oral é administrada para menores de cinco anos, independentemente da situação vacinal, e do estoque estratégico de vacina pólio inativada. Os custos estimados foram os de 2011. RESULTADOS Os custos anuais do programa apenas-vacina de pólio oral (de rotina e de dois Dias Nacionais de Imunização) foram estimados em US$19.873.170. Os custos incrementais da inclusão da vacina pólio inativada dependeram: do número de doses da vacina, da apresentação da vacina (frascos com dose única ou dez doses) e do número de “Dias Nacionais de Imunização” realizados. O esquema adotado, com duas doses de VIP seguidas de três doses de VOP e um “Dia Nacional de Imunização”, foi estimado em US$29.653.539. A concomitante substituição das vacinas DTPw/Hib e HepB pela vacina pentavalente permitiu a introdução da vacina pólio inativada sem aumento do número de injeções ou visitas necessárias para completar a vacinação. CONCLUSÕES A introdução da vacina pólio inativada aumentou os custos anuais das vacinas de pólio em 49,2%, comparado ao esquema apenas-vacina de pólio oral. Esse aumento representou 1,13% dos gastos do Programa Nacional de Imunização com a compra de vacinas em 2011. .

Spontaneous reporting of adverse events following pandemic influenza A (H1N1) immunization in a reference center in the State of Sao Paulo, Brazil

Introduction This paper describes adverse events (AEs) temporally associated to the pandemic influenza A (H1N1) vaccine observed in a reference center in São Paulo, Brazil, during a 2010 mass vaccination campaign. Methods A retrospective study involving persons who sought medical care for AEs following influenza vaccination. Data were retrieved from medical records, vaccine AE notification forms, and a computerized system for immunobiological registration. Results Sixty-six vaccinees sought medical care for AEs after immunization. The most frequent AEs were fever, headache, myalgia, and pain at the injection site. No serious AEs were reported. Conclusions Few vaccinees spontaneously reported AEs to influenza A (H1N1) vaccine at this center. .

Contributions from the systematic review of economic evaluations: the case of childhood hepatitis A vaccination in Brazil / Contribuições da revisão sistemática de avaliações econômicas: o exemplo da vacinação infantil contra hepatite A no Brasil

The aim of this study was to present the contributions of the systematic review of economic evaluations to the development of a national study on childhood hepatitis A vaccination. A literature review was performed in EMBASE, MEDLINE, WOPEC, HealthSTAR, SciELO and LILACS from 1995 to 2010. Most of the studies (8 of 10) showed favorable cost-effectiveness results. Sensitivity analysis indicated that the most important parameters for the results were cost of the vaccine, hepatitis A incidence, and medical costs of the disease. Variability was observed in methodological characteristics and estimates of key variables among the 10 studies reviewed. It is not possible to generalize results or transfer epidemiological estimates of resource utilization and costs associated with hepatitis A to the local context. Systematic review of economic evaluation studies of hepatitis A vaccine demonstrated the need for a national analysis and provided input for the development of a new decision-making model for Brazil.

O objetivo deste estudo foi apresentar as contribuições da revisão sistemática de avaliações econômicas para o desenvolvimento de um estudo nacional, o caso da vacinação infantil contra hepatite A. Foi realizada revisão da literatura nas bases de dados EMBASE, MEDLINE, WOPEC, HealthSTAR, SciELO e LILACS, no período de 1995 a 2010. A maioria dos estudos (8 em 10) mostrou resultados favoráveis de custo-efetividade. As análises de sensibilidade indicaram como parâmetros mais importantes para os resultados os custos da vacina, incidência de hepatite A e custos médicos da doença. Foi observada variabilidade nas características metodológicas e estimativas de variáveis-chaves dos 10 estudos revisados. Não é possível generalização dos resultados e transferibilidade de estimativas epidemiológicas, de usos de recursos e custos associados à hepatite A para o contexto local. A revisão sistemática dos estudos de avaliação econômica da vacina contra hepatite A demonstrou a necessidade de uma análise nacional e forneceu elementos para o desenvolvimento de um novo modelo de decisão para o Brasil.

Hospitalization rates for pneumococcal disease in Brazil, 2004 - 2006 / Hospitalizações por doença pneumocócica no Brasil, 2004 - 2006 / Hospitalizaciones por enfermedad neumocócica en Brasil, 2004-2006

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 percent of all hospitalizations in the public sector). Pneumococcal pneumonia accounted for 64.8 percent 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.

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 por cento de todas as hospitalizações). Pneumonia pneumocócica foi responsável por 64,8 por cento 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.

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 por ciento de todas las hospitalizaciones). Neumonía neumocócica fue responsable por 64,8 por ciento 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.

Cost-effectiveness analysis of routine rotavirus vaccination in Brazil / Análisis de la relación costo-efectividad de la vacunación programada contra rotavirus en Brasil

OBJECTIVE: The objective of this study was to conduct a cost-effectiveness analysis of a universal rotavirus vaccination program among children < 5 years of age in Brazil. METHODS: Considering a hypothetical annual cohort of approximately 3 300 000 newborns followed over 5 years, a decision-tree model was constructed to examine the possible clinical and economic effects of rotavirus infection with and without routine vaccination of children. Probabilities and unit costs were derived from published research and national administrative data. The impact of different estimates for key parameters was studied using sensitivity analysis. The analysis was conducted from both healthcare system and societal perspectives. RESULTS: The vaccination program was estimated to prevent approximately 1 735 351 (54 percent) of the 3 210 361 cases of rotavirus gastroenteritis and 703 (75 percent) of 933 rotavirus-associated deaths during the 5-year period. At a vaccine price of 18.6 Brazilian reais (R$) per dose, this program would cost R$121 673 966 and would save R$38 536 514 in direct costs to the public healthcare system and R$71 778 377 in direct and indirect costs to society. The program was estimated to cost R$1 028 and R$1 713 per life-years saved (LYS) from the societal and healthcare system perspectives, respectively. CONCLUSIONS: Universal rotavirus vaccination was a cost-effective strategy for both perspectives. However, these findings are highly sensitive to diarrhea incidence rate, proportion of severe cases, vaccine coverage, and vaccine price.

OBJETIVO: Analizar la relación costo-efectividad de un programa universal de vacunación contra rotavirus en niños de hasta 5 años en Brasil. MÉTODOS: Se consideró una cohorte hipotética anual de aproximadamente 3 300 000 recién nacidos con un seguimiento de 5 años. Mediante un modelo de árbol de decisión se analizaron los posibles efectos clínicos y económicos de la infección por rotavirus con la vacunación programada de niños y sin ella. Las probabilidades y los costos unitarios se tomaron de investigaciones publicadas y de los datos oficiales nacionales. Para evaluar el impacto de diferentes estimados de los parámetros clave se realizó un análisis de sensibilidad. El análisis se efectuó tanto desde la perspectiva del sistema sanitario como de la sociedad. RESULTADOS: Se estimó que el programa de vacunación evitaría aproximadamente 1 735 351 (54 por ciento) de los 3 210 361 casos de gastroenteritis por rotavirus y 703 (75 por ciento) de las 933 muertes asociadas con la infección por rotavirus en un período de 5 años. A un precio de la vacuna de 18,6 reales brasileños (R$) por dosis, este programa costaría R$ 121 673 966 y ahorraría R$ 38 536 514 en costos directos al sistema de salud pública y R$ 71 778 377 en costos directos e indirectos a la sociedad. El costo estimado del programa por año de vida salvado sería de R$ 1 028 y R$ 1 713, desde el punto de vista de la sociedad y del sistema de salud, respectivamente. CONCLUSIONES: La estrategia de vacunación universal contra rotavirus presentó una buena relación costo-efectividad según ambas perspectivas. Sin embargo, estos resultados son muy sensibles a cambios en la incidencia de diarreas, la proporción de casos graves, la cobertura de vacunación y el precio de la vacuna.

Rotavirus morbidity and mortality in children in Brazil

OBJECTIVE: To study the epidemiology of rotavirus and estimate rotavirus-associated morbidity and mortality in children < 5 years of age in Brazil in 2004 before introducing the rotavirus vaccine in Brazil's National Immunization Program (Programa Nacional de Imunizações, PNI). METHODS: To estimate rotavirus morbidity, published studies (1999-2006) addressing incidence of acute diarrhea among children < 5 years of age and frequency of rotavirus infection among children with diarrhea in Brazil were reviewed. Diarrhea episodes were divided into three categories of severity by level of care: mild cases requiring only home-based care; moderate cases requiring a visit to an outpatient healthcare facility; and severe cases requiring hospitalization. To estimate rotavirus mortality, information on the number of registered deaths from diarrhea in children < 5 years of age was obtained from the Mortality Information System (Sistema de Informação sobre Mortalidade, SIM) of Brazil's public healthcare system (Sistema Único de Saúde, SUS) and the proportion of deaths due to rotavirus was calculated. RESULTS: Rotavirus infections were estimated to cause 3 525 053 episodes of diarrhea, 655 853 visits to outpatient healthcare facilities, 92 453 hospitalizations, and 850 deaths of children < 5 years of age each year in Brazil. CONCLUSION: Rotavirus infections are an important cause of child morbidity and mortality in Brazil.

OBJETIVOS: Analizar la epidemiología del rotavirus y estimar la morbilidad y la mortalidad asociadas con las infecciones por rotavirus en niños < 5 años de edad en Brasil en 2004, antes de incluir la vacuna contra el rotavirus en el Programa Nacional de Inmunizaciones (PNI). MÉTODOS: Para estimar la morbilidad por rotavirus se revisaron los estudios publicados (1999-2006) que abordaban la incidencia de diarrea aguda en niños < 5 años de edad y la frecuencia de las infecciones por rotavirus en niños con diarrea en Brasil. Los casos de diarrea se dividieron en tres categorías de gravedad según el nivel de atención que requirieron: casos leves que solo requirieron atención domiciliaria, casos moderados que requirieron la visita a un servicio ambulatorio de salud y casos graves que requirieron hospitalización. Para estimar la mortalidad por rotavirus se utilizó el número de muertes registradas por diarrea en niños de < 5 años, según el Sistema de Información sobre Mortalidad (SIM) del Sistema Único de Salud (SUS) de Brasil, y se calculó la proporción de muertes causadas por este virus. RESULTADOS: Se estimó que las infecciones por rotavirus causan anualmente 3 525 053 casos de diarrea, 655 853 visitas a servicios ambulatorios de salud, 92 453 hospitalizaciones y 850 muertes en niños < 5 años de edad en Brasil. CONCLUSIONES: Las infecciones por rotavirus constituyen una importante causa de morbilidad y mortalidad en Brasil.