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1.
Mem Inst Oswaldo Cruz ; 115: e200287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533869

RESUMO

BACKGROUND: The heat-labile nature of Dengue virus (DENV) in serum samples must be considered when applying routine diagnostic tests to avoid issues that could impact the accuracy of test results with direct implications for case management and disease reporting. OBJECTIVES: To check if pre-analytical variables, such as storage time and temperature, have an impact on the accuracy of the main routine diagnostic tests for dengue. METHODS: Virus isolation, reverse transcription real-time polymerase chain reaction (RT-PCR) and NS1 enzyme-linked immunosorbent assay (ELISA) were evaluated using 84 samples submitted to different pre-analytical conditions. FINDINGS: Sensitivity and negative predictive value were directly affected by sample storage conditions. RT-PCR and virus isolation showed greater dependence on well-conserved samples for an accurate diagnosis. Interestingly, even storage at -30ºC for a relatively short time (15 days) was not adequate for accurate results using virus isolation and RT-PCR tests. On the other hand, NS1 ELISA showed no significant reduction in positivity for aliquots tested under the same conditions as in the previous tests. MAIN CONCLUSIONS: Our results support the stability of the NS1 marker in ELISA diagnosis and indicate that the accuracy of routine tests such as virus isolation and RT-PCR is significantly affected by inadequate transport and storage conditions of serum samples.


Assuntos
Antígenos Virais/sangue , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Testes Imunológicos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteínas não Estruturais Virais/imunologia , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Dengue/sangue , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Humanos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Proteínas não Estruturais Virais/genética
2.
Nat Commun ; 12(1): 151, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420058

RESUMO

Mosquito-borne viruses threaten the Caribbean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.


Assuntos
Febre de Chikungunya/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Dengue/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Doenças Endêmicas/estatística & dados numéricos , Infecção por Zika virus/epidemiologia , Adolescente , Aedes/virologia , Animais , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Surtos de Doenças/prevenção & controle , República Dominicana/epidemiologia , Doenças Endêmicas/prevenção & controle , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Controle de Mosquitos , Mosquitos Vetores/virologia , Análise Espaço-Temporal , Adulto Jovem , Zika virus/isolamento & purificação , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
3.
BMC Infect Dis ; 21(1): 96, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478432

RESUMO

BACKGROUND: Dengue virus infection has been an important and serious public health concern in Taiwan, where local outbreaks of dengue fever occurred almost every year. To our knowledge, no nationwide investigation has been carried out to determine the actual extent of infection in the general population. METHODS: A total of 1308 random serum samples were collected from the general population in Taiwan in 2010. The antibody-captured enzyme-linked immunosorbent assays were used to detect DENV-specific IgM and IgG. Demographics data were used for risk analysis. RESULTS: The weighted overall seroprevalence was 1.96% for anti-DENV IgM, and 3.4% for anti-DENV IgG, respectively. A significant rise of DENV IgG seropositive rate had been noted since late adulthood stage, from 1.1% at the age group of 50-59 years to 7.6% at the age group of 60-69 years. For people aged over 70 years, the seropositive rate reached 19%. Age, nationality, and regions of residency were associated with the IgG seropositivity. There was no statistically significant difference in seroprevalence of anti-Dengue IgM, indicating recent infection, among univariate predictors we proposed, including gender, age, residency, nationality, and household size. CONCLUSIONS: Our results indicated that the majority of population in Taiwan born after 1940 is naive to dengue virus and the prevalence of IgG antibody against dengue virus rises with age. Nationality, and regions of residency are associated with the exposure of population to infection by dengue viruses. Further studies are needed to realize the current situation of seroprevalence of dengue fever in Taiwan.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Dengue/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Dengue/sangue , Vírus da Dengue/isolamento & purificação , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estudos Soroepidemiológicos , Taiwan/epidemiologia , Adulto Jovem
4.
BMC Infect Dis ; 21(1): 104, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482756

RESUMO

BACKGROUND: Dengue virus (DENV) infection is increasingly common in southern China and can be transmitted through blood transfusion but is not currently part of donor screening throughout the region. We assessed DENV prevalence among donors at the Xishuangbanna Blood Center, Yunnan, to support development of DENV screening strategies. METHODS: Blood samples were collected randomly between June 2019 and August 2019. These were screened for anti-DENV IgG and IgM using enzyme-linked immunosorbent assay (ELISA). Then, all reactive samples and some randomly-chosen non-reactive samples were used to detect DENV RNAs using real-time polymerase-chain-reaction (RT-PCR) assays. After RT-PCR, samples were further tested for soluble nonstructural protein 1 (NS1) using the colloidal gold method. Donors demographics were also collected and assessed. RESULTS: Over the study period, 2254 donor samples were collected and tested for anti-DENV IgG and IgM by ELISA. This revealed 598 anti-DENV IgG and/or IgM reactive samples, a serological prevalence of 26.53%. Of these, 26 were RT-PCR positive and/or NS1 positive. Significant differences in DENV prevalence were noted by occupation (P = 0.001), education (P < 0.001), and ethnicity (P = 0.026). CONCLUSION: The prevalence of DENV in Xishuangbanna Blood Center was higher than most other blood centers that have implemented DENV donor screening. Our study provides first-hand data about the prevalence of DENV and allows the development of a screening strategy for clinical use.


Assuntos
Doadores de Sangue , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Dengue/epidemiologia , Programas de Rastreamento/métodos , Adulto , Anticorpos Antivirais/sangue , China/epidemiologia , Dengue/sangue , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Feminino , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Prevalência , RNA Viral/genética , Proteínas não Estruturais Virais/genética , Adulto Jovem
5.
Arch Virol ; 166(3): 863-870, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33495898

RESUMO

A dengue virus serotype 1 (DENV-1) epidemic occurred from October to December 2018 in Xishuangbanna, Yunnan, Southwest China, neighboring Myanmar, Laos, and Vietnam. In this study, we investigated the molecular characteristics, evolution, and potential source of DENV from Xishuangbanna. The C (capsid), prM (premembrane), and E (envelope) genes of DENV isolated from 87 serum samples obtained from local patients were amplified and sequenced, and the sequences were evaluated by identification of mutations, phylogenetic and homologous recombination analysis, and secondary structure prediction. Phylogenetic analysis showed that all of the epidemic DENV strains from Xishuangbanna could be grouped in a branch with DENV-1 isolates, and were most similar to the Fujian 2005 (China, DQ193572) and Singapore 2016 (MF314188) strains. When compared with DENV-1SS (the standard strain), there were 31 non-synonymous mutations, but no obvious homologous recombination signal was found. Secondary structure prediction showed that some changes had occurred in a helical region in proteins of the MN123849 and MN123854 strains, but there were few changes in the disordered region. This study reveals the molecular characteristics of the structural genes of the Xishuangbanna epidemic strains in 2018 and provides a reference for molecular epidemiology, infection, and pathogenicity research and vaccine development.


Assuntos
Proteínas do Capsídeo/genética , Vírus da Dengue/genética , Dengue/epidemiologia , Proteínas do Envelope Viral/genética , Sequência de Aminoácidos , China/epidemiologia , Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Surtos de Doenças , Genótipo , Humanos , Epidemiologia Molecular , Filogenia , RNA Viral/genética , Alinhamento de Sequência , Análise de Sequência de RNA , Sorogrupo
6.
PLoS One ; 15(12): e0243239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332373

RESUMO

In the last 40 years, Latin America countries, including Brazil, have suffered from the emergence and reemergence of arboviruses, first Dengue (DENV) and recently Zika (ZIKV) and Chikungunya (CHIKV). All three arboviruses are currently endemic in Brazil and have caused major outbreaks in recent years. Rio de Janeiro city, host of the last Summer Olympic Games and the Football World Cup, has been specially affected by them. A surveillance system based on symptomatic reports is in place in Rio, but the true number of affected individuals is unknown due to the great number of Zika, Dengue and Chikungunya asymptomatic cases. Seroprevalence studies are more suitable to evaluate the real number of cases in a given population. We performed a populational seroprevalence survey in Rio, with recruitment of a sample of volunteers of all ages and gender from July to October 2018, within randomly selected census tracts and household. A total of 2,120 volunteers were interviewed and tested with rapid immunochromatographic test for ZIKV, DENV and CHIKV. Individuals with positive results for IgG and/or IgM from only one virus were classified accordingly, while those with test results positive for both ZIKV and DENV were classified as flaviviruses. We corrected for sample design and non-response in data analysis, and calculated point estimate prevalence and 95% confidence intervals for each virus. Arbovirus prevalence in the Rio's population (n = 6,688,927) was estimated at 48.6% [95% CI 44.8-52.4] (n = 3,254,121) for flaviviruses and at 18.0% [95% CI 14.8-21.2] (n = 1,204,765) for CHIKV. Approximately 17.0% [95% CI 14.1-20.1] (n = 1,145,674) of Rio´s population had no contact with any of the three arboviruses. The reported cases of Zika, Dengue and Chikungunya by the current surveillance system in place is insufficient to estimate their real numbers, and our data indicate that Zika seroprevalence could be at least five times and Chikungunya 45 times bigger. The high number of individuals having never been infected by any of the three arboviruses, may indicate a proper scenario for future outbreaks.


Assuntos
Febre de Chikungunya/epidemiologia , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Vírus Chikungunya/isolamento & purificação , Criança , Pré-Escolar , Estudos Transversais , Vírus da Dengue/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Soroepidemiológicos , Adulto Jovem , Zika virus/isolamento & purificação
7.
BMC Infect Dis ; 20(1): 948, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308178

RESUMO

BACKGROUND: Dengue patients develop different disease severity ranging from mild (dengue fever [DF]) to severe forms (dengue hemorrhagic fever [DHF] and the fatal dengue shock syndrome [DSS]). Host genetics are considered to be one factor responsible for the severity of dengue outcomes. To identify genes associated with dengue severity that have not been studied yet, we performed genetic association analyses of interferon lambda 3 (IFNL3), CD27, and human leukocyte antigen-DPB1 (HLA-DPB1) genes in Thai dengue patients. METHODS: A case-control association study was performed in 877 children (age ≤ 15 years) with dengue infection (DF, n = 386; DHF, n = 416; DSS, n = 75). A candidate single nucleotide polymorphism of each of IFNL3, CD27, and HLA-DPB1 was selected to be analyzed. Genotyping was performed by TaqMan real-time PCR assay, and the association with dengue severity was examined. RESULTS: The rs9277534 variant of HLA-DPB1 was weakly associated with DHF. The genotype GG and G allele conferred protection against DHF (p = 0.04, odds ratio 0.74 for GG genotype, p = 0.03, odds ratio 0.79 for G allele). The association became borderline significant after adjusting for confounders (p = 0.05, odds ratio 0.82). No association was detected for IFNL3 or CD27. CONCLUSIONS: The present study demonstrated the weak association of the rs9277534 variant of HLA-DPB1 with protection against DHF. This variant is in the 3' untranslated region and affects HLA-DPB1 surface protein expression. Our finding suggests that HLA-DPB1 may be involved in DHF pathogenesis.


Assuntos
Vírus da Dengue/genética , Vírus da Dengue/imunologia , Cadeias beta de HLA-DP/genética , Interferons/genética , Dengue Grave/epidemiologia , Dengue Grave/genética , Índice de Gravidade de Doença , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Regiões 3' não Traduzidas/genética , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Vírus da Dengue/isolamento & purificação , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Dengue Grave/virologia , Tailândia/epidemiologia
8.
PLoS One ; 15(10): e0227239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064724

RESUMO

Species of the genus Flavivirus are widespread in Brazil and are a major public health concern. The country's largest city, São Paulo, is in a highly urbanized area with a few forest fragments which are commonly used for recreation. These can be considered to present a potential risk of flavivirus transmission to humans as they are home simultaneously to vertebrate hosts and mosquitoes that are potential flavivirus vectors. The aim of this study was to conduct flavivirus surveillance in field-collected mosquitoes in the Capivari-Monos Environmental Protection Area (EPA) and identify the flavivirus species by sequence analysis in flavivirus IFA-positive pools. Monthly mosquito collections were carried out from March 2016 to April 2017 with CO2-baited CDC light traps. Specimens were identified morphologically and grouped in pools of up to 10 individuals according to their taxonomic category. A total of 260 pools of non-engorged females were inoculated into C6/36 cell culture, and the cell suspensions were analyzed by indirect immunofluorescence assay (IFA) after the incubation period. IFA-positive pools were tested by qRT-PCR with genus-specific primers targeting the flavivirus NS5 gene to confirm IFA-positive results and sequenced to identify the species. Anopheles cruzii (19.5%) and Wyeomyia confusa (15.3%) were the most frequent vector species collected. IFA was positive for flaviviruses in 2.3% (6/260) of the sample pools. This was confirmed by qRT-PCR in five pools (83.3%). All five flavivirus-positive pools were successfully sequenced and the species identified. DENV serotype 2 (DENV-2) was detected in Culex spp. and Culex vaxus pools, while ZIKV was identified in An. cruzii, Limatus durhamii and Wy. confusa pools. To the best of our knowledge, detection of flavivirus species of medical importance has never previously been reported in these species of wild-caught mosquitoes. The finding of DENV-2 and ZIKV circulating in wild mosquitoes suggests the existence of an enzootic cycle in the area. In-depth studies of DENV-2 and ZIKV, including investigation of mosquito infection, vector competence and infection in sylvatic hosts, are needed to shed light on the transmission dynamics of these important viruses and the potential risk of future outbreaks of DENV-2 and ZIKV infections in the region.


Assuntos
Vírus da Dengue/isolamento & purificação , Mosquitos Vetores/virologia , Proteínas não Estruturais Virais/genética , Zika virus/isolamento & purificação , Animais , Anopheles/virologia , Brasil/epidemiologia , Culex/virologia , Vírus da Dengue/genética , Feminino , Vigilância da População , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Meio Selvagem , Zika virus/genética
9.
Artigo em Inglês | MEDLINE | ID: mdl-33027393

RESUMO

The Northeast of Brazil has experienced a triple epidemic, with the simultaneous circulation of dengue virus (DENV), chikungunya virus (CHIKV) and Zika virus (ZIKV), which may have contributed to the observed increase across this region of atypical forms of disease and deaths. In view of this fact, non-congenital neurological disorders related to arboviruses were compared with other etiologies, mortality and survival rates of patients admitted to referral neurology hospitals in Pernambuco State, Northeast Brazil, from 2015 to 2018. Blood and cerebrospinal fluid samples were collected and tested using molecular and serological assays. The arbovirus-exposed groups were compared with respect to epidemiological, clinical and neurologic characteristics by using the Pearson's chi-square test. For the survival analysis, the Kaplan-Meier and Hazard Ratio (HR) tests were used, with a 95% confidence interval (CI). Encephalitis and encephalomyelitis were more frequent in arboviruses, while myelitis predominated in the neurological disorders of other etiologies. Guillain-Barré Syndrome (GBS) was similarly distributed amongst the groups. Exposure to one of the arboviruses caused a six-fold increase in the risk of death (HR: 6.37; CI: 2.91 - 13.9). Amongst the arbovirus-exposed groups, infection (DENV/CHIKV) increased nine times the risk of death (HR: 9.07; CI: 3.67 - 22.4). The survival curve indicates that have been exposed to some arbovirus decreased the likelihood of survival compared to those with other etiologies (Log-Rank: p<0.001). Within this scenario, neurologic manifestations of DENV, CHIKV and ZIKV have the potential to increase mortality and decrease survival, and concomitant infection (DENV/CHIKV) is an aggravating factor in reducing the likelihood of survival when compared to monoinfections.


Assuntos
Febre de Chikungunya/diagnóstico , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Encefalite Viral/epidemiologia , Encefalomielite/virologia , Doenças do Sistema Nervoso/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Brasil , Febre de Chikungunya/complicações , Dengue/complicações , Encefalomielite/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Doenças do Sistema Nervoso/diagnóstico , Análise de Sobrevida , Infecção por Zika virus/complicações
10.
Euro Surveill ; 25(36)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32914745

RESUMO

In August 2020, during the coronavirus disease (COVID-19) pandemic, five locally acquired cases of dengue virus type 1 were detected in a family cluster in Vicenza Province, North-East Italy where Aedes albopictus mosquitoes are endemic. The primary case was an importation from West Sumatra, Indonesia. This is the first outbreak of autochthonous dengue reported in Italy. During the COVID-19 pandemic, screening of febrile travelers from endemic countries is crucial in areas where competent vectors are present.


Assuntos
Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Viagem , Adulto , Pré-Escolar , Dengue/epidemiologia , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/genética , Surtos de Doenças , Transmissão de Doença Infecciosa , Feminino , Febre/etiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Indonésia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
PLoS One ; 15(8): e0237384, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764809

RESUMO

Dengue fever is one of the major public health problems in Lao PDR. Over the last decade, dengue virus (DENV) epidemics were characterized by a novel predominant serotype accompanied by at least two other serotypes. Since 2008, DENV-2 circulated at a low level in Lao PDR but its epidemiologic profile changed at the end of 2018. Indeed, the number of confirmed DENV-2 cases suddenly increased in October 2018 and DENV-2 became predominant at the country level in early 2019. We developed a Genotype Screening Protocol (GSP) to determine the origin(s) of the Lao DENV-2 and study their genetic polymorphism. With a good correlation with full envelope gene sequencing data, this molecular epidemiology tool evidence the co-circulation of two highly polymorphic DENV-2 genotypes, i.e. Asian I and Cosmopolitan genotypes, over the last five years, suggesting multiple introductions of DENV-2 in the country. GSP approach provides relevant first line information that may help countries with limited laboratory resources to reinforce their capabilities to DENV-2 and to follow the epidemics progresses and assess situations at the regional level.


Assuntos
Vírus da Dengue/genética , Técnicas de Genotipagem/métodos , Inquéritos e Questionários , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/fisiologia , Humanos , Laos , Sorotipagem , Fatores de Tempo , População Urbana/estatística & dados numéricos
12.
BMC Infect Dis ; 20(1): 466, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615988

RESUMO

BACKGROUND: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. METHODS: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. RESULTS: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. CONCLUSIONS: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.


Assuntos
Vírus da Dengue/genética , Vírus da Dengue/imunologia , Dengue/epidemiologia , Febre/epidemiologia , Variação Genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colômbia/epidemiologia , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Doenças Endêmicas , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/virologia , Genótipo , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
13.
PLoS One ; 15(7): e0235166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609737

RESUMO

BACKGROUND: Monitoring of blood pressure is an important part of management of dengue illness. Large scale studies of temporal trend of blood pressure in adult dengue are lacking. In this study, we examined the differences in time trend of systolic (SBP) and diastolic blood pressure (DBP) in patients with and without severe dengue (SD), dengue hemorrhagic fever (DHF) and pre-existing hypertension, and elderly versus non-elderly patients. METHODS: We studied a retrospective cohort from 2005 to 2008 of 6,070 hospitalized adult dengue patients confirmed by polymerase chain reaction or clinical criteria plus positive dengue serology. Dengue severity was defined according to World Health Organization 1997 and 2009 guidelines. We used Bayesian hierarchical Markov models to compare the daily mean SBP and DBP between different subgroups. Analysis was conducted by day of defervescence (denoted as day 0), and day of illness onset (denoted as day 1) respectively. RESULTS: SBP decreased to a nadir during the critical phase before defervescence and was significantly lower for patients with SD or DHF, compared with patients without SD or DHF. DBP increased marginally more for patients with SD or DHF in the critical phase before defervescence. By day of defervescence, comparison of patients with and without SD showed significant difference in SBP from day -6 to day +6, except days +1, +3 and +5, and similarly in DBP except days 0, and +4 to +6. Comparison of patients with and without DHF showed significant difference in SBP from day -6 to day -1, but for DBP, significant difference was noted from day -6 to day +6, except day -2 to day 0. By day of illness, SBP differed significantly between patients with and without SD from illness days 1 to 10, and DBP from illness days 7 to 12. Between patients with and without DHF, SBP differed significantly on illness days 1, 2, 4 to 7, while DBP from days 7 to 12. On analysis by days of defervescence or by days of illness, elderly patients and those with hypertension showed consistently higher SBP and DBP throughout their hospitalization, as compared with their younger and non-hypertensive counterparts. CONCLUSION: In SD or DHF, SBP decreased to a nadir around the day of defervescence, and recovered to a level exceeding that in febrile phase by days 2 or 3 post-defervescence. Elderly patients and patients with pre-existing hypertension maintained higher SBP and DBP throughout the duration of dengue infection.


Assuntos
Pressão Sanguínea , Dengue/fisiopatologia , Adulto , Dengue/complicações , Vírus da Dengue/isolamento & purificação , Feminino , Hospitalização , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Arch Virol ; 165(9): 2029-2035, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32617762

RESUMO

Only a minority of dengue infections lead to plasma leakage (critical phase [CP]). Early identification of the risk for CP is helpful for triage of patients. This study aimed to identify early clinical predictors of CP that will aid in patient triage during early illness. A retrospective, case-record-based analysis was performed on all microbiologically confirmed (NS1-antigen- or dengue-IgM-antibody-positive), dengue patients (n = 697), admitted to our unit from 01.01.2017 to 30.06.2017. Bivariate analysis was performed to identify clinical and laboratory parameters that predicted CP. Stepwise multivariate logistic regression with backward elimination (p < 0.05) was used to identify independent risk factors for CP. CP developed in 226 (32.4%) patients. Mortality was 1.0%. Predictors for CP (p < 0.05) within the first three days included age category 41-50 years (OR = 1.96), females (OR = 2.09), diabetes (OR = 1.30), persistent vomiting (OR = 2.18), platelet count < 120,000/mm-3 (OR = 1.91) and AST > 60 IU/L (OR = 3.72). On multivariate analysis, other variables except diabetes remained significant. Elevated transaminase levels remained the strongest independent predictor of CP (OR 2.83). The absence of all five risk factors excluded CP (negative predictive value: 97.2%). Age 41-50 years, female gender, persistent vomiting, thrombocytopenia, and elevated transaminases were early predictors of CP in dengue fever. The absence of these can be used to identify patients who may not require hospital admission. Elevated transaminase was the strongest predictor of CP during early illness.


Assuntos
Vírus da Dengue/isolamento & purificação , Dengue Grave/virologia , Adolescente , Adulto , Idoso , Vírus da Dengue/classificação , Vírus da Dengue/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Dengue Grave/sangue , Dengue Grave/diagnóstico , Adulto Jovem
15.
PLoS Negl Trop Dis ; 14(6): e0008203, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32579555

RESUMO

BACKGROUND: Dengue virus (DENV) infections pose one of the largest global barriers to human health. The four serotypes (DENV 1-4) present different symptoms and influence immune response to subsequent DENV infections, rendering surveillance, risk assessments, and disease control particularly challenging. Early diagnosis and appropriate clinical management is critical and can be achieved by detecting DENV nonstructural protein 1 (NS1) in serum during the acute phase. However, few NS1-based tests have been developed that are capable of differentiating DENV serotypes and none are currently commercially available. METHODOLOGY/PRINCIPLE FINDINGS: We developed an enzyme-linked immunosorbent assay (ELISA) to distinguish DENV-1-4 NS1 using serotype-specific pairs of monoclonal antibodies. A total of 1,046 antibodies were harvested from DENV-immunized mice and screened for antigen binding affinity. ELISA clinical performance was evaluated using 408 polymerase chain reaction-confirmed dengue samples obtained from patients in Brazil, Honduras, and India. The overall sensitivity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 serotyping were 79.1% (38/48), 80.41% (78/97), 100% (45/45), and 79.6% (98/123), respectively. Specificity reached 94.07-100%. SIGNIFICANCE: Our study demonstrates a robust antibody screening strategy that enabled the development of a serotype NS1-based ELISA with maximized specific and sensitive antigen binding. This sensitive and specific assay also utilized the most expansive cohort to date, and of which about half are from Latin America, a geographic region severely underrepresented in previous similar studies. This ELISA test offers potential enhanced diagnostics during the acute phase of infection to help guide patient care and disease control. These results indicate that this ELISA is a promising aid in early DENV-1-4 diagnosis and surveillance in regions of endemicity in addition to offer convenient monitoring for future vaccine interventions.


Assuntos
Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Dengue/virologia , Ensaio de Imunoadsorção Enzimática/métodos , Sorogrupo , Proteínas não Estruturais Virais/análise , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Brasil , Estudos de Coortes , Honduras , Humanos , Índia , América Latina , Camundongos Endogâmicos C57BL , Sensibilidade e Especificidade
16.
PLoS Negl Trop Dis ; 14(6): e0008362, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32559197

RESUMO

Arboviruses are among the most important emerging pathogens due to their increasing public health impact. In Kenya, continued population growth and associated urbanization are conducive to vector spread in both urban and rural environments, yet mechanisms of viral amplification in vector populations is often overlooked when assessing risks for outbreaks. Thus, the characterization of local arbovirus circulation in mosquito populations is imperative to better inform risk assessments and vector control practices. Aedes species mosquitoes were captured at varying stages of their life cycle during different seasons between January 2014 and May 2016 at four distinct sites in Kenya, and tested for chikungunya (CHIKV), dengue (DENV) and Zika (ZIKV) viruses by RT-PCR. CHIKV was detected in 45 (5.9%) and DENV in 3 (0.4%) mosquito pools. No ZIKV was detected. Significant regional variation in prevalence was observed, with greater frequency of CHIKV on the coast. DENV was detected exclusively on the coast. Both viruses were detected in immature mosquitoes of both sexes, providing evidence of transovarial transmission of these arboviruses in local mosquitoes. This phenomenon may be driving underlying viral maintenance that may largely contribute to periodic re-emergence among humans in Kenya.


Assuntos
Febre de Chikungunya/transmissão , Vírus Chikungunya/isolamento & purificação , Culicidae/virologia , Vírus da Dengue/isolamento & purificação , Dengue/transmissão , Aedes/fisiologia , Aedes/virologia , Animais , Arbovirus , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Culicidae/fisiologia , Dengue/epidemiologia , Dengue/virologia , Feminino , Humanos , Quênia/epidemiologia , Estágios do Ciclo de Vida , Masculino , Zika virus , Infecção por Zika virus/virologia
17.
PLoS One ; 15(6): e0234508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555732

RESUMO

Dengue virus (DENV) infection remains a major public health concern in many parts of the world, including Southeast Asia and the Americas. Sri Lanka experienced its largest dengue outbreak in 2017. Neurological symptoms associated with DENV infection have increasingly been reported in both children and adults. Here, we characterize DENV type 2 (DENV-2) strains, which were isolated from cerebrospinal fluid (CSF) and/or serum of patients with dengue encephalitis. Acute serum and CSF samples from each patient were subjected to dengue-specific non-structural protein 1 (NS1) antigen test, IgM and IgG enzyme-linked immunosorbent assay (ELISA), virus isolation, conventional and real-time polymerase chain reaction (PCR), and next-generation sequencing (NGS). Among the 5 dengue encephalitis patients examined, 4 recovered and 1 died. DENV-2 strains were isolated from serum and/or CSF samples of 3 patients. The highest viral genome levels were detected in the CSF and serum of the patient who succumbed to the illness. A phylogenetic tree revealed that the DENV-2 isolates belonged to a new clade of cosmopolitan genotype and were genetically close to strains identified in China, South Korea, Singapore, Malaysia, Thailand, and the Philippines. According to the NGS analysis, greater frequencies of nonsynonymous and synonymous mutations per gene were identified in the nonstructural genes. The full genomes of serum- and CSF-derived DENV-2 from the same patient shared 99.7% similarity, indicating that the virus spread across the blood-brain barrier. This is the first report to describe neurotropic DENV-2 using whole-genome analysis and to provide the clinical, immunological, and virological characteristics of dengue encephalitis patients during a severe dengue outbreak in Sri Lanka in 2017.


Assuntos
Dengue/genética , Encefalite/genética , Genoma Viral/genética , Proteínas não Estruturais Virais/genética , Adulto , Criança , Dengue/líquido cefalorraquidiano , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Encefalite/líquido cefalorraquidiano , Encefalite/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/genética , Imunoglobulina M/sangue , Imunoglobulina M/genética , Masculino , Adulto Jovem
18.
Int J Infect Dis ; 98: 241-249, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32593623

RESUMO

OBJECTIVES: Dengue and Zika infections cause illnesses with overlapping clinical manifestations. The aim of this study was to explore the association of each of these infections with single or grouped clinical and laboratory parameters. METHODS: Clinical and laboratory data were collected prospectively from a cohort of patients seeking care for symptoms meeting the Pan American Health Organization's modified case-definition criteria for probable Zika virus infection. Zika and dengue were diagnosed with RT-PCR. The relationship of clinical characteristics and laboratory data with Zika, dengue, and undefined acute illness (UAI) was examined. RESULTS: In the univariate models, localized rash and maculopapular exanthema were associated with Zika infection. Generalized rash, petechiae, and petechial purpuric rash were associated with dengue. Cough and confusion/disorientation were associated with UAI. Platelets were significantly lower in the dengue group. A conditional inference tree model showed poor sensitivity and positive predictive value for individual viral diagnoses. CONCLUSIONS: Clusters of signs, symptoms, and laboratory values evaluated in this study could not consistently differentiate Zika or dengue cases from UAI in the clinical setting at the individual patient level. We identified symptoms that are important to Zika and dengue in the univariate analyses, but predictive models were unreliable. Low platelet count was a distinctive feature of dengue.


Assuntos
Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Doença Aguda/epidemiologia , Adolescente , Adulto , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/fisiologia , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem , Zika virus/genética , Zika virus/isolamento & purificação , Zika virus/fisiologia , Infecção por Zika virus/virologia
19.
Arch Virol ; 165(8): 1739-1748, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32409874

RESUMO

In Korea, dengue infection has been frequently reported in travelers to tropical and subtropical countries. Global warming increases the probability of autochthonous dengue outbreaks in Korea. In this report, the molecular and evolutionary properties of four dengue virus (DENV) type 2 isolates from Korean overseas travelers were examined. Three of these isolates were classified as Cosmopolitan genotypes and further divided into sublineages 1 (43,253, 43,254) and 2 (43,248), while the other isolate (KBPV-VR29) was related to American genotypes. The variable amino acid motifs related to virulence and replication were identified in the structural and non-structural proteins. A negative selection mechanism was clearly verified in all of the DENV proteins. Potential recombination events were identified in the NS5 protein of the XSBN10 strain. The substitution rate (5.32 × 10-4 substitutions per site) and the time of the most recent common ancestor (TMRCA) for each evolutionary group were determined by the Bayesian skyline coalescent method. This study shows that DENV type 2 strains with distinct phylogenetic, evolutionary, and virulence characteristics have been introduced into Korea by overseas travelers and have the potential to trigger autochthonous dengue outbreaks.


Assuntos
Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Substituição de Aminoácidos/genética , Dengue/virologia , Surtos de Doenças , Evolução Molecular , Genoma Viral/genética , Genótipo , Humanos , Filogenia , RNA Viral/genética , República da Coreia , Sorogrupo , Proteínas Virais/genética , Virulência/genética , Replicação Viral/genética
20.
PLoS Negl Trop Dis ; 14(5): e0008303, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32407315

RESUMO

In New Caledonia (NC), Aedes aegypti is the only proven vector of dengue virus (DENV), which is the most prevalent arbovirosis in NC. Since World War II, the four DENV serotypes have circulated regularly in NC. The epidemiological profile, however, has evolved over the last ten years, with the persistence of DENV-1 circulation and the co-circulation of several DENV serotypes. The current study evaluated the ability of Ae. aegypti from NC to transmit four DENV serotypes (and two DENV-1 genotypes) isolated during recent outbreaks in NC. An Ae. aegypti F1 generation was twice independently orally challenged with each DENV strain (107 FFU/ml). Infection, dissemination and transmission rates and transmission efficiency were measured at day 7 and 14 post-exposure, as well as the quantity of infectious virus particles. Mosquito infection was observed as early as 7 days post-infection. Infection rates between 18 and 58% were measured for all DENV serotypes/genotypes tested. Although dissemination rates ranged from 78 to 100%, transmission efficiencies were low, with values not exceeding 21% at 14 days post-infection for all DENV strains. This study shows that NC Ae. aegypti are moderately competent for DENV in laboratory conditions. In link with epidemiological data, these results suggest implication of other factors in the sustained circulation of DENV-1 in New Caledonia.


Assuntos
Aedes/virologia , Vírus da Dengue/isolamento & purificação , Dengue/transmissão , Mosquitos Vetores/virologia , Animais , Dengue/epidemiologia , Vírus da Dengue/classificação , Surtos de Doenças , Transmissão de Doença Infecciosa , Feminino , Genótipo , Humanos , Nova Caledônia/epidemiologia , Sorogrupo
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