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![Phylogenetic analysis of DENV-1 based on the complete genome sequence. The evolutionary history was inferred using the maximumlikelihood method, using the general time-reversible model for nucleotide substitution with discrete gamma distribution to model evolutionary rate differences among sites (6 categories [? G, parameter = 0.2785]). The tree with the highest log likelihood (-42583.6960) is shown. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 59 nucleotide sequences with a total of 10,176 positions in the final dataset. A total of 1000 bootstrap replicates were run, and some values are represented as percentage in respective nodes. The evolutionary divergence (%) within each lineage is shown in parentheses, and the dN/dS ratio for each lineage is presented in brackets. The lineages and Latin America cluster are indicated, and the Brazilian DENV-1 sequences are shown in bold. Evolutionary analysis was conducted in MEGA5 [23] and PAML [25]](profile/Diane-Schmidt/publication/229061862/figure/fig1/AS:388116474023936@1469545586447/Phylogenetic-analysis-of-DENV-1-based-on-the-complete-genome-sequence-The-evolutionary.png)
Phylogenetic analysis of DENV-1 based on the complete genome sequence. The evolutionary history was inferred using the maximumlikelihood method, using the general time-reversible model for nucleotide substitution with discrete gamma distribution to model evolutionary rate differences among sites (6 categories [? G, parameter = 0.2785]). The tree with the highest log likelihood (-42583.6960) is shown. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 59 nucleotide sequences with a total of 10,176 positions in the final dataset. A total of 1000 bootstrap replicates were run, and some values are represented as percentage in respective nodes. The evolutionary divergence (%) within each lineage is shown in parentheses, and the dN/dS ratio for each lineage is presented in brackets. The lineages and Latin America cluster are indicated, and the Brazilian DENV-1 sequences are shown in bold. Evolutionary analysis was conducted in MEGA5 [23] and PAML [25]
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Following successive outbreaks of dengue fever caused predominantly by dengue virus (DENV) 2 and 3, DENV-1 is now the primary serotype circulating in Brazil. We sequenced and analyzed Brazilian DENV-1 genomes and found that all isolates belong to genotype V and are subdivided into three lineages, which were intro-duced during four different events....
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Citations
... In Brazil, the numbers of cases and deaths related to dengue have been increasing over time because of the introduction or reintroduction of virus serotypes and the simultaneous circulation of the four serotypes (Drumond et al., 2012(Drumond et al., , 2013Figueiredo et al., 2008;Teixeira et al., 2013Teixeira et al., , 2005. In the state of São Paulo, the number of dengue cases have followed the same pattern, increasing from 2001 (51,668 cases) to 2007 (92,345 cases), 2010 (189,330 cases), and 2013 (201,498 cases) (CVE, 2014). ...
... Even then, the use of these indicators is restricted because the indicators should not be considered alone. The indicators make sense only if they are analyzed with other variables related to the dynamics of transmission, such as the degree of immunity of the population for the different serotypes of the dengue virus; the serotypes, genotypes and circulating clades; vector behavior; and weather, environmental and socioeconomic characteristics (Drumond et al., 2013(Drumond et al., , 2012Focks et al., 1995;Ghouth et al., 2012;Kuno, 1977;Lee et al., 2012;Morrison et al., 2008;Teixeira et al., 2005;Yamanaka et al., 2011). ...
The aims of this study were to describe the occurrence of dengue in space and time and to assess the relationships between dengue incidence and entomologic indicators. We selected the dengue autochthonous cases that occurred between September 2005 and August 2007 in São José do Rio Preto to calculate incidence rates by month, year and census tracts. The monthly incidence rates of the city were compared to the monthly Breteau indices (BI) of the São José do Rio Region. Between December 2006 and February 2007, an entomological survey was conducted to collect immature forms of Aedes aegypti in Jaguaré, a São José do Rio Preto neighborhood, and to obtain entomological indices. These indices were represented using statistical interpolation. To represent the occurrence of dengue in the Jaguaré neighborhood in 2006 and 2007, we used the Kernel ratio and to evaluate the relationship between dengue and the entomological indices, we used a generalized additive model in a spatial case-control design. Between September 2005 and August 2007, the occurrence of dengue in São José do Rio Preto was almost entirely caused by DENV3, and the monthly incidence rates presented high correlation coefficients with the monthly BI. In Jaguaré neighborhood, the entomological indices calculated by hectare were better predictors of the spatial distribution of dengue than the indices calculated by properties, but the pupae quantification did not show better prediction qualities than the indices based on the container positivity, in relation to the risk of dengue occurrence. The fact that the municipality's population had a high susceptibility to the serotype DENV3 before the development of this research, along with the almost total predominance of the occurrence of this serotype between 2005 and 2007, facilitated the analysis of the epidemiological situation of the disease and allowed us to connect it to the entomological indicators.
Copyright © 2014. Published by Elsevier B.V.
Over 400 million people are estimated to be at risk of acquiring dengue virus (DENV). Despite efforts to mitigate the impact of DENV epidemics, the virus remains a public health problem in the Americas: more than one million DENV cases were reported in the continent between January and July 2019 DENV was first detected in Brazil in 1982, and Brazil has reported 88% (1,127,244 cases) of all DENV cases in the Americas during 2019 to date. São Paulo state in the southeast of Brazil has reported nearly half of all DENV infections in the country. Here we characterised the genetic diversity of DENV strains circulating in São Paulo state in 2019, at the epicentre of the ongoing DENV epidemic. Using portable nanopore sequencing we generated 20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Notably, phylogenetic analysis indicated that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Our genetic analysis further indicates that the introduction and onwards spread of the outbreak lineage (named here DENV2-III BR-4) indicates a new DENV2 lineage replacement in Brazil. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.
Author Summary
Dengue is the most important mosquito-borne viral disease of humans. The disease is caused by the dengue virus (DENV) that is classified within genus Flavivirus . DENV infections are caused by 4 serotypes (DENV 1-4) that are genetically related but antigenically distinct. Dengue infection results in a variety of symptoms that range from mild fever to dengue hemorrhagic fever and/or dengue shock syndrome (DHF/DSS). Clinical outcomes are associated with different types of infection, viral serotypes, genotypes, lineages, and host genetic factors. As a re-emerging infectious disease, DENV has become a serious threat to public health in the Americas, and particularly in Brazil, where it was introduced in the 1980s and became well established due to the country-wide re-infestation of the Aedes aegypti mosquito vector species. During the first six months of 2019, 1,282,183 DENV cases were reported in the Americas, with Brazil reporting a staggering 1,127,244 (88%) of all dengue cases in the continent. To date, no information exists on the genetic composition of the DENV lineage or lineages causing the current epidemic. Here we use portable sequencing to rapidly generate virus genome data from cases occurring in two different are severely-affected municipalities in São Paulo state, Brazil. We find that the 2019 dengue outbreak in Brazil is caused by a newly introduced DENV serotype 2 genotype III (Asian/American) that seems to be replacing previously-circulating DENV2 lineages. We discuss the potential implications of our results regarding the current outbreak in the context of previous outbreaks in the same region.
Background:
Roughly half the world's population live in dengue-endemic countries, but no vaccine is licensed. We investigated the efficacy of a recombinant, live, attenuated tetravalent dengue vaccine.
Methods:
In this observer-masked, randomised, controlled, monocentre, phase 2b, proof-of-concept trial, healthy Thai schoolchildren aged 4-11 years were randomly assigned (2:1) to receive three injections of dengue vaccine or control (rabies vaccine or placebo) at months 0, 6, and 12. Randomisation was by computer-generated permuted blocks of six and participants were assigned with an interactive response system. Participants were actively followed up until month 25. All acute febrile illnesses were investigated. Dengue viraemia was confirmed by serotype-specific RT-PCR and non-structural protein 1 ELISA. The primary objective was to assess protective efficacy against virologically confirmed, symptomatic dengue, irrespective of severity or serotype, occurring 1 month or longer after the third injection (per-protocol analysis). This trial is registered at ClinicalTrials.gov, NCT00842530.
Findings:
4002 participants were assigned to vaccine (n=2669) or control (n=1333). 3673 were included in the primary analysis (2452 vaccine, 1221 control). 134 cases of virologically confirmed dengue occurred during the study. Efficacy was 30·2% (95% CI -13·4 to 56·6), and differed by serotype. Dengue vaccine was well tolerated, with no safety signals after 2 years of follow-up after the first dose.
Interpretation:
These data show for the first time that a safe vaccine against dengue is possible. Ongoing large-scale phase 3 studies in various epidemiological settings will provide pivotal data for the CYD dengue vaccine candidate.
Funding:
Sanofi Pasteur.
