During the 2009 H1N1 pandemic, the City of Ottawa implemented a program to disseminate vaccination clinic information using the microblogging tool Twitter. The purpose of this thesis is to examine and evaluate whether this program constitutes a communicative model. The challenge for crisis communicators has been to convince a confused and skeptical public to be vaccinated against the virus. Drawing on Aristotle’s Rhetoric and Rousseau’s The Social Contract, the theoretical framework of this thesis feeds from Heidegger’s (1977) views on technology, new media, Web 2.0 technologies, Eid’s (2008) Crisis Decision-Making Model for Media Rational Responsibility, Rowan, Botan, Krepes, Samoilenko and Farnsworth’s (2008) CAUSE model, Crozier’s (1967) Theory of Bureaucratic Dysfunction and New Public Management. The thesis employs a case study approach and utilizes a qualitative research design to analyze the Twitter messages and internal City of Ottawa documents, and to conduct in-depth interviews with employees. Findings reveal and explain that the City of Ottawa’s program constitutes a flawed communicative model. A recommended communicative model is put forth in order to improve the areas of planning, human resources and message design. This model contributes to the emerging field of social media, and is intended to help health crisis decision-makers communicate their messages effectively.

<p>The aim of this thesis has been to examine how the risk for the swine flu was represented in the Swedish Radio news broadcast Ekot 16.45 during different phases of the pandemic in 2009. We wanted to study how the risk was described in different discourses and periods? Were the participants in the reporting calming or warning the listeners in relations to different aspects of the swine flu? What consequences for the community were reported in the broadcasting?</p><p>To find the answers to our questions, we analysed 13 features about the swine flu broadcasted in Ekot’s main news broadcast Ekot 16.45. We used critical discourse analysis inspired by Norman Fairclough.</p><p>We identified four types of discourses in our text, a journalistic discourse, a medical discourse, a nationalistic discourse and an authority discourse. The main discourse was the medical one. We also discovered power relations in each discourse but also between them.</p><p>We noticed that the media transmitted the information from the authorities like a megaphone, rather than handling it in their traditionally critical way. In addition most people interviewed were representatives from the authorities and not ordinary people, manifesting the above mentioned authoritative perspective/discourse and leading to an absence of descriptions on effects at an everyday level. We also observed that the risk was talked about in various ways depending on if the feature belonged to the warning or acute phase of the pandemic. In the way the features were presented, it was clear that the presentations of the swine flu also had effects on the community, the healthcare and the whole nation as if preparing for an outbreak.</p>

O vírus influenza A (IAV) é um agente zoonótico de grande relevância tanto para saúde humana como animal. A influenza suína teve seu primeiro reconhecimento clínico em 1918, em suínos do Meio Oeste dos EUA, coincidindo com a pandemia de influenza em humanos. Desde então, o IAV permanece como um importante patógeno para a indústria suinícola em todo o mundo. A grande variabilidade genética destes vírus é causada por dois principais mecanismos genéticos: mutações pontuais e recombinações genéticas. A influenza é endêmica em muitos países e a emergências de recombinantes tem desafiado o controle e o diagnóstico desta enfermidade. No Brasil, a infecção pelo IAV em suínos (swIAV) não está bem caracterizada; poucos relatos evidenciam a prevalência deste agente antes do ano de 2009, especialmente no Estado do Rio Grande do Sul, que alberga um dos maiores rebanhos de suínos do Brasil. Em vista disso, este trabalho teve como objetivo investigar ocorrência de swIAV em alguns rebanhos suínos comerciais do Estado do Rio Grande do Sul, Brasil, no período de 2013-2014, e determinar os tipos e subtipos de vírus circulantes naquelas propriedades. O primeiro capítulo deste estudo reporta os aspectos clínicos, patológicos e virológicos da ocorrência de influenza suína e co-infecções identificadas em seis propriedades suinícolas selecionadas na região do Vale do Taquari. Neste estudo foram analisados suabes nasais coletados de 66 animais e 6 amostras de tecido pulmonar de suínos com sinais de infecção respiratória. A detecção viral foi feita através de uma PCR de triagem e confirmada através do isolamento viral em células MDCK. A identificação dos subtipos virais foi feita através de uma PCR em Tempo Real (rRT-PCR) para o subtipo A(H1N1)pdm09 ou através de uma PCR multiplex (RT-PCR) para outros subtipos de swIAV. A detecção de agentes bacterianos foi realizada apenas nas amostras de tecido pulmonar, através da pesquisa de genomas bacterianos por PCR. O subtipo A(H1N1)pdm09 foi identificado em 4/6 granjas e o subtipo H1N2 em 2/6 granjas. Além disso, agentes envolvidos no complexo respiratório dos suínos foram identificados em todas as granjas; Pasteurella multocida foi identificada em 5/6 granjas e Mycoplasma hyopneumoniae em 3/6 granjas. Actinobacillus pleuropneumoniae (1/6), Haemophilus parasuis (1/6) e PCV2 (1/6) também foram detectados. O segundo capítulo deste estudo teve como objetivo o sequenciamento do genoma completo de um novo recombinante H1N2 de origem humana, detectado em suínos. O genoma completo foi gerado através de uma RT-PCR. Os produtos foram purificados e submetidos ao sequenciamento utilizando a plataforma MiSeq (illumina). A análise filogenética revelou que as sequencias dos genes HA e NA correspondem a genes de IAV de origem humana, enquanto que as sequencias dos genes que codificam as proteínas internas do vírus (PB1, PB2, PA, NP, M e NS) correspondem a genes de amostras do vírus A(H1N1)pdm09. O terceiro capítulo reporta o sequenciamento completo dos genomas de 8 amostras de vírus influenza identificados nas populações de suínos amostradas. Foram identificados dois subtipos virais de origem humana (H1N2 e H3N2), além do vírus A(H1N1)pdm09. Os subtipos de origem humana possuem os genes HA e NA similares a vírus sazonais de humanos e os genes internos são estreitamente relacionados com o vírus A(H1N1)pdm09. / Influenza A virus (IAV) is a zoonotic agent of great relevance to human and animal health. Swine influenza was first recognized clinically in pigs in the Midwestern U.S., in 1918, coinciding with the human influenza pandemic. Since that time swine influenza has remained of importance to the swine industry throughout the world. The great genetic variability of influenza viruses is caused by two main genetic mechanisms: point mutations (antigenic drift) and gene reassortment (antigenic shift). Influenza is endemic in pigs in many countries and the emergence of new viruses has been challenging its control and diagnostics. Influenza virus (swIAV) infection in Brazilian swine population is not well characterized, and little evidence existed of swIAV circulation before 2009, especially in Rio Grande do Sul State, which hosts one of the largest swine populations in Brazil. Thus, this study aimed to investigate the occurrence of IAV in commercial swine herds in the state of Rio Grande do Sul, Brazil, between 2013-2014 and to know the types and subtypes of swine influenza viruses that are circulating in these herd. The first chapter of this study reports the clinical, pathological and virological aspects of the occurrence of swine influenza and related co-infections in six pig properties of the Taquari Valley region. In this study were analyzed nasal swabs collected from 66 animals and six lung tissue samples from pigs showing clinical signs of respiratory disease. IAV detection was performed by PCR screening and confirmed by virus isolation in MDCK cells and hemagglutination (HA). Influenza A subtyping was performed by real-time reverse transcription PCR (rRT-PCR) to detect the 2009 H1N1pandemic A(H1N1)pdm09; other swIAV subtypes were identifieded by multiplex RT-PCR. Bacterial infections were identified through detection of bacterial genomes by PCR, only in lung samples. Influenza A was detected by screening PCR in 46/66 swab samples and from 5/6 lungs. Virus was recovered from pigs of the six herds. Subtype A(H1N1)pdm09 was detected in 4/6 herds and H1N2 in the other 2/6 herds. In lung tissues, further agents involved in porcine respiratory disease complex were detected in all cases; Pasteurella multocida was identified in 5/6 samples and Mycoplasma hyopneumoniae in 3/6. Actinobacillus pleuropneumoniae (1/6), Haemophilus parasuis (1/6) and PCV2 (1/6) were also detected. The aim of the second chapter was to sequence the whole-genome of a novel human-like H1N2 swine influenza virus. Wholegenome sequences were generated by RT-PCR. Amplicons were purified followed by sequencing in the MiSeq sequencing platform (Illumina). Phylogenetic analyses revealed that the HA and NA genes clustered with influenza viruses of human lineage, whereas the internal genes (PB1, PB2, PA, NP, M and NS) clustered with the A(H1N1)pdm09. The third chapter reports the genetic sequencing of the full genomes of eight swine influenza viruses circulating in the sampled pig population. Two swine human-like subtypes (H1N2 and H3N2) and the A(H1N1)pdm09 virus were identified. The human-like subtypes have the HA and NA genes similar to the human seasonal strains and the internal genes are closely related to the virus A(H1N1)pdm09.

An influenza is an illness annually affecting 5-15 percent of the world population. During the influenza pandemy 40-50 percent of world population can be affected and millions of people can die.The measures resulting from the pandemic plans help to limit the influenza virus spreading, to reduce morbidity and mortality. In April 2009 the first cases of the flue pandemic caused by Pandemic A (H1N1) 2009 virus occurred on the American continent, in the Czech Republic there was the first case registered in May, in the Pilsen region in July. Based on these facts I decided to assess the pandemic plans at the level of the Pilsen region and to analyse the course of the pandemy in the Pilsen region too. Having studied the Pandemic plan of the Pilsen region and the Pandemic plan of the Regional Hygiene Station of the Pilsen Region I got to the conclusion that in case of the pandemy caused by the highly virulent tribe of the influenza it would not be possible to use up the pandemic plans efficiently. The disadvantages concern mainly the way of the distribution of the pandemic vaccine and antivirotics. The other disadvantage is the absence of a parenteral form of antivirotics. A bad awarness of the inhabitants also came out effecting mass rejection of vaccination by the pandemic vaccine and preventative taking antivirotics. The analyse of the course of the pandemy in the Pilsen region proved that at many patients with the flue pandemic there was present a risky factor of more serious course of the influenza in the anamnesis. If these patients had been vaccinated by the pandemic vaccine they had been entitled for, they could have been protected against this illness, for some of them the vaccination might have meant life-saving. It was also proved that originally the pandemic tribe of Pandemic A (H1N1) 2009 virus became the causer of the common seasonal influenza in the season of 2010-2011.

In the thesis there are chronologically processed data about incidence of influenza Pandemic (H1N1) 2009 from its first incidence in spring 2009 in Mexico until the official end of the 6th phase of pandemic announced by the WHO in august 2010. These data were collected by means of secondary analysis. The thesis is focused on the Region of South Bohemia from the first proved incidence of Pandemic influenza (H1N1) 2009 here. The data necessary to meet the objectives of the work and to answer the research questions were collected in cooperation with the Regional Hygienic Station of the South Bohemia in České Budějovice. 3 deaths were analysed in the context of incidence of Pandemic influenza (H1N1) 2009 in the Region of South Bohemia and anti-epidemic measures were assessed. Differences in 121 people with Pandemic influenza (H1N1) 2009 in the Region of South Bohemia from the point of view of age and sex were described. In 52 people with the flu from the Region of South Bohemia ?traveller? history was recorded (these people were infected during their stays abroad) and most of them had stayed in Germany. Indicators of morbidity (ARI) in the Region of South Bohemia and in the whole Czech Republic were also processed and then graphically compared.

O vírus influenza A (IAV) é um agente zoonótico de grande relevância tanto para saúde humana como animal. A influenza suína teve seu primeiro reconhecimento clínico em 1918, em suínos do Meio Oeste dos EUA, coincidindo com a pandemia de influenza em humanos. Desde então, o IAV permanece como um importante patógeno para a indústria suinícola em todo o mundo. A grande variabilidade genética destes vírus é causada por dois principais mecanismos genéticos: mutações pontuais e recombinações genéticas. A influenza é endêmica em muitos países e a emergências de recombinantes tem desafiado o controle e o diagnóstico desta enfermidade. No Brasil, a infecção pelo IAV em suínos (swIAV) não está bem caracterizada; poucos relatos evidenciam a prevalência deste agente antes do ano de 2009, especialmente no Estado do Rio Grande do Sul, que alberga um dos maiores rebanhos de suínos do Brasil. Em vista disso, este trabalho teve como objetivo investigar ocorrência de swIAV em alguns rebanhos suínos comerciais do Estado do Rio Grande do Sul, Brasil, no período de 2013-2014, e determinar os tipos e subtipos de vírus circulantes naquelas propriedades. O primeiro capítulo deste estudo reporta os aspectos clínicos, patológicos e virológicos da ocorrência de influenza suína e co-infecções identificadas em seis propriedades suinícolas selecionadas na região do Vale do Taquari. Neste estudo foram analisados suabes nasais coletados de 66 animais e 6 amostras de tecido pulmonar de suínos com sinais de infecção respiratória. A detecção viral foi feita através de uma PCR de triagem e confirmada através do isolamento viral em células MDCK. A identificação dos subtipos virais foi feita através de uma PCR em Tempo Real (rRT-PCR) para o subtipo A(H1N1)pdm09 ou através de uma PCR multiplex (RT-PCR) para outros subtipos de swIAV. A detecção de agentes bacterianos foi realizada apenas nas amostras de tecido pulmonar, através da pesquisa de genomas bacterianos por PCR. O subtipo A(H1N1)pdm09 foi identificado em 4/6 granjas e o subtipo H1N2 em 2/6 granjas. Além disso, agentes envolvidos no complexo respiratório dos suínos foram identificados em todas as granjas; Pasteurella multocida foi identificada em 5/6 granjas e Mycoplasma hyopneumoniae em 3/6 granjas. Actinobacillus pleuropneumoniae (1/6), Haemophilus parasuis (1/6) e PCV2 (1/6) também foram detectados. O segundo capítulo deste estudo teve como objetivo o sequenciamento do genoma completo de um novo recombinante H1N2 de origem humana, detectado em suínos. O genoma completo foi gerado através de uma RT-PCR. Os produtos foram purificados e submetidos ao sequenciamento utilizando a plataforma MiSeq (illumina). A análise filogenética revelou que as sequencias dos genes HA e NA correspondem a genes de IAV de origem humana, enquanto que as sequencias dos genes que codificam as proteínas internas do vírus (PB1, PB2, PA, NP, M e NS) correspondem a genes de amostras do vírus A(H1N1)pdm09. O terceiro capítulo reporta o sequenciamento completo dos genomas de 8 amostras de vírus influenza identificados nas populações de suínos amostradas. Foram identificados dois subtipos virais de origem humana (H1N2 e H3N2), além do vírus A(H1N1)pdm09. Os subtipos de origem humana possuem os genes HA e NA similares a vírus sazonais de humanos e os genes internos são estreitamente relacionados com o vírus A(H1N1)pdm09. / Influenza A virus (IAV) is a zoonotic agent of great relevance to human and animal health. Swine influenza was first recognized clinically in pigs in the Midwestern U.S., in 1918, coinciding with the human influenza pandemic. Since that time swine influenza has remained of importance to the swine industry throughout the world. The great genetic variability of influenza viruses is caused by two main genetic mechanisms: point mutations (antigenic drift) and gene reassortment (antigenic shift). Influenza is endemic in pigs in many countries and the emergence of new viruses has been challenging its control and diagnostics. Influenza virus (swIAV) infection in Brazilian swine population is not well characterized, and little evidence existed of swIAV circulation before 2009, especially in Rio Grande do Sul State, which hosts one of the largest swine populations in Brazil. Thus, this study aimed to investigate the occurrence of IAV in commercial swine herds in the state of Rio Grande do Sul, Brazil, between 2013-2014 and to know the types and subtypes of swine influenza viruses that are circulating in these herd. The first chapter of this study reports the clinical, pathological and virological aspects of the occurrence of swine influenza and related co-infections in six pig properties of the Taquari Valley region. In this study were analyzed nasal swabs collected from 66 animals and six lung tissue samples from pigs showing clinical signs of respiratory disease. IAV detection was performed by PCR screening and confirmed by virus isolation in MDCK cells and hemagglutination (HA). Influenza A subtyping was performed by real-time reverse transcription PCR (rRT-PCR) to detect the 2009 H1N1pandemic A(H1N1)pdm09; other swIAV subtypes were identifieded by multiplex RT-PCR. Bacterial infections were identified through detection of bacterial genomes by PCR, only in lung samples. Influenza A was detected by screening PCR in 46/66 swab samples and from 5/6 lungs. Virus was recovered from pigs of the six herds. Subtype A(H1N1)pdm09 was detected in 4/6 herds and H1N2 in the other 2/6 herds. In lung tissues, further agents involved in porcine respiratory disease complex were detected in all cases; Pasteurella multocida was identified in 5/6 samples and Mycoplasma hyopneumoniae in 3/6. Actinobacillus pleuropneumoniae (1/6), Haemophilus parasuis (1/6) and PCV2 (1/6) were also detected. The aim of the second chapter was to sequence the whole-genome of a novel human-like H1N2 swine influenza virus. Wholegenome sequences were generated by RT-PCR. Amplicons were purified followed by sequencing in the MiSeq sequencing platform (Illumina). Phylogenetic analyses revealed that the HA and NA genes clustered with influenza viruses of human lineage, whereas the internal genes (PB1, PB2, PA, NP, M and NS) clustered with the A(H1N1)pdm09. The third chapter reports the genetic sequencing of the full genomes of eight swine influenza viruses circulating in the sampled pig population. Two swine human-like subtypes (H1N2 and H3N2) and the A(H1N1)pdm09 virus were identified. The human-like subtypes have the HA and NA genes similar to the human seasonal strains and the internal genes are closely related to the virus A(H1N1)pdm09.

Estudos recentes têm apresentado resultados in vitro satisfatórios em pacientes com Imunodeficiência Comum Variável (ICV) que receberam vacinas contra tétano, influenza e meningococo. No entanto, existem poucos ensaios clínicos que avaliem a resposta clínica e laboratorial após a exposição a antígenos específicos. O presente estudo tem como objetivo avaliar a resposta clínica à imunização contra antígenos protéicos e polissacarídicos (influenza, H1N1 e pneumococo) em pacientes com diagnóstico de ICV seguidos no ambulatório de Imunodeficiências Primárias do Serviço de Imunologia Clínica e Alergia do HC-FMUSP. O diagnóstico dos pacientes foi estabelecido de acordo com os critérios da OMS / PAGID / ESID. Um grupo de 37 pacientes foi vacinado contra a influenza A (H2N3), gripe H1N1 e pneumococo e outro grupo com 16 pacientes, não foi vacinado. A avaliação clínica foi realizada através da aplicação de um score com avaliação dos seguintes parâmetros clínicos: pneumonia, sinusite, otite média, infecções de vias aéreas superiores (IVAS), amigdalites, diarréia, bronquiectasias, hospitalizações, uso de antibióticos, uso de antibióticos profiláticos, sepse e meningite. O score foi aplicado durante os 12 meses que precederam a vacinação e 12 meses posteriores à administração das vacinas. O mesmo score foi aplicado ao grupo controle, com os pacientes que não foram vacinados. A determinação da IgG contra os sorotipos do pneumococo foi feita por ELISA. A determinação da IgG específica H1N1 foi feita por hemaglutinação indireta, enquanto que a dosagem da IgG específica para influenza, por ELISA, utilizando o kit comercial RIDASCREEN ® Influenza. O grupo de pacientes vacinados incluiu 37 pacientes (51% mulheres), com idade entre 20 e 78 anos (mediana= 33 anos). Observou-se uma mediana de 7 anos de atraso no diagnóstico de ICV. A mediana de idade do grupo de pacientes (n=16, 37,5% mulheres) que não receberam a vacina foi de 41 anos e a mediana de atraso no diagnóstico foi de 8 anos. Observamos que as infecções de vias aéreas superiores (IVAS), sinusites e pneumonias foram as manifestações mais freqüentes no grupo controle. IVAS seguida por pneumonia e sinusite foram as manifestações infecciosas mais freqüentes em mulheres (80%, 78% e 55%, respectivamente). Entretanto, em homens observamos IVAS seguido por sinusite e pneumonia (78%, 65% e 35%, respectivamente). Observou-se redução significativa no score relativo ao número de infecções respiratórias superiores, sinusites e pneumonias um ano após a administração das vacinas (p <0,001). Os dados foram comparados com pacientes ICV não vacinados e neste grupo não houve diferença entre os scores dos dois períodos de 12 meses . Após a vacinação, observou-se uma tendência a aumento no título de anticorpos específicos para a H2N3, mas sem resultado significativo. Em relação aos resultados obtidos com as sorologias para o H1N1 e o pneumococo, não se observou resposta após a vacinação. Concluindo, houve redução do número de infecções, principalmente das IVAS, sinusites e pneumonias em pacientes com ICV após a vacinação contra a influenza, H1N1 e pneumococo. Embora não tenhamos encontrado correlação entre a redução do número de infecções e os títulos de anticorpos específicos para as vacinas testadas, a melhora clínica observada nos pacientes com ICV reforça o benefício da vacinação / Recent studies have shown satisfactory in vitro results in patients with CVID who received immunization against tetanus, influenza and meningococcus. However, there are only a few studies that evaluate the clinical and laboratory response after exposure to specific antigens in these patients. This study aims to evaluate the clinical response to immunization with protein and polysaccharide antigens (influenza, H1N1 and pneumococcus) in CVID patients followed at the Primary Immunodeficiency outpatient clinic of the Division of Clinical Immunology and Allergy, Hospital das Clínicas, FMUSP. CVID patients were diagnosed according the WHO/PAGID/ ESID criteria. Thirty-seven patients were immunized against influenza (H2N3), H1N1 and pneumococcal polysaccharide vaccine while another group with 16 CVID patients were not vaccinated. Clinical evaluation was performed through a score with assessment of the following parameters: pneumonia, sinusitis, otitis media, upper respiratory infections (URI), tonsillitis, diarrhea, bronchiectasis, hospitalizations, use of antibiotic therapy, and use of prophylactic antibiotics, sepsis and meningitis. The score was applied during the 12 months prior to immunization and one year after the administration of vaccines. The same score was applied to the group of CVID patients who weren´t immunized. Determination of IgG antibodies to pneumococcal serotypes was made by ELISA. H1N1-specific IgG was detected by indirect hemagglutination while the determination of influenzaspecific IgG was performed by ELISA, using the RIDASCREEN ® Influenza kit. The group of patients who were vaccinated included 37 patients (51% women), aged 20 to 78 years (mean 33 years). This group presented a median delay in the diagnosis of 7 years. The control group consisted of 16 patients (37.5% females) who were not immunized. Their median age was 41 years and the median delay in the diagnosis was 8 years. URI followed by pneumonia and sinusitis were the most frequent infections in women (80%, 78% and 55% respectively). However in men, URI followed by sinusitis and pneumonia were the most frequent (78%, 65% and 35% respectively). We observed a significant reduction in the score of URI, sinusitis and pneumonias in the year post administration of the vaccines (p <0.001). Conversely, there was no difference in the infections pre and post supposed vaccination scores in the group of CVID patients who were not immunized. There was no significant change in specific antibody titers to influenza and pneumococcus after vaccination. Regarding H1N1, there was no statistically significant production of antibodies to H1N1, although we observed a slight non-durable increase in antibody titers. In conclusion, there was a reduction in the number of infections, mainly sinusitis, URIs and pneumonias in patients with CVID vaccinated against influenza, H1N1 and pneumococcus. While we found no correlation between the reduction in the number of infections and specific antibody titers for the vaccines administered, the clinical improvement observed in CVID patients reinforces the benefit of vaccination

During the 2009 H1N1 pandemic, the City of Ottawa implemented a program to disseminate vaccination clinic information using the microblogging tool Twitter. The purpose of this thesis is to examine and evaluate whether this program constitutes a communicative model. The challenge for crisis communicators has been to convince a confused and skeptical public to be vaccinated against the virus. Drawing on Aristotle’s Rhetoric and Rousseau’s The Social Contract, the theoretical framework of this thesis feeds from Heidegger’s (1977) views on technology, new media, Web 2.0 technologies, Eid’s (2008) Crisis Decision-Making Model for Media Rational Responsibility, Rowan, Botan, Krepes, Samoilenko and Farnsworth’s (2008) CAUSE model, Crozier’s (1967) Theory of Bureaucratic Dysfunction and New Public Management. The thesis employs a case study approach and utilizes a qualitative research design to analyze the Twitter messages and internal City of Ottawa documents, and to conduct in-depth interviews with employees. Findings reveal and explain that the City of Ottawa’s program constitutes a flawed communicative model. A recommended communicative model is put forth in order to improve the areas of planning, human resources and message design. This model contributes to the emerging field of social media, and is intended to help health crisis decision-makers communicate their messages effectively.

La grippe est une infection respiratoire aiguë, due au virus Influenza, qui touche en moyenne chaque hiver 2,5 millions de personnes. C'est un enjeu de santé publique majeur par son impact économique et en santé humaine. Les traitements actuellement disponibles contre le virus Influenza repose sur des antiviraux ciblant la neuraminidase (inhibiteur de la neuraminidase). Jusqu'en 2007 moins de 5% des souches de virus Influenza circulantes dans le monde étaient résistantes à ces INA. Contre toute attente, l'hiver 2007/2008 a été marqué par l'émergence simultanée d'une nouvelle souche apparentée au virus A/Brisbane/59/2007(H1N1) et d'une augmentation massives des résistances à l'Oseltamivir. Nous avons caractérisés les propriétés enzymatiques des souches sensibles et résistantes isolées dans la communauté au cours des saisons 2007/2008, 2008/2009 pour les comparer à un panel de souches de référence des virus A(H1N1). Les résultats obtenus soulignent la particularité des propriétés enzymatiques de la NA de A/Brisbane/59/2007(H1N1) et le rôle de la balance HA-NA dans la diffusion mondiale de cette souche résistante en l'absence de pression de sélection La pandémie de 2009 au virus A(H1N1)pdm09 a été l'occasion de décrire le rôle de l'infection respiratoire basse, virale isolée ou dans le cadre d'une co-infection bactérienne, dans les patients décédés d'un syndrome de détresse respiratoire. La forte proportion de pneumonies virales observées dans les études épidémiologiques réalisées au cours de la pandémie de 2009/2010 et de la saison 2010/2011 suggère la présence de facteurs de virulence permettant au virus A(H1N1)pdm09 de se lier aux récepteurs présents au niveau de l'appareil respiratoire bas. Nous avons étudié l'impact du polymorphisme en position 222 de la HA du virus A(H1N1)pdm09 sur les propriétés de liaison de la HA à son récepteur, sur la balance HA-NA et, in fine, sur le phénotype des virus in vitro et in vivo. Nos résultats montrent que les substitutions D222G, D222E et D222N de la HA du virus A(H1N1)pdm09 favorisent la liaison aux acides sialiques présents au niveau de l'alvéole pulmonaire. Cette propriété pourrait expliquer la plus forte pathogénicité pulmonaire de ce virus. Par ailleurs nos résultats montrent également une association entre l'équilibre de la balance HA-NA et le profil de réplication de ces souches in vitro / Influenza is responsible of 2,5 million cased of respiratory infection, each winter, in France. It is a main human health threat and a main public health concern. The current treatment of flu relies on antiviral drug targeting viral proteins that can induce the appearance of resistant virus. Until 2007, less than 5% of all circulating Influenza strains were resistant to neuraminidase inhibitors. Against all odds, Oseltamivir resistant A/Brisbane/59/2007(H1N1) emerged and spread during 2007/2008 and 2008/2009 season. To understand the driving force of this emergence we tested clinical strains from 2007 to 2011 for Oseltamivir and Zanamivir resistance, sequenced their HA and NA gene, and compared their NA enzymatic properties with A(H1N1) reference strain from 1977 to 2007. Our results showed that A/Brisbane/59/2007 displayed a high affinity compare with NA of previous A(H1N1) reference strains. Moreover these results suggested that HA-NA balance underlie the worldwide emergence of the Oseltamivir resistance without any selection pressure. The A(H1N1)pdm09 pandemic highlighted the importance of lower tract respiratory infection in the severe influenza case. The high proportion of viral pneumonia observed during the 2009 pandemic and the following season suggest that A(H1N1)pdm harbored a virulence factor that allowed the virus replication in the lower respiratory tracts. We studied the effect of HA 222 polymorphism on HA properties, HA-NA balance and in vitro and in vivo Influenza phenotype. Our results demonstrated that G222, E222 or N222 HA mutation increased the binding of A(H1N1)pdm09 mutation to the lower respiratory tract receptor. This may explain the A(H1N1)pdm09 increase pathogenicity. Moreover our results show than an optimal HA-NA balance is link to an efficient replication profile in vitro

Orientadores: Maria Laura Costa do Nascimento, José Guilherme Cecatti / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T01:47:22Z (GMT). No. of bitstreams: 1 Pfitscher_LuciaChaves_M.pdf: 6366056 bytes, checksum: 9a70e9992cbec443ea7d924bdc77f7bb (MD5) Previous issue date: 2015 / Resumo: Introdução: A infecção representa importante causa de morbidade e mortalidade materna, sendo uma preocupação crescente no mundo todo. As doenças respiratórias, especialmente as virais, têm se destacado justamente pelo potencial de epidemia com que ameaçam a saúde da população mundial e pela vulnerabilidade identificada durante a gestação. Objetivo: Avaliar o impacto da morbidade materna grave (MMG) atribuível à infecção (sepse, meningite e doença respiratória) e os fatores associados ao pior resultado materno (near miss e óbito), entre mulheres da Rede Brasileira de Vigilância da Morbidade Materna Grave. Métodos: análise secundária de um estudo transversal, multicêntrico, que incluiu 27 centros de referência obstétrica das cinco regiões do Brasil no período de 2009 e 2010. A vigilância prospectiva dos casos de infecção grave foi realizada utilizando os critérios da OMS de condições potencialmente ameaçadoras da vida (CPAV) e near miss materno (NMM). Os principais focos de infecção foram identificados e comparados a outras causas de MMG. Mulheres com complicação devido à doença respiratória também foram avaliadas em dois grupos: com e sem suspeita de A(H1N1)pdm09 e também comparadas a outras causas de MMG. Casos com suspeita de A(H1N1)pdm09 foram revisados e separados em três grupos: não-testados, confirmados e não confirmados para A(H1N1)pdm09 e os seus resultados foram comparados. Complicações devidas à infecção e a doenças respiratórias foram comparadas com complicações devidas a outras causas de MMG. Os fatores associados com desfecho materno grave (DMG) foram avaliados para os casos de infecção e doença respiratória. Resultados: Dentre os 9555 casos de MMG, apenas 502 (5,3%) apresentaram infecção grave, entretanto foram responsáveis por cerca de um quarto dos casos de NMM e quase metade dos casos de morte materna (MM). Os indicadores de saúde avaliados demonstram maior gravidade dos casos complicados por infecção, com índice de mortalidade (IM) superior a 26% em comparação com 11% para as demais causas de MMG. Para doença respiratória, 206 mulheres apresentaram suspeita de A(H1N1)pdm09, cerca de 60% foram testados para a doença e 49 mulheres apresentaram resultado positivo. A gravidade dos desfechos maternos foi pior entre os casos de A(H1N1)pdm09 positivo, com uma taxa de NMM:MM abaixo de 1 (0,9:1), em comparação a 12:1 para outras causas de MMG. O IM para doença respiratória foi superior a 50% (7,4% outras causas de MMG). Demoras no atendimento foram associadas com pior prognóstico materno e estiveram presentes em mais de 50% entre os casos de infecção, aumentando em duas vezes o risco de DMG para doença respiratória. Resultados perinatais foram piores dentre os casos de doença respiratória, com aumento da prematuridade, morte fetal, baixo peso ao nascer e Apgar <7. HIV/AIDS, histerectomia, hospitalização prolongada, admissão em UTI e demoras no atendimento foram alguns fatores independentes associados DMG. Conclusão: complicações por infecção e em especial por influenza A(H1N1)pdm09 geram grande impacto sobre morbidade e mortalidade materna no Brasil e compreender os fatores associados à maior gravidade pode gerar medidas capazes de colaborar para a melhoria do cuidado obstétrico. Investir em intervenções específicas para gravidez, visando diagnóstico precoce e tratamento oportuno são essenciais para melhorar a saúde materna e reduzir o número de mortes maternas evitáveis no país / Abstract: Background: Infection represents the major cause of maternal morbidity and mortality, and a growing concern worldwide. Respiratory diseases, especially viral, have stood out because of their epidemic potential and the identified vulnerability towards infection during pregnancy. Objective: To assess the impact of severe maternal morbidity (SMM) due to infection (sepsis, meningitis and respiratory disease) and the factors associated with worse maternal outcome (near miss and death) among women of the Brazilian Network for the Surveillance of Severe Maternal Morbidity. Methods: secondary analysis of a cross-sectional, multicenter study that included 27 obstetric referral centers in five regions of Brazil between 2009 and 2010. Prospective surveillance of severe infection was performed using WHO criteria of potentially life threatening conditions (PLTC) and maternal near miss (MNM). The main sources of infection were identified and compared to other causes of SMM. Women with complications due to respiratory disease were also assessed in two groups: with and without suspected A(H1N1)pdm09 and also compared to other causes of SMM. Cases of suspected A(H1N1)pdm09 were reviewed and divided into three groups: non-tested, confirmed and unconfirmed for A(H1N1)pdm09 and their results were compared. Complications due to infection and respiratory disease were compared with complications due to other causes of SMM. Factors associated with SMO were assessed for cases of infection and respiratory disease. Results: Among the 9555 cases of SMM, only 502 (5.3%) had severe infection, however they were responsible for about a quarter of cases of MNM and almost half of the cases of maternal mortality (MM). The assessed health indicators demonstrate greater severity of cases complicated by infection, with a mortality index (MI) above 26% compared to 11% for other causes of SMM. For respiratory disease, 206 women had suspected A(H1N1)pdm09, about 60% were tested for the disease and 49 women were positive. The severity of the maternal outcomes was worse between the cases of A(H1N1)pdm09 positive, with a rate of MNM: MM below 1 (0.9: 1), compared to 12: 1 for other SMM causes. The MI among respiratory disease was superior to 50% (7.4% other causes SMM). Delays in care were associated with worse maternal prognosis and were present in over 50% of cases of infection. Perinatal results were worse in cases of respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar <7. HIV/AIDS, hysterectomy, prolonged hospitalization, ICU admission and delays in care were independent factors associated with severe maternal outcome. Conclusion: infections and especially those caused by A(H1N1)pdm09 presented great impact on maternal morbidity and mortality in Brazil and the identification of factors associated with the increased severity can contribute to the improvement of obstetric care. There is need for specific interventions during pregnancy, seeking early diagnosis and timely treatment of infections, which are essential for improving maternal health and to reducing the number of preventable maternal deaths in the country / Mestrado / Saúde Materna e Perinatal / Mestra em Ciências da Saúde