Thèse d'exercice : Pharmacie : Université de Nantes : 2003. / Bibliogr. f. 113-119 [78 réf.].

Made available in DSpace on 2014-06-11T19:27:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-04-25Bitstream added on 2014-06-13T20:35:43Z : No. of bitstreams: 1 terzian_acb_me_sjrp.pdf: 523455 bytes, checksum: 5ab90df637c408759e16b50b2d873184 (MD5) / As arboviroses freqüentemente são associadas com surtos nos seres humanos e representam um sério problema de saúde pública, com impactos econômico e social. Entre os arbovírus brasileiros, os vírus Mayaro (MAYV), Dengue (DENV), Febre Amarela (Yellow Fever – YFV), Rocio (ROCV) e Oropouche (OROV) são responsáveis por mais de 95% dos casos de arboviroses humanas no Brasil, causando muitas vezes a mesma sintomatologia clínica, especialmente na fase aguda das infecções. Este estudo teve como objetivo analisar a presença de arbovírus em soros de pacientes com doença febril aguda, durante epidemia de Dengue no município de São José do Rio Preto (SP), bem como de pacientes com doença febril aguda, negativos para Malária e arbovírus do município de Acrelândia (AC). Foi utilizada a técnica de RT-Nested-PCR para a detecção e identificação dos principais arbovírus brasileiros pertencentes aos gêneros Flavivirus, Alphavirus e Orthobunyavirus. Na análise molecular das amostras de São José do Rio Preto, 320 (98%) foram positivas para DENV-3, 3 (1%) para DENV-2, 6 (2%) para o SLEV. Uma destas amostras apresentou co-infecção por DENV-2 e DENV-3 e três amostras apresentaram co-infecção por DENV-3 e SLEV. A alta positividade para o DENV-3 está relacionada com a introdução deste sorotipo no município. Em amostras de Acrelândia, 5 positivas para DENV-3, 1 para MAYV e 2 positivas para OROV. A análise filogenética do gene do envelope mostrou que a amostra isolada de SLEV agrupou-se próxima às estirpes de Belém, que pertencem ao genótipo V. A amostra de OROV agrupou-se ao genótipo I, sendo este o mais distribuído na região Amazônica. Estes dados indicam a circulação de diferentes arbovírus em duas regiões distintas do Brasil e demonstram a necessidade de um sistema de vigilância eficiente para controlar a disseminação destes na população. / Arboviruses are frequently associated with outbreaks in humans and represent a serious public health problem, with economic and social impacts. Among the Brazilian arboviruses, Mayaro virus (MAYV), Dengue virus (DENV), Yellow Fever virus (YVF), Rocio virus (ROCV) and Oropouche virus (OROV) are responsible for more than 95% of human cases in Brazil. These arboviruses usually present the same clinical symptoms, especially on the acute phase of infection. The aim of this study was to investigate the presence of arboviruses in serum of patient presenting acute febrile illness, during a dengue outbreak in the city of São José do Rio Preto (state of São Paulo) and the serum of patients who were tested negatively for malaria and arboviruses in the city of Acrelândia (state of Acre). The RT-Nested-PCR technique was applied to detect and to identify the main brazilian arboviruses, especially in Flavivirus, Alphavirus e Orthobunyavirus genera. The molecular analysis in the samples of São José do Rio Preto samples showed that 320 (98%) were positive for DENV-3, 3 (1%) to DENV-2, 6 (2%) to SLEV. Among the positive samples, one presented coinfection with DENV-2 and DENV-3 and three presented coinfection with DENV-3 and SLEV. The high positivity of DENV-3 is associated with the introduction of a new DENV serotype in the city. In the samples from Acrelândia, 5 were positive to DENV-3, 1 to MAYV and 2 positive to OROV. The phylogenetic analysis of the envelope gene from a positive SLEV sample indicated that the virus circulating in São José do Rio Preto is most related to strains from Belém, which belong to lineage V. The OROV belongs to lineage I, the most widespread in Amazon region. These results indicate the circulation of different arboviruses in two distinct regions of Brazil and they demonstrate the need of an efficient surveillance system to control the dissemination of these arbovirus in the population.

Foi realizado um estudo epidemiológico da epidemia de encefalite por arbovírus na região do Vale do Ribeira, São Paulo, Brasil, durante o período de março de 1975 a julho de 1978. A epidemia, iniciada em 1975, atingiu o pico em 1976. A partir de 1978 a moléstia se manteve em níveis baixos sob presumível endemicidade. A letalidade nos anos epidêmicos de 1976 e 1977 variou em sentido inverso ao da morbidade, que apresentou picos nas épocas de maior temperatura e pluviosidade. Ao que parece, a epidemia teria se deslocado em onda em direção leste-oeste e leste-sudoeste tendo atingido a região litorânea vizinha. A cadeia montanhosa situada ao norte e noroeste teria atuado como barreira à propagação da moléstia. Considerou-se a hipótese que o agente etiológico, arbovírus Rocio, só recentemente deva ter começado a infectar a população humana, tendo sido veiculado ao homem a partir de reservatórios silvestres, aves e pequenos mamíferos, por culicídeos silvestres. Discutiram-se também prováveis formas de transmissão domiciliar da arbovirose ocorrida em número bem menor de casos. Verificou-se que os grupos populacionais que apresentaram as formas mais graves da doença foram os das idades extremas e os de piores condições de vida. Considerou-se que a perspectiva epidemiológica desta arbovirose é que ela persista na região, uma vez que existem condições ótimas para o desenvolvimento dO agente etiológico, de reservatórios e de vetores biológicos, além do contínuo afluxo de população suscetível, constituída por migrantes ou por turistas. / An epidemiological study of the encephalitis epidemic by arbovirus was carried out in Ribeira River Valley, State of São Paulo, Brazil, from March 1975 to July 1978. The epidemic began in 1975 and reached its peak in 1976. From 1978 onwards the disease maintained low levels in a presurnable endemicity. The lethality of the disease in the epidemic years of 1976 and 1977 varied in the opposite direction of its morbility, which presented peaks when the temperature and pluvial levels were higher. It seems that the epidemic swept from east to west and from east to southwest in a wave towards the neighbouring coastland region. The mountain chain situated towards the north and northwest acted as a barrier to the spreading of the disease. The hypothesis that the etiological agent, arbovirus Rocio, must have infected the human population recently, having been veiculated to man from forest reservoirs, birds and small mammals, by wild mosquitoes, was considered. Probable forms of domiciliar transmission of the arbovirosis which ocurred in a significantly smaller number of cases were also discussed. It was verified that the population groups which presented the worst forms of the disease were those at extreme ages and those under worst living conditions. It was considered that the epidemiological perspective of the arbovirosis is that it ought to persist in the area, as it presents excellent conditions for the development of the etiological agent, reservoirs and biological vectors, besides continuously receiving susceptible people, migrants or tourists.

Objective: To assess the presence of Dengue, Chikungunya, and Zika in serum samples of patients with acute febrile illness in Piura, Peru and describe the most common clinical features. Results: Dengue was the most common arbovirus detected in 170/496 (34.3%), followed by Zika in 39/496 (7.9%) and Chikungunya in 23/496 (4.6%). Among the 170 samples positive for Dengue, 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 Dengue and Zika. No symptoms predominance was observed in patients with Chikungunya.Dengue 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 Zika and Chikungunya in our population, which may suggest the circulation of other arboviruses that have not been detected.

Objective: To evaluate the frequency of infection caused by the Oropouche virus (OROV) in 496 patients with acute febrile disease (AFI), whose samples were obtained for the analysis of endemic arboviruses in a previous investigation carried out in 2016. Results: OROV was detected in 26.4% (131/496) of serum samples from patients with AFI. Co-infections with Dengue virus (7.3%), Zika virus (1.8%) and Chikungunya (0.2%) were observed. The most common clinical symptoms reported among the patients with OROV infections were headache 85.5% (112/131), myalgia 80.9% (106/131), arthralgia 72.5% (95/131) and loss of appetite 67.9% (89/131). Headache and myalgia were predominant in all age groups. Both OROV infections and co-infections were more frequent in May, June and July corresponding to the dry season of the region. / Revisión por pares

Objective: To describe the prevalence of dengue virus serotypes, as well as other viral and bacterial pathogens that cause acute febrile illness during an outbreak in Cajamarca in 2016. Results: Dengue virus (DENV) was the most frequent etiologic agent detected in 25.8% of samples (32/124), followed by Rickettsia spp. in 8.1% (10/124), Zika virus in 4.8% (6/124), Chikungunya virus 2.4% (3/124) and Bartonella bacilliformis 1.6% (2/124) cases. No positive cases were detected of Oropouche virus and Leptospira spp. DENV serotypes identification was only achieved in 23% of the total positive for DENV, two samples for DENV-2 and four samples for DENV-4. During the 2016 outbreak in Cajamarca-Peru, it was observed that in a large percentage of positive samples for DENV, the infecting serotype could not be determined by conventional detection assays. This represents a problem for the national surveillance system and for public health due to its epidemiological and clinical implications. Other viral and bacterial pathogens responsible for acute febrile syndrome were less frequently identified. / Revisión por pares

Objective: To describe frequency and clinical characteristics of MAYV infection in Piura, as well as the association of this pathogen with DENV. Results: A total of 86/496 (17.3%) cases of MAYV were detected, of which 54 were MAYV mono-infection and 32 were co-infection with DENV, accounting for 10.9% and 6.4%, respectively. When evaluating monoinfection by MAYV the main groups were 18–39 and 40–59 years old, with 25.9% and 20.4% respectively. Co-infections were more common in the age group 18–39 and those > 60 years old, with 34.4% and 21.9%, respectively. The most frequent clinical presentation were headaches (94.4%, 51/54) followed by arthralgias (77.8%, 42/54). During the 8-month study period the most cases were identified in the months of May (29.1%) and June (50.0%). / National Research Foundation of Korea / Revisión por pares

Microfilarial enhancement of viral transmission is well documented, however only one previously studied model used components that occur together in nature and therefore has realistic implications. La Crosse (LAC) virus encephalitis is the most common mosquito-borne illness affecting children in the United States. LAC virus is prevalent in the Great Lake and Mid-Atlantic states and coincidently this area overlaps the region of highest infection for Dirofilaria immitis, the nematode that cause canine heartworm disease. Ae. albopictus and Oc. triseriatus are important vectors of La Crosse virus and among the numerous species able to transmit D. immitis. In this study, Aedes albopictus and Ochlerotatus triseriatus were infected with La Crosse virus and Dirofilaria immitis to determine the effects of dual infection on the dissemination and transmission of the virus. The effects of dual infection varied between the species tested. Ae. albopictus had significantly higher tolerance to D. immitis infection than Oc. triseriatus. Dissemination for dually infected Ae. albopictus were higher than the control group for all days tested, except one. Transmission rates for D. immitis infected Ae. albopictus were significantly higher than the control group on day 14 post infection. No microfilarial enhancement of viral dissemination or transmission was observed for Oc. triseriatus. The infection, dissemination, and tranmission rates were low for both species compared to rates of previous studies. Low rates could be a result of low susceptibility for the strains tested. In a second study, mosquitoes were collected from two counties in Southwestern Virginia to determine the abundance of potential La Crosse virus and D. immitis vector species. The abundance and distribution of mosquito species were examined in 2003 and 2004 using gravid traps. An unexpected finding was the significant increase in the abundance of Ochlerotatus japonicus. In 2003, collections were made over 192 trap nights from June to August yielding 5,879 mosquitoes of which only 24 were Oc. japonicus. In 2004, 12,151 mosquitoes were trapped from June to September over 160 trap nights. Oc. japonicus was the second most abundant mosquito species and the dominant Ochlerotatus species collected in gravid traps. Oc. japonicus was collected in low numbers in June, but the abundance increased significantly in July and remained consistent throughout the rest of the season. Of the other major mosquito species collected in this study, only Aedes albopictus exhibited a similar seasonal pattern as Oc. japonicus. Other biological similarities of Oc. japonicus and Ae. albopictus are discussed. / Master of Science in Life Sciences

Les zoonoses émergentes sont en augmentation au cours des dernières décennies. Ainsi, il y est urgent de comprendre les mécanismes de cette émergence, en particulier d’étudier les facteurs écologiques sous-jacents qui déterminent les transferts de ces maladies de l’animal à l’homme.Originaire d’Asie, le moustique tigre Aedes albopictus est arrivé au Brésil dans les années 80 et s’est établi dans 60% des villes brésiliennes. Les forêts brésiliennes sont considérées comme un point chaud de la biodiversité mondiale, abritant des centaines d'arbovirus zoonotiques. Ces forêts que, par fois, cercles des grandes agglomérations urbaines, souffrent de la transformation du paysage réalisé par l’homme, un terreau idéal pour l'apparition de zoonoses. Cette espèce représente une préoccupation majeure pour la transmission d’arbovirus épidémiques (Dengue, Chikungunya, Zika) mais également une menace potentielle pour l’émergence de maladies zoonotiques en raison de sa présence dans les interfaces ville / forêt, de son comportement alimentaire opportuniste et de sa compétence vectorielle pour nombreux virus. Ainsi, Ae. albopictus pourrait potentiellement jouer le rôle de vecteur pont pour le transfert en milieu urbain de arbovirus zoonotiques qui circulent dans les forêts brésiliennes. Dans cette étude, nous évaluons le potentiel de cette espèce à servir de vecteur de pont entre la faune et l'homme. Pour cette proposition (i) Nous avons effectué une recherche et une analyse bibliographiques portant sur trois éléments clés permettant d’évaluer la capacité de ce moustique à assurer le transfert interspécifique des arbovirus dans les zones sylvatiques : 1) la capacité à exploiter les sites de reproduction larvaire naturels, 2) le comportement alimentaire et 3) la compétence vectorielle pour les dif férentes arbovirus. (ii) Nous avons étudié sur le terrain la colonisation, la dispersion, le comportement trophic et l'impact sur la biodiversité d'Ae. albopictus dans l'interface ville / forêt au Brésil. Ce travail de terrain a été réalisé à partir de dix écosystèmes de fragments de forêts dans trois Biomes au Brésil: 1) Biome Amazonia dans la réserve forestière d'Adolpho Ducke à Manaus; 2) Biome Mata Atlantica dans la réserve forestière de Pedra Branca à Rio de Janeiro, dans les fragments de forêt urbaine à Salvador, Serra, Belo Horizonte et dans les fragments de forêt rurale à Domingos Martins, Simonésia, Casimiro de Abreu, Marica-RJ; Biome Cerrado dans la forêt de Morro dos Macacos à Goiania. Dans cette thèse nous avons confirmé qu’Ae. albopictus a la capacité de coloniser des sites de reproduction naturels avec un comportement alimentaire opportuniste et une claire préférence pour les sources de sang humain, suivi par d'autres mammifères et oiseaux. Nous observons que le processus de colonisation et de dispersion est limité à la bordure de la forêt avec un impact sur la composition des espèces dans ces environnements. Nous avons observé également que ce moustique est capable de transmettre 13 arbovirus dans notre recherche bibliografic, mais aucun arbovirus n’a été détecté chez des moustiques prélevés lors du travail de terrain. Globalement, nos résultats confirment et estiment le rôle potentiel d’Ae. albopictus comme vecteur pont des maladies zoonotiques aux interfaces forêt / ville au Brésil. Ces travaux ouvrent un domaine de recherche dans lequel de nouvelles investigations pourraient évaluer le risque potentiel de propagation des maladies zoonotiques des zones forestières aux zones urbaines, dans le but de limiter les futures émergences virales. / Zoonotic emerging diseases are increasing during the last decades. There is an urgent need to understand the mechanisms of this emergence, in particular to study the underlying ecological factors determining spill-over events, the transfer from animals to humans. Being native from Asia, the tiger mosquito Aedes albopictus arrived to Brazil in the 80’s being nowadays established in 60% of brazilian cities. Brazilian forests are considered a hotspot of wildlife biodiversity, harbouring hundreds of zoonotic arboviruses, suffering human landscape transformation and surrounding large urban cities, an optimal breeding ground for the emergence of zoonotic diseases. This species represents a major concern for the transmission of epidemic arboviruses (dengue, chikungunya, Zika) but also a potential threat for the emergence of zoonotic diseases due to its presence in urban/forest interfaces, its opportunistic feeding behavior and its vector competence to transmit numerous viruses. Thus, Ae. albopictus might potentially participate as a bridge vector for the transfer to urban environments of zoonotic arboviruses that are circulating on Brazilian forests. In this study we evaluate the potential of this species to act as a bridge vector between wildlife and humans. For this propose (i) we performed a bibliographic research and analysis focusing on three key components for assessing the ability of a mosquito to ensure interspecies transfer of arboviruses in sylvatic areas: 1) the capacity to exploit natural larval breeding sites, 2) blood-feeding behaviour and 3) the vector competence for arboviruses. (ii) We investigated from fieldwork the colonization, dispersion, host feeding and potential impact of biodiversity patterns of Ae. albopictus in the urban/forest interface in Brasil. This field work was realized from ten forest-fragments ecosystems in tree Brazilians Biome: Biome Amazonia in Adolpho Ducke forest reserve-Manaus; Biome Mata Atlantica in Pedra Branca forest reserve- Rio de Janeiro, in the urban forest fragment Salvador, Serra, Belo Horizonte and in the rural forest fragment Domingos Martins, Simonésia, Casimiro de Abreu, Marica-RJ; Biome Cerrado in Morro dos Macacos forest – Goiania. This work confirmed that Ae. albopictus has the capacity to colonize natural breeding sites with the opportunistic feeding behavior with a preference for human blood sources, followed by other mammals and birds. We observe that the colonization and dispersion process is limited to the edge forest with an impact in species composition in this environments. We observed that this mosquitos is vector competence for 13 arbovirus from bibliographic recherché, but no arbovirus was detected from fildework collected mosquitos. Globally our results confirm and estimates the potential role of Ae. albopictus to act as a bridge vector of zoonotic diseases at the forest/urban interfaces in Brazil. This work opens a research area in which further investigations may assess the potential spill-over risk of zoonotic disease from forested to urban areas with the aim to mitigate potential future viral emergences.

Le virus Zika (ZIKV) est un phénomène épidémiologique sans précédent qui surprit le monde entier. Pendant de nombreuses années, il fut considéré comme un virus anodin responsable d’une poignée d’infections humaines, auto-limitées et bénignes, en Afrique et en Asie du Sud-est. Mais, après des décennies de propagation silencieuse, une première épidémie éclata en Micronésie en 2007 - tel un signal d'alarme. Quelques années plus tard, une soudaine épidémie de ZIKV de plus grande ampleur se déclara dans les îles du Pacifique avant d'atteindre le Brésil en 2015. Au cours de cette période, Zika fut associé à de graves complications neurologiques, mettant en évidence son fort potentiel pathogène pour l'homme. Depuis son émergence, plus de 80 pays et territoires ont été touchés par la pandémie de ZIKV, désormais reconnu comme un virus neurotrope et tératogène. L'association des souches contemporaines de ZIKV à des formes graves de maladie chez l'homme, qui n'ont jamais été signalées auparavant, a soulevé l'hypothèse d'une pathogénicité nouvellement acquise. Ainsi, mes travaux de doctorat visaient à déterminer si l'ampleur de l'épidémie actuelle pouvait en partie avoir été facilitée par des facteurs viraux qui auraient renforcé la fitness du ZIKV. À cette fin, mon projet de recherche s'est concentré sur l'identification des facteurs moléculaires viraux impliqués dans la pathogénicité du virus Zika chez l’homme à partir du développement de clones moléculaires. / Zika virus (ZIKV) is an unprecedented epidemiological phenomenon which surprised the world. For many years, it was considered a trivial virus responsible for only a handful of human infections, self-limited and benign, in Africa and Southeast Asia. But then, after decades of silent spread, a first epidemic broke out in Micronesia in 2007 – like a warning signal. A few years later, a sudden Zika outbreak of larger scale occurred in the Pacific islands before reaching Brazil in 2015. During this period, Zika was associated with severe neurological complications, highlighting its serious pathogenic potential for humans. Since its emergence, more than 80 countries and territories have been affected by the ZIKV pandemic, which is now recognized as a neurotropic and teratogenic virus. The association of contemporary ZIKV strains with severe forms of disease in humans, that have never been reported before, has raised the hypothesis of newly acquired pathogenicity. In this regard, my doctoral research aimed to determine whether the scope of the current epidemic was partly facilitated by viral factors that improved ZIKV fitness. To this end, my research project focused on the identification of the viral molecular factors involved in Zika virus pathogenicity in humans based on the development of molecular clones.