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1.
Arch Virol ; 165(3): 671-681, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31942645

RESUMO

Dengue virus (DENV) is the most common mosquito-borne viral disease. The World Health Organization estimates that 400 million new cases of dengue fever occur every year. Approximately 500,000 individuals develop severe and life-threatening complications from dengue fever, such as dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF), which cause 22,000 deaths yearly. Currently, there are no specific licensed therapeutics to treat DENV illness. We have previously shown that the MEK/ERK inhibitor U0126 inhibits the replication of the flavivirus yellow fever virus. In this study, we demonstrate that the MEK/ERK inhibitor AZD6244 has potent antiviral efficacy in vitro against DENV-2, DENV-3, and Saint Louis encephalitis virus (SLEV). We also show that it is able to protect AG129 mice from a lethal challenge with DENV-2 (D2S20). The molecule is currently undergoing phase III clinical trials for the treatment of non-small-cell lung cancer. The effect of AZD6244 on the DENV life cycle was attributed to a blockade of morphogenesis. Treatment of AG129 mice twice daily with oral doses of AZD6244 (100 mg/kg/day) prevented the animals from contracting dengue hemorrhagic fever (DHF)-like lethal disease upon intravenous infection with 1 × 105 PFU of D2S20. The effectiveness of AZD6244 was observed even when the treatment of infected animals was initiated 1-2 days postinfection. This was also followed by a reduction in viral copy number in both the serum and the spleen. There was also an increase in IL-1ß and TNF-α levels in mice that were infected with D2S20 and treated with AZD6244 in comparison to infected mice that were treated with the vehicle only. These data demonstrate the potential of AZD6244 as a new therapeutic agent to treat DENV infection and possibly other flavivirus diseases.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Vírus da Dengue/crescimento & desenvolvimento , Dengue Grave/prevenção & controle , Animais , Linhagem Celular , Cricetinae , Vírus da Dengue/efeitos dos fármacos , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Interleucina-1beta/sangue , Camundongos , Dengue Grave/virologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
2.
Pan Afr Med J ; 34: 74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819790

RESUMO

The report describes a 32-year-old man with dengue hemorrhagic fever presenting with acute onset high-grade intermittent fever with chills and rigors, headache, myalgia, abdominal pain, and vomiting. His laboratory results revealed neutrophilia, thrombocytopenia, microscopic hematuria, and a markedly elevated D-dimer. While on admission, he developed diarrhea, hypertension, and respiratory symptoms which evolved into respiratory distress with low oxygen saturation, eventually warranting his admission to the Intensive Care Unit (ICU). Despite his adverse prognostic indices, the patient made an uneventful recovery with conservative management after 16 days of admission. Thus illustrating how aggressive management could influence the outcome of dengue illness.


Assuntos
Unidades de Terapia Intensiva , Dengue Grave/terapia , Adulto , Humanos , Masculino , Prognóstico , Dengue Grave/fisiopatologia , Resultado do Tratamento
4.
PLoS Negl Trop Dis ; 13(12): e0007974, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31877138

RESUMO

BACKGROUND: Severe dengue virus (DENV) infection involves plasma leakage and vascular collapse, and leads to significant morbidity and death. Serum soluble ST2 (sST2 [interleukin (IL)-1 receptor like-1 protein: IL-1-RL-1]) levels are high in pediatric cases of DENV infection, and the disease progresses. However, the correlation between serum sST2 levels and the outcomes of DENV infection in the elderly (≥65 years) is unclear. We thus explored the mechanisms of serial sST2 level changes involved in the coagulopathy and bloodstream infections of elderly patients in Taiwan's 2015 DENV outbreak. METHODS: This retrospective study was done in a tertiary medical center in southern Taiwan during the outbreak. All DENV-infected patients who, between July 1, 2015, and December 31, 2015, provided a written informed consent for at least two blood sample analyses were enrolled and reviewed. The serum levels of sST2 were quantified. ΔsST2 is defined as the "changes of sST2 levels in serially paired samples". Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) analyses were used to evaluate the prognostic ability of ΔsST2. RESULTS: Forty-three patients with DENV infection were enrolled. Mean patient age was 75.0 ± 12.2 years and the case fatality rate was 44.2% (19/43). Significantly more non-survivors than survivors had increased ST2 level (78.9% vs. 12.5%, p < 0.001). The AUC value for serum ΔsST2 level was 0.857 for predicting DENV fatality. Moreover, patients given frozen fresh plasma (FFP) transfusions were significantly (p = 0.025) more likely to have higher serum ST2 level changes than were those who had not. DENV-infected patients with early bloodstream infections (BSIs) seemed to have higher ST2 levels than those who did not have BSIs. CONCLUSIONS: Serum ST2 levels increased in the elderly (≥ 65 years of age) with DENV infection. The changes in serum sST2 levels might be a critical indicator of DENV infection severity for the elderly; sST2 is an important modulator of coagulopathy in severe DENV infections.


Assuntos
Biomarcadores/sangue , Testes Diagnósticos de Rotina/métodos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Dengue Grave/diagnóstico , Dengue Grave/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida , Taiwan
5.
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
6.
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
7.
Rev Soc Bras Med Trop ; 52: e20180353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778418

RESUMO

INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.


Assuntos
Selectina E/fisiologia , Endotélio/fisiopatologia , Molécula 1 de Adesão Intercelular/fisiologia , Dengue Grave/sangue , Dengue Grave/fisiopatologia , Molécula 1 de Adesão de Célula Vascular/fisiologia , Adolescente , Adulto , Antígenos CD/sangue , Antígenos CD/fisiologia , Antígenos Virais/sangue , Biomarcadores/sangue , Caderinas/sangue , Caderinas/fisiologia , Criança , Pré-Escolar , Progressão da Doença , Selectina E/sangue , Feminino , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto Jovem
9.
J Med Case Rep ; 13(1): 278, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31488206

RESUMO

BACKGROUND: Dengue fever and dengue hemorrhagic fever incidence is increasing in Sri Lanka, especially among the young population. Uncommon presentations of this common illness make diagnostic dilemmas and can delay standard treatment which leads to unfavorable outcomes. CASE PRESENTATION: An 18-year-old Sri Lankan Sinhalese boy presented with a history of 1 day of fever and an episode of seizure followed by left-side hemiparesis. He was diagnosed to have dengue complicated by dengue hemorrhagic fever and recovered with minimal residual weakness. He presented with neurological symptoms; cerebrospinal fluid analysis, electroencephalogram, and magnetic resonance imaging showed evidence of encephalitis. Positive dengue antigen and antibody in serum and cerebrospinal fluid with the exclusion of other possible etiologies confirmed parainfectious dengue encephalitis. He was started on sodium valproate 200 mg 8 hourly and made a slow neurological recovery with mild residual weakness (grade 4+ power) in his left upper limb at 2 months with intensive supervised physiotherapy. CONCLUSION: Standard national guideline-based management of dengue illness has significantly reduced its mortality rates in Sri Lanka. However, uncommon presentations of a common illness often cause diagnostic dilemmas. Hence, reporting of these presentations and knowing the epidemiologic patterns of the disease help physicians to arrive at the correct diagnosis even though they do not have sophisticated serological investigations. Overall, this can improve the quality of health care and reduce mortalities, especially in a resource-poor setup.


Assuntos
Encefalite Viral/diagnóstico , Dengue Grave/diagnóstico , Adolescente , Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Encefalite Viral/tratamento farmacológico , Humanos , Imagem por Ressonância Magnética , Masculino , Sri Lanka , Ácido Valproico/uso terapêutico
10.
BMC Res Notes ; 12(1): 604, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547852

RESUMO

OBJECTIVE: Objective of the study is to evaluate the on-admission day symptoms and signs, clinical, hematological parameters and liver transaminases of the dengue NS1 positive patients who got admitted on different clinical phases [Febrile phase (day 1-3) and Critical phase(day 4-5)] of dengue at medical wards of Jaffna Teaching Hospital. RESULTS: Blood samples were collected from 150 suspected dengue patients from day 1 to 5 of the illness. Seventy-eight patients were positive for dengue NS1, according to the WHO proposed dengue clinical phase framework 37 patients were from febrile phase and 41 patients from critical phase. Patients who admitted on critical phase framework suffered from leukopenia and thrombocytopenia. Nine patients had the evidence of leakage with fever and the leakers had significant rise in hemoglobin, hematocrit and liver transaminase levels which are considered as severe form of the disease.


Assuntos
Vírus da Dengue/patogenicidade , Febre/diagnóstico , Hospitais de Ensino , Leucopenia/diagnóstico , Dengue Grave/diagnóstico , Trombocitopenia/diagnóstico , Proteínas não Estruturais Virais/sangue , Adolescente , Adulto , Vírus da Dengue/imunologia , Progressão da Doença , Feminino , Febre/sangue , Febre/imunologia , Febre/virologia , Hospitalização , Humanos , Leucopenia/sangue , Leucopenia/imunologia , Leucopenia/virologia , Fígado/patologia , Fígado/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dengue Grave/sangue , Dengue Grave/imunologia , Dengue Grave/virologia , Sri Lanka , Trombocitopenia/sangue , Trombocitopenia/imunologia , Trombocitopenia/virologia , Transaminases/sangue , Proteínas não Estruturais Virais/imunologia
11.
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
12.
PLoS Negl Trop Dis ; 13(8): e0007144, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31430283

RESUMO

The objective of this study was to assess the validity of the new dengue classification proposed by the World Health Organization (WHO) in 2009 and to develop pragmatic guidelines for case triage and management. This retrospective study involved 357 laboratory-confirmed cases of dengue infection diagnosed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 4-year period from 2014 to 2017. The sensitivity of the new classification for identifying severe cases was limited (65%) but higher than the old one (30%). It had a higher sensitivity for identifying patients who needed advanced healthcare compared to the old one (72% versus 32%, respectively). We propose adding decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification. This modification improves sensitivity from 72% to 98% for identifying patients who need advanced healthcare without altering specificity (97%). It also improves sensitivity in predicting severe outcomes from 32% to 88%. In conclusion, the new classification had a low sensitivity for identifying patients needing advanced care and for predicting morbidity and mortality. We propose to include decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification to improve the sensitivity of predicting cases requiring advanced care.


Assuntos
Dengue/classificação , Dengue/diagnóstico , Organização Mundial da Saúde , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Medicina Clínica/métodos , Medicina Clínica/normas , Dengue/fisiopatologia , Feminino , Hemorragia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita , Sensibilidade e Especificidade , Dengue Grave/classificação , Dengue Grave/diagnóstico , Índice de Gravidade de Doença , Trombocitopenia , Adulto Jovem
13.
PLoS One ; 14(8): e0218939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469845

RESUMO

Dengue fever is the most important arthropod-borne viral infection worldwide. Secondary prevention to reduce mortality through improved clinical case management has substantially lowered the mortality rate for severe dengue during the past two decades. Gallbladder wall thickening (GBWT) is a nonspecific finding often associated with more severe cases of dengue infection. This study had the aim to describe the ultrasonographic findings in hospitalized patients with dengue infection from Manaus (in the Western Brazilian Amazon) and to correlate the GBWT with dengue severity, symptoms and laboratorial analysis. Patients from 13-84 years admitted to the emergency department at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) were enrolled in this study. Patients' selection occurred during the most recent and huge dengue outbreak within the first semester of 2011. All enrolled subjects were systematically tested in order to rule out other possible etiologies for gallbladder inflammation. Abdominal ultrasound was performed by a single physician through bedside portable equipment and all other clinical and laboratorial information were retrieved from patients' electronic files. 54 subjects were considered for analysis, with confirmed dengue infection by NS1 and/or RT-PCR positivity. From all enrolled patients, 50 (42.4%) presented GBWT. GBWT was significantly and independently related to: age under 31 years, pregnancy, presence of bleeding, presence of any cavitary effusion, DHF classification and severe dengue classifications. During dengue outbreaks, the GBWT identification through a non-invasive and bedside procedure is a confident marker for prompt recognition of potential severe cases.


Assuntos
Vesícula Biliar/patologia , Dengue Grave/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Acta Trop ; 199: 105134, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31415737

RESUMO

The disease caused by each of the four serotypes of dengue virus (DENV) have plagued humans since last century. Symptoms of dengue virus (DENV) infection range from asymptomatic to dengue fever (DF) to severe dengue disease (SDD). One third of the world's population lives in regions with active urban DENV transmission, and thousands of serologically naïve travelers visit these areas annually, making a significant portion of the human population at risk of being infected. Even though lifelong immunity to the homotypic serotype is achieved after a primary DENV infection. Heterotypic DENV infections may be exacerbated by a pre-existing immune memory to the primary infection and can result in an increased probability of severe disease. Not only, age, comorbidities and presence of antibodies transferred passively from dengue-immune mother to infants are considered risk factors to dengue severe forms. Plasma leakage and multiple organ impairment are well documented in the literature, affecting liver, lung, brain, muscle, and kidney. However, unusual manifestation, severe or not, have been reported and may require medical attention. This review will summarize and discuss the increasing reports of unusual manifestations in the clinical course of dengue infection.


Assuntos
Dengue/complicações , Dengue Grave/etiologia , Lesão Renal Aguda/etiologia , Adolescente , Criança , Pré-Escolar , Vírus da Dengue/imunologia , Humanos , Lactente , Pancreatite/etiologia , Síndrome de Reye/etiologia , Ruptura Esplênica/etiologia , Acidente Vascular Cerebral/etiologia
15.
Virol J ; 16(1): 93, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345242

RESUMO

BACKGROUND: Dengue fever is a febrile disease caused by dengue virus (DENV), which affects people throughout the tropical and subtropical regions of the world, including Indonesia. East Kalimantan (Borneo) province suffered a dramatic increase in dengue cases in 2015 and 2016, making it the province with the second highest incidence of dengue in Indonesia. Despite this, dengue in East Kalimantan is understudied; leaving transmission dynamics of the disease in the area are mostly unknown. In this study, we investigate the factors contributing to the outbreaks in East Kalimantan. METHODS: Prospective clinical and molecular virology study was conducted in two main cities in the province, namely Samarinda and Balikpapan, in 2015-2016. Patients' clinical, hematological, and demographic data were recorded. Dengue detection and confirmation was performed using NS1-antigen and IgG/IgM antibody detection. RT-PCR was conducted to determine the serotypes of the virus. Phylogenetic analysis was performed based on envelope gene sequences. RESULTS: Three hundred patients with suspected dengue were recruited. Among these, 132 (44%) were diagnosed with dengue by NS1 antigen and/or nucleic acid detection. The majority of the infections (60%) were primary, with dengue hemorrhagic fever (DHF) the predominant manifestation (71.9%). Serotyping detected all four DENV serotypes in 112 (37.3%) cases, with the majority of patients (58.9%) infected by DENV-3. Phylogenetic analysis based on envelope gene sequences revealed the genotypes of the viruses as DENV-1 Genotype I, DENV-2 Cosmopolitan, and DENV-3 Genotype I. Most virus strains were closely-related to strains from cities in Indonesia. CONCLUSIONS: Our observations indicate that multiple introductions of endemic DENV from surrounding cities in Indonesia, coupled with relatively low herd immunity, were likely responsible for the outbreak of the dominant viruses. The study provides information on the clinical spectrum of the disease, together with serology, viral genetics, and demographic data, which will be useful for better understanding of dengue disease in Borneo.


Assuntos
Vírus da Dengue/classificação , Dengue/epidemiologia , Dengue/virologia , Surtos de Doenças , Monitoramento Epidemiológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Genótipo , Humanos , Indonésia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , Sorogrupo , Dengue Grave/epidemiologia , Dengue Grave/virologia , Adulto Jovem
17.
Rev Soc Bras Med Trop ; 52: e20190060, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31188919

RESUMO

INTRODUCTION: In this study, we aimed to identify DENV-2 subtypes in Aedes aegypti pools collected between 2011 and 2017 in a rural area of Northern Cordoba, Colombia ("La Balsa"). METHODS: RT-PCR was performed to analyze the capsid/pre-membrane region (C-PrM). Sequencing and phylogenetic bayesian inference using reference DENV-2 sequences were performed. RESULTS: Twelve pools that tested positive for DENV-2 were characterized based on the C-PrM region and grouped under the Asian/American clade. CONCLUSIONS: This study is the first to report the DENV-2 Asian-American subtype in a rural area of Cordoba region, which is associated with severe dengue and local epidemics.


Assuntos
Aedes/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Dengue/virologia , Mosquitos Vetores/virologia , Filogenia , Animais , Teorema de Bayes , Colômbia/epidemiologia , Dengue/epidemiologia , Vírus da Dengue/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sorogrupo , Sorotipagem , Dengue Grave
18.
Arch Virol ; 164(8): 2131-2135, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31102050

RESUMO

A large-scale dengue fever (DF) outbreak occurred in Chaozhou, Guangdong province, China 2015. In our study, 528 dengue-positive patient samples were collected for clinical and laboratory data analysis. 491 cases (93.0%) were primary dengue fever (PDF), 22 cases (4.2%) were dengue hemorrhagic fever (DHF) and 15 cases (2.8%) were diagnosed with severe dengue fever (SDF). All cases were infected by dengue virus serotype 2 (DENV-2), and the isolated strains belonged to cosmopolitan genotype, which were grouped closely with Malaysia strains from 2010 to 2014. Moreover, the study showed that laboratory indices have significantly difference in PDF, DHF and SDF patients. A comprehensive analysis of these data could assist and guide the clinical diagnosis for DF, which has an important significance for the control of dengue virus infection.


Assuntos
Dengue/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Dengue/virologia , Vírus da Dengue/genética , Surtos de Doenças , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Sorogrupo , Dengue Grave/epidemiologia , Adulto Jovem
19.
PLoS One ; 14(5): e0215061, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042724

RESUMO

INTRODUCTION: The early identification of patients at risk of severe dengue infection (DI) is critical to guide clinical management. There is currently no validated laboratory test which can predict severe complications of DI. The Atypical lymphocyte count (ALC) is a research parameter generated at no extra cost when an automated Full Blood Count (FBC) is performed. The purpose of this study was to assess the association of ALC with the severity of DI. METHODS: We prospectively collected data on patients admitted to Nawaloka Hospital Sri Lanka (NH) with DI between December 2016 and November 2017. DI was diagnosed based on a positive Non-structural antigen 1 (NS1) or dengue IgM antibody. ALC (absolute ALC and percentage) data were extracted from the Sysmex XS500i automated full blood count (FBC) analyzer (Sysmex Corporation Kobe, Japan). Clinical data was recorded from medical records and the computerized data base maintained by NH. RESULTS: 530 patients were enrolled. Patients with clinical manifestations of severe dengue have a significantly higher AL % compared to dengue without warning signs. Patients who presented with respiratory compromise had statistically significantly higher AL% compared to those without. (AL%; 8.65±12.09 vs 2.17±4.25 [p = 0.01]). Similarly, patients who developed hypotension had higher AL% compared to those who did not suffered from shock (AL%; 8.40±1.26 vs 2.18±4.25 [p = 0.001]). The AL% of dengue patients presenting with bleeding, at 4.07%, is also higher than those without bleeding complications, at 2.15%. There was a significant negative association between platelet count and AL% (p = 0.04). CONCLUSIONS: Clinical manifestations of severe dengue have a significantly higher AL % compared to dengue without warning signs. AL % at presentation may be predictive of severe DI and future larger prospective longitudinal studies should be done to determine if AL % on admission is predictive of the complications of DI.


Assuntos
Hipotensão/epidemiologia , Dengue Grave/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipotensão/etiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Dengue Grave/complicações , Índice de Gravidade de Doença , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-31027310

RESUMO

Objective: This study was conducted to identify the association between rs4804803 polymorphism in DC-SIGN with the susceptibility of severe dengue. Methods: A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). Results: A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession (GG versus GA/AA: OR = 0.44, 95%CI, 0.23-0.82) and a codominant model (GG versus AA: OR = 0.43, 95%CI, 0.23-0.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in rs4804803 was a risk factor for severe dengue under dominant (GG/GA versus AA: OR = 1.86,95%CI, 1.01-3.45), superdominant (GA versus GG/AA: OR = 1.81,95%CI, 1.02-3.21) and a codominant (GA versus AA: OR=1.82,95%CI, 1.02-3.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive (GG versus GA/AA: OR = 0.27,95%CI, 0.10-0.70) and codominant (GG versus AA: OR=0.24,95%CI, 0.09-0.64) models. The results from subgroup analysis were robust. Conclusions: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) promoter-336G/A (rs4804803) polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Moléculas de Adesão Celular/genética , Lectinas Tipo C/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Receptores de Superfície Celular/genética , Dengue Grave/genética , China , Predisposição Genética para Doença , Humanos , Razão de Chances , Fatores de Risco , Dengue Grave/etnologia , América do Sul
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