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1.
PLoS Negl Trop Dis ; 13(12): e0007882, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31809504

RESUMO

BACKGROUND: In Africa, the magnitude of dengue virus (DENV) transmission is largely unknown. In Burkina Faso, several outbreaks have been reported and data are often based on findings from outbreak investigations. METHODS: To better understand dengue epidemiology and clinical characteristics in Burkina Faso, a fever surveillance study was conducted among patients aged 1-55 years, who presented with non-malarial febrile illness at five primary healthcare facilities in Ouagadougou, Burkina Faso from December 2014 to February 2017, encompassing a 3-month dengue outbreak in September-November 2016. Acute and convalescent blood samples were collected within an interval of 10-21 days between visits. Acute samples were tested with dengue rapid diagnostic tests (RDT) and a selected subset with RT-PCR, and all acute/convalescent samples with IgM/IgG ELISA. RESULTS: Among 2929 non-malarial febrile patients, 740 (25%) were dengue-positive based on RT-PCR and/or IgM/IgG ELISA; 428 out of 777 patients (55%) and 312 out of 2152 (14%) were dengue-positive during outbreak and non-outbreak periods, respectively. There were 11% (316/2929) and 4% (129/2929) patients showing positive for NS1 and IgM, on the RDT, respectively. DENV 2 predominated during the outbreak, whereas DENV 3 predominated before the outbreak. Only 25% of dengue-positive cases were clinically diagnosed with suspected dengue. The odds of requiring observation for ≤3 days (versus routine outpatient care) were 11 times higher among dengue-positive cases than non-dengue cases. In adjusted analyses, dengue-positivity was associated with rash and retro-orbital pain (OR = 2.6 and 7.4, respectively) during the outbreak and with rash and nausea/vomiting (OR = 1.5 and 1.4, respectively) during the non-outbreak period. CONCLUSION: Dengue virus is an important pathogen in Burkina Faso, accounting for a substantial proportion of non-malarial fevers both during and outside outbreak, but is only infrequently suspected by clinicians. Additional longitudinal data would help to further define characteristics of dengue for improved case detection and surveillance.


Assuntos
Dengue/epidemiologia , Dengue/patologia , Surtos de Doenças , Febre/epidemiologia , Febre/etiologia , Instalações de Saúde , Adolescente , Adulto , Anticorpos Antivirais/sangue , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Vírus da Dengue/classificação , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Monitoramento Epidemiológico , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
2.
Emerg Microbes Infect ; 8(1): 1626-1635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31711408

RESUMO

Dengue fever is one of those unique diseases where host immune responses largely determine the pathogenesis and its severity. Earlier studies have established the fact that dengue virus (DENV) infection causes haemorrhagic fever and shock syndrome, but it is not directly responsible for exhibiting these clinical symptoms. It is noteworthy that clinically, vascular leakage syndrome does not develop for several days after infection despite a robust innate immune response that elicits the production of proinflammatory and proangiogenic cytokines. The onset of hyperpermeability in severe cases of dengue disease takes place around the time of defervescence and after clearance of viraemia. Extracellular vesicles are known to carry biological information (mRNA, miRNA, transcription factors) from their cells of origin and have emerged as a significant vehicle for horizontal transfer of stress signals. In dengue virus infection, the relevance of exosomes can be instrumental since the majority of the immune responses in severe dengue involve heavy secretion and circulation of pro-inflammatory cytokines and chemokines. Here, we present an updated review which will address the unique and puzzling features of hyperpermeability associated with DENV infection with a special focus on the role of secreted extracellular vesicles.


Assuntos
Vírus da Dengue/fisiologia , Exossomos/virologia , Dengue Grave/virologia , Animais , Citocinas/genética , Citocinas/metabolismo , Vírus da Dengue/genética , Exossomos/genética , Exossomos/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Humanos , Dengue Grave/genética , Dengue Grave/metabolismo
3.
BMC Infect Dis ; 19(1): 997, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771564

RESUMO

BACKGROUND: Dengue fever is prevalent in the world; in recent years, several outbreaks occurred in West Africa. It affects pregnant women. We aimed to assess the consequences of dengue fever on pregnant women and their fetuses during dengue epidemic in Burkina Faso. METHODS: We conducted a cross-sectional study from November 1, 2015 to January 31, 2017 in 15 public and private health facilities in Ouagadougou, using secondary data. Immunochromatographic rapid test Duo detecting specific antibodies, immunoglobin M/G and /or dengue non structural antigen1 virus was used to diagnose dengue cases. RESULTS: Out of 399 (48%) women registered during the study period, 25 (6%) were pregnant. The average age of pregnant women was 30 years, with 18 and 45 years as extremes. The main symptoms were fever (92%) and headache (92%). Nine patients (36%) had severe dengue characterized by bleeding (16%), neurological symptoms (16%) and acute respiratory distress (8%). Eight (32%) of the 25 women had early miscarriage and 8 (32%) women gave birth to viable fetuses. Among those with viable babies, 5 (20%) presented post-partum hemorrhage and 3 (12%) presented early delivery. The main fetal complications included 3 cases of acute fetal distress (12%). One case of maternal death (4%) and 4 cases of neonatal mortality (44.5%) were notified. CONCLUSION: Dengue fever occurring during pregnancy increases maternal and neonatal mortality. Its severe complications require specific monitoring of pregnant women until delivery.


Assuntos
Dengue/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/virologia , Adolescente , Adulto , Burkina Faso/epidemiologia , Estudos Transversais , Dengue/etiologia , Vírus da Dengue/genética , Vírus da Dengue/patogenicidade , Feminino , Febre/epidemiologia , Febre/etiologia , Febre/virologia , Humanos , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Prevalência , Dengue Grave/epidemiologia , Dengue Grave/etiologia , Fatores Socioeconômicos , Adulto Jovem
4.
PLoS Negl Trop Dis ; 13(10): e0007785, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31634352

RESUMO

BACKGROUND: Dengue virus (DENV) infection is a major cause of acute febrile illness in Indonesia. Diagnostic inaccuracy may occur due to its varied and non-specific presentation. Characterization of DENV epidemiology, clinical presentation, and virology will facilitate appropriate clinical management and public health policy. METHODOLOGY/PRINCIPAL FINDINGS: A multicenter observational cohort study was conducted in Indonesia to assess causes of acute fever requiring hospitalization. Clinical information and specimens were collected at enrollment, 14-28 days, and 3 months from 1,486 children and adults. Total of 468 (31.9%) cases of DENV infection were confirmed by reference laboratory assays. Of these, 414 (88.5%) were accurately diagnosed and 54 had been misdiagnosed as another infection by sites. One hundred initially suspected dengue cases were finally classified as 'non-dengue'; other pathogens were identified in 58 of those cases. Mortality of DENV infection was low (0.6%). Prior DENV exposure was found in 92.3% of subjects >12 years. DENV circulated year-round in all cities, with higher incidence from January to March. DENV-3 and DENV-1 were the predominant serotypes. This study identified DENV-1 with TS119(C→T) substitution in the serotyping primer annealing site, leading to failure of serotype determination. CONCLUSIONS/SIGNIFICANCE: DENV is a common etiology of acute febrile illness requiring hospitalization in Indonesia. Diagnostic accuracy at clinical sites merits optimization since misdiagnosis of DENV infection and over-estimation of dengue can negatively impact management and outcomes. Mutation at the annealing site of the serotyping primer may confound diagnosis. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing. Policy-makers should prioritize development of laboratory capacity for diagnosis of DENV.


Assuntos
Vírus da Dengue/genética , Dengue/diagnóstico , Dengue/epidemiologia , Dengue/virologia , Mutação , Adolescente , Adulto , Algoritmos , Criança , Pré-Escolar , Técnicas de Laboratório Clínico/métodos , Estudos de Coortes , Dengue/fisiopatologia , Vírus da Dengue/classificação , Feminino , Febre , Genótipo , Mapeamento Geográfico , Política de Saúde , Hospitalização , Humanos , Incidência , Indonésia/epidemiologia , Masculino , Filogenia , Saúde Pública , Sorogrupo , Sorotipagem , Adulto Jovem
5.
J Immunol Res ; 2019: 7239347, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565661

RESUMO

Zika virus (ZIKV), an emerging mosquito-borne flavivirus, has quickly spread in many regions around the world where dengue virus (DENV) is endemic. This represents a major health concern, given the high homology between these two viruses, which can result in cross-reactivity. The aim of this study was to determine the cross-reacting antibody response of the IgM and IgG classes against the recombinant envelope protein of ZIKV (rE-ZIKV) in sera from patients with acute-phase infection of different clinical forms of dengue, i.e., dengue fever (DF) and dengue hemorrhagic fever (DHF) (before the arrival of ZIKV in Mexico 2010), as well as acute-phase sera of ZIKV patients, together with the implications in neutralization and antibody-dependent enhancement. Differences in IgM responses were observed in a number of DF and DHF patients whose sera cross-reacted with the rE-ZIK antigen, with 42% recognition between acute-phase DHF and ZIKV but 27% recognition between DF and ZIKV. Regarding IgG antibodies, 71.5% from the DF group showed cross-reactivity to rE-ZIKV in contrast with 50% and only 25% of DHF and ZIKV serum samples, respectively, which specifically recognized the homologous antigen. The DHF group showed more enhancement of ZIKV infection of FCRγ-expressing cells compared to the DF group. Furthermore, the DHF group also showed a higher cross-neutralizing ability than that of DF. This is the first report where DF and DHF serum samples were evaluated for cross-reactivity against Zika protein and ZIKV. Furthermore, DENV serum samples cross-protect against ZIKV through neutralizing antibodies but at the same time mediate antibody-dependent enhancement in the sequential ZIKV infection.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Adolescente , Adulto , Linhagem Celular , Criança , Pré-Escolar , Dengue/epidemiologia , Vírus da Dengue/genética , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Testes de Neutralização , Vigilância da População , Adulto Jovem , Zika virus/genética , Infecção por Zika virus/epidemiologia
6.
PLoS Pathog ; 15(9): e1007996, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31536610

RESUMO

The ability of DENV2 to display different morphologies (hence different antigenic properties) complicates vaccine and therapeutics development. Previous studies showed most strains of laboratory adapted DENV2 particles changed from smooth to "bumpy" surfaced morphology when the temperature is switched from 29°C at 37°C. Here we identified five envelope (E) protein residues different between two alternative passage history DENV2 NGC strains exhibiting smooth or bumpy surface morphologies. Several mutations performed on the smooth DENV2 infectious clone destabilized the surface, as observed by cryoEM. Molecular dynamics simulations demonstrated how chemically subtle substitution at various positions destabilized dimeric interactions between E proteins. In contrast, three out of four DENV2 clinical isolates showed a smooth surface morphology at 37°C, and only at high fever temperature (40°C) did they become "bumpy". These results imply vaccines should contain particles representing both morphologies. For prophylactic and therapeutic treatments, this study also informs on which types of antibodies should be used at different stages of an infection, i.e., those that bind to monomeric E proteins on the bumpy surface or across multiple E proteins on the smooth surfaced virus.


Assuntos
Vírus da Dengue/classificação , Vírus da Dengue/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Antígenos Virais/química , Antígenos Virais/genética , Linhagem Celular , Microscopia Crioeletrônica , Vírus da Dengue/ultraestrutura , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutação , Domínios e Motivos de Interação entre Proteínas , Homologia de Sequência de Aminoácidos , Sorogrupo , Temperatura Ambiente , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
7.
Int J Infect Dis ; 88: 88-99, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521850

RESUMO

OBJECTIVES: This study examined the epidemiological, clinical, and immunological characteristics of the 2015 dengue outbreak in Taiwan. METHODS: Clinical data were collected from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients. A phylogenetic tree was used to analyze the source of the outbreak strain. Paired plasma samples from DF/DHF patients were used for antibody-dependent enhancement (ADE) assay and cytokine multiplex biometric immunoassay to validate the immunological mechanism. RESULTS: This outbreak mainly occurred in two of the southern cities of Taiwan: Tainan (n=22 777; 52%) and Kaohsiung (n=19 784; 45%). A high DHF death rate was noted (34.6%). The case (DHF) and control (DF) study indicated that older age (>60 years), type II diabetes, and hypertension were risk factors correlated with the development of DHF (p< 0.0001). The phylogenetic tree results suggested that the outbreak-associated strain was dengue virus serotype 2 and cosmopolitan genotype, forming a stable cluster with the isolates from Thailand and Indonesia (bootstrap value of 99%). Cytokine analyses demonstrated that levels of interleukin (IL)-6, IL-4, IL-13, IL-1ß, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in DHF patients compared to DF patients (p< 0.001). The ADE assay showed that diluted plasma containing preexisting dengue antibodies from DHF patients significantly enhanced dengue infection (p< 0.05). CONCLUSION: The results suggest that older age, type II diabetes, hypertension, immunological cytokine dysregulation, and preexisting dengue antibodies inducing ADE infection are correlated with dengue severity. This study also indicates that the largest dengue outbreak in Taiwan might have been a result of imported DF from dengue epidemic regions.


Assuntos
Vírus da Dengue/isolamento & purificação , Dengue/epidemiologia , Adulto , Idoso , Citocinas/genética , Citocinas/imunologia , Dengue/genética , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Surtos de Doenças , Epidemias , Feminino , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Filogenia , Fatores de Risco , Sorogrupo , Taiwan/epidemiologia , Adulto Jovem
8.
PLoS Negl Trop Dis ; 13(9): e0007266, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545819

RESUMO

Long term surveillance of vectors and arboviruses is an integral aspect of disease prevention and control systems in countries affected by increasing risk. Yet, little effort has been made to adjust space-time risk estimation by integrating disease case counts with vector surveillance data, which may result in inaccurate risk projection when several vector species are present, and when little is known about their likely role in local transmission. Here, we integrate 13 years of dengue case surveillance and associated Aedes occurrence data across 462 localities in 63 districts to estimate the risk of infection in the Republic of Panama. Our exploratory space-time modelling approach detected the presence of five clusters, which varied by duration, relative risk, and spatial extent after incorporating vector species as covariates. The Ae. aegypti model contained the highest number of districts with more dengue cases than would be expected given baseline population levels, followed by the model accounting for both Ae. aegypti and Ae. albopictus. This implies that arbovirus case surveillance coupled with entomological surveillance can affect cluster detection and risk estimation, potentially improving efforts to understand outbreak dynamics at national scales.


Assuntos
Aedes/fisiologia , Vírus da Dengue/fisiologia , Dengue/epidemiologia , Mosquitos Vetores/fisiologia , Aedes/classificação , Aedes/virologia , Animais , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Monitoramento Ambiental , Monitoramento Epidemiológico , Humanos , Mosquitos Vetores/classificação , Mosquitos Vetores/virologia , Panamá/epidemiologia
9.
Mol Biotechnol ; 61(11): 852-859, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473916

RESUMO

To explore virus-like particles formation of dengue virus serotype type 2 (DENV-2) structural proteins of, C, prM, E were expressed in silkworm larvae using recombinant Bombyx mori nucleopolyhedroviruses (BmNPV). Each recombinant BmNPV bacmid coding the 2C-prM-E polypeptide and E protein fused with the signal peptide of bombyxin from B. mori was injected into silkworm larvae. The expressed proteins were collected from hemolymph and fat body, and purified using affinity chromatography. E protein was observed at 55 kDa. The DENV virus-like particles (DENV-LPs) with a diameter approximately 35 nm was observed using transmission electron microscopy (TEM) and immunogold-labelling TEM analysis. The binding of each partially purified proteins to heparin, one of receptors for DENV was confirmed. DENV-LPs were secreted in silkworm larval hemolymph even still low amount, but the E protein and heparin binding function were confirmed.


Assuntos
Proteínas do Capsídeo/metabolismo , Vírus da Dengue/genética , Proteínas do Envelope Viral/metabolismo , Proteínas Estruturais Virais/metabolismo , Vírion/genética , Animais , Bombyx/crescimento & desenvolvimento , Bombyx/metabolismo , Proteínas do Capsídeo/biossíntese , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/isolamento & purificação , Vírus da Dengue/metabolismo , Corpo Adiposo/metabolismo , Expressão Gênica , Vetores Genéticos , Hemolinfa/metabolismo , Heparina/metabolismo , Larva/metabolismo , Sinais Direcionadores de Proteínas/genética , Sorogrupo , Proteínas do Envelope Viral/biossíntese , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/isolamento & purificação , Proteínas Estruturais Virais/biossíntese , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/isolamento & purificação , Vírion/ultraestrutura
10.
PLoS Negl Trop Dis ; 13(9): e0007047, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487279

RESUMO

BACKGROUND: Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis. METHODOLOGY: We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections. RESULTS: Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue-caused by DENV-1 and/or DENV-2 -and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment. DISCUSSION: Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will-ultimately and hopefully-improve the clinical care of outpatients in low-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02656862.


Assuntos
Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Febre/diagnóstico , Adolescente , Adulto , Idoso , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Vírus Chikungunya/fisiologia , Criança , Pré-Escolar , Estudos Transversais , República Democrática do Congo/epidemiologia , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/fisiologia , Feminino , Febre/epidemiologia , Febre/virologia , Humanos , Malária/diagnóstico , Malária/epidemiologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Adulto Jovem
11.
Nucleic Acids Res ; 47(18): 9789-9802, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31392996

RESUMO

Members of the Flaviviridae family, including dengue virus (DENV) and yellow fever virus, cause serious disease in humans, whilst maternal infection with Zika virus (ZIKV) can induce microcephaly in newborns. Following infection, flaviviral RNA genomes are translated to produce the viral replication machinery but must then serve as a template for the transcription of new genomes. However, the ribosome and viral polymerase proceed in opposite directions along the RNA, risking collisions and abortive replication. Whilst generally linear, flavivirus genomes can adopt a circular conformation facilitated by long-range RNA-RNA interactions, shown to be essential for replication. Using an in vitro reconstitution approach, we demonstrate that circularization inhibits de novo translation initiation on ZIKV and DENV RNA, whilst the linear conformation is translation-competent. Our results provide a mechanism to clear the viral RNA of ribosomes in order to promote efficient replication and, therefore, define opposing roles for linear and circular conformations of the flavivirus genome.


Assuntos
Vírus da Dengue/genética , Flavivirus/genética , Biossíntese de Proteínas , Zika virus/genética , Vírus da Dengue/patogenicidade , Flavivirus/patogenicidade , Genoma Viral/genética , Genômica , Humanos , Recém-Nascido , RNA Viral/genética , Replicação Viral/genética , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/patogenicidade , Zika virus/patogenicidade , Infecção por Zika virus/genética , Infecção por Zika virus/virologia
12.
BMC Infect Dis ; 19(1): 680, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370795

RESUMO

BACKGROUND: A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before. METHODS: Colombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers. RESULTS: Only 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no "gold standard", LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p < 0.05). CONCLUSION: Clinical suspicion overestimates the true number of dengue patients. RT-LAMP is a potentially useful low-cost diagnostic tool for dengue diagnosis. Confirmed dengue patients had significantly higher AST levels and lower lymphocyte counts in early disease compared to others. In confirmed dengue patients, younger age and a higher AST level in early infection were associated with subsequent plasma leakage.


Assuntos
Aspartato Aminotransferases/sangue , Técnicas de Amplificação de Ácido Nucleico/métodos , Dengue Grave/diagnóstico , Dengue Grave/etiologia , Adulto , Teorema de Bayes , Biomarcadores/sangue , Estudos de Coortes , Dengue/diagnóstico , Vírus da Dengue/genética , Feminino , Febre/virologia , Humanos , Testes Imunológicos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Medição de Risco , Sensibilidade e Especificidade , Dengue Grave/sangue , Sri Lanka
13.
Int J Mol Sci ; 20(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398956

RESUMO

Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems. The capsid is a homodimeric protein that contains a disordered N-terminal region, an intermediate flexible fold section and a very stable conserved fold region. Since a better understanding of its structure can give light into its biological activity, here, first, we compared and analyzed relevant mosquito-borne Flavivirus capsid protein sequences and their predicted structures. Then, we studied the alternative conformations enabled by the N-terminal region. Finally, using dengue virus capsid protein as main model, we correlated the protein size, thermal stability and function with its structure/dynamics features. The findings suggest that the capsid protein interaction with host lipid systems leads to minor allosteric changes that may modulate the specific binding of the protein to the viral RNA. Such mechanism can be targeted in future drug development strategies, namely by using improved versions of pep14-23, a dengue virus capsid protein peptide inhibitor, previously developed by us. Such knowledge can yield promising advances against Zika, dengue and closely related Flavivirus.


Assuntos
Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Vírus da Dengue , Flavivirus , Sequência de Aminoácidos , Animais , Proteínas do Capsídeo/genética , Sequência Conservada , Vírus da Dengue/genética , Vírus da Dengue/metabolismo , Evolução Molecular , Flavivirus/genética , Flavivirus/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Filogenia , Conformação Proteica , Estabilidade Proteica , Relação Estrutura-Atividade
14.
BMC Evol Biol ; 19(1): 163, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375065

RESUMO

BACKGROUND: Ancestral character states computed from the combination of phylogenetic trees with extrinsic traits are used to decipher evolutionary scenarios in various research fields such as phylogeography, epidemiology, and ecology. Despite the existence of powerful methods and software in ancestral character state inference, difficulties may arise when interpreting the outputs of such inferences. The growing complexity of data (trees, annotations), the diversity of optimization criteria for computing trees and ancestral character states, the combinatorial explosion of potential evolutionary scenarios if some ancestral characters states do not stand out clearly from others, requires the design of new methods to explore associations of phylogenetic trees with extrinsic traits, to ease the visualization and interpretation of evolutionary scenarios. RESULT: We developed PastView, a user-friendly interface that includes numerical and graphical features to help users to import and/or compute ancestral character states from discrete variables and extract ancestral scenarios as sets of successive transitions of character states from the tree root to its leaves. PastView provides summarized views such as transition maps and integrates comparative tools to highlight agreements or discrepancies between methods of ancestral annotations inference. CONCLUSION: The main contribution of PastView is to assemble known numerical and graphical methods into a multi-maps graphical user interface dedicated to the computing, searching and viewing of evolutionary scenarios based on phylogenetic trees and ancestral character states. PastView is available publicly as a standalone software on www.pastview.org .


Assuntos
Filogenia , Software , Interface Usuário-Computador , Albânia/epidemiologia , Dengue/epidemiologia , Vírus da Dengue/genética , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Fenótipo , Filogeografia
15.
Arch Virol ; 164(11): 2789-2792, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414286

RESUMO

Replication of the dengue virus (DENV) genome occurs in a vesicle in the endoplasmic reticulum by a complex of host and viral proteins. Two host proteins, STT3A and STT3B, as members of the oligosaccharyl transferase complex, have been implicated in playing structural roles in the vesicle in mammalian cells, and the absence of these proteins has been shown to decrease DENV replication. Aedes aegypti is the main vector of the virus and has been used previously as a model organism to study mosquito-virus interactions. In this study, we found that genes of the oligosaccharyl transferase complex have no effect on replication of DENV in mosquito cells.


Assuntos
Aedes/virologia , Vírus da Dengue/crescimento & desenvolvimento , Vírus da Dengue/genética , Hexosiltransferases/genética , Proteínas de Membrana/genética , Replicação Viral/genética , Animais , Benzamidas/farmacologia , Linhagem Celular , Dengue/virologia , Retículo Endoplasmático/virologia , Genoma Viral/genética , Glicosilação , Hexosiltransferases/antagonistas & inibidores , Interações Hospedeiro-Patógeno , Proteínas de Membrana/antagonistas & inibidores , RNA Viral/genética , Sulfonamidas/farmacologia , Células Vero
16.
Arch Virol ; 164(11): 2793-2797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31440811

RESUMO

The DC-SIGN glycoprotein is responsible for the initial adhesion of dengue virus (DENV) to immune cells by the carbohydrate recognition domain (CRD). There are thirteen soluble and membrane-bound DC-SIGN isoforms, but the role of soluble isoforms in the DENV internalization process is not known. Five isoforms with an altered or absent CRD were identified, and three different soluble isoforms were used to confirm the interactions with mannose residues. The results show the loss of binding ability of one soluble isoform and binding ability of two of them. All of them will be used to verify their role in the DENV internalization process.


Assuntos
Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Vírus da Dengue/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Manose/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Ligação Viral , Internalização do Vírus , Sequência de Aminoácidos , Sequência de Bases , Dengue/virologia , Vírus da Dengue/genética , Ligantes , Ligação Proteica/genética , Isoformas de Proteínas/genética
17.
Nat Microbiol ; 4(11): 1832-1839, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31451771

RESUMO

The dengue, Zika and chikungunya viruses are transmitted by the mosquito Aedes aegypti and pose a substantial threat to global public health. Current vaccines and mosquito control strategies have limited efficacy, so novel interventions are needed1,2. Wolbachia are bacteria that inhabit insect cells and have been found to reduce viral infection-a phenotype that is referred to as viral 'blocking'3. Although not naturally found in A. aegypti4, Wolbachia were stably introduced into this mosquito in 20114,5 and were shown to reduce the transmission potential of dengue, Zika and chikungunya6,7. Subsequent field trials showed Wolbachia's ability to spread through A. aegypti populations and reduce the local incidence of dengue fever8. Despite these successes, the evolutionary stability of viral blocking is unknown. Here, we utilized artificial selection to reveal genetic variation in the mosquito that affects Wolbachia-mediated dengue blocking. We found that mosquitoes exhibiting weaker blocking also have reduced fitness, suggesting the potential for natural selection to maintain blocking. We also identified A. aegypti genes that affect blocking strength, shedding light on a possible mechanism for the trait. These results will inform the use of Wolbachia as biocontrol agents against mosquito-borne viruses and direct further research into measuring and improving their efficacy.


Assuntos
Aedes/genética , Vírus da Dengue/patogenicidade , Proteínas de Insetos/genética , Wolbachia/fisiologia , Aedes/microbiologia , Aedes/virologia , Animais , Vírus da Dengue/genética , Evolução Molecular , Feminino , Frequência do Gene , Aptidão Genética , Genoma Bacteriano , Masculino , Mosquitos Vetores/fisiologia , Polimorfismo de Nucleotídeo Único
18.
Indian J Med Microbiol ; 37(1): 12-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424004

RESUMO

Purpose: Dengue viruses (DENVs), the causative agents of dengue (DEN), are classified into four serotypes and several genotypes. Identifying circulating serotypes and genotypes has clinical and epidemiological importance; however, limited information in this regard is available from Central India. This laboratory-based study was done to fill this lacuna. Materials and Methods: The samples collected in the acute phase of illness were subjected to DEN NS1 ELISA, and NS1-positive samples (n = 80) were subjected to serotyping; representative samples from each serotype were sequenced to identify genotypes. Results: Seventy-one (88.75%) samples could be serotyped. All the four DENV serotypes with dominance of DENV-3 (n = 33; 47%) were detected. DENV-4 was detected after a gap of 3 years. Cases with multiple DENV serotype infection were identified. Genotyping showed that DENV-1 belonging to genotype III, DENV-2 cosmopolitan (IV), DENV-3 genotype III lineage C and DENV-4 genotype I were in circulation in the year 2016. Conclusion: Our study documents the molecular characteristics of DENV circulating in the area. Detection of heterologous DENV serotype with dominance of DENV-3 emphasises the need for regular molecular monitoring.


Assuntos
Vírus da Dengue , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Surtos de Doenças/estatística & dados numéricos , Ensaio de Imunoadsorção Enzimática , Genótipo , Glicoproteínas/genética , Humanos , Índia , RNA Viral/genética , Sorotipagem , Proteínas não Estruturais Virais/genética
19.
PLoS Negl Trop Dis ; 13(8): e0007659, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31415559

RESUMO

BACKGROUND: The reported incidence of dengue fever increased dramatically in recent years in China. This study aimed to investigate and to assess the effectiveness of intervention implemented in a dengue outbreak in Ningbo City, Zhejiang Province, China. METHODS: Data of a dengue outbreak were collected in Ningbo City in China by a field epidemiological survey according to a strict protocol and case definition. Serum specimens of all cases were collected for diagnosis and the virological characteristics were detected by using polymerase chain reaction (PCR) and gene sequencing. Vector surveillance was implemented during the outbreak to collect the larva and adult mosquito densities to calculate the Breteau Index (BI) and human biting rate (HBR), respectively. Data of monthly BI and light-trap density in 2018 were built to calculate the seasonality of the vector. A transmission mathematical model was developed to dynamic the incidence of the disease. The parameters of the model were estimated by the data of the outbreak and vector surveillance data in 2018. The effectiveness of the interventions implemented during the outbreak was assessed by the data and the modelling. RESULTS: From 11 August to 8 September, 2018, a dengue outbreak was reported with 27 confirmed cases in a population of 5536-people community (community A) of Ningbo City. Whole E gene sequences were obtained from 24 cases and were confirmed as dengue virus type 1 (DENV-1). The transmission source of the outbreak was origin from community B where a dengue case having the same E gene sequence was onset on 30 July. Aedes albopictus was the only vector species in the area. The value of BI and HBR was 57.5 and 12 per person per hour respectively on 18 August, 2018 and decreased dramatically after interventions. The transmission model fitted well (χ2 = 6.324, P = 0.388) with the reported cases data. With no intervention, the total simulated number of the cases would be 1728 with a total attack rate (TAR) of 31.21% (95%CI: 29.99%- 32.43%). Case isolation and larva control (LC) have almost the same TAR and duration of outbreak (DO) as no intervention. Different levels of reducing HBR (rHBR) had different effectiveness with TARs ranging from 1.05% to 31.21% and DOs ranging from 27 days to 102 days. Adult vector control (AVC) had a very low TAR and DO. "LC+AVC" had a similar TAR and DO as that of AVC. "rHBR100%+LC", "rHBR100%+AVC", "rHBR100%+LC+AVC" and "rHBR100%+LC+AVC+Iso" had the same effectiveness. CONCLUSIONS: Without intervention, DENV-1 could be transmitted rapidly within a short period of time and leads to high attack rate in community in China. AVC or rHBR should be recommended as primary interventions to control rapid transmission of the dengue virus at the early stage of an outbreak.


Assuntos
Controle de Doenças Transmissíveis/métodos , Dengue/epidemiologia , Surtos de Doenças , Transmissão de Doença Infecciosa/prevenção & controle , Controle de Mosquitos/métodos , Adolescente , Adulto , Aedes/crescimento & desenvolvimento , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , China/epidemiologia , Cidades/epidemiologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Métodos Epidemiológicos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Mosquitos Vetores/crescimento & desenvolvimento , Adulto Jovem
20.
Elife ; 82019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31385805

RESUMO

Dengue virus (DENV) exists as four genetically distinct serotypes, each of which is historically assumed to be antigenically uniform. Recent analyses suggest that antigenic heterogeneity may exist within each serotype, but its source, extent and impact remain unclear. Here, we construct a sequence-based model to directly map antigenic change to underlying genetic divergence. We identify 49 specific substitutions and four colinear substitution clusters that robustly predict dengue antigenic relationships. We report moderate antigenic diversity within each serotype, resulting in genotype-specific patterns of heterotypic cross-neutralization. We also quantify the impact of antigenic variation on real-world DENV population dynamics, and find that serotype-level antigenic fitness is a dominant driver of dengue clade turnover. These results provide a more nuanced understanding of the relationship between dengue genetic and antigenic evolution, and quantify the effect of antigenic fitness on dengue evolutionary dynamics.


Assuntos
Variação Antigênica , Vírus da Dengue/classificação , Vírus da Dengue/genética , Dengue/virologia , Evolução Molecular , Genótipo , Sorogrupo , Análise por Conglomerados , Variação Genética , Testes de Neutralização , Homologia de Sequência
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