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1.
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
2.
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
3.
Am J Trop Med Hyg ; 103(3): 1223-1227, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32618241

RESUMO

Dengue-related mortality has significantly reduced with early and appropriate fluid resuscitation. However, we continue to see dengue-related fatalities in patients despite early intervention and advanced critical care support. This was a retrospective study conducted at a tertiary care private hospital in Mumbai, India. All patients dying of dengue in the calendar year 2017 were studied. Details related to age, gender, condition at presentation, laboratory parameters, treatment administered, and time to death were abstracted from case records. A total of 575 patients with a diagnosis of dengue were admitted to the hospital in 2017, of which 15 died (mortality rate 2.6%). Four patients died in the emergency medical unit; 11 patients who died after admission to the inpatient unit had multi-organ dysfunction at the time of presentation, with shock, severe liver dysfunction, and severe metabolic acidosis. Only 4/11 patients had hemoconcentration, and 10/11 patients had high white cell counts. In five patients where serum ferritin was performed, it was more than 40,000 ng/mL. Death occurred at a median time of 2 days after hospitalization despite good supportive care. Although there is scope for improvement of supportive care in these patients, it appears that other interventions are urgently needed to improve outcomes in severe dengue. This calls for more research into the immunopathology of dengue, evaluation of anti-inflammatory drugs, intravenous immunoglobulins, antivirals, and improved vaccines.


Assuntos
Dengue/diagnóstico , Dengue Grave/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cuidados Críticos , Dengue/imunologia , Dengue/terapia , Dengue/virologia , Feminino , Hidratação , Hospitalização , Hospitais Privados , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dengue Grave/imunologia , Dengue Grave/terapia , Dengue Grave/virologia , Atenção Terciária à Saúde , Adulto Jovem
4.
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
5.
Cell Rep ; 29(13): 4482-4495.e4, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31875555

RESUMO

Dengue virus (DENV) can cause diseases ranging from dengue fever (DF) to more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Whether antiviral T cells contribute to the protection against or pathogenesis of severe disease is not well defined. Here, we identified antigen-specific IL-10+IFN-γ+ double-positive (DP) CD4 T cells during acute DENV infection. While the transcriptomic signatures of DP cells partially overlapped with those of cytotoxic and type 1 regulatory CD4 T cells, the majority of them were non-cytotoxic/Tr1 and included IL21, IL22, CD109, and CCR1. Although we observed a higher frequency of DP cells in DHF, the transcriptomic profile of DP cells was similar in DF and DHF, suggesting that DHF is not associated with the altered phenotypic or functional attributes of DP cells. Overall, this study revealed a DENV-specific DP cell subset in patients with acute dengue disease and argues against altered DP cells as a determinant of DHF.


Assuntos
Vírus da Dengue/imunologia , Regulação da Expressão Gênica/imunologia , Interferon gama/imunologia , Interleucina-10/imunologia , Dengue Grave/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Antígenos CD/genética , Antígenos CD/imunologia , Estudos de Casos e Controles , Vírus da Dengue/patogenicidade , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Humanos , Interferon gama/genética , Interleucina-10/genética , Interleucinas/genética , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Receptores CCR1/genética , Receptores CCR1/imunologia , Dengue Grave/genética , Dengue Grave/patologia , Dengue Grave/virologia , Índice de Gravidade de Doença , Transdução de Sinais , Linfócitos T Citotóxicos/virologia , Linfócitos T Reguladores/virologia , Transcriptoma/imunologia
6.
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
7.
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
9.
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
10.
BMC Res Notes ; 12(1): 214, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961645

RESUMO

OBJECTIVE: Dengue haemorrhagic fever (DHF) is a major public health concern responsible for significant morbidity in both adult and paediatric populations in Sri Lanka. This study examined if persistent non structural protein 1 (NS1) antigen positivity beyond day 3 was predictive of the occurrence of dengue haemorrhagic fever. The patients were followed up during their in-hospital stay and the severity of the illness was classified according to the WHO classification. The NS1 antigen test was repeated after day 3 of the onset of illness, at least 2 days after the initial test. RESULTS: One hundred and fifty-seven patients were enrolled. Persistent NS1 antigen test positivity after day 3 of the illness was not predictive of subsequent development of DHF. Out of multiple other demographic and illness related factors assessed, only having a secondary dengue infection was associated with a high risk of DHF (relative risk = 3.077, 95% CI 1.361, 6.954). Persistent NS1 positivity on day 3 may not be indicative of disease severity. However results need to be confirmed by a larger study with quantitative NS1 testing.


Assuntos
Antígenos Virais/sangue , Coinfecção/diagnóstico , Vírus da Dengue/imunologia , Dengue Grave/diagnóstico , Proteínas não Estruturais Virais/sangue , Adolescente , Antígenos Virais/imunologia , Criança , Pré-Escolar , Coinfecção/imunologia , Coinfecção/patologia , Coinfecção/virologia , Vírus da Dengue/patogenicidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Dengue Grave/imunologia , Dengue Grave/patologia , Dengue Grave/virologia , Índice de Gravidade de Doença , Sri Lanka , Proteínas não Estruturais Virais/imunologia
11.
Sci Total Environ ; 656: 889-901, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30625675

RESUMO

OBJECTIVES: The burden of dengue fever in Thailand is considerable, yet there are few large-scale studies exploring the drivers of transmission. This study aimed to investigate the spatiotemporal patterns and climatic drivers of severe dengue in Thailand. METHODS: Geographic Information System (GIS) techniques and spatial cluster analysis were used to visualize the spatial distribution and detect high-risk clusters of severe dengue in 76 provinces of Thailand from January 1999 to December 2014. The seasonal patterns of severe dengue cases in different provinces were identified. A two-stage modelling approach combining a generalized linear model with a distributed lag non-linear model was used to quantify the effects of monthly mean temperature and relative humidity on the occurrence of severe dengue cases in 51 provinces of Thailand. RESULTS: Significant severe dengue clustering was detected, especially during epidemic years, and the location of these clusters showed substantial inter-annual variation. Severe dengue cases in Northern and Northeastern Thailand peaked in June to August and this pattern was stable across the study period, whereas the seasonality of severe dengue cases in other regions (especially Central Thailand) was less predictable. The risk of the occurrence of severe dengue cases increased with an increase in mean temperature in Northeastern Thailand, Central Thailand, and Southern Thailand, with peaks occurring between 24 °C to 30 °C in Northeastern Thailand and 27 °C to 29 °C in Southern Thailand West Coast, respectively. Relative humidity significantly affected the occurrence of severe dengue cases in Northeastern and Central Thailand, with optimal ranges observed for each region. CONCLUSIONS: Our findings substantiate the potential for developing climate-based dengue early warning systems for Thailand, and have implications for informing pre-emptive vector control.


Assuntos
Umidade , Dengue Grave/epidemiologia , Análise Espaço-Temporal , Temperatura , Análise por Conglomerados , Humanos , Incidência , Estações do Ano , Dengue Grave/virologia , Tailândia/epidemiologia
12.
Am J Trop Med Hyg ; 100(2): 411-419, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30652671

RESUMO

According to the World Health Organization, 98% of fatal dengue cases can be prevented; however, endemic countries such as Colombia have recorded higher case fatality rates during recent epidemics. We aimed to identify the predictors of mortality that allow risk stratification and timely intervention in patients with dengue. We conducted a hospital-based, case-control (1:2) study in two endemic areas of Colombia (2009-2015). Fatal cases were defined as having either 1) positive serological test (IgM or NS1), 2) positive virological test (RT-PCR or viral isolation), or 3) autopsy findings compatible with death from dengue. Controls (matched by state and year) were hospitalized nonfatal patients and had a positive serological or virological dengue test. Exposure data were extracted from medical records by trained staff. We used conditional logistic regression (adjusting for age, gender, disease's duration, and health-care provider) in the context of multiple imputation to estimate exposure to case-control associations. We evaluated 110 cases and 217 controls (mean age: 35.0 versus 18.9; disease's duration pre-admission: 4.9 versus 5.0 days). In multivariable analysis, retro-ocular pain (odds ratios [OR] = 0.23), nausea (OR = 0.29), and diarrhea (OR = 0.19) were less prevalent among fatal than nonfatal cases, whereas increased age (OR = 2.46 per 10 years), respiratory distress (OR = 16.3), impaired consciousness (OR = 15.9), jaundice (OR = 32.2), and increased heart rate (OR = 2.01 per 10 beats per minute) increased the likelihood of death (AUC: 0.97, 95% confidence interval: 0.96, 0.99). These results provide evidence that features of severe dengue are associated with higher mortality, which strengthens the recommendations related to triaging patients in dengue-endemic areas.


Assuntos
Diarreia/diagnóstico , Icterícia/diagnóstico , Náusea/diagnóstico , Dengue Grave/diagnóstico , Taquicardia/diagnóstico , Adolescente , Adulto , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Colômbia , Vírus da Dengue/imunologia , Vírus da Dengue/isolamento & purificação , Diarreia/mortalidade , Diarreia/fisiopatologia , Diarreia/virologia , Doenças Endêmicas , Feminino , Cefaleia , Humanos , Imunoglobulina M/sangue , Icterícia/mortalidade , Icterícia/fisiopatologia , Icterícia/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Náusea/mortalidade , Náusea/fisiopatologia , Náusea/virologia , /fisiopatologia , Medição de Risco , Dengue Grave/mortalidade , Dengue Grave/fisiopatologia , Dengue Grave/virologia , Análise de Sobrevida , Taquicardia/mortalidade , Taquicardia/fisiopatologia , Taquicardia/virologia
13.
J Infect Dev Ctries ; 13(12): 1127-1134, 2019 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-32088700

RESUMO

INTRODUCTION: Dengue virus (DENV) infection is currently a major cause of morbidity in the world, and its incidence has mainly increased during the last years in Latin America, including Paraguay. The objective of this study was to compare the clinical and laboratory findings of dengue and assess whether the serotype is a risk factor for severity. METHODOLOGY: We included patients ≤ 15 years old hospitalized with dengue at the Institute of Tropical Medicine, from Paraguay, from 2007 to 2018. Patients were classified according to the 2009 WHO dengue classification guidelines and were stratified by serotype into three groups according to the hospitalization period: the 2007 epidemic (DENV-3), the 2012-2013 epidemic (DENV-2) and the 2016-2018 epidemic (DENV-1). RESULTS: Of 784 children hospitalized for dengue, 50 cases (6.3%) were caused by DENV-3, 471 (60%) by DENV-2, and 263 (33.5%) by DENV-1. Myalgias and headache were associated with DENV-3 cases and abdominal pain was associated with DENV-2 cases. Bleeding was observed mainly in DENV-1 and 2 cases. Patients with DENV-2 infections experienced more severe disease, required fluid expansion more frequently, and exhibited more often shock and admission in the ICU. Secondary cases of dengue were more severe that primary cases. Patients with infection by DENV-2 had longer hospital stays (5.1 ± 2.8 days) when compared to DENV-3 o DENV-1 infection cases (2.9 ± 1.6 days and 4.36 ± 2.7 days, respectively) (p < 0.05). CONCLUSIONS: The DENV serotype has a profound impact on the clinical manifestations and severity of dengue. DENV-2 infections were associated more frequently to requirement of fluid expansion, shock, and longer hospital stay.


Assuntos
Vírus da Dengue/classificação , Dengue/epidemiologia , Dengue/virologia , Adolescente , Criança , Pré-Escolar , Dengue/diagnóstico , Vírus da Dengue/patogenicidade , Doenças Endêmicas , Epidemias , Feminino , Humanos , Masculino , Paraguai/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Sorogrupo , Dengue Grave/diagnóstico , Dengue Grave/epidemiologia , Dengue Grave/virologia
14.
Lancet Infect Dis ; 19(1): e31-e38, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30195995

RESUMO

The Strategic Advisory Group of Experts (SAGE) on Immunization advises WHO on global policies for vaccines. In April, 2016, SAGE issued recommendations on the use of the first licenced dengue vaccine, CYD-TDV. In November, 2017, a retrospective analysis of clinical trial data, stratifying participants according to their dengue serostatus before the first vaccine dose, showed that although in high seroprevalence settings the vaccine provides overall population benefit, there was an excess risk of severe dengue in seronegative vaccinees. SAGE's working group on dengue vaccines met to discuss the new data and mainly considered two vaccination strategies: vaccination of populations with dengue seroprevalence rates above 80% or screening of individuals before vaccination, and vaccinating only seropositive individuals. We report on the deliberations that informed the recommendation of the pre-vaccination screening strategy, in April, 2018. Important research and implementation questions remain for CYD-TDV, including the development of a highly sensitive and specific rapid diagnostic test to determine serostatus, simplified immunisation schedules, and assessment of the need for booster doses.


Assuntos
Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Imunização Secundária , Dengue Grave/prevenção & controle , Vacinação , Vacinas Atenuadas/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Programas de Rastreamento , Estudos Soroepidemiológicos , Dengue Grave/virologia , Resultado do Tratamento , Organização Mundial da Saúde
15.
Nat Commun ; 9(1): 5242, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30531923

RESUMO

The role of NS1-specific antibodies in the pathogenesis of dengue virus infection is poorly understood. Here we investigate the immunoglobulin responses of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) to NS1. Antibody responses to recombinant-NS1 are assessed in serum samples throughout illness of patients with acute secondary DENV1 and DENV2 infection by ELISA. NS1 antibody titres are significantly higher in patients with DHF compared to those with DF for both serotypes, during the critical phase of illness. Furthermore, during both acute secondary DENV1 and DENV2 infection, the antibody repertoire of DF and DHF patients is directed towards distinct regions of the NS1 protein. In addition, healthy individuals, with past non-severe dengue infection have a similar antibody repertoire as those with mild acute infection (DF). Therefore, antibodies that target specific NS1 epitopes could predict disease severity and be of potential benefit in aiding vaccine and treatment design.


Assuntos
Anticorpos Antivirais/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Proteínas não Estruturais Virais/imunologia , Sequência de Aminoácidos , Anticorpos Antivirais/sangue , Formação de Anticorpos/imunologia , Antígenos Virais/imunologia , Reações Cruzadas/imunologia , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/patogenicidade , Humanos , Peptídeos/imunologia , Homologia de Sequência de Aminoácidos , Sorogrupo , Dengue Grave/imunologia , Dengue Grave/virologia , Virulência/genética , Virulência/imunologia , Vírus do Nilo Ocidental/genética , Vírus do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/patogenicidade
16.
J Biomed Sci ; 25(1): 77, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30409217

RESUMO

Dengue virus, the causative agent of dengue disease which may have hemorrhagic complications, poses a global health threat. Among the numerous target cells for dengue virus in humans are monocytes, macrophages and mast cells which are important regulators of vascular integrity and which undergo dramatic cellular responses after infection by dengue virus. The strategic locations of these three cell types, inside blood vessels (monocytes) or outside blood vessels (macrophages and mast cells) allow them to respond to dengue virus infection with the production of both intracellular and secretory factors which affect virus replication, vascular permeability and/or leukocyte extravasation. Moreover, the expression of Fc receptors on the surface of monocytes, macrophages and mast cells makes them important target cells for antibody-enhanced dengue virus infection which is a major risk factor for severe dengue disease, involving hemorrhage. Collectively, these features of monocytes, macrophages and mast cells contribute to both beneficial and harmful responses of importance to understanding and controlling dengue infection and disease.


Assuntos
Vírus da Dengue/fisiologia , Dengue/virologia , Macrófagos/virologia , Mastócitos/virologia , Monócitos/virologia , Dengue Grave/virologia
17.
DNA Cell Biol ; 37(10): 805-807, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30113225

RESUMO

Dengue is a pandemic-prone viral disease which is endemic in more than 100 countries and which puts half of the world's population at risk. While the disease presents as subclinical infection or mild fever in the majority of cases, approximately a quarter of the infected individuals experience severe forms of disease like dengue hemorrhagic fever/dengue shock syndrome that cause significant rates of mortality and morbidity. The pathogenesis of this differential outcome of infection is determined by a complex interplay of factors associated with the virus, vector, and host; much of which is not completely understood. In this review, we present an update on the various host genetic polymorphisms that have been reported to influence the susceptibility to dengue. For the convenience of discussion, we have categorized the genetic factors according to the different arms of the immune system with which the corresponding immune determinants are associated.


Assuntos
Vírus da Dengue/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Interações Hospedeiro-Patógeno/genética , Polimorfismo Genético , Dengue Grave/genética , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Vírus da Dengue/crescimento & desenvolvimento , Vírus da Dengue/patogenicidade , Antígenos HLA/genética , Antígenos HLA/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Regiões Promotoras Genéticas , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Dengue Grave/imunologia , Dengue Grave/patologia , Dengue Grave/virologia , Transdução de Sinais , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia
18.
Am J Trop Med Hyg ; 99(4): 1053-1054, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30062992

RESUMO

Dengue is a vector-borne viral illness of major public health importance. It is endemic in many parts of India and also causes frequent epidemics. Platelet transfusions are given in severe cases of dengue fever to treat and prevent hemorrhagic complications. Here, we report three patients in North India with development of panophthalmitis and endophthalmitis shortly after receiving platelet transfusion.


Assuntos
Endoftalmite/etiologia , Panoftalmite/etiologia , Transfusão de Plaquetas/efeitos adversos , Dengue Grave/terapia , Trombocitopenia/terapia , Adulto , Criança , Vírus da Dengue/crescimento & desenvolvimento , Endoftalmite/diagnóstico , Endoftalmite/patologia , Endoftalmite/virologia , Humanos , Masculino , Panoftalmite/diagnóstico , Panoftalmite/patologia , Panoftalmite/virologia , Contagem de Plaquetas , Dengue Grave/patologia , Dengue Grave/virologia , Trombocitopenia/patologia , Trombocitopenia/virologia
19.
Sci Rep ; 8(1): 11826, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087415

RESUMO

Dengue fever is a viral condition that has become a recurrent issue for public health in tropical countries, common endemic areas. Although viral structure and composition have been widely studied, the infection phenotype in terms of small molecules remains poorly established. This contribution providing a comprehensive overview of the metabolic implications of the virus-host interaction using a lipidomic-based approach through direct-infusion high-resolution mass spectrometry. Our results provide further evidence that lipids are part of both the immune response upon Dengue virus infection and viral infection maintenance mechanism in the organism. Furthermore, the species described herein provide evidence that such lipids may be part of the mechanism that leads to blood-related complications such as hemorrhagic fever, the severe form of the disease.


Assuntos
Vírus da Dengue/imunologia , Dengue/imunologia , Lipídeos/imunologia , Dengue Grave/imunologia , Adulto , Dengue/sangue , Dengue/virologia , Vírus da Dengue/fisiologia , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metabolismo dos Lipídeos/imunologia , Lipídeos/sangue , Masculino , Espectrometria de Massas/métodos , Metabolômica/métodos , Fator de Ativação de Plaquetas/imunologia , Fator de Ativação de Plaquetas/metabolismo , Análise de Componente Principal , Dengue Grave/sangue , Dengue Grave/virologia
20.
BMC Infect Dis ; 18(1): 375, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30086716

RESUMO

BACKGROUND: Dengue virus infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic infection through to severe dengue. Although prior infection with another viral serotype, i.e. secondary dengue, is known to be an important factor influencing disease severity, current methods to determine primary versus secondary immune status during the acute illness do not consider the rapidly evolving immune response, and their accuracy has rarely been evaluated against an independent gold standard. METHODS: Two hundred and ninety-three confirmed dengue patients were classified as experiencing primary, secondary or indeterminate infections using plaque reduction neutralisation tests performed 6 months after resolution of the acute illness. We developed and validated regression models to differentiate primary from secondary dengue on multiple acute illness days, using Panbio Indirect IgG and in-house capture IgG and IgM ELISA measurements performed on over 1000 serial samples obtained during acute illness. RESULTS: Cut-offs derived for the various parameters demonstrated progressive change (positively or negatively) by day of illness. Using these time varying cut-offs it was possible to determine whether an infection was primary or secondary on single specimens, with acceptable performance. The model using Panbio Indirect IgG responses and including an interaction with illness day showed the best performance throughout, although with some decline in performance later in infection. Models based on in-house capture IgG levels, and the IgM/IgG ratio, also performed well, though conversely performance improved later in infection. CONCLUSIONS: For all assays, the best fitting models estimated a different cut-off value for different days of illness, confirming how rapidly the immune response changes during acute dengue. The optimal choice of assay will vary depending on circumstance. Although the Panbio Indirect IgG model performs best early on, the IgM/IgG capture ratio may be preferred later in the illness course.


Assuntos
Infecções Assintomáticas , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/imunologia , Testes de Neutralização , Doença Aguda , Adolescente , Adulto , Algoritmos , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Dengue/virologia , Diagnóstico Diferencial , Progressão da Doença , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Humanos , Hospedeiro Imunocomprometido/imunologia , Imunoglobulina G/análise , Imunoglobulina G/sangue , Imunoglobulina M/análise , Imunoglobulina M/sangue , Masculino , Testes de Neutralização/métodos , Testes de Neutralização/normas , Sensibilidade e Especificidade , Sorogrupo , Dengue Grave/diagnóstico , Dengue Grave/imunologia , Dengue Grave/virologia , Índice de Gravidade de Doença , Licença Médica , Adulto Jovem
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