Chez les patients avec maladies neuromusculaires (MNM) ou lésions médullaires, les modifications musculaires et squelettiques perturbent le mécanisme de toux. Les in-exsufflations mécaniques (IE-M) et les hyper-insufflations (H-I) constituent une aide instrumentale pour avoir une toux plus efficace. En France, ces dispositifs médicaux (DM) sont remboursés via des forfaits de location avec prestations de services. Cette thèse a pour objectif d'étudier le bénéfice clinique des IE-M et H-I par l'évaluation : 1) du niveau de preuve disponible via une revue systématique, 2) de leurs modalités de remboursement en France, via la constitution d'un groupe de travail, puis à l'international, via une enquête auprès du réseau international des agences d'évaluation, et, 3) des populations éligibles à ces DM via l'exploitation des bases administratives. Notre revue systématique souligne l'absence de donnée fiable disponible sur les IE-M utilisées chez les patients avec MNM. Elle rend compte de la particularité française d'utiliser des H-I. Malgré le faible niveau de preuves, le contraste avec la pratique des professionnels de santé qui considèrent ces DM efficaces et souhaitent le maintien du remboursement, peut s'expliquer par le peu d'alternatives disponibles et la possibilité d'utiliser ces DM non invasifs à domicile. Il s'agit de la seule évaluation de ces DM menée par une agence. La population éligible aux IE-M et H-I a été estimée à 3 100 par an. Ce travail encourage d'autres recherches pour assurer le meilleur traitement pour les patients comme les essais contrôlés randomisés (bien que difficiles en population rare) ou d'explorer d'autres modèles (essais randomisés par groupes) / Patients with neuromuscular disease (NMD) or spinal cord injury suffered from muscle and skeletal changes which impair cough mechanism. Mechanical in-exsufflations (MI-E) and Intermittent Positive Pressure Breathing (IPPB) are instrumental methods used for having a more effective cough. In France, theses medical devices (MD) are available to rent on a weekly fee schedule including associated services.This thesis aimed to study the clinical benefit of MI-E and IPPB by assessing: 1) the level of evidence available through a systematic review, 2) reimbursement arrangements in France, through the set-up of a multidisciplinary working group, and then internationally, through a survey of the International Network of Agencies for Health Technology Assessment, and, 3) the patient population treated with these MD through public databases’ queries.Our systematic review points lack of reliable data available on the use of MI-E in patients with NMD. It highlights the French particularity of using IPPB. The scientific evidence does not support the use of these MD but healthcare professionals are faced with the reality of medical practice. They consider these MD effective and want to keep their refund. This can be explained by the few available alternatives and the home-used possibility of these non-invasive MD. This is the only assessment of these MD conducted by an agency. The patient population treated with MI-E and IPPB has been estimated at 3 100 per year.This work stresses the need for further research to ensure best treatment for the patients such as randomized controlled trials (although difficult in a rare population) or explore other designs (cluster randomized trials).

No description available.

Expiratory muscle strength training (EMST) is a resistance exercise targeting the expiratory musculature that has predominated rehabilitation research for cough and swallowing. While there have been consistent improvements in expiratory muscle strength with EMST, and promising findings in cough and swallowing, there remains a substantial gap in our understanding of the physiologic adaptations associated with training and how to optimize rehabilitative outcomes. This dissertation consists of two studies aimed at refining EMST protocols for cough and swallowing rehabilitation. Chapter 1 is an introduction that provides an overview of exercise prescription principles, outlines what is known related to exercise protocols and EMST outcome measures, and finally describes the current research gaps and dissertation aims. Chapter 2 focuses on quantifying the relationship between resistive load and ratings of perceived exertion (RPE) during EMST, examines variability in RPE in healthy adults, and compares RPE using two respiratory devices. In Chapter 3, we examine the impact of modifying exercise parameters on physiologic adaptations and RPE, while also beginning to establish links between EMST, cough, and swallowing by assessing task specificity. Chapter 4 synthesizes the research findings into the greater scientific literature, discusses the clinical implications of this work, outlines limitations, and suggests avenues for future research.

A coqueluche é uma doença contagiosa, causada por Bordetella pertussis e B. parapertussis e as vacinas de células inteiras (WCPs) contra pertussis, embora eficazes, foram associadas a efeitos indesejáveis. Já as vacinas pertussis acelulares são menos reatogênicas, mas caras, o que as torna inviáveis para países em desenvolvimento. Nesse estudo, avaliamos a resposta imune induzida por uma vacina pertussis celular com menor teor de LOS (Plow), desenvolvida pelo Instituto Butantan. Para isso, camundongos C57BL-6 foram imunizados com WCP tradicional ou Plow, formulada com MPL-A de B. pertussis ou com Hidróxido de Alumínio e vacinas tríplice bacterianas com componente pertussis acelular, Pertacel ou Adacel. Após o esquema de imunização, foi avaliada a resposta imune humoral e celular contra a B. pertussis, e B. parapertussis, além de resposta inata a um antígeno não relacionado, BCG. Ensaio de transmissão também foi realizado, após desafio com B. pertussis ou B. parapertussis. Nossos resultados consolidam a avaliação da resposta imune humoral e celular induzida pela Plow, além de apresentar resultados bastante interessantes relativos à atividade da Plow na diminuição da transmissão bacteriana, tanto de pertussis quanto de parapertussis. / Bordetella pertussis and B. parapertussis are the causative agents of whooping cough. Whole cell pertussis (wPs) vaccines, although effective, were associated with undesirable effects. On the other hand, aP vaccines are less reactogenic, but expensive, which made their use unable for developing countries. In this study, we assessed the immunological response, induced by a whole cell pertussis vaccine with low LOS content (Plow), developed by Instituto Butantan. To this, C57BL-6 mice were immunized with traditional whole cell pertussis vaccine or Plow, administrated with Monophosporil lipid A from B.pertussis or Aluminum hydroxide, and diphtheria-tetanus-acellular pertussis vaccines, Pertacel or Adacel. After the immunization scheme, were evaluated humoral and cellular immune responses against B. pertussis and B. parapertussis, in addition to innate response to an unrelated antigen, BCG. Transmission assay was also performed, after B. pertussis or B. parapertussis challenge. Our results consolidated the immune humoral and cellular responses induced by Plow, besides interesting results with regards the efficacy of the vaccine in decreasing the transmission of B. pertussis and B. parapertussis in mice.

Introdução: A vacina tríplice acelular de adultos (dTpa) foi introduzida no Programa Nacional de Imunizações (PNI) em novembro de 2014, sendo recomendada para gestantes e profissionais de saúde (PS) que têm contato com gestantes e recém-nascidos. De abril a dezembro de 2015, foram implementadas várias estratégias para aumentar a cobertura vacinal entre os profissionais do Instituto Central do Hospital das Clínicas da FMUSP. Objetivos: Avaliar a cobertura vacinal entre os PS após implementação de cada estratégia e ao término de um ano; avaliar as variáveis associadas à vacinação; e avaliar os principais motivos de não vacinação entre os PS com indicação para tal. Métodos: Estratégias implementadas: divulgação, no boletim do hospital, de texto relembrando da necessidade de vacinação de coqueluche; reforço da necessidade da vacinação, via correio eletrônico, para as chefias de enfermagem das Divisões de Clínica Obstétrica, Neonatologia e Anestesia; aulas sobre a vacina dTpa nas reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; e vacinação ativa dos profissionais na Divisão de Clínica Obstétrica, Neonatologia e Anestesia. A cobertura vacinal foi avaliada ao fim de cada mês até abril de 2016, por meio do sistema informatizado de vacinação usado no CRIE-HC. Foi usado o modelo de regressão de Poisson com variância robusta para avaliação das variáveis associadas com a vacinação com dTpa. As razões de prevalência foram calculadas e seus intervalos de confiança de 95% estimados. Para avaliar os motivos de não vacinação, foram realizadas ligações telefônicas para os profissionais que não receberam a vacina e aplicado questionário padronizado. Resultados: Entre os 515 PS elegíveis para vacinação, 59 não possuíam registro no sistema informatizado de vacinação e foram excluídos. Assim, este estudo incluiu 456 PS. Após as intervenções, a cobertura vacinal com dTpa aumentou de 2,9% para 41,2%. As coberturas vacinais após a implementação de cada estratégia foram: 3,7% após publicação no Boletim do hospital; 10,5% após mensagem de correio eletrônico para as chefias de enfermagem; 16,2% após aula sobre a vacina em reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; 27,9% após vacinação ativa na Divisão de Clínica Obstétrica; 40,6% após vacinação ativa na Divisão de Neonatologia e 41,2% após vacinação ativa na Divisão de Anestesia. Na análise multivariada, ser médico (a), trabalhar nas Divisões de Clínica Obstétrica ou Anestesia e ter recebido a vacina de influenza de 2015 foram associados à vacinação com dTpa. Foi feito contato telefônico com 39 profissionais que não receberam a vacina em nosso serviço; apenas 9 (23%) referiram ter recebido a vacina em outros serviços; e dos 30 não vacinados, 27 (90%) alegaram desconhecimento da recomendação. Conclusões: Conhecimento sobre a doença e a recomendação de vacinação são importantes para aumentar a cobertura vacinal entre PS. Porém, mesmo sabendo do efeito cumulativo na cobertura vacinal a cada estratégia realizada, a vacinação ativa dos PS em seus locais de trabalho parece ter sido a estratégia que mais contribuiu para o aumento da cobertura. A cobertura vacinal final de dTpa permanece baixa e maiores esforços são necessários para aumentá-la / Introduction: The acellular pertussis vaccine for adults (Tdap) was introduced in the Brazilian National Immunization Program (PNI) in November 2014, being recommended for pregnant women and healthcare workers (HCWs) who have contact with pregnant women and newborns. From April to December 2015, interventions to raise Tdap coverage among HCWs of the Instituto Central do Hospital das Clínicas were implemented. Objective: To evaluate the cumulative vaccine coverage after each intervention; identify factors associated to Tdap vaccination among HCWs; and evaluate the main reasons for HCWs not receiving Tdap. Methods: Interventions implemented: a note on the hospital\'s internal newsletter, reminding HCWs of the importance of pertussis vaccination; email to the nurse´s teams leaders strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. The vaccine coverage was evaluated at the end of each month until April-2016. A multivariate Poisson regression model with robust error variance was used to evaluate variables associated with Tdap vaccination. Prevalence ratios (PR) and their 95%CI were estimated. To evaluate the reasons for HCWs not to be vaccinated, those who have not received Tdap were called by phone and a standard questionnaire was applied. Results: Among 515 HCWs eligible for immunization, 59 professionals were not registered in the vaccination data system and were excluded because information about Tdap vaccine could not be achieved. The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.9% to 41.2%. The vaccine coverage after each intervention was: 3.7% after a note on the hospital\'s internal newsletter; 10.5% after email to the nurse´s teams leaders strengthening vaccine recommendations; 16.2% after lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; 27.9% after on-site vaccination by mobile teams at the Obstetrics Clinic; 40.6% after on-site vaccination at the Neonatology Clinic and 41.2% after on-site vaccination at the Anesthesiology Clinic. In the multiple analysis, occupation, working place and having received influenza vaccination in 2015 were independently associated to Tdap vaccination. Thirty-nine HCWs that have not received Tdap were contacted by phone: 90% of them claimed they did not know the vaccine recommendation. Conclusions: Knowledge about pertussis and the recommendation of vaccination are important to raise vaccine coverage between HCWs. Even knowing the cumulative effect of each strategy on vaccine coverage, HCWs vaccination in their workplaces seems to be the most effective strategy in raising coverage. The final Tdap coverage remains low and greater efforts are needed to increase it

A proteína Cpn60 faz parte de um grupo de proteínas altamente conservadas que estão envolvidas em funções celulares essenciais. camundongos BALB\\c foram imunizados com 5 ou 10 µg da proteína recombinante (Cpn60r) sozinha ou adicionada à vacina DTP sem hidróxido de alumínio (NADTP). A vacina DTP do Instituto Butantan (DTP) foi usada como controle. Foi avaliada a produção de citocinas por células esplênicas após reestímulo in vitro com a Cpn60r. Os animais foram desafiados após o protocolo de imunização. A Cpn60r sozinha ou misturada à vacina NADTP foi capaz de induzir níveis de anticorpos contra pertussis mais altos do que os induzidos pela DTP. Os níveis de IgG1 e IgG2a foram similares para todos os grupos. Pôde-se observar a produção de de IL-6 e IFN-&#947 nos grupos imunizados com Cpn60r. Os grupos imunizados com Cpn60r+NADTP apresentaram um índice de proteção entre 60 e 80% contra o desafio pela bactéria virulenta, semelhante ao grupo imunizado com DTP. A proteína Cpn60r é bastante promissora não somente como imunógeno, mas também como adjuvante. / The Cpn60 protein is a member of a group of higly conserved proteins linked to essencial cell functions. The Cpn60 was cloned, expressed and its immune response has been evaluated. BALB\\c mice were immunized with 5 or 10 µg of the recombinant protein (Cpn60r) alone or mixed with DPT vaccine without aluminum hidroxyde (NADPT). The DPT vaccine from Instituto Butantan was used as control. We evaluated the cytokines production by spleen cells after they have been reestimulated in vitro with Cpn60r. The animals were challenged after the immunization protocol. The Cpn60r alone or mixed with NADPT vaccine was able to induce higher antibodies levels than DPT. IgG1 and IgG2a levels were similar in all groups. We could detect levels of IL-6 and IFN-&#947 on groups immunized with Cpn60r. The groups immunized with Cpn60r+NADTP showed a 60 and 80% protection rate against the challenge with the live bacteria, similar to the group immunized with DPT. These results show the immune response of the recombinant protein that could be included in immunization protocols for pertussis.

A coqueluche vem reemergindo enquanto importante problema de saúde pública em vários países do mundo, apesar das altas coberturas vacinais na infância. O objetivo geral deste estudo foi avaliar a morbimortalidade da coqueluche no Brasil e os objetivos específicos foram: estimar as taxas de mortalidade, incidência e letalidade anuais, geral e por faixa etária, por unidade da federação e regiões do país; caracterizar a sazonalidade da doença; estimar as taxas de hospitalização anuais por faixa etária e verificar as características clínicas, histórico de contato e vacinação prévia dos casos notificados da doença. Métodos: estudo descritivo, baseado nos casos de coqueluche notificados ao Sistema de Informação de Agravos de Notificação (SINAN), de 2006 a 2013. Os resultados mostraram aumento nas taxas de incidência de coqueluche no Brasil, a partir de 2011. Em 2013, foram confirmados 6.523 casos de coqueluche no país, três vezes o número de casos confirmados em 2011, com incidência geral de 3,24 /100.000 habitantes e incidência em menores de um ano de 125,82/100.000 habitantes, as maiores durante o período estudado. As crianças menores de um ano foram as mais acometidas pela doença em todas as macrorregiões. Em 2013, todas as regiões, exceto a região sul, apresentaram suas maiores taxas de incidência geral, com destaque para as regiões sudeste e centro-oeste com 4,0 e 3,1 por 100.000 habitantes, respectivamente. As maiores taxas de letalidade foram observadas na faixa etária menor de dois meses de idade, variando de 4,0% (2008) a 9,5% (2010). As taxas de letalidade foram maiores em crianças menores de seis meses em todas as regiões, sendo as regiões nordeste e sudeste as que apresentaram maiores taxas ao longo dos anos, exceto em 2013, quando o centro-oeste superou o nordeste. Houve predomínio dos casos nos meses mais quentes, entre novembro e março. A maioria das hospitalizações ocorreu na faixa etária de menores de um ano, principalmente em menores de quatro meses, cuja frequência de hospitalização ficou em torno de 75%. A tosse e o paroxismo foram os sintomas mais frequentes, independente da faixa etária, e a cianose foi importante sintoma nos menores de dois meses, com uma frequência de 80% nos casos confirmados desta faixa etária. A complicação mais comum foi pneumonia (13,93%), principalmente na faixa etária menor de dois meses, com frequência de 27,5%. O critério mais utilizado para diagnóstico de coqueluche foi o clínico, seguido pelo laboratorial que aumentou a partir de 2011, ano em que foi responsável por 49,9% dos diagnósticos. A maioria dos casos confirmados (51%) não relatou contato prévio com casos suspeitos ou confirmados de coqueluche, no entanto quando presente, a maioria dos contatos ocorreu no domicílio (70,6%). Os resultados mostraram aumento dos casos de coqueluche no Brasil, a partir de 2011, com as maiores taxas de incidência, hospitalizações, complicações e letalidade na faixa etária de menores de um ano / Pertussis has reemerged as important public health problem in many countries, despite the high childhood vaccination coverage. The general aim of this study was to evaluate the morbimortality of pertussis in Brazil, and the specific objectives were: estimate the annual mortality, incidence and case-fatality rates, general and by age group, by federative units and country\'s regions; evaluate the disease seasonality; estimate the annual hospitalization rates by age group and verify the clinical characteristics, contact history and the previous vaccination status of the reported pertussis cases. Methods: Descriptive study, based on the pertussis cases reported to the Notifiable Diseases Information System (SINAN), from 2006 to 2013. In 2013, there were 6.523 confirmed pertussis cases in the country, three times the number of confirmed cases in 2011, with general incidence of 3.24/100,000 inhabitants, and incidence in children under one year of age of 125.82/100,000 inhabitants, the highest during the study period. Pertussis incidence rates were higher in children under one year old in all macroregions during the study. In 2013, higher general incidence rates were observed in all regions, except the south, particularly the southwest and Midwest with 4.0 and 3.1 per 100,000 inhabitants, respectively. The highest case-fatality rates were observed in infants under two months of age, varying from 4.0% (2008) to 9.5% (2010). Case-fatality rates were higher in children under six months in all regions; the northeast and southeast had the highest rates throughout the studied years, except in 2013, when the Midwest surpassed the northeast. More cases were reported in the warmer months, between November and March. Most hospitalizations occurred in the age group of children under one year old, mainly those under four months, for whom hospitalization rates were close to 75%. Cough and paroxysm were the most frequently symptoms, regardless of age, and cyanosis was important in children under two months, occurring in 80% of confirmed cases in this age group. The most common complication was pneumonia (13.93%), mainly in children under two months of age (27.5%). Clinical criteria were most frequent used for diagnosis, followed by laboratory, which increased since 2011, when 49.9% of cases had laboratory-confirmed diagnosis. Most confirmed cases (51%) had no recognized previous contact with pertussis cases. Among those with recognized previous contact, it mostly occurred at residence (70.6%).The results showed an increase in pertussis cases in Brazil, since 2011, with the highest incidence and lethality rates in children under one year of age

Le paludisme, la tuberculose et les infections respiratoires aiguës constituent un enjeu majeur de santé publique à Madagascar, les deux premières de ces maladies faisant l’objet de programmes nationaux de lutte largement inspirés et financés par des organisations internationales. Les méthodes diagnostiques, thérapeutiques et de prévention recommandées officiellement dans le système de santé conventionnel sont standardisées et reposent sur un corpus de connaissances scientifiques solidement établi. Parmi d’autres maladies, elles font explicitement partie des cibles des objectifs du développement durable (ODD). Pour les atteindre, les nations unies recommandent la mise en œuvre d’une Couverture Sanitaire Universelle (CSU). Madagascar a adopté les ODD et s’est engagé dans la voie de la mise en œuvre d’une CSU. Ces travaux sur le paludisme, la tuberculose et les infections respiratoires aiguës ont été menés dans le cadre de cette thèse de sociologie, en utilisant une approche qualitative (auprès de 83 individus) et quantitative (auprès d’environ 26.000 personnes interrogées, par enquêtes en populations), sur plusieurs terrains de Madagascar, impliquant des soignants, des soignés et des acteurs institutionnels. L’acceptation et la mise en œuvre des méthodes de prise en charge des maladies dépendent de facteurs logistiques et organisationnels, mais aussi des croyances et pratiques adoptées par les individus, les familles et les groupes sociaux ou professionnels. En pratique, les obstacles sont nombreux sur la voie d’un accès effectif des populations aux soins contre les maladies ciblées par les ODD et la CSU, y compris celles faisant déjà l’objet de programmes de lutte verticaux et soutenus internationalement. Les éléments représentatifs des zones étudiées dans cette thèse apportent un éclairage qui peut être utile pour la mise en œuvre d’une CSU à l’échelle du pays. Ils révèlent aussi les défis, pas seulement financiers, qui restent à surmonter. / Malaria, tuberculosis and acute respiratory infections constitute a major public health issue in Madagascar, the first two of which are the subject of national control programs largely inspired and financed by international organizations. The diagnostic, therapeutic and preventive methods recommended officially in the conventional health system are standardized and are based on a solid corpus of scientific knowledge. Among other diseases, they are explicitly targeted by the universal sustainable development goals (SDG). To reach them, the United nations recommend the implementation of an universal health coverage (UHC). Madagascar has adopted the SDG and is committed to the implementation of a UHC. The acceptance and implementation of these disease management methods depend on logistical and organizational factors, but also on the beliefs and practices of individuals, families and social or professional groups. In practice, there are many obstacles in the way of effective access to health care for diseases targeted by SDG and UHC, including those already covered by vertical and internationally supported control programs. These works on malaria, tuberculosis and acute respiratory infections were carried out within the framework of this sociological thesis, using a qualitative methods (among 83 individuals) and quantitative methods (with about 26,000 people interviewed), by population surveys, on several fields in Madagascar, involving caregivers, cared population and institutional actors. The acceptance and implementation of these disease management methods depend on logistical and organizational factors, but also on the beliefs and practices of individuals, families and social or professional groups. In practice, there are many obstacles in the way of effective access to health care for diseases targeted by SDGs and UHC, including those already covered by vertical and internationally supported control programs. The representative elements of the studied zones of Madagascar presented in this thesis provide an insight that could be useful for the implementation of a CSU across the country. They also reveal the challenges, not just financial, that remain to be overcome.

INTRODUÇÃO: Uma epidemia de coqueluche ocorreu no Brasil, de 2011 a 2014. Isto levou à introdução da vacina tríplice acelular de adultos (dTpa) no calendário público de vacinação da gestante. Existem outras estratégias de vacinação envolvendo a dTpa, que poderiam complementar o controle da doença. Os objetivos deste estudo são descrever a epidemiologia da doença e avaliar custo-efetividade da vacinação de adultos com dTpa. MÉTODOS: 1) Uma revisão de literatura foi realizada nas bases MEDLINE, Excerpta Medica, CRD e Lilacs a partir de 2000. 2) Foi desenvolvido estudo observacional incluindo dados de vacinação e os casos notificados para o sistema de vigilância no Estado de São Paulo (ESP), de 2001 a 2015. 3) Foi realizado estudo descritivo dos pacientes com idade de 20 a <40 anos atendidos em um hospital do ESP entre 2010 e 2014, destacando-se a utilização de serviços de saúde. 4) Foi desenvolvido modelo dinâmico, para comparar a estratégia de vacinação com dTpa aos 20 anos de idade com o programa atual (vacinação com dT). Dados epidemiológicos e de custos foram retirados de sistemas de informação de saúde e da literatura nacional e internacional. Foram considerados como desfecho número de casos e mortes por coqueluche e anos de vida ganho (AVG). Considerouse a perspectiva do sistema de saúde, horizonte temporal de vinte anos e custos em Reais (R$) de 2015. Os resultados foram sumarizados em razão de custo-efetividade incremental (RCEI). Análises de sensibilidade uni e multivariadas foram realizadas. RESULTADOS: 1) Foram revisadas 28 avaliações econômicas de estratégias com dTpa. A vacinação de adolescentes e de adultos foram as mais avaliadas. A correção da subnotificação, uso de modelos dinâmicos, proteção de rebanho e altas coberturas vacinas influenciaram para o bom desempenho das estratégias. 2) Houve aumento de incidência da coqueluche entre 2011 e 2014 e queda da mesma em 2015, em todas as faixas etárias no ESP. Os lactentes foram os principais acometidos, mas a proporção de casos nessa faixa etária apresentou tendência de queda ao longo dos anos. A proporção de casos com idade de 1 a < 4, 5 a = 20 anos aumentou significativamente. Houve queda não significativa na proporção dos casos com idade < 2 meses de idade. 3) Entre 36 casos estudados no hospital, 33,3% passou por consulta prévia, 25,3% por consulta de retorno e 8,33% foram hospitalizados. Hemograma e radiografia de tórax foram os exames mais realizados. Não houve complicações ou óbito. 4) A vacinação de adultos com dTpa, com cobertura vacinal de 40% e efetividade de 75%, incluindo proteção de rebanho para os menores de um ano, evitaria 19.300 casos sintomáticos e 221 óbitos em 10 anos. A RCEI seria R$28.054,38/AVG. Na análise de sensibilidade, os resultados foram mais sensíveis a variações da incidência e à retirada da proteção de rebanho. CONCLUSÃO: O comportamento cíclico da doença é a principal causa da epidemia de coqueluche entre 2011 e 2014 e queda da incidência em 2015. A vacinação de adultos com dTpa não se mostrou custo-efetiva na realidade brasileira de 2015 / INTRODUCTION: A pertussis outbreak occurred in Brazil from 2011 to 2014. This led to the introduction of the maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) in the public immunization schedule. There are other vaccination strategies involving Tdap, which could complement the strategies of disease control. The objectives of this study are to describe the epidemiology of the disease and to evaluate cost-effectiveness of vaccination of adults with Tdap. METHODS: 1) A review was performed in the MEDLINE, Excerpta Medica, CRD and Lilacs databases from 2000. 2) Observational study was performed including vaccination data and the cases reported data from health surveillance datasets in the State of São Paulo from 2001 to 2015. 3) A descriptive study of patients aged 20 to < 40 years attended at a State of São Paulo hospital between 2010 and 2014 was performed, highlighting the use of health services.4) A dynamic model was developed to compare the vaccination strategy with Tdap at the age of 20 years with the current program (dT vaccination). Epidemiological and cost data were collected from health information systems and national and international studies. Number of cases and deaths by pertussis and life years saved (LYS) were considered as outcome. It was considered the health system perspective, a time horizon of 20 years and costs in 2015 Real (R$). The results were summarized by incremental costeffectiveness ration (ICER). Univariate and multivariate sensitivity analyzes were performed. RESULTS: 1) 28 economic evaluations of strategies with Tdap were reviewed. Vaccination of adolescents and adults were the most evaluated strategies. Underreporting correction, use of dynamic models, herd protection and high vaccination coverage influenced positively the performance of strategies. 2) The incidence of pertussis increased between 2011 and 2014, and its fall in 2015, among all age groups. Infants were the main affected, but the proportion of cases in this age group showed a downward trend over the years. The proportion of cases aged 1 to < 4, 5 to = 20 years increased significantly. There was a non-significant decrease in the proportion of cases aged < 2 months of age. 3) Among 36 cases studied in the hospital, 33.3% had a prior medical visit, 25.3% a return visit, and 8.33% were hospitalized. Blood count and chest X-ray were the most performed exams. There were no complications or death. 4) Vaccination of adults with Tdap, with 40% vaccine coverage and 75% effectiveness, including herd protection for children less than one year, would prevent 19,300 symptomatic cases and 221 deaths in 10 years. The ICER would be R$ 28,054.38/AVG. In the sensitivity analysis, the results were more sensitive to variations in incidence and withdrawal of herd protection. CONCLUSION: The cyclical pattern of the disease is the main cause of the pertussis epidemic between 2011 and 2014, and decreasing incidence in 2015. Adult vaccination with Tdap was not cost-effective in the 2015 Brazilian scenario

Introdução: A vacina tríplice acelular de adultos (dTpa) foi introduzida no Programa Nacional de Imunizações (PNI) em novembro de 2014, sendo recomendada para gestantes e profissionais de saúde (PS) que têm contato com gestantes e recém-nascidos. De abril a dezembro de 2015, foram implementadas várias estratégias para aumentar a cobertura vacinal entre os profissionais do Instituto Central do Hospital das Clínicas da FMUSP. Objetivos: Avaliar a cobertura vacinal entre os PS após implementação de cada estratégia e ao término de um ano; avaliar as variáveis associadas à vacinação; e avaliar os principais motivos de não vacinação entre os PS com indicação para tal. Métodos: Estratégias implementadas: divulgação, no boletim do hospital, de texto relembrando da necessidade de vacinação de coqueluche; reforço da necessidade da vacinação, via correio eletrônico, para as chefias de enfermagem das Divisões de Clínica Obstétrica, Neonatologia e Anestesia; aulas sobre a vacina dTpa nas reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; e vacinação ativa dos profissionais na Divisão de Clínica Obstétrica, Neonatologia e Anestesia. A cobertura vacinal foi avaliada ao fim de cada mês até abril de 2016, por meio do sistema informatizado de vacinação usado no CRIE-HC. Foi usado o modelo de regressão de Poisson com variância robusta para avaliação das variáveis associadas com a vacinação com dTpa. As razões de prevalência foram calculadas e seus intervalos de confiança de 95% estimados. Para avaliar os motivos de não vacinação, foram realizadas ligações telefônicas para os profissionais que não receberam a vacina e aplicado questionário padronizado. Resultados: Entre os 515 PS elegíveis para vacinação, 59 não possuíam registro no sistema informatizado de vacinação e foram excluídos. Assim, este estudo incluiu 456 PS. Após as intervenções, a cobertura vacinal com dTpa aumentou de 2,9% para 41,2%. As coberturas vacinais após a implementação de cada estratégia foram: 3,7% após publicação no Boletim do hospital; 10,5% após mensagem de correio eletrônico para as chefias de enfermagem; 16,2% após aula sobre a vacina em reuniões científicas das Divisões de Clínica Obstétrica e Neonatologia; 27,9% após vacinação ativa na Divisão de Clínica Obstétrica; 40,6% após vacinação ativa na Divisão de Neonatologia e 41,2% após vacinação ativa na Divisão de Anestesia. Na análise multivariada, ser médico (a), trabalhar nas Divisões de Clínica Obstétrica ou Anestesia e ter recebido a vacina de influenza de 2015 foram associados à vacinação com dTpa. Foi feito contato telefônico com 39 profissionais que não receberam a vacina em nosso serviço; apenas 9 (23%) referiram ter recebido a vacina em outros serviços; e dos 30 não vacinados, 27 (90%) alegaram desconhecimento da recomendação. Conclusões: Conhecimento sobre a doença e a recomendação de vacinação são importantes para aumentar a cobertura vacinal entre PS. Porém, mesmo sabendo do efeito cumulativo na cobertura vacinal a cada estratégia realizada, a vacinação ativa dos PS em seus locais de trabalho parece ter sido a estratégia que mais contribuiu para o aumento da cobertura. A cobertura vacinal final de dTpa permanece baixa e maiores esforços são necessários para aumentá-la / Introduction: The acellular pertussis vaccine for adults (Tdap) was introduced in the Brazilian National Immunization Program (PNI) in November 2014, being recommended for pregnant women and healthcare workers (HCWs) who have contact with pregnant women and newborns. From April to December 2015, interventions to raise Tdap coverage among HCWs of the Instituto Central do Hospital das Clínicas were implemented. Objective: To evaluate the cumulative vaccine coverage after each intervention; identify factors associated to Tdap vaccination among HCWs; and evaluate the main reasons for HCWs not receiving Tdap. Methods: Interventions implemented: a note on the hospital\'s internal newsletter, reminding HCWs of the importance of pertussis vaccination; email to the nurse´s teams leaders strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. The vaccine coverage was evaluated at the end of each month until April-2016. A multivariate Poisson regression model with robust error variance was used to evaluate variables associated with Tdap vaccination. Prevalence ratios (PR) and their 95%CI were estimated. To evaluate the reasons for HCWs not to be vaccinated, those who have not received Tdap were called by phone and a standard questionnaire was applied. Results: Among 515 HCWs eligible for immunization, 59 professionals were not registered in the vaccination data system and were excluded because information about Tdap vaccine could not be achieved. The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.9% to 41.2%. The vaccine coverage after each intervention was: 3.7% after a note on the hospital\'s internal newsletter; 10.5% after email to the nurse´s teams leaders strengthening vaccine recommendations; 16.2% after lectures on pertussis and Tdap for physicians at the clinical meetings of the Obstetrics and Neonatology Clinics; 27.9% after on-site vaccination by mobile teams at the Obstetrics Clinic; 40.6% after on-site vaccination at the Neonatology Clinic and 41.2% after on-site vaccination at the Anesthesiology Clinic. In the multiple analysis, occupation, working place and having received influenza vaccination in 2015 were independently associated to Tdap vaccination. Thirty-nine HCWs that have not received Tdap were contacted by phone: 90% of them claimed they did not know the vaccine recommendation. Conclusions: Knowledge about pertussis and the recommendation of vaccination are important to raise vaccine coverage between HCWs. Even knowing the cumulative effect of each strategy on vaccine coverage, HCWs vaccination in their workplaces seems to be the most effective strategy in raising coverage. The final Tdap coverage remains low and greater efforts are needed to increase it