Two Lineages of Dengue Virus Type 2, Brazil

Our results suggest the circulation of genetically different DENV-2 in Brazil and that these viruses may have a role in severity of dengue diseases. These fi ndings can help to further understand the complex dynamic pathogenic profi le of dengue viruses and their circulation in dengue-endemic regions.Submitted by Sandra Infurna ([email protected]) on 2017-10-19T12:29:42Z No. of bitstreams: 1 jmg_araujo_etal_IOC_2010.pdf: 90948 bytes, checksum: becf560ca2fc3c395d59080bbdfcaf2c (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-10-19T12:45:14Z (GMT) No. of bitstreams: 1 jmg_araujo_etal_IOC_2010.pdf: 90948 bytes, checksum: becf560ca2fc3c395d59080bbdfcaf2c (MD5)Made available in DSpace on 2017-10-19T12:45:14Z (GMT). No. of bitstreams: 1 jmg_araujo_etal_IOC_2010.pdf: 90948 bytes, checksum: becf560ca2fc3c395d59080bbdfcaf2c (MD5) Previous issue date: 2010Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, BrasilUniversidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil

Spatial Evaluation and Modeling of Dengue Seroprevalence and Vector Density in Rio de Janeiro, Brazil

Dengue is a major public health problem in many tropical regions of the world, including Brazil, where Aedes aegypti is the main vector. We present a household study that combines data on dengue fever seroprevalence, recent dengue infection, and vector density, in three neighborhoods of Rio de Janeiro, Brazil, during its most devastating dengue epidemic to date. This integrated entomological–serological survey showed evidence of silent transmission even during a severe epidemic. Also, past exposure to dengue virus was highly associated with age and living in areas of high movement of individuals and social/commercial activity. No association was observed between household infestation index and risk of dengue infection in these areas. Our findings are discussed in the light of current theories regarding transmission thresholds and relative role of mosquitoes and humans as vectors of dengue viruses

Vírus dengue sorotipo 3 (DENV-3) no Brasil: estudos sobre patogenia, sítios de replicação, filogenia e evolução molecular

Made available in DSpace on 2016-03-04T13:59:28Z (GMT). No. of bitstreams: 2 joselio_araujo_ioc_dout_2009.pdf: 11696830 bytes, checksum: 45f6a57d0a27af32727404bbd7154585 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2016-01-13Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilDengue é uma importante arbovrirose (arthropod-bone virus) e contitui um grave problema de saúde pública não só no Brasil, mas também nos países de clima tropical. A Aedes aegypti é o principal vetor dos vírus dengue (DENV) e está presente na maioria dos países entre as latitudes 35ºN e 35ºS. Neste trabalho, apresentamos quatro estudos. No primeiro estudo, analisamos os níveis de RNA viral do DENV-3 e sua correlação com o tipo de infecção (primária ou secundária) em casos fatais e não fatais por dengue, ocorridos no estado do Rio de Janeiro, 2002. O grupo de casos fatais apresentou uma média de título viral significativamente mais elevada do que o grupo de casos não fatais. Considerando que infecções primárias foram confirmadas entre os casos fatais (52,1%), a teoria da infecção seqüencial por si só não explica todos os casos graves da doença. Estes resultados sugerem que altos níveis de DENV-3 podem ter contribuído para a forma grave do dengue no Rio de Janeiro, 2002.No segundo estudo, diferentes métodos de diagnóstico foram aplicados para investigar a presença dos DENV em amostras de tecidos humanos obtidos a partir de casos fatais (n = 29), ocorridos durante e grande epidemia em 2002 no estado do Rio de Janeiro, Brasil. A combinação de quatro métodos permitiu a confirmação da infecção por DENV-3 em 26 (89,6%) dos 29 casos suspeitos. . O isolamento viral foi obtido em 2,7% (2/74) das amostras, a partir da inoculação em cultura de células C6/36. A técnica de nested RT-PCR permitiu a identificação do DENV-3 em 30,5% (22/72) das analisadas. O método de RT-PCR em tempo real possuiu maior sensibilidade, detectando o RNA viral em 58,4% (45/77) dos espécimes clínicos, incluindo fígado (n=18), pulmão (n=8), cérebro (n=6), rim (n=3), medula óssea (n=1) e coração (n=1). A técnica de imunohistoquímica detectou o antígeno viral em 44% (26/59) das amostras analisadas A precisão e eficácia do RT-PCR em tempo real fez desta técnica uma ferramenta importante no diagnóstico rápido das infecções por dengue. No terceira estudo, revisamos a filogeografia dos três principais genótipos do DENV-3 e estimamos sua taxa de evolução, como base na análise do gene do envelope (E) de 200 isolados, provenientes de 31 países ao redor do mundo, durante um período de 50 anos (1956 \2013 2006). Nossa análise filogenética revelou uma subdivisão geográfica da população dos DENV-3, com grupamentos específicos em vários países. Os padrões migratórios dos principais genótipos dos DENV-3 mostraram que genótipo I circula principalmente na porção marítima do Sudeste Asiático do Sul do Pacífico, o genótipo II permaneceu dentro das zonas continentais do Sudeste Asiático, enquanto o genótipo III foi disseminado na Ásia, Leste da África e Américas. Não foi observada co-circulação de diferentes genótipos em uma única localidade, sugerindo que alguns fatores, além da distância geográfica podem limitar a contínua dispersão e re-introdução de novas variantes de DENV-3. As estimativas das taxas evolutivas não revelaram diferenças significativas entre os principais genótipos do DENV-3. A média da taxa de evolução em regiões que sofreram epidemias de dengue desde a década de 70 (por exemplo, Indonésia e Tailândia) foi semelhante ao observado em regiões que presenciam estas epidemias desde a década de 90 (por exemplo, Américas). Neste estudo, estimamos o ano de origem das atuais linhagens do DENV-3 em torno de 1890, e o surgimento da atual diversidade dos seus principais genótipos entre meados de 1960-1970, coincidindo com o crescimento da população humana, urbanização, movimento humano e descrição dos primeiros casos de febre hemorrágica por DENV-3 na Ásia No quarto estudo, examinamos a atual classificação filogenética dos DENV-3 circulantes no Globo, com destaque para o novo genótipo (GV) descrito no Brasil. A circulação de um novo genótipo de DENV-3 foi recentemente descrito no Brasil e na Colômbia, porém, sua classificação exata tem sido controversa. Análises de distância nucleotídica do gene E apóia a subdivisão do DENV-3 em cinco linhagens distintas, denominadas genótipos (GI-GV), e confirma a classificação deste novo genótipo na América do Sul como pertencente ao GV. Distâncias genéticas extremamente baixas entre isolados brasileiros pertencentes ao GV e a amostra protótipo Philippines/L11423 isolada em 1956 levantam questões impor tantes sobre a origem deste genótipos na América do SulDengue is an important arbovirus (arthropod-borne virus) and constitutes a serious problem of public health not only in Brazil but also in the major tropical countries. Aedes aegypti is the main vector of dengue virus (DENV) and is present in most countries between latitudes 35ºN and 35ºS. In this manuscript, we present four distinct studies. In study 1, we examined levels of dengue virus type 3 RNA in association with the type of infection (primary or secondary) in patients with fatal and nonfatal outcomes in Rio de Janeiro State, 2002. Subjects with fatal outcomes had mean virus titers significantly higher than those who survived. Because primary infections were confirmed among the fatal cases (52.1%), antibody-dependent enhancement alone did not explain all the cases of severe disease in this study population. These findings suggest that high levels of DENV-3 may have contributed to the severe form of dengue in Rio de Janeiro, 2002. In the second study, we investigate by different diagnostic methods dengue virus in human tissue specimens obtained from fatal cases (n=29) during a large-scale dengue fever epidemic in 2002 in the State of Rio de Janeiro, Brazil. The combination of four procedures provided diagnostic confirmation of DENV-3 infection in 26 (89.6%) out of the 29 suspected fatal cases. Dengue virus (DENV) was isolated from 2/74 (2.7%) tissue samples, inoculated into C6/36 cells and identified as DENV-3, nested RT-PCR accusing 22/72 (30.5%) samples as DENV-3. Real-time RT-PCR yielded the highest positivity rate, detecting viral RNA in 45/77 (58.4%) clinical specimens, including the liver (n=18), lung (n=8), spleen (n=8), brain (n=6), kidney (n=3), bone marrow (n=1) and heart (n=1). Immunohistochemical tests recognized the DENV antigen in 26/59 (44%) specimens. Given the accuracy and effectiveness of real-time RTPCR in this investigation, this approach may play an important role for rapid diagnosis of dengue infections. In the third study, we revisited the phylogeography of the three of major DENV-3 genotypes and estimated its rate of evolution, based on the analysis of the envelope (E) gene of 200 strains isolated from 31 different countries around the world over a time period of 50 years (1956 to 2006). Our phylogenetic analysis revealed a geographical subdivision of DENV-3 population in several country-specific clades. Migration patterns of the main DENV-3 genotypes showed that genotype I was mainly circumspect to the maritime portion of Southeast-Asia and South Pacific, genotype II stayed within continental areas in South-East Asia, while genotype III spread across Asia, East Africa and into the Americas. No evidence for rampant co-circulation of distinct genotypes in a single locality was found, suggesting that some factors, other than geographic proximity, may limit the continual dispersion and reintroduction of new DENV-3 variants. Estimates of the evolutionary rate revealed no significant differences among major DENV-3 genotypes. The mean evolutionary rate of DENV-3 in areas with long-term endemic transmissions (i.e., Indonesia and Thailand) was similar to that observed in the Americas, which have been experiencing a more recent dengue spread. We estimated the origin of DENV-3 virus around 1890, and the emergence of current diversity of main DENV-3 genotypes between the middle 1960s and the middle 1970s, coinciding with human population growth, urbanization, and massive human movement, and with the description of the first cases of DENV-3 hemorrhagic fever in Asia. In the fourth study, we re-examined the current phylogenetic classification of DENV-3 strains, with emphasis on the new genotype (GV) described in Brazil. Circulation of a new DENV-3 genotype was recently described in Brazil and Colombia, but the precise classification has been controversial. Phylogenetic and nucleotide distance analyses of the envelope (E) gene support the subdivision of DENV-3 strains into five distinct genotypes (GI to GV), confirming the classification of this new genotype in South America as GV. The extremely low genetic distances of Brazilian GV strains to the prototype Philippines/L11423 strain isolated in the 1956 GV sample raise important questions regarding the origin of this genotype in South America

Implantação da técnica de PCR em tempo real (Sistema TaqMan) para dengue tipo 3 (DENV-3) e vigilância virológica na estado do Rio de Janeiro nos anos 2004-2005

Submitted by Repositório Arca ([email protected]) on 2019-07-02T18:34:38Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) joselio_araujo_ioc_mest_2006.pdf: 2431240 bytes, checksum: 139a9e849cbd8a88088d1c36292eff12 (MD5)Approved for entry into archive by Raquel Dinelis ([email protected]) on 2019-09-25T18:45:02Z (GMT) No. of bitstreams: 2 joselio_araujo_ioc_mest_2006.pdf: 2431240 bytes, checksum: 139a9e849cbd8a88088d1c36292eff12 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-09-25T18:45:02Z (GMT). No. of bitstreams: 2 joselio_araujo_ioc_mest_2006.pdf: 2431240 bytes, checksum: 139a9e849cbd8a88088d1c36292eff12 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2006Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Neste estudo são apresentados a implantação da técnica de PCR em tempo real (Sistema TaqMan\2122) para o vírus dengue tipo 3 (DENV-3), a qual constitui uma nova abordagem no diagnóstico de dengue no país. Esta técnica foi aplicada a 30 amostras de fígado provenientes de 28 casos fatais ocorridos durante a epidemia de dengue de 2002 no estado do Rio de Janeiro, sendo o vírus DENV-3 o único sorotipo identificado e admitido como o agente etiológico daquela casuística. A positividade dos casos por esta nova metodologia 64,2% (18/28), foi superior quando comparados a outras metodologias como o PCR convencional (RT-PCR) que confirmou 29,6% (8/27) e o isolamento viral 7,6% (2/26). Na mesma população a imunohistoquímica confirmou 63,6% (14/22) dos casos. Esses dados demonstram a importância do PCR em tempo real em tecidos na confirmação de casos fatais suspeitos de dengue e confirmou seis casos os quais resultaram negativos por outros métodos A Vigilância Virológica no período 2004-2005 envolveu 839 casos suspeitos de dengue sendo confirmados 4% (34/839) considerando-se o isolamento viral e/ou RT-PCR. Considerando-se cada metodologia, o isolamento viral confirmou 0,4% (3/723) e o RT-PCR 3,8% (31/815). O DENV-3 foi o único sorotipo identificado no período 2004-2005. Entretanto, a maior circulação do vírus ocorreu em 2005 com dois surtos, um deles no município de Campos dos Goytacazes (Região Norte Fluminense) e o outro no município do Rio de Janeiro, com dois óbitos confirmados. A caracterização genética das amostras confirmou o genótipo III, o mesmo circulante até o momento no estado do Rio de Janeiro.In this study, the implantation of Real Time PCR (TaqMan™ System) for dengue virus type 3 (DENV-3) is presented, which constitutes a new approach to dengue diagnosis in Brazil. This technique was applied to 30 liver samples originating from 28 fatal cases occurring during the dengue epidemic of 2002 due to DENV-3 in Rio de Janeiro State. DENV-3 was the only serotype identified as the etiological agent of this casuistic. Positivity in 64.2% (18/28) of cases by this new methodology was higher when compared to other methodologies like conventional PCR (RT-PCR), which confirmed 29.6% (8/27), and viral isolation, 7.6% (2/26). In the same population, immunohistochemistry verified DENV-3 in 63.6% (14/22) of cases. These data demonstrate the importance of Real Time PCR on tissues in the confirmation of dengue fatal cases and confirmed six cases that showed negative results by the other methods. Virological Surveillance involved 839 suspected dengue cases in the period 2004-2005, with 4% (34/839) confirmed considering viral isolation and/or RT-PCR. When considering each methodology, viral isolation confirmed 0.4% (3/723) and RT-PCR 3.8% (31/815). DENV-3 was the only serotype identified in the period 2004-2005. However, greater circulation of the virus occurred in 2005 with two outbreaks, one in the municipality of Campos dos Goytacazes (Northern Fluminense Region) and the other in the City of Rio de Janeiro, with two confirmed death. Genetic characterization of the samples showed genotype III, the same which is in circulation at present in Rio de Janeiro State

Dengue viruses in Brazil, 1986-2006 Virus del dengue en Brasil, 1986-2006

A total of 4 243 049 dengue cases have been reported in Brazil between 1981 and 2006, including 5 817 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) and a total of 338 fatal cases. Although all Brazilian regions have been affected, the Northeast and Southeast regions have registered the highest number of notifications. DENV-1 and DENV-4 were isolated for the first time in the Amazon region of Brazil in 1981 and 1982. The disease became a nationwide public health problem following outbreaks of DENV-1 and DENV-2 in the state of Rio de Janeiro in 1986 and 1990, respectively. The introduction of DENV-3 in 2000, also in the state of Rio de Janeiro, led to a severe epidemic with 288 245 reported dengue cases, including 91 deaths. Virus strains that were typed during the 2002 epidemic show that DENV-3 has displaced other dengue virus serotypes and entered new areas, a finding that warrants closer evaluation. Unusual clinical symptoms, including central nervous system involvement, have been observed in dengue patients in at least three regions of the country.<br>En Brasil se han notificado 4 243 049 casos de dengue entre 1981 y 2006, de ellos 5 817 casos de dengue hemorrágico/síndrome de choque por dengue (DH/SCD) y un total de 338 casos mortales. A pesar de que la enfermedad ha afectado a todas las regiones brasileñas, el mayor número de casos se ha notificado en las regiones nororiental y suroriental. Los virus del dengue (DENV) 1 y 4 se aislaron por primera vez en la región amazónica de Brasil en 1981 y 1982. La enfermedad se convirtió en un problema nacional de salud pública después de los brotes de DENV-1 y DENV-2 en el Estado de Río de Janeiro en 1986 y 1990, respectivamente. La introducción del DENV-3 en 2000, también en el Estado de Río de Janeiro, llevó a una grave epidemia con 288 245 casos notificados de dengue y 91 muertes. Las cepas del virus identificadas durante la epidemia de 2002 demostraron que el DENV-3 ha desplazado a los otros serotipos y se ha expandido a nuevas zonas, algo que merece una evaluación más profunda. En los pacientes con dengue de al menos tres regiones del país se han observado síntomas clínicos atípicos, entre ellos alteraciones del sistema nervioso central

Origin and evolution of dengue virus type 3 in Brazil

Submitted by Sandra Infurna ([email protected]) on 2016-09-15T14:10:41Z No. of bitstreams: 1 gonzalo3_bello_etal_IOC_2012.pdf: 861973 bytes, checksum: 44f514ca14f66b506635797d554f42cd (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2016-09-15T14:23:10Z (GMT) No. of bitstreams: 1 gonzalo3_bello_etal_IOC_2012.pdf: 861973 bytes, checksum: 44f514ca14f66b506635797d554f42cd (MD5)Made available in DSpace on 2016-09-15T14:23:10Z (GMT). No. of bitstreams: 1 gonzalo3_bello_etal_IOC_2012.pdf: 861973 bytes, checksum: 44f514ca14f66b506635797d554f42cd (MD5) Previous issue date: 2012Universidade Federal do Rio Grande do Norte. Laboratório de Biologia Molecular para Doenças Infecciosas e Câncer. Natal, RN, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Universidad de la República. Facultad de Ciencias. Laboratório de Organización y Evolución del Genoma. Sección Biomatemáticas. Montevideo, Uruguay.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.The incidence of dengue fever and dengue hemorrhagic fever in Brazil experienced a significant increase since the emergence of dengue virus type-3 (DENV-3) at the early 2000s. Despite the major public health concerns, there have been very few studies of the molecular epidemiology and time-scale of this DENV lineage in Brazil. In this study, we investigated the origin and dispersion dynamics of DENV-3 genotype III in Brazil by examining a large number (n=107) of E gene sequences sampled between 2001 and 2009 from diverse Brazilian regions. These Brazilian sequences were combined with 457 DENV-3 genotype III E gene sequences from 29 countries around the world. Our phylogenetic analysis reveals that there have been at least four introductions of the DENV-3 genotype III in Brazil, as signified by the presence of four phylogenetically distinct lineages. Three lineages (BR-I, BR-II, and BR-III) were probably imported from the Lesser Antilles (Caribbean), while the fourth one (BR-IV) was probably introduced from Colombia or Venezuela. While lineages BR-I and BR-II succeeded in getting established and disseminated in Brazil and other countries from the Southern Cone, lineages BR-III and BR-IV were only detected in one single individual each from the North region. The phylogeographic analysis indicates that DENV-3 lineages BR-I and BR-II were most likely introduced into Brazil through the Southeast and North regions around 1999 (95% HPD: 1998-2000) and 2001 (95% HPD: 2000-2002), respectively. These findings show that importation of DENV-3 lineages from the Caribbean islands into Brazil seems to be relatively frequent. Our study further suggests that the North and Southeast Brazilian regions were the most important hubs of introduction and spread of DENV-3 lineages and deserve an intense epidemiological surveillance

Dengue virus type 3 in Brazil: a phylogenetic perspective

Submitted by Sandra Infurna ([email protected]) on 2017-08-15T12:39:36Z No. of bitstreams: 1 joselio_araujo_etal_IOC_2009.pdf: 424048 bytes, checksum: d1531c5f43d450ae9da88da8471d91cc (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-08-15T12:46:53Z (GMT) No. of bitstreams: 1 joselio_araujo_etal_IOC_2009.pdf: 424048 bytes, checksum: d1531c5f43d450ae9da88da8471d91cc (MD5)Made available in DSpace on 2017-08-15T12:46:53Z (GMT). No. of bitstreams: 1 joselio_araujo_etal_IOC_2009.pdf: 424048 bytes, checksum: d1531c5f43d450ae9da88da8471d91cc (MD5) Previous issue date: 2009Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Moelcular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivirus. Rio de Janeiro, RJ. Brasil.Circulation of a new dengue virus (DENV)-3 genotype was recently described in Brazil and Colombia, but the precise classification of this genotype has been controversial. Here we perform phylogenetic and nucleotide-distance analyses of the envelope gene, which support the subdivision of DENV-3 strains into five distinct genotypes (GI to GV) and confirm the classification of the new South American genotype as GV. The extremely low genetic distances between Brazilian GV strains and the prototype Philippines/L11423 GV strain isolated in 1956 raise important questions regarding the origin of GV in South America

DENV-3 data set.

<p>DENV-3 data set.</p

Time-scaled Bayesian Maximum Clade Credibility tree for the DENV-3 Caribbean/South America III lineage.

<p>Terminal branches of the tree are colored according to the sampled location of the taxon at the tip. Internal branches are colored according to the most probable location of their parental node. The age (with 95% HPD in parentheses) and the posterior probabilities for the geographic locations of parental nodes of the Caribbean/South America III, BR-I and BR-II lineages are shown. Branch lengths of the trees correspond to length of time (see the time scale bar). The tree is automatically rooted under the assumption of a relaxed molecular clock.</p