Realizou-se estudo analitico transversal relacionando caracteristicas individuais e familiares de 182 moradores pertencentes a 58 famílias de área de reserva ecológica à presença de infecções por arbovirus e hantavirus de interesse sanitário local. Pesquisou-se anticorpos para os antigenos dos virus Rocio, Ilhéus, da encefalite de st. Louis, das encefalites equinas do leste, oeste e venezuelana e Hantaan. Foram utilizados os testes de inibição de hemaglutinação, neutralização com redução de placas, imunofluorescência indireta e ensaio imunoenzimático com captura de anticorpos IgM (MAC-ELISA).· A associação estatistica foi pesquisada utilizando-se o teste de qui-quadrado e o grau de associação foi obtido calculando-se o odds ratio. Também foram pesquisadas a sensibilidade, a especificidade e os valores preditivos positivo e negativo das caracteristicas investigadas para avaliar seu poder de discriminar infectados de não infectados e de predizer infecções por arbovirus e hantavirus. A prevalência observada de anticorpos para arbovirus nos individuos foi de 26,9% e nas familias foi de 62,1%. Observou-se uma prevalência de 1,6% de anticorpos para hantavirus nos individuos e 5,2% nas familias. Não foram encontrados anticorpos para o virus da encefalite equina do oeste e nem anticorpos da classe IgM para os antigenos testados. Entre as caracteristicas estudadas, a idade, a ocupação, a naturalidade e o hábito de entrar na mata mostraram-se fatores de risco para infecções por arbovirus. Foram considerados fatores preditivos de infecção por arbovirus a presença de galinheiro anexo à casa, o hábito de criar galinhas e a presença de ratos no domicilio. Não foram observados fatores de risco ou de predição para infecção por hantavirus entre as caracteristicas estudadas. Os resultados obtidos sugerem que as caracteristicas, que mostraram ser fator de risco ou predição, poderiam ser usadas no diagnostico presuntivo preliminar de infecções por arbovirus e hantavirus, permitindo priorizar medidas de intervenção. O uso de um questionário ofereceria aos serviços de saúde ferramenta de simples aplicação e baixo custo, especialmente em condições de campo em áreas que, como a estudada, dispõe de escassos recursos humanos e laboratoriais. / In order to identify risk factors and predictive factors to arbovirus and hantavirus infections among individual and family characteristics, a cross-sectional study was carried out among 182 persons belonging to 58 families living at ecological reserve. The characteristics were associated with the presence of antibodies to the following virus of local interest: Hantaan, Rocio, Ilheus, Eastern, Western and Venezuelan equine encephalitis virus and st. Louis encephalitis virus using inhibition hemagglutination test, plaque reduction neutralization test, indirect immunofluorescence test and immunoglobulin M antibody capture enzyme immunoassay (MAC-ELISA). The associations were calculated using chi-square statistics and the odds ratio. Sensitivity, especificity, positive and negative predictive values of the individual and familiar characteristics were also analyzed to evaluate their capacity to discriminate between infected and non-infected people and to predict arbovirus and hantavirus infections. The prevalence of antibodies to arbovirus was 26.9% and 62.1% of the families had at least one member infected by these agents. Hantavirus antibodies were found in 1.6% of the sera analysed and 5.2% of the families had members infected by these agents. Antibodies to western equine encephalitis virus were not found. IgM antibodies were not observed sugesting no recent infection for those agents in that population. Age, ocupation, nativity and the habit to enter the forest were shown to be risk factors to arbovirus infections. The presence of annexes to the house, to breed chickens and the presence of rodents inside the house were considered predictive factors to arbovirus infections. Risk or predictive factors to hantavirus infections were not observed. The results suggest the use of some of the individual or family characteristics as a tool on the surveillance of arbovirus infections, to discriminate people with major probability of infections, specially in fie1d conditions, where human and laboratorial resources are scarce.

Devido a existência de 2 alphavírus artritogênicos no Brasil, os vírus Mayaro (MAYV) e Chikungunya (CHIKV) tornou-se importante desenvolver testes diagnósticos eficazes para discriminar suas infecções. No presente trabalho, desenvolvemos ELISAs indiretos para diagnóstico de CHIKV e MAYV utilizando proteínas de envelope viral E2 recombinantes, produzidas em Escherichia coli, as rE2-CHIKV e rE2-MAYV ELISAs. As proteínas E2 recombinantes tiveram suas antigenicidades verificadas nos ensaios utilizando anticorpos policlonais oriundos de camundongos hiperimunizados com CHIKV, MAYV e outros alphavírus. O rE2-CHIKV ELISA detectou anticorpos murinos de forma homotípica e não produziu reações cruzadas evidenciáveis utilizando anticorpos murinos específicos contra outros Alphavírus. O rE2-MAYV ELISA detectou anticorpos murinos homotípicos e também, reagiu cruzadamente com anticorpos murinos anti-CHIKV, mas não para outros Alphavírus. Esses ELISAs, também, foram usados na detecção de anticorpos em soros de pacientes com suspeita de infecção arboviral. Pelo o rE2-CHIKV ELISA, testaram-se 59 soros, resultando em 26 amostras IgG positivas. Resultados desse ELISA, quando comparados aos obtidos por teste de neutralização, demonstraram sensibilidade de 89,66% e especificidade de 100%. Soros humanos IgG positivos foram detectados em altas diluições pelo rE2-CHIKV ELISA. Quanto a detecção de IgM, o rE2- CHIKV ELISA apresentou moderada concordância com outros ensaios sorológicos. Com rE2- MAYV ELISA, testaram-se 68 soros resultando em 23 amostras IgG positivas, das quais 11 também mostraram-se positivas em teste de neutralização, demonstrando sensibilidade de 100% e especificidade de 78,95%. Portanto, os rE2-CHIKV e rE2 MAYV ELISAs, particularmente para detecção de IgG, mostraram-se adequadamente sensíveis e específicos para serem validados em estudos com maiores números de amostras e serem aplicados ao diagnóstico de pacientes infectados com CHIKV e MAYV. / Due the existence of 2 arthritogenic alphaviruses in Brasil, the viruses Mayaro (MAYV) and Chikungunya (CHIKV), it became important the development of efficient diagnose tests to discriminate their infections. In the present work, we developed indirect ELISAs for CHIKV and MAYV diagnosis using viral recombinant envelope proteins E2, produced in Escherichia coli, the rE2-CHIKV and rE2-MAYV. The recombinant E2 proteins had their antigenicity confirmed in the assay by using polyclonal antibodies produced in hyperimmunized mice with CHIKV, MAYV and other alphaviruses. The rE2-CHIKV ELISA detected homotypic murine antibodies and did not produced detectable cross-reactivity signal when using murine antibodies from other alphaviruses. The rE2-MAYV ELISA detected homotypic antibodies and also cross-reacted with murine anti-CHIKV antibodies, but not to other alphaviruses. These ELISAs were also tested for the detection of human antibodies, using patient sera suspected of arboviral infection. For rE2- CHIKV ELISA, it were tested 59 sera, resulting in 26 positive IgG samples. These ELISA results, when compared to those of a neutralizing assay, demonstrated a sensibility of 89.66% and specificity of 100%. The IgG positive human sera were detected in high dilutions by rE2-CHIKV ELISA. Regarding the detection of IgM, the rE2-CHIKV ELISA showed a moderate samples detection agreement when compared to other serologic assays. For rE2-MAYV ELISA, it were tested 68 sera, resulting in 23 positive IgG samples, of which 11 demonstrated to be positive by the neutralization assay, demonstrating a sensibility of 100% and specificity of 78.95%. Therefore, the rE2-CHIKV and rE2-MAYV ELISAs, especially for IgG detection, demonstrated to be properly sensitive and specific to be validated in studies using a greater number of samples, and also to be applied in the diagnosis of infected CHIKV and MAYV patients.

Submitted by Luanna Matias (lua_matias@yahoo.com.br) on 2015-03-17T11:06:01Z No. of bitstreams: 2 Tese - Alessandro Pecego Martins Romano - 2012.pdf: 2327686 bytes, checksum: 033dd453809133aad159a6730bbcab88 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luanna Matias (lua_matias@yahoo.com.br) on 2015-03-17T11:10:04Z (GMT) No. of bitstreams: 2 Tese - Alessandro Pecego Martins Romano - 2012.pdf: 2327686 bytes, checksum: 033dd453809133aad159a6730bbcab88 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-03-17T11:10:04Z (GMT). No. of bitstreams: 2 Tese - Alessandro Pecego Martins Romano - 2012.pdf: 2327686 bytes, checksum: 033dd453809133aad159a6730bbcab88 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2012-09-19 / This study sought to describe the use of surveillance of non-human primates in surveillance of Sylvatic Yellow Fever and evaluate the usefulness in the prevention of human cases in Brazil. The epizootic surveillance began its records in 1999 and expanded the activity and the number of notifications after 2006, when the deaths or illnesses of nonhuman primates came to be considered an event of epidemiological relevance and therefore compulsory notification, as currently defines the ordinance 104/GM/MS/2011. 2748 epidemics were recorded in non-human primates in Brazil. The confirmation of yellow fever occurred in 8.8% of notifications. It was characteristic of yellow fever during the study period, two epizootic epidemic periods, with dispersal occurring from areas of Northern and central west with subsequent spread to the South and Southeast regions. During the study period yellow fever hit areas unvaccinated populations where the activity of epizootic surveillance helped to identify affected areas preventing human cases were recorded. The surveillance of NHP revealed the involvement of other infectious agents possibly involved in epizootics reported and highlights the potential contribution of this surveillance strategy for other infectious causes of public health importance and has been identified as seropositive for other arboviruses in primate populations in free life, demonstrating that this surveillance strategy animal may be useful to other map areas of occurrence of other arboviruses. The surveillance strategy allowed animals to detect areas of circulation of YF virus and direct vaccination campaigns, especially in outbreak situations, preventing human cases of the disease and demonstrating its utility and contribution to the monitoring of YF. This monitoring strategy can be enhanced by broadening their purposes as may possibly contribute to the surveillance of other diseases as an important interface of human and animal health. / Este estudo buscou descrever o uso da vigilância de primatas não humanos na vigilância da Febre Amarela Silvestre e avaliar a utilidade na prevenção de casos humanos no Brasil. A vigilância de epizootias iniciou seus registros em 1999 e ampliou a atividade assim como o número de notificações depois de 2006, quando a morte ou adoecimentos de primatas não humanos passou a ser considerado um evento de relevância epidemiológica e, portanto, de notificação compulsória, conforme atualmente define a portaria 104/GM/MS/2011. Foram registradas 2.748 epizootias de primatas não humanos no Brasil. A confirmação para a febre amarela ocorreu em 8,8% das notificações. Foi característica da febre amarela no período do estudo, dois períodos epizoóticos epidêmicos, com dispersão das áreas de ocorrência a partir do norte e centro oeste com disseminação posterior para as regiões sudeste e sul. No período do estudo a febre amarela atingiu áreas de populações não vacinadas, na qual a atividade de vigilância de epizootias contribuiu para identificar áreas afetadas evitando que casos humanos fossem registrados. A vigilância de primatas não humanos revelou a participação de outros agentes etiológicos possivelmente envolvidos nas epizootias notificadas e destaca o potencial de contribuição dessa ferramenta de vigilância para outras causas infecciosas de importância em saúde pública assim como quando foi identificada sorologia reagente para outros arbovírus em populações de primatas em vida livre, demonstrando que essa estratégia de vigilância animal pode ser útil para outras arboviroses com importância em saúde pública. A estratégia de vigilância animal permitiu detectar áreas de circulação do vírus da FA e orientar as campanhas de vacinação, principalmente, em situações de surto, prevenindo casos humanos da doença e demonstrando sua utilidade e contribuição para a vigilância da FA. Essa estratégia de vigilância pode ser aprimorada ampliando as suas finalidades já que possivelmente pode contribuir para a vigilância de outras doenças como importante interface da saúde humana e animal.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As arboviroses são doenças causadas por vírus transmitidos por vetor artrópode (artropod-born viruses). A transmissão ocorre para os hospedeiros vertebrados susceptíveis no momento do repasto sanguíneo realizado pelos artrópodes hematófagos ou pode ocorrer entre artrópodes através da via transovariana e possivelmente venérea. A região Amazônica possui um grande número de artrópodes hematófagos (culicídeos, flebotomíneos, ceratopogonídeos) e vertebrados silvestres que juntamente com o clima tropical propiciam a manutenção dos arbovírus na natureza. O manejo inadequado da natureza através do desmatamento decorrente da abertura de estradas, construção de barragens, garimpo e mineração são alguns dos eventos responsáveis por surtos de arboviroses identificados na região Norte do Brasil. O Estado de Roraima está localizado no extremo norte do país, com fronteira internacional com a Venezuela e com a Guiana e ainda com o Estado do Amazonas e Pará. Estudos regulares a respeito da circulação de arbovírus no Estado são feitos apenas para dengue e febre amarela, nos quais foi identificada a circulação dos quatro sorotipos de dengue. O grande número de casos notificados para dengue cujo diagnóstico laboratorial é negativo para este arbovírus demonstrou a necessidade de se ampliar a pesquisa para outros vírus. Foram analisadas 150 amostras cujo teste NS1 apresentou-se negativo, provenientes do Laboratório Central de Saúde Pública do Estado de Roraima, pertencentes a pacientes que manifestaram síndrome febril no período agudo da doença (até 5 dias de início dos sintomas) e que possuiam outros sintomas como: artralgia, cefaleia, dor retrorbital, calafrio, mialgia, diarreia, vômito e exantema. Conhecendo-se a maior sensibilidade da técnica de qPCR por sonda as amostras(150) foram submetidas à técnica qPCR para DENV, das quais obtivemos 33 (22%) amostras positivas para DEN tendo identificado os sorotipos por RT-PCR convencional obtendo os seguintes resultados: DENV-1(1), DENV-2(4), DENV-3(2), DENV-4(21), além de obtermos amostras negativas(3) e inconclusivas(2). Posteriormente 72 amostras que permaneceram negativas no qPCR para DENV foram submetidas a qPCR para MAYV/ORO obtendo-se positividade para MAYV(7) e para OROV(13). A identificação de outros arbovírus circulantes no Estado de Roraima torna-se necessária para que se conheça a população viral presente e assim desenvolver mecanismos de monitoramento e detecção, em tempo oportuno, da entrada de um arbovírus emergente, responsável por um possível surto. / The arboviruses are diseases caused by viruses transmitted by arthropod vector (artropod-born viruses). Transmission occurs for vertebrate hosts susceptible at the time of blood meal held by arthropod vectors or can occur between arthropods through transovarially and possibly venereal. The Amazon region has a large number of arthropod vectors (mosquitoes, sand flies, ceratopogonídeos) and wild vertebrates that coupled with the tropical climate favor the maintenance of arboviruses in nature. Inadequate management of nature through deforestation caused by the opening of roads, dams, mining and mining are some of the events responsible for outbreaks of arboviruses identified in northern Brazil. The State of Roraima is located in the extreme north of the country, with international border with Venezuela and Guyana and with the state of Amazonas and Pará. Regular studies regarding the circulation of arboviruses in the state are made just for dengue and yellow fever, which was identified in in the circulation of four dengue serotypes. The large number of reported cases of dengue laboratory diagnosis which is negative for this arbovirus demonstrated the need to expand the research to other vírus. We analyzed 150 samples with NS1 test appeared negative, from the Central Laboratory of Public Health of the State of Roraima, belonging to patients who manifested febrile syndrome in acute period of the disease (up to 5 days of onset of symptoms) and who possessed other symptoms such as arthralgia, headache, retrorbital, chills, myalgia, diarrhea, vomiting and rash. Knowing the greater sensitivity of the qPCR technique to probe the samples (150) were subjected to qPCR technique for DENV, which obtained 33 (22%) samples were positive for DEN serotypes and identified by conventional RT-PCR obtaining the following results : DENV-1 (1), DENV-2 (4), DENV-2 (3), DENV-4 (21), and obtain negative samples (3) and inconclusive (2). Subsequently 72 samples that remained negative for DENV in the qPCR were subjected to qPCR MAYV/OROV positive for obtaining MAYV (7) and OROV (13). Identification of other arboviruses circulating in the State of Roraima is necessary for knowing the viral population present and well developed mechanisms for monitoring and detection, timely entry of an emerging arbovirus responsible for a possible outbreak.

Dans une ère où les moustiques modifiés commencent à être utilisés ou envisagés pour contrôler les épidémies de Dengue ou malaria, le manque de connaissance sur l’immunité des insectes vecteurs envers certains pathogènes se fait cruellement ressentir. Pourtant la possibilité de changements de vecteurs, dû à un changement de leur immunité, provoquée par l’Homme est réelle. Pour déterminer la contribution de l’immunité dans différents compartiments du vecteur contre divers pathogènes avons étudié la réponse antivirale dans la première barrière de transmission chez le moustique vecteur de la malaria après une infection par un repas sanguin. Nous montrons que les réponses antivirales sont différentes entre compartiments, et proposons un modèle où des interactions tripartites entre le virus, l’immunité du moustique et la flore entérique interagissent pour contrôler l’infection précoce du moustique après le repas sanguin. De façon surprenante, nous avons également montré que la voie de l’ARN interférence n’a pas d’effet antiviral dans ce compartiment. Nous suggérons que cette voie est utilisée par le parasite Plasmodium pour détourner la réponse antiparasitaire médiée par Toll, grâce à un facteur de virulence de nature ARN double brin. Nous avons également montré que des biais expérimentaux lors de l’infection des insectes ont conduit à l’élaboration d’un dogme disant que la voie de l’ARN interférence est la voie antivirale principale des insectes, mais nos resultats suggèrent que malgré l’importance de cette voie pour controler l’intensité de la réplication virale lors de l’infection disséminée, cette voie n’a aucune fonction antivirale lors de l’infection initiale du tube digestif. Néanmoins, le séquençage des produits de cette voie permet d’assembler de-novo des génomes de virus commensaux. Les résultats de ces travaux montrent très clairement qu’il faut évaluer le rôle et l’impact de toute modification d’insectes vecteurs pour plusieurs classes de pathogènes. Cela ouvre également de nombreux nouveaux champs de recherches et pose de nombreuses nouvelles questions. / In an era where modified mosquitoes are starting to be used in nature for controlling malaria and Dengue, lack of knowledge about immunity of mosquito vectors to some pathogen classes are becoming more evident. The risks for human-provoked vector shifts of pathogens transmission have not been examined. To fill these gaps, we assessed the antiviral immunity of the malaria vector, Anopheles gambiae, in the strongest mosquito bottleneck for pathogens, the midgut infection barrier after an infective bloodmeal. This work shows that the antiviral responses are different and highly compartmentalized between the midgut and systemic immunity. We propose a model where tripartite interactions between virus, mosquito immunity and enteric flora control early arboviral infection in the midgut. Surprisingly, we showed that while the siRNA pathway had no evident anti-arbovirus activity in the midgut, it was used by Plasmodium to evade mosquito immunity. A virus-like elicitor of double strand RNA nature is transferred from the parasite at the ookinete stage to the mosquito midgut cells, resulting in a shift of immune balance from anti-parasite response to an antiviral-like response. Importantly, our work shows that biases in experimental infection methods led to the misconstruction of a dogma stating that siRNA is the main antiviral pathways in insects, at least in the midgut compartment. And that the use of the pathway products can be successfully used to de-novo assemble previously unknown viruses from the virome. This work indicates that immune modifications in vectors need to be evaluated for changes of vectorial competence to different pathogens. It also opens numerous avenues of research and raises a lot of interesting questions that will need to be investigated in the future.

Depuis 2007, le Gabon est régulièrement confronté à des infections par les virus Chikungunya (CHIKV) et Dengue (DENV). Au total, près de 4300 prélèvements provenant de patients se présentant avec un syndrome fébrile algique, en phase clinique aiguë, ont pu être collectés et analysés pour la période de 2007 à 2010. En effet, deux importantes épidémies concomitantes de CHIKV et de DENV ont sévi au Gabon (i.e. Libreville en 2007 et Franceville en 2010). Entre ces deux flambées épidémiques, de nombreux cas sporadiques d'infection à CHIKV ou à DENV ont continué à être enregistrés à travers le pays. Des cas de co-infection à CHIKV/DENV ont également été diagnostiqués lors des deux flambées épidémiques. Ces deux arbovirus se sont ainsi propagés en quelques années dans un mouvement de nord-ouest à sud-est à travers le pays. L’étude plus avancée des cas de co-infection à CHIKV/DENV a pu démontrer que ce phénomène pouvait survenir soit de manière simultanée soit séquentielle au cours du repas sanguin d'Aedes albopictus, principal vecteur du CHIKV et du DENV au Gabon.(…)En conclusion, ce travail de thèse décrit précisément la survenue brutale d’épidémies imputables à plusieurs arbovirus circulant simultanément au Gabon et responsables de nombreux cas cliniques se présentant sous la forme d'un syndrome fébrile algique. La co-circulation de ces virus suggère l’apparition d’une dynamique de type épidémique/endémique et implique un problème de santé publique latent dans cette région d’Afrique, voire dans l’ensemble de la sous-région d’Afrique Centrale. / Following to the first simultaneous Chikungunya (CHIKV) and Dengue (DENV) viruses outbreak in 2007, an active surveillance of febrile syndromes was set up in Gabon, a central African country. During a three-year period, we observed a rapid spread of CHIKV and DENV in a southward movement from north-west to south-east of the country. Indeed, CHIKV and DENV have disseminated within a non-immune population, widely favored by the extraordinary capacity of Aedes albopictus vector to colonize diverse environments and to replace local mosquito’s species. In 2010, a second outbreak occurred in Gabon with further CHIKV/DENV co-infections in both human and mosquito. This is the first documented evidence of co-infection in a wild-caught Aedes albopictus. Additionally, an underlying Zika (ZIKV) virus epidemic transmission by the same invasive vector was retrospectively recorded during the outbreak in 2007. These data reveal an unusual ZIKV natural life cycle, occurring in an urban environment and potentially representing a new arboviral emerging threat from Aedes albopictus.(…)In conclusion, these data highlighted the recent introduction and rapid dissemination of CHIKV and DENV in Gabon. The Aedes albopictus vector has shown its extraordinary capacity to sustain epidemic transmissions, leading to arboviral co-circulations (i.e. CHIKV, DENV-2, DENV-1, DENV-3, ZIKV) and notably to some CHIKV/DENV-2 co-infection cases. This multiple arboviral circulation suggests an epidemic/endemic dynamic in Gabon, involving a latent public health problem in this region of Africa.

Background: Arboviral diseases has reemerged in the last years affecting primarily the coast of Peru. Piura is an endemic region of Dengue, where the recent appearance of Chikungunya (CHIKV) and Zika (ZIKV) has been renewed. Aim: To assess the presence of DENV, CHIKV, and ZIKV in serum samples of patients with acute febrile illness in a locality of Piura, Peru and describe associated clinical features. Methodology: Descriptive cross-sectional study, sampling was done for convenience where it was obtained a total of 496 serum samples from patients with acute febrile illness were collected from 18 primary care centers. All samples were analyzed via real-time RT-PCR to detect DENV, CHIKV, and ZIKV. In addition, positive samples for DENV were also processed for serotypes 1 to 4 classification via RT-PCR. Results: DENV was the most common arbovirus detected in 170/496 (34.3%), followed by ZIKV in 39/496 (7.9%) and CHIKV in 23/496 (4.6%). Among the 170 samples positive for DENV, serotype 2 was the most predominant type present in 97/170 (57.1%) of samples, followed by the serotype 3 in 9/170 (5.3%). Headaches, muscle pain, and joint pain were the most common symptoms associated with fever in patients with DENV and ZIKV. No symptoms predominance was observed in patients with CHIKV. Conclusions: DENV is considered the most frequent arbovirus in Peru and the number of cases has increased dramatically in the last 5 years. However, it is not the only arbovirus that circulates along the northern coast of Peru. It has also been determined the presence of ZIKV and CHIKV in our population, which may suggest the circulation of other arboviruses that have not been detected. / Tesis

Objectif de la thèse est de fournir République de Djibouti inventaire de la pandémie de grippe A/H1N1/2009-H1N1p et arbovirus hiver 2010. Elle a confirmé la capacité de surveillance locale pour détecter la grippe SG pic lors de la première vague de la pandémie, dont le profil était compatible avec H1N1p. Dans l'enquête CoPanFlu, une prévalence élevée (30%) de H1N1p a été confirmée par la jeune et District 4 résidents (plus de inégalités sociales) portant le plus lourd fardeau. Par conséquent, le contrôle futur de SG exigerait une approche queue pour atteindre des individus spécifiques et vulnérables. L'absence de données de surveillance robustes dans les pays du Sud pourrait être responsable de la sous-estimation de la charge, même lorsque le profil de la maladie ressemblait à ceux des pays développés. Sur arbovirus, la plupart des facteurs prédictifs de cas étaient statistiquement mieux décrits par de l'espace de logement et les caractéristiques environnementales du quartier, qui en corrélation avec les acteurs écologiques de leurs vecteurs de la survie des individus dans la niche locale. Cela confirme circulations arbovirus autochtones dans la République de Djibouti et a fourni l'inventaire pour la cartographie des risques et les futurs programmes de prévention et de contrôle. Les arbovirus sont les plus répandus dans le centre-ville (quartier 1), mais des cas ont diminué vers la périphérie de la banlieue (District 4). L'inverse est vrai pour les cas de grippe, ce qui démontre que des solutions sur mesure convenant à un des besoins de santé de la région, se garantir un rendement optimal sur les ressources allouées. / Thesis purpose was to provide Republic of Djibouti inventory of pandemic Influenza A/H1N1/2009 (H1N1p) and arboviruses events in the winter of 2010. The demonstrated local surveillance was capable of detecting (influenza) ILI peaking during the first pandemic wave, whose profile was consistent with H1N1p. In a Copanflu investigation that occurred during second pandemic wave, a high prevalence (30%) of H1N1p was confirmed and conspicuously, the young and District 4 residents (highest social inequalities) bored the greatest burden. Therefore, concluded that future ILI control would require a tailed approach to reach specific and vulnerable individuals. Lack of robust ILI data from surveillance in southern countries could be responsible for the underestimation of burden, even when the illness profile resembled those of developed countries. On arboviral, most case predictors were statistically best described by individuals' housing space and neighbourhood environmental characteristics, which correlated with the ecological actors of their respective transmission vectors' survival in the local niche. This study confirmed autochthonous arboviral circulations in the republic of Djibouti and provided an epidemiological inventory for risk mapping and future prevention and control programs. The arboviruses were most prevalent in city centre (District 1), but cases declined towards the periphery of the suburb (District 4). The inverse was true for pandemic and ILI cases, demonstrating that a tailored solutions suiting local area health needs, would guarantee an optimal return on allocated resources.

Le virus Schmallenberg (SBV) appartient au genre Orthobunyavirus, au sein de la famille des Bunyaviridae. Ce nouveau virus, découvert en 2011 au nord-ouest de l’Europe, affecte les ruminants domestiques. Il est responsable de signes cliniques discrets chez les adultes et de malformations congénitales chez les nouveau-nés. Ces travaux de thèse s’inscrivent dans les projets d’étude de la pathogenèse de l’infection à SBV et de l’épidémiologie de la maladie, dans le cadre d’un programme de recherche européen sur le virus. Ce manuscrit inclut de nouvelles données, telles les cinétiques de la virémie et de la séroconversion chez les ovins et caprins, après infection expérimentale par SBV. La possibilité d’infection par SBV par voie vaginale est démontrée expérimentalement chez la chèvre. Après infection expérimentale de chèvres gestantes entre 28 et 42 jours de gestation, une mortalité fœtale ou des lésions du système nerveux central des fœtus peuvent survenir. Enfin, la sensibilité de plusieurs espèces de ruminants sauvages et exotiques de parcs zoologiques vis-à-vis de SBV est démontrée pour la première fois. / Schmallenberg virus (SBV) belongs to the genus Orthobunyavirus in the family Bunyaviridae. This new virus was discovered in 2011 in Northwestern Europe in domestic ruminants. Infection by SBV is associated with mild clinical signs in adult and congenital malformations in the progeny. In the scope of the European research program on SBV in the pathogenesis and epidemiology areas, the works included in this thesis provide new data about SBV infection in livestock and wild and exotic ruminants. The kinetics of viremia and seroconversion after experimental SBV infection are described in sheep and goats. This manuscript includes evidence of SBV infection via vaginal route in goats. Experimental SBV infection in pregnant goats between 28 and 42 days of gestation can lead to death or central nervous system lesions in fetuses. Evidence of susceptibility to SBV in several species of wild and exotic ruminants kept in zoos is described for the first time.

[Truncated abstract] Ross River virus (RRV) causes the most common arboviral disease in Australia, with approximately 5000 new cases reported each year, making this virus a major public health concern. The aim of this thesis was to link results from virological, pathogenesis and epidemiological studies to further define RRV disease in the south-west (SW) of Western Australia (WA), a region of endemic and epizootic RRV activity. A crosssectional seroprevalence study was used to show that 7.8 percent of SW communities were seropositive to RRV, comparable to other regions of Australia with similar temperate climates to the SW . . . RRV-specific IgM antibodies were found to persist for at least two years following RRV infection. A murine model was used to conclusively show differences in pathogenesis between RRV genotypes, the SW and northern-eastern (NE) genotypes, which are known to circulate throughout Australia. The SW genotype, unique to the SW of WA induced only poor neutralising antibody production and nonneutralising antibodies after the acute phase of infection. In comparison, the NE genotype which currently predominates in mosquito populations in the SW of WA, induced the most efficient neutralising antibody response and consequently produced the mildest disease in the mouse. These data in the mouse suggest that the infecting genotype will mostly likely influence disease outcome in humans and could at least partially explain why more severe and persistent disease has been reported from the SW of WA. Collectively, results from this thesis provide an important benchmark against which future investigations into BFV and RRV diseases can be measured.