La truite arc-en-ciel (Oncorhynchus mykiss), espèce d'élevage majeure en Europe et notamment en France, est l'une des espèces de poisson les mieux connues dans un grand nombre de domaines, y compris l'immunologie. Les virus qui l'infectent ont aussi été bien caractérisés, en particulier deux Novirhabdovirus, le virus de la septicémie hémorragique virale (VSHV) et le virus de la nécrose hématopoïétique infectieuse (VNHI), tous deux connus pour provoquer des pertes importantes dans les élevages aquacoles. Quelques travaux, conduits notamment à l'INRA, ont mis en évidence l'existence d'une variabilité génétique de la résistance à ces infections chez la truite (Quillet et al., 2007). Une approche combinant analyse génétique et étude des réponses cellulaires a été développée pour tenter de mieux caractériser la réponse de la truite contre le VSHV. L'objectif est de développer des outils d'amélioration de la santé dans les élevages piscicoles et de mieux comprendre les mécanismes de résistance antivirale chez les vertébrés. Tout d'abord, une démarche de cartographie de QTL (quantitative trait locus) a permis de détecter un QTL majeur de résistance au VSHV dans la région télomérique du groupe de liaison 31 de la truite arc-en-ciel. Ce QTL contrôle la survie des poissons et la croissance in vitro du virus sur explants de nageoire (VREFT), ce qui suggère fortement l'implication de mécanismes innés dans la résistance. Le QTL est retrouvé dans des croisements impliquant des reproducteurs de résistance variée, et peut expliquer jusqu'à 65% (survie) et 49% (VREFT) de la variance phénotypique observée. Enfin, l'effet du QTL est conservé quel que soit le mode d'infection employé (balnéation ou injection intrapéritonéale), suggérant que la résistance n'est pas liée à des particularités des tissus superficiels (peau, mucus), premiers sites de contact entre le virus et son hôte. En parallèle, des lignées cellulaires ont été dérivées à partir d'ovaires de truites appartenant à des lignées isogéniques présentant des niveaux de résistance variable à l'infection par le VSHV. Une corrélation remarquable est observée entre la résistance à l'infection des lignées cellulaires et la survie des poissons dont elles sont issues, confirmant définitivement le rôle déterminant de mécanismes innés dans la résistance. Ce modèle cellulaire a également permis de montrer que le contrôle précoce de la prolifération virale était une étape clé de la résistance. Le parallélisme entre résistance in vitro et in vivo semble conservé lors de l'infection par un second rhabdovirus, le VNHI, bien qu'aucune corrélation dans la résistance à ces deux infections n'ait été observée dans cette étude. Par ailleurs, le QTL à effet fort identifié pour la résistance au VSHV ne joue pas un rôle majeur dans la variabilité de résistance au VNHI. Ceci suggère que, même si ils concourent à l'activation de voies de signalisation communes, les facteurs clés de la résistance aux deux virus sont différents, et leur expression contrôlée par des zones génomiques distinctes. Les résultats obtenus dans cette étude ont permis de démontrer sans équivoque le rôle clé des mécanismes innés dans la résistance de la truite à l'un de ses principaux virus, et l'existence d'une forte variabilité génétique sous-tendant l'expression des facteurs impliqués. En proposant des bases nouvelles pour aborder l'analyse des interactions hôte-virus chez la truite, ils ouvrent la voie à la découverte de mécanismes potentiellement nouveaux dans la réponse des poissons à ces infections et à une meilleure compréhension de ces mécanismes chez les vertébrés. / The rainbow trout (Oncorhynchus mykiss) is one of most significant fish model in many scientific fields, including immunology. Due to its importance in aquaculture, viruses that can infect this species have been well characterized. Two well-known Novirhabdoviruses, the viral haemorrhagic septicemia virus (VHSV) and the infectious hematopoietic necrosis virus (IHNV) cause serious damage in fish farms and represent a significant threat for aquaculture in a number of countries. Our laboratories have previously reported a wide range of susceptibility to these infections in rainbow trout depending on the host genetic background (Quillet et al., 2007). In this work, we undertook a dual approach to better characterize the antiviral response in fish. A without a priori approach led to the detection of a major QTL (quantitative trait locus) for resistance to VHSV in the telomeric region of the rainbow trout linkage group 31. This QTL controls both fish survival and viral replication in excised fin tissue (VREFT), suggesting the involvement of innate mechanisms in the resistance, and can explain up to 65% (survival) and 49% (VREFT) of the observed phenotypic variation. Additionally, this major locus was retrieved in a number of genetic backgrounds, and regardless of the infection route (waterborne infection or injection), suggesting that the virus entry in fish is not the main factor of resistance. In parallel, cell lines were derived from ovaries of several rainbow trout isogenic lines with various levels of susceptibility to infection with VHSV. Resistance of cell lines to infection by the virus was remarkably correlated with the survival of fish from which they were derived, confirming the importance of innate factors for the resistance. This model also showed that the early stage response is critical for the cellular fate after infection. The parallelism between resistance in vitro and in vivo has finally been observed after infection by a second rhabdovirus, IHNV, although no correlation in resistance to these two viruses could be detected. Moreover, no major QTL for IHNV resistance was found in the region of the VHSV QTL. This observation suggests that the key factors of resistance are different, even if they contribute to the activation of common signaling pathways. The expression of these factors is in any case controlled by distinct regions of the genome. Our work demonstrates a strong genetic determinism of resistance to a major virus in rainbow trout, based on innate mechanisms. We believe that these results pave the way for the discovery of new host response mechanisms against viruses, leading to a better understanding of antiviral immunity in vertebrates.

Nosokomiale Infektionen (NKI) gehören zu den häufigsten Komplikationen eines Krankenhausaufenthaltes, insbesondere auf Intensivstationen mit einer Prävalenz von rund 18,65%. Die Folgen sind eine längere Verweildauer, erhöhte Morbidität und Letalität sowie höhere Kosten für das Gesundheitssystem. Die Erfassung NKI stellt einen wichtigen Qualitäts- Parameter für Intensivstationen dar. Ziel dieser Arbeit war es, die Übereinstimmung von nur nach KISS (Krankenhaus-InfektionsSurveillance System)- Definitionen erfassten Infektionen mit der klinisch diagnostizierten nosokomialen Infektion zu prüfen und den Zusammenhang zwischen ärztlicher Diagnose und den laborchemischen und klinisch erhobenen Kriterien darzustellen. Hierfür wurden auf einer interdisziplinären operativen Intensivstation nosokomiale Infektionen sowohl nach ITS- KISS (VAP, ZVK- assoziierte Infektionen und HWI), als auch nach ärztlicher Diagnose plus Beginn oder Eskalation einer Antibiotikatherapie erfasst. Zusätzlich zu den KISS-Parametern wurden laborchemische Entzündungsparameter (CRP und PCT) registriert. Es traten 32 Infektionen nach ITS- KISS und 69 Infektionen nach ärztlicher Diagnose auf. Acht Infektionen wurden ausschließlich nach KISS und 45 ausschließlich nach der ärztlichen Diagnose erfasst. Die Infektionsrate nach KISS für VAP lag bei 20,6, für ZVK bei 5,9 und für HWI bei 2 Infektionen, jeweils pro 1000 Devicetage. Spezifität und positiv prädiktiver Wert hinsichtlich der Vorhersage einer ärztlich diagnostizierten Infektion waren gering. Auch durch Kombination verschiedener Parameter wurden keine höheren prädiktiven Werte erreicht. Die geringe Übereinstimmung der beiden Methoden legt nahe, dass KISS die klinisch relevanten Infektionen nicht wesentlich erfasst und relevante Infektfoci nicht berücksichtigt werden, beispielsweise abdominelle Infektionen. Zudem erlauben die erfassten Laborparameter keine zuverlässige Diagnose bzw. Prädiktion einer nosokomialen Infektion. Die ärztliche Diagnose in Verbindung mit dem Beginn oder der Eskalation einer Antibiotikatherapie könnte eine vereinfachte Methode zur Surveillance nosokomialer Infektionen darstellen.

Les poux sont de véritables marqueurs pour l'étude de l'évolution humaine car ils ont été associés à l’homme depuis nos ancêtres et se sont dispersés à travers le monde avec ses différentes migrations. Les poux de tête et les poux de corps ont été étudiés morphologiquement depuis longtemps. Les poux de tête vivent et pondent leurs lentes dans les cheveux tandis que les poux de corps vivent et pondent leurs lentes dans les vêtements. Ces derniers sont associés à une mauvaise hygiène de vie et sont responsables de la transmission du typhus épidémique, de la fièvre des tranchées et de la fièvre récurrente. L’un des objectifs de ma thèse était d'accroître les connaissances sur les poux de tête et les poux de corps de l’homme afin d’assurer un meilleur contrôle. Il est essentiel de déterminer si les poux de tête et les poux de corps sont allopatriques ou s’ils pourraient exister en sympatrie. Ainsi, les études d'ADN mitochondrial ont montré qu'il y a trois clades clairement divergents des poux de tête (A, B et C) et un seul clade des poux de corps qui est partagé avec les poux de tête (clade A). Chaque clade a une répartition géographique bien déterminée. / Lice are effective markers for studying human evolution because they have been parasitizing humans since the emergence of our hominid ancestors and have been dispersed throughout the world by early human migrations. Human head and body lice have been studied morphologically for a long time. Head lice live and lay their eggs in human hair. Body lice live and lay their eggs in clothes, are associated with poor hygiene in clothing and are responsible for the transmission of epidemic typhus, trench fever and relapsing fever. One aim of my thesis was to increase the knowledge of human head lice and body lice for a better control. It is critical to determine if head lice and body lice are allopatric, with distinct epidemiology, or if they might exist in sympatry. Then, mitochondrial DNA studies have shown that there are three clearly divergent clades of head lice (A, B and C) and that only one clade of body lice is shared with head lice (clade A). Each clade has a unique geographic distribution. During the thesis work, extensive literature survey was done to write a review. Then we aimed to establish a molecular tool in order to distinguish between head and body lice. We found that only one gene (Phum_PHUM540560 gene) was able to differentiate the two ecotypes of Pediculus humanus. Moreover, we aimed to estimate the correlation between phenotypes and genotypes among human lice, and we found that the lice phylogeny (based on intergenic spacers) was correlated to the geographic origin of lice, but no correlation between the color and the phylogeny.

No description available.

L’infection congénitale à cytomégalovirus (CMV) représente l’infection congénitale la plus fréquente et est la cause principale de retard mental acquis et de déficience auditive neurosensorielle d’origine infectieuse chez le nouveau-né. Le risque de transmission au fœtus en cas de primo-infection maternelle est de 30 à 40%, et d’environ 1.4% chez les femmes séropositives pour le CMV avant la grossesse. L’analyse de la littérature montre que de nombreuses questions subsistent dans le domaine du CMV congénital. Le screening sérologique des femmes enceintes n’est pas systématique, entre autres à cause des difficultés fréquentes d’interprétation sérologique et des possibilités limitées de prévention et de traitement de l’infection fœtale. L’amélioration du diagnostic sérologique de l’infection à CMV est donc une étape importante dans la prise en charge des femmes enceintes. Dans la première partie de notre travail, nous avons montré les bonnes performances des tests automatisés LIAISON®CMV IgG II, LIAISON®CMV IgM II and LIAISON®CMV IgG Avidity II tant en prospectif sur des échantillons de routine que sur des sérums sélectionnés avec date de primo-infection connue. Ces nouveaux tests sont donc utiles pour le diagnostic de la primo-infection à CMV et la détermination du statut immunitaire, avec l’avantage d’une automatisation complète. Cependant, dans 18% des cas, la mesure de l’avidité des IgG se situe dans une zone intermédiaire ne permettant pas de dater l’infection. Dans la deuxième partie de ce travail, nous avons évalué les capacités des immunoblots Mikrogen recomLine CMV IgG and IgG Avidity à dater une infection primaire en utilisant des sérums pour lesquels la date de primo-infection à CMV est précisément connue, et montré que ces tests donnent une interprétation correcte dans 83.1%, un résultat incorrect dans 4.5% et un résultat non concluant dans 12.4% des cas. En particulier, la combinaison des tests Mikrogen montre une meilleure sensibilité à diagnostiquer une infection <14 semaines comparé au test VIDAS IgG Avidity (85.96% vs 76.92%). Sur un second panel d’échantillons avec une avidité des IgG VIDAS intermédiaire, ces nouveaux tests ont apporté une information complémentaire quant à la datation de la primo-infection dans 79% (70/89) des cas. L’impact clinique direct est prometteur :une analyse préliminaire sur 10 femmes enceintes de moins de 14 semaines d’âge gestationnel avec une sérologie difficile à interpréter, montre que ces tests ont permis d’éviter une amniocentèse chez 5 d’entre elles.Enfin, lorsqu’un diagnostic de primo-infection maternelle à CMV est posé ou suspecté chez une femme enceinte, nous manquons de marqueurs prédictifs de transmission materno-fœtale non invasifs pour la grossesse. Dans la troisième partie de notre travail, sur une cohorte de 150 femmes enceintes présentant une primo-infection, nous avons montré que la présence de CMV dans le sang et les urines maternelles est corrélée avec la transmission verticale et que la charge virale urinaire est plus élevée chez les femmes transmetteuses. Ces marqueurs virologiques peuvent être utiles dans l’évaluation du risque de transmission en cas de primo-infection maternelle mais nécessitent des études sur de plus larges cohortes afin de confirmer ces résultats et d’établir un seuil quantitatif. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Introdução: A formação de um sistema consistente de vigilância para gerar informação sobre infecções relacionadas à assistência à saúde (IRAS) é medida essencial para realizar um diagnóstico fidedigno de situação buscando formular estratégias de prevenção e controle deste fenômeno. No Brasil, diversas iniciativas em busca do desenvolvimento de um sistema eficiente e eficaz vêm se estabelecendo, algumas com merecido destaque; entretanto esta é uma realidade ainda desconhecida, o que pode gerar a constituição de redes desintegradas e individualizadas. Objetivo: O presente estudo objetiva caracterizar as regiões Sudeste e Sul do Brasil, as quais possuem a maior concentração de serviços de saúde, no que se refere ao sistema de informação de IRAS, reconhecendo estratégias definidas pelas Secretarias Estaduais de Saúde (SES) e discutindo os resultados à luz dos principais Sistemas de Informação de IRAS internacionais e referenciais teóricos sobre Sistemas de Informação. Metodologia: Estudo transversal, descritivo e exploratório, com abordagem quantitativa para diagnóstico de situação dos sistemas de informação sobre IRAS implantados pelas SES das regiões Sudeste e Sul do Brasil. Os dados foram coletados em websites do Governo Federal Brasileiro e por entrevistas com responsáveis pela Coordenação Estadual de Controle e Prevenção de IRAS e Resultados: Todos os Estados avaliados possuem algum tipo de sistema de informação sobre IRAS implantado. Estes sistemas apresentaram-se sobre três formas básicas: cadeia, círculo e roda. Apenas um Estado possui software próprio para notificação de dados em tempo real, os demais têm o seu sistema estruturado 9 por meio de planilhas eletrônicas ou documento impresso. Três Estados possuem legislação complementar que obriga esta notificação. A periodicidade de envio dos dados em parte dos Estados é mensal, porém existem outros em que esta notificação é semanal, trimestral ou mesmo semestral. Todos os Estados apontam o estabelecimento de processo educacional direcionado ao desenvolvimento deste sistema. A interface com o governo federal é realizada por todos os Estados por meio do formulário eletrônico FormSUS. Há também a participação do Município nesta interface de informações. Apenas dois Estados não realizam a retroalimentação de dados para os notificantes. Na formação destes sistemas existe uma tendência em seguir o modelo americano, entretanto o modelo europeu é o que mais se assemelha a realidade brasileira. As implantações destes sistemas são relativamente recentes, ocorridas na última década, sendo que todos apontam necessidade de melhorias. Conclusão: O presente estudo apresentou uma diversidade de fluxos e modos de obtenção de informações sobre IRAS, com o envolvimento de esferas dos governos federal, estadual e municipal. Embora se evidencie uma busca constante por melhorias nos Estados, a diversidade de formas e abrangência nos sistemas estaduais aponta para uma potencial dificuldade voltada a sua unificação no âmbito nacional / Background: The formation of a consistent surveillance system for generating information about healthcare associated infections (HAI) is an essential measure to perform a reliable diagnosis of situation in order to formulate strategies for prevention and control of this phenomenon. In Brazil, several initiatives seeking the development an efficient and effective system are being established, some with deserved prominence; however this is a reality yet unknown, which can generate networking disintegrated and individualized. Objective: This study aims to characterize the Southeast and South of Brazil, which has the largest concentration of health services, with regard to the information system of HAI`s, recognizing strategies defined by State Health Departments and discussing the outcome based on the internationally acknowledged systems. Metodology: A cross-sectional study, exploratory and descriptive, with quantitative approach, for diagnostic status of HAI`s information systems deployed by State Health Departments from Southeast and South of Brazil. The data were collected in the Brazilian Federal Government websites and through interviews with Managers State responsible for the control and prevention of HAI. Results: All States measured have some kind of HAI`s information system deployed. These systems presented on three basic shapes: chain, wheel and circle. Only one State has its own software for data reporting in real time, others have their structured system through electronic spreadsheets or printed document. Three States have additional law obliging this notification. The frequency of data transmission in the States is monthly, but there are others in which this notification is weekly, 11 quarterly or semiannual. All States refer educational process directed to the development of this system. The interface with the Federal Government is held by all States through electronic form FormSUS. There is also the participation of the Municipality in this interface information. Only two States do not realize the feedback data to the notifiers. In the formation of these systems there is a tendency to follow the american model, however the european model is what most resembles the Brazilian reality. The implementation of these systems is relatively recent, occurring in the last decade, but everyone indicate the need for improvements. Conclusion: The present study showed a diversity of flows and ways of obtaining information about HAI, with the involvement of levels of federal, state and municipal government. Although if evidence of a constant search for improvements in all States, the diversity of forms and extent in state systems points to a potential difficulty directed its unification at the national level

Introdução: as infecções de sítio cirúrgico (ISC) estão entre as infecções relacionadas à assistência à saúde (IRAS) de maior frequência. Autoridades governamentais devem estabelecer prioridades para a vigilância epidemiológica, reconhecida como um importante instrumento para a redução das taxas de ISC. Vários países em desenvolvimento não possuem condições de conduzir um Sistema de Vigilância das Infecções de Sítio Cirúrgico (SVISC) que inclua todos os tipos de cirurgia; portanto, critérios devem ser utilizados para selecionar os indicadores mais adequados a serem monitorados. Desde 2004, o SVISC do estado de São Paulo tem focado somente as taxas de ISC dos procedimentos classificados como limpos; entretanto, em 2011 reconheceu a necessidade de implementar alterações no sistema vigente até então. Objetivos: o principal objetivo deste estudo foi selecionar e implementar indicadores para o novo SVISC do estado de São Paulo. Métodos: o estudo foi conduzido de agosto de 2011 a julho de 2013; uma combinação de três métodos foi utilizada sequencialmente: 1) Estudo metodológico de revisão da literatura e consulta a especialistas objetivando identificar os critérios mais adequados para a seleção dos indicadores a serem monitorados em âmbito governamental; 2) Elaboração de ferramenta documental para apoiar a implementação do novo sistema de VE das ISC; 3) Estudo epidemiológico descritivo dos resultados dos indicadores de ISC após a implementação do sistema. As instituições de saúde notificantes do novo sistema (n=555) representaram 82,7% de todas as instituições consideradas com potencial para notificação. Resultados: os principais critérios identificados para a seleção dos indicadores de ISC foram a) magnitude da realização do procedimento cirúrgico pelo Sistema Único de Saúde brasileiro; b) severidade do dano em caso de ISC; c) potencial impacto de estratégias de prevenção; d) recomendação por norma federal; e) potencial para futuro benchmarking com pelo menos três outros SVISC. A seguir são apresentados os procedimentos cirúrgicos selecionados para a vigilância no novo sistema e suas respectivas taxas de ISC para o percentil 75 e número de procedimentos cirúrgicos notificados referentes ao ano de 2012: parto cesariano: 0,79% (n=304.198), revascularização do miocárdio: 9,0% (n=12.000); artroplastia do joelho: 2,2% (n=10.225), artroplastia do quadril: 3,9% (n=9.984), craniotomia: 6,8% (n=8.514), mastectomia: 0,0% (n=9.515) e os seguintes procedimentos realizados por laparoscopia: colecistectomia: 0,0% (n=54.960), herniorrafia: 0,0% (n=21.627), histerectomia: 0,0% (n=9.071), apendicectomia: 0,0% (n=8.122) e colectomia 0,0% (n=1.963). Conclusões: o desenvolvimento de critérios suporta a seleção racional de indicadores de ISC para o monitoramento no âmbito governamental. Apesar da adesão satisfatória das instituições, os dados obtidos sugerem que algumas taxas podem ser subnotificadas. Esforços devem focar a melhoria da qualidade dos dados / Introduction: the surgical site infections (SSI) are among the most frequently healthcare associated infection (HAI). Governmental authorities should establish priorities for the epidemiologic surveillance which is recognized as an important strategy to reduce the SSI rates. Many developing countries cannot afford to manage Surgical Site Infection Surveillance System (SSISS) that includes all types of surgeries; therefore a criterion should be used to select the most appropriate indicators to be monitored. Since 2004, the SSISS in São Paulo have been focused on only crude rates of SSI in clean surgeries; however, in 2011 it was recognized that was necessary to implement changes in the ongoing system. Objective: the present study aimed to select and to implement indicators for the new SSISS in the São Paulo State. Methods: this study was carried out from August 2011 to July 2013; three methods were used sequentially 1) Methodological study carried out by means of literature review and consulting to HAI experts aiming to identify the best criteria for selection of SSI indicators to be monitored at the governmental level; 2) Development of a written tool to support the implementation of the new SSISS; 3) Epidemiological descriptive study on SSI indicators results after implementation. The participating healthcare institutions (n=555) represented 82.7% of total acute care hospitals in the State which were considered to be potential participants. Results: the main criteria identified to select the SSI indicators were: a) magnitude of the surgery in the Brazilian Universal Health System; b) severity of harm in case of SSI; c) potential impact of prevention strategies; d) recommendation by federal normative; d) potential for benchmarking against at least other three SSISS worldwide. The surgical procedures selected, the SSI rates identified (3rd quartiles) and the number of surgeries monitored in 2012 were respectively: cesarean section: 0.79% (n=304,198); coronary artery bypass graft: 9.0% (n=12,000); knee arthroplasty: 2.2% (n=10,225), hip arthroplasty: 3.9% (n=9,984), craniotomy: 6.8% (n=8,514), mastectomy: 0.0% (n=9,515) and the following laparoscopic procedures: cholecystectomy: 0.0% (n=54,960), herniorrhaphy: 0.0% (n=21,627), histerectomy: 0.0% (n=9,071), apendicectomy: 0.0% (n=8,122) and colectomia 0.0% (n=1,963). Conclusion: The development of criteria supported the rational selection of indicators for governmental monitoring of SSI. Despite good adherence to the project, data suggest that SSI may be underestimated. Efforts should be focused on the improvement of data quality for SSISS

Estudo de desenvolvimento metodológico de elaboração e validação de medidas de avaliação em saúde. Teve como objetivo geral contribuir para o desenvolvimento de Indicadores de Avaliação de Programas de Controle de Infecção Hospitalar (PCIH) e específicos construir e validar o conteúdo dos indicadores construídos. Os procedimentos teóricos para validação dos indicadores de PCIH foram: a-seleção e construção dos indicadores; b-fundamentação do conteúdo científica dos indicadores; c-validação dos indicadores construídos. Foram construídos cinco indicadores: 1- (PCET) Estrutura Técnico-operacional do PCIH; 2- (PCDO) Diretrizes Operacionais de Controle e Prevenção de IH; 3- (PCVE) Sistema de Vigilância Epidemiológica de IH; 4- (PCCP) Atividades de Controle e Prevenção de IH; 5- (PCAE) Atividades Educacionais e Capacitação Técnica em controle de IH. A validação de conteúdo dos indicadores foi realizada por oito profissionais especialistas na área de controle de IH, a partir de um instrumento previamente elaborado e referiu-se a: 1º - manual operacional; 2º - atributos do conjunto dos indicadores; 3º - atributos individuais dos componentes de cada indicador; 4º - valoração da relevância dos componentes de cada indicador. Com exceção do indicador 5- PCAE, os demais foram todos validados / This aim of this study is to create methodology for the development and validation of evaluation measurements in healthcare. The overall objective was to contribute to the development of Performance Indicators for Hospital Infection Control (HIC) programs and more specifically to create and validate the content of the indicators developed. The theoretical procedures for the validation of the indicators for HIC programs were: a-the selection and creation of the indicators; b-determination of the scientific basis for indicator content; c-validation of created indicators. In all, five indicators were created: 1- (PCET) Technical/operational structure of HIC program; 2- (PCDO) Operational Guidelines for the Control and Prevention of HI; 3- (PCVE) Epidemiological Surveillance System; 4- (PCCP) Activities for the Control and Prevention of HI; 5- (PCAE) Educational Activities and Technical Education in the control of HI. The validation of the content of the indicators was conducted by eight specialists in the area of HIC using a previously developed instrument and addressed: 1º - operational manual; 2º - indicator set attributes; 3º - individual attributes of the components of each indicator; 4º - assessment of the relevance of the components of each indicator. With the exception of indicator 5-PCAE, all of the indicators were validated

Introdução: A assistência à saúde é desafiada por eventos adversos evitáveis e mais da metade destes corresponde a Infecções Relacionadas à Assistência à Saúde (IRAS), com expressivas taxas de morbimortalidade e altos custos hospitalares. No entanto, não há investimentos em avaliação e reconhecimento da qualidade dos Programas de Prevenção e Controle de Infecções Relacionadas à Assistência à Saúde (PCIRAS). Objetivo: Realizar um diagnóstico de situação da estrutura e atuação dos PCIRAS em hospitais de pequeno porte, tendo como hipótese a conformidade mínima de 70%. Método: Estudo transversal, prospectivo e de avaliação processual no qual foram entrevistadas enfermeiras que atuam nos PCIRAS de catorze hospitais, de um total de 27, com até setenta leitos, adscritos no Departamento Regional de Saúde XVII, Estado de São Paulo, no período de 2015 a 2016. A avaliação aplicou quatro indicadores previamente validados: Estrutura Técnico-Operacional do Programa de Controle de Infecção Hospitalar (PCET), Diretrizes Operacionais de Controle e Prevenção de Infecção Hospitalar (PCDO), Sistema de Vigilância Epidemiológica de Infecção Hospitalar (PCVE) e Atividades de Controle e Prevenção de Infecção Hospitalar (PCCP). Resultados: O índice de conformidade geral dos indicadores foi de 69%, dispersão (dp) de (12,3), com valores médios de 61% (20,3 dp) para PCET, 85% (18,7 dp) para PCDO, 58% (39,5 dp) para PCVE e 75% (24,1 dp) para PCCP. O desempenho geral ficou pouco abaixo do esperado (70%) em decorrência dos indicadores PCET e PCVE. As instituições privadas apresentaram maiores índices de conformidade, bem como as que possuíam Unidade de Terapia Intensiva (UTI). Apesar, dos hospitais possuírem enfermeiros designados para PCIRAS (92,9%), somente em 23,1% das instituições privadas eles atuavam com dedicação exclusiva de seis horas. Foi observada relevância estatisticamente significativa para correlação entre os indicadores e as seguintes variáveis: presença de UTI (PCET e PCVE), representação do SCIH (PCDO) e carga horária diária do enfermeiro (PCET). Ao contrário, não foi observada relevância estatística para: presença de acreditação e carga horária do segundo profissional do SCIH. Conclusões: diante do exposto, os hospitais de pequeno porte apresentam dificuldades para instituir PCIRAS nos moldes preconizados pela legislação (Portaria 8 n. 2.616/1998). Faz-se necessário o estabelecimento de recomendações e políticas públicas viáveis e que permitam um programa efetivo de prevenção de infecções nestas instituições. / Introduction: Healthcare is challenged by preventable adverse events and more than half of these events are Healthcare-Associated Infections (HAI), with significant morbidity and mortality rates and high hospital costs. However, there is no investment in the assessment and recognition of the quality of the Prevention and Control Programs Related to Healthcare-Associated Infections. Purpose: Provide a diagnosis of the situation of the structure and performance of Programs of HAI in small-sized hospitals, with the hypothesis of a minimal compliance of 70%. Method: Cross-sectional, prospective and process evaluation study presenting interviews with nurses working in Programs of HAI of 14 hospitals, out of a total of 27, with up to 70 beds, ascribed in the Regional Health Department XVII of the state of Sao Paulo, in the period from 2015 to 2016. The evaluation applied four previously validated indicators: Technical-Operational Structure of the Hospital-Acquired Infection Control Program (PCET), Operational Guidelines for the Control and Prevention of Hospital-Acquired Infections (PCDO), Hospital-Acquired Infection Epidemiological Surveillance System (PCVE) and Activities of Infection Control and Prevention (PCCP). Results: The overall compliance rate of the indicators was 69%, dispersion (dp) of (12.3), with average values of 61% (20.3 dp) for PCET, 85% (18.7 dp) for PCDO, 58 % (39.5 dp) for PCVE and 75% (24.1 dp) for PCCP. The overall performance was slightly lower than expected (70%) as a result of PCET and PCVE indicators. Private institutions had higher rates of compliance, as well as those having an Intensive Care Unit (ICU). Though the hospitals have nurses assigned to PCIRAS (92.9%), they worked in an exclusive six hours system only in 23.1% of the private institutions. A statistically significant relevance was observed for correlation between the indicators and the following variables: presence of ICU (PCET and PCVE), representation of the SCIH (PCDO) and daily workload of nurses (PCET). On the contrary, there was no statistical significance for: presence of accreditation and workload of the second professional of the SCIH. Conclusions: considering the above, the small hospitals find it difficult to use PCIRAS along the lines recommended by law (Ordinance no. 2,616/1998). It is necessary to establish recommendations and viable public policies, as well as providing an effective program to prevent infections in these institutions.

Le virus influenza peut être responsable d’infections respiratoires sévères. Les pneumonies bactériennes post-influenza font partie des complications les plus graves et S. aureus est l’une des bactéries les plus fréquemment retrouvée dans ce contexte. L’efficacité des traitements dans ces infections graves est modérée ce qui souligne l’importance de progresser dans la compréhension de la physiopathologie de ces infections graves. Une réponse immunitaire inadéquate (soit excessive, soit trop faible) à l’infection pulmonaire joue un rôle considérable dans la gravité du tableau clinique et le pronostic du patient. Nous avons montré que le virus influenza potentialise l’inflammation et la cytotoxicité engendrée par des facteurs de virulence de S. aureus dans des monocytes isolés de témoins sains. Cependant l’étude du système immunitaire de patients hospitalisés pour grippe grave, a montré qu’au lieu d’être dans un état d’activation massive, il était en phase d’anergie et possédait une altération de la réponse immunitaire fonctionnelle en cas d’exposition à des facteurs de virulence de S. aureus. L’immunomonitoring de ces patients au pronostic sévère, qui permet la détermination de l’état pro- ou anti-inflammatoire dans lequel se trouve le patient pourrait participer à l’amélioration de la prise en charge de ces patients en permettant l’utilisation de traitements immunomodulateurs adaptés à la situation clinique de chaque patient. Cette problématique peut être étendue à d’autres co-infections virus bactérie et notamment au VRS. Nous avons étudié l’épidémiologie des co-infections VRS/bactérie chez l’adulte dans le contexte d’une pneumonie et nous avons observé qu’elle était similaire à celle des co-infections influenza bactérie. Cette connaissance de l’épidémiologie est importante afin d’adapter la prise en charge des patients / Post-influenza bacterial pneumonia is a leading cause of morbidity and mortality with severe influenza virus illness. Staphylococcus aureus is one of the most common pathogen found in this context. The severity of post-influenza Staphylococcus aureus pneumonia is due both to an inadequate responsiveness of the immune system (either too important or too weak) and to the weak efficacy of treatments used during these severe infections. A better knowledge of the pathophysiology of influenza/S. aureus co-infection is needed in order to improve patients care. In this study, we showed using in vitro experiments that influenza virus increased the inflammation and cytotoxicity induced by S. aureus virulence factors in human monocytes. However ex vivo experiments performed on leucocytes isolated from hospitalized patients with severe influenza showed an anergy of the immune system after exposition to S. aureus virulence factors. Immunomonitoring of patients with severe post-influenza Staphylococcus aureus pneumonia may allow to optimize the therapeutic regimen towards a more individualized immunomodulatory therapy. This can be extended to other viral bacterial co-infections including RSV. We studied the epidemiology of bacterial superinfections associated with RSV pneumonia in adults. Our results suggested that there was no main differences between the microbiological epidemiology of RSV/bacterial co-infections and influenza/bacterial co-infections. Knowledge of this epidemiology is important to assess to improve patients care