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Resultados 1 - 20 de 20.478

A dual marker label free electrochemical assay for Flavivirus dengue diagnosis.

Biosens Bioelectron; 100: 519-525, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28985612


Dengue is a RNA viral illness of the genus Flavivirus which can cause, depending on the pervasiveness of the infection, hemorrhagic dengue fever or dengue shock syndrome. Herein we present an electrochemical label free approach enabling the rapid sensitive quantification of NS1 and IgG (supporting an ability to distinguish primary and secondary infections). Using a bifunctional SAM containing PEG moieties and a tethered redox thiol, both markers are detectable across clinically relevant levels by label free impedance derived redox capacitance. A subsequent frequency specific immittance function approach enables assaying (within seconds) with no impairment of analytical quality (linearity, sensitivity and variance).

Detection of Virus-Antibody Immune Complexes in Secondary Dengue Virus Infection.

Methods Mol Biol; 1604: 331-337, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28986846


It has been reported that virus-antibody immune complexes formed during secondary dengue virus infection are associated with increased disease severity. Here, we describe the details of a plaque titration method that uses FcγR -expressing BHK cells to detect and quantify infectious virus-immune complexes and a quantitative real-time PCR method for the quantification of virus genome in patients with secondary dengue infection. These methods detect both viruses in free-form and in immune complexes in patients with dengue infection, and are useful for determining viremia levels and patterns that better reflect in vivo conditions.

Identifying Restriction Factors for Hemorrhagic Fever Viruses: Dengue and Junín.

Methods Mol Biol; 1604: 351-370, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28986848


Host restriction factors are cellular components that interfere with viral multiplication. They are up-regulated and expressed upon viral infection and in consequence their activity is specific. So far several important restriction factors have been described against diverse viruses. The cellular antiviral mechanisms defined include proteins with the ability to interfere with early steps of viral replication and others that have been shown to block viral morphogenesis. However, other strategies by which the antiviral action is exerted still remain elusive. An additional interesting matter is how viruses also developed ways to by-pass these host-specific obstacles. Thus, unusual cell localization or re-localization represents a frequent virus choice to evade the cellular surveillance. In the present chapter, we summarize methods to identify cell restriction factors, their antiviral activity, and possible subcellular locations where their activity can take place.

Drug repurposing approaches to fight Dengue virus infection and related diseases.

Front Biosci (Landmark Ed); 23: 997-1019, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28930586


Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of Dengue Virus (DENV), namely DENV1-4 and is currently considered the most important arthropod-born viral disease in the world. An effective antiviral therapy to treat Dengue Virus infection is still missing and a number of replicative cycle inhibitors are currently under study. Considering the rapid spreading of DENV and the common timeframe required for bringing a new drug on the market, the repurposing of approved drugs used for different diseases to identify novel inhibitors of this pathogen represents an attractive approach for a rapid therapeutic intervention. Herein, we will describe the most recent drug repurposing approaches to fight DENV infection and their implications in antiviral drug-discovery.

Increased efficiency in the second-hand tire trade provides opportunity for dengue control.

J Theor Biol; 437: 126-136, 2018 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-29079324


Dengue fever is increasing in geographical range, spread by invasion of its vector mosquitoes. The trade in second-hand tires has been implicated as a factor in this process because they act as mobile reservoirs of mosquito eggs and larvae. Regional transportation of tires can create linkages between rural areas with dengue and disease-free urban areas, potentially giving rise to outbreaks even in areas with strong local control measures. In this work we sought to model the dynamics of mosquito transportation via the tire trade, in particular to predict its role in causing unexpected dengue outbreaks through vertical transmission of the virus across generations of mosquitoes. We also aimed to identify strategies for regulating the trade in second-hand tires, improving disease control. We created a mathematical model which captures the dynamics of dengue between rural and urban areas, taking into account the movement and storage time of tires, and mosquito diapause. We simulate a series of scenarios in which a mosquito population is introduced to a dengue-free area via movement of tires, either as single or multiple events, increasing the likelihood of a dengue outbreak. A persistent disease state can be induced regardless of whether urban conditions for an outbreak are met, and an existing endemic state can be enhanced by vector input. Finally we assess the potential for regulation of tire processing as a means of reducing the transmission of dengue fever using a specific case study from Puerto Rico. Our work demonstrates the importance of the second-hand tire trade in modulating the spread of dengue fever across regions, in particular its role in introducing dengue to disease-free areas. We propose that reduction of tire storage time and control of their movement can play a crucial role in containing dengue outbreaks.

A network model for control of dengue epidemic using sterile insect technique.

Math Biosci Eng; 15(2): 441-460, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29161844


In this paper, a network model has been proposed to control dengue disease transmission considering host-vector dynamics in n patches. The control of mosquitoes is performed by SIT. In SIT, the male insects are sterilized in the laboratory and released into the environment to control the number of offsprings. The basic reproduction number has been computed. The existence and stability of various states have been discussed. The bifurcation diagram has been plotted to show the existence and stability regions of disease-free and endemic states for an isolated patch. The critical level of sterile male mosquitoes has been obtained for the control of disease. The basic reproduction number for n patch network model has been computed. It is evident from numerical simulations that SIT control in one patch may control the disease in the network having two/three patches with suitable coupling among them.

Clinical, laboratory, and demographic determinants of hospitalization due to dengue in 7613 patients: A retrospective study based on hierarchical models.

Acta Trop; 177: 25-31, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28964768


In Brazil, the incidence of hospitalization due to dengue, as an indicator of severity, has drastically increased since 1998. The objective of our study was to identify risk factors associated with subsequent hospitalization related to dengue. We analyzed 7613 dengue confirmed via serology (ELISA), non-structural protein 1, or polymerase chain reaction amplification. We used a hierarchical framework to generate a multivariate logistic regression based on a variety of risk variables. This was followed by multiple statistical analyses to assess hierarchical model accuracy, variance, goodness of fit, and whether or not this model reliably represented the population. The final model, which included age, sex, ethnicity, previous dengue infection, hemorrhagic manifestations, plasma leakage, and organ failure, showed that all measured parameters, with the exception of previous dengue, were statistically significant. The presence of organ failure was associated with the highest risk of subsequent dengue hospitalization (OR=5·75; CI=3·53-9·37). Therefore, plasma leakage and organ failure were the main indicators of hospitalization due to dengue, although other variables of minor importance should also be considered to refer dengue patients to hospital treatment, which may lead to a reduction in avoidable deaths as well as costs related to dengue.

Associations of DC-SIGN (CD209) promoter -336G/A polymorphism (rs4804803) with dengue infection: A systematic review and meta-analysis.

Acta Trop; 177: 186-193, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29054571


BACKGROUND AND AIM: Dengue virus entry into a host is associated with a cell surface protein, DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin). A common CD209-336G/A (rs4804803) polymorphism in DC-SIGN may affect severity of dengue virus infection (DEN) and incidence of dengue fever (DF) or the more severe dengue hemorrhagic fever (DHF). However, the reported associations of these two outcomes and CD-209 have been inconsistent, which prompted a meta-analysis to obtain more precise estimates. METHODS: A literature search yielded seven case-control studies. We calculated pooled odds ratios (OR) and 95% confidence intervals using standard genetic models. Outlier treatment examined sources of potential heterogeneity. Subgroup analysis was performed for ethnicity and age. RESULTS: All significant outcomes for association indicating reduced risk were pegged at P=0.007-0.05. In the homozygous and recessive models, these were observed in the overall analysis (OR 0.52-0.55), and subgroups of South/Central Americans (OR 0.30-0.32) and school-age children (OR 0.44) in the DHF analysis as well as the codominant model among Asians in DF (OR 0.59). These significant outcomes are strengthened by their non-heterogeneity (P>0.10) and robustness of the effects. Most pooled effects in DF and DEN were variable. CONCLUSIONS: The DC-SIGN -336G/A polymorphism significantly affects DHF and DF incidence with the effect more pronounced in certain analyzed patient subgroups.

Dípteros ectoparásitos hematófagos: ¿reservorios potenciales del virus del dengue? / Ectoparasitic hematophagous dipters: potential reservoirs of dengue virus?

Gac Med Mex; 153(Supl. 2): S82-S90, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-29099114


Recently, the presence of antibodies and dengue virus (DV) RNA in neotropical wild mammals, including Desmodus rotundus, was reported. In a previous study, DV was also found in a high percentage (39.6%) of ectoparasitic hematophagous dipters specifics of these hematophagous bats. In order to verify the susceptibility of these ectoparasites to DV, in this work experimental infections with VD2 of organs explants of Strebla wiedemanni and of Melophagus ovinus were performed using C6/36 cells as control. Viral titers (UFP/mL) were determined at 0, 48 and 96 hrs pi. Infected organs were observed by electron microscopy and under the confocal microscopy indirect immunofluorescence (IIF) using specific conjugates against DV. The infected organs of both species of ectoparasites replicated DV at titers similar to those obtained with the C6/36 cell line (≥10 UFP/mL). Electron microscopy and IIF showed DV replication in the digestive tract, tracheoles, reproductive organs of males but not in females, and milk glands (MG) of both species. In the fatty bodies of the MG of M. ovinus, zones with a high affinity for the DV were observed. In this work the susceptibility of S. wiedemanni and M. ovinus to DV was demonstrated and consequently the probable role of this ectoparasites as wild reservoirs of DV.

"An Uncommon Complication of Dengue".

J Stroke Cerebrovasc Dis; 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29103866


Intracranial hemorrhage is an uncommon complication of dengue fever, which is caused by a flavivirus and transmitted via Aedes mosquito. We present here bilateral cerebellar bleed because of dengue virus infection.

Surveillance of intensity level and geographical spreading of dengue outbreak among males and females in Punjab, Pakistan: A case study of 2011.

J Infect Public Health; 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29103928


BACKGROUND: Dengue fever is viral disease which spreads due to the bite of the Aedes aegypti mosquito. In recent years, it has affected around 40% population of the world. Its endemic flow has led to a large disease burden, in terms of human and financial resources. METHODS: Geographical Information Systems (GIS) are normally used to develop epidemiological thematic maps. This study explores the patterns and hotspots, associated with the catastrophic outbreak of dengue, in Punjab, in 2011. The ArcView software was used to analyze the data reported by the district hospitals of Punjab. Twenty-one-thousand cases were reported from March to December 2011, with 300 causalities. RESULTS AND CONCLUSION: This research reveals that from among the total 37 epidemiological weeks, the maximum impact was observed between weeks 22 and 27. The geographical flow and hotspots associated with dengue have been shown through thematic maps. A positive correlation between the risk for dengue and age was observed. The findings of this research can help health officials and decision-makers alert the public about future outbreaks and take preventive measures to considerably reduce the mortality and morbidity associated with the disease.

Differences in activation and tissue homing markers of natural killer cell subsets during acute dengue infection.

Immunology; 2017 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-29105052


Dengue virus (DENV) infection is considered as one of the most important mosquito-borne diseases. It causes a spectrum of illness that could be due to qualitative and/or quantitative difference(s) of the natural killer (NK)-cell responses during acute DENV infection. This view prompted us to perform a detailed phenotypic comparative characterization of NK cell subsets from DENV-infected patients with dengue fever (DF), dengue hemorrhagic fever (DHF) and healthy controls. The activation/differentiation molecules, CD69 and CD57 and a variety of tissue homing molecules were analyzed on the CD56 CD16 and CD56 CD16 NK cells. While there was no increase in the frequency of the total NK cells during DENV infection as compared with the healthy subjects, there was a significant increase in the frequency of the CD56 CD16 subset and the frequency of CD69 expression by both NK cell subsets during the febrile phase of infection. We also found an increase in the frequencies of cells expressing CD69 and CD57 in the CD56 CD16 subset than those in the CD56 CD16 subset. Moreover, while the CD56 CD16 subset contained a high frequency of cells expressing skin-homing markers, the CD56 CD16 subset contained a high frequency of cells expressing bone marrow and lymph node trafficking markers. Interestingly, no differences of these NK cell subsets were noted in samples from DF versus DHF patients. These findings suggest that activation and differentiation and the patterns of tissue homing molecules of the two major NK cell subsets are different and these might play a critical role in the immune response against acute DENV infection. This article is protected by copyright. All rights reserved.

Interplay between Keratinocytes and Myeloid Cells Drives Dengue Virus Spread in Human Skin.

J Invest Dermatol; 2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-29106931


The skin is the site of dengue virus (DENV) transmission following the bite of an infected mosquito, but the contribution of individual cell types within skin to infection is unknown. We studied the dynamics of DENV infection in human skin explants using quantitative in situ imaging. DENV replicated primarily in the epidermis and induced a transient interferon-α response. DENV infected a wide range of cells, including Langerhans cells, macrophages, dermal dendritic cells (DC), mast cells, fibroblasts and lymphatic endothelium, but keratinocytes were the earliest targets of infection and made up 60% of infected cells over time. Virus inoculation led to recruitment and infection of Langerhans cells, macrophages and dermal DC, and these cells emigrated from skin in increased numbers as a result of infection. DENV induced expression of proinflammatory cytokines and chemokines by infected keratinocytes. Blocking keratinocyte-derived IL-1ß alone reduced infection of Langerhans cells, macrophages and dermal DC by 75 to 90% and reduced the overall number of infected cells in dermis by 65%. These data show that the innate response of infected keratinocytes attracts virus-permissive myeloid cells that inadvertently spread DENV infection. Our findings highlight a previously undescribed role for keratinocytes and their interplay with myeloid cells in dengue.

Relevance of transportation to correlations among criticality, physical means of propagation, and distribution of dengue fever cases in the state of Bahia.

Sci Total Environ; 2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-29107376


Dengue infection is a public health problem with a complex distribution. The physical means of propagation and the dynamics of diffusion of the disease between municipalities need to be analysed to direct efficient public policies to prevent dengue infection. The present study presents correlations of occurrences of reported cases of dengue infection among municipalities, self-organized criticality (SOC), and transportation between areas, identifying the municipalities that play an important role in the diffusion of dengue across the state of Bahia, Brazil. The significant correlation found between the correlation network and the SOC demonstrates that the pattern of intramunicipal diffusion of dengue is coupled to the pattern of synchronisation between the municipalities. Transportation emerges as influential in the dynamics of diffusion of epidemics by acting on the aforementioned variables.

A young female presenting with unilateral sacroiliitis following dengue virus infection: a case report.

J Med Case Rep; 11(1): 307, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29089045


BACKGROUND: Dengue is a common arthropod-borne viral infection in Sri Lanka which is spread by the mosquitos of the genus Aedes. The clinical features of dengue include high-grade fever associated with arthralgia and myalgia. However, dengue virus is not considered an arthritogenic virus. We report a case of a previously healthy young female who presented with imaging-confirmed right-sided sacroiliitis 10 days after developing dengue fever. This is the first reported case that shows a possible link between dengue infection and development of arthritis. CASE PRESENTATION: A 14-year-old Sri Lankan female presented to our medical unit with right buttock and hip pain of 3 weeks' duration. She had serologically confirmed dengue infection 10 days prior to the onset of buttock pain. A clinical examination revealed features of right sacroiliitis. An X-ray of her sacroiliac joint showed joint space widening and reactive bone changes. Magnetic resonance imaging of her pelvis and sacroiliac joint confirmed the diagnosis of acute sacroiliitis. She had an erythrocyte sedimentation rate of 110 mm first hour with a normal C-reactive protein. Her human leukocyte antigen-B27, rheumatoid factor, antinuclear antibody, chikungunya antibody, hepatitis serology, Brucella serology, and tuberculin skin test were negative. She was treated with nonsteroidal anti-inflammatory drugs and showed gradual improvement. CONCLUSIONS: After excluding possible causes for sacroiliitis, we postulated that sacroiliitis in the index case could have been caused or triggered by dengue virus infection. However there is a possibility that the sacroiliitis merely coincided with the dengue virus infection. This case illustrates the possibility that dengue virus could have a link with the development of arthritis in the same manner as other arthritogenic viruses; possible mechanisms for this include direct invasion of the synovium and the joint tissue by the virus, immune complex formation and deposition in the joint tissue, and immune dysregulation. Further studies are needed in this field to gain more knowledge, as dengue infection is highly prevalent in Sri Lanka.

Involvement of caspase-4 in IL-1 beta production and pyroptosis in human macrophages during dengue virus infection.

Immunobiology; 2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-29113699


Caspase-4 physically interacts with caspase-1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin (IL)-1ß. However, the function of caspase-4 in dengue virus infection is not yet fully understood. We examined the function of caspase-4 in IL-1ß production and pyroptosis during dengue virus serotype-2 (DENV-2) infection in human macrophages. In this study, DENV-2 infection increased IL-1ß protein level with activated caspase-4 activity. Using primary macrophages, we observed that caspase-4 induces activation of caspase-1 and secretion of IL-1ß in response to DENV-2 infection, without the need for secondary signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by capsase-4 could represent a unique mechanism. Our data suggest that caspase-4 is upstream of caspase-1 in the pathway that regulates pyroptosis and IL-1ß synthesis in macrophages during DENV-2 infection.


Lancet; 390(10106): 1941, 2017 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-29115222

Specific detection of dengue and Zika virus antibodies using envelope proteins with mutations in the conserved fusion loop.

Emerg Microbes Infect; 6(11): e99, 2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29116222


Detection of antibodies is widely used for the diagnosis of infections with arthropod-borne flaviviruses including dengue (DENV) and Zika virus (ZIKV). Due to the emergence of ZIKV in areas endemic for DENV, massive co-circulation is observed and methods to specifically diagnose these infections and differentiate them from each other are mandatory. However, serological assays for flaviviruses in general, and for DENV and ZIKV in particular, are compromised by the high degree of similarities in their proteins which can lead to cross-reacting antibodies and false-positive test results. Cross-reacting flavivirus antibodies mainly target the highly conserved fusion loop (FL) domain in the viral envelope (E-) protein, and we and others have shown previously that recombinant E-proteins bearing FL-mutations strongly reduce cross-reactivity. Here we investigate whether such mutant E-proteins can be used to specifically detect antibodies against DENV and ZIKV in an ELISA-format. IgM antibodies against DENV and ZIKV virus were detected with 100% and 94.2% specificity and 90.7% and 87.5% sensitivity, respectively. For IgG the mutant E-proteins showed cross-reactivity, which was overcome by pre-incubation of the sera with the heterologous antigen. This resulted in specificities of 97.1% and 97.9% and in sensitivities of 100% and 100% for the DENV and ZIKV antigens, respectively. Our results suggest that E-proteins bearing mutations in the FL-domain have a high potential for the development of serological DENV and ZIKV tests with high specificity.

Dengue vaccine supplies under endemic and epidemic conditions in three dengue-endemic countries: Colombia, Thailand, and Vietnam.

Vaccine; 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29110932


BACKGROUND: Dengue fever has been a major public health concern in Colombia, Thailand, and Vietnam. Unlike other infectious diseases, dengue vaccines had not been available for a long time, causing difficulties to control the disease. However, the first live attenuated, tetravalent dengue vaccine (CYD-TDV) became available in 2016 and has been already licensed in some dengue-endemic countries. Because several second-generation dengue vaccines are also in the pipeline, it is critical to understand the efficient allocation of dengue vaccines considering the geographical variation of the disease. METHODS: The Climate Risk Factor (CRF) index was created using the climate and non-climate factors in the three countries. A random-coefficient negative binomial model was chosen to validate the relationship between the CRF index and dengue incidence proxy. Given the statistical significance of the CRF index, high risk areas for dengue fever were identified at the 5 km by 5 km resolution and used to estimate vaccination coverage rates and the number of doses required for various types of vaccination scenarios by country. RESULTS AND CONCLUSIONS: Based upon a three-dose scheme, the estimated number of vaccines required for routine vaccination targeting 9 years old ranged from 1 to 2.6 million doses across the countries during the first year of introduction. A one-off catch-up campaign targeting the age group of 10-17 year olds would require 8 to 18 million additional doses. Routine vaccination (with or without a catch-up campaign) covered 63%, 90%, and 91% of the targeted age group populations in Colombia, Thailand, and Vietnam respectively. Given that many dengue-endemic countries face limited resources and that the costs for mass vaccination campaigns may not be trivial, the findings of this study can guide the decision makers in the three countries regarding the efficient distribution of vaccines by identifying populations at high risk at 5 km by 5 km resolution.

Asymptomatic dengue infection in adults of major cities of Pakistan.

Asian Pac J Trop Med; 10(10): 1002-1006, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29111183


OBJECTIVE: To determine the asymptomatic dengue infection in adults of Pakistani population. METHODS: This study was conducted in five major cities (Islamabad, Karachi, Lahore, Multan, and Peshawar) of Pakistan. A total of 5 230 adults aged 18 years and above without a history of dengue fever at any point in their life were enrolled from participating laboratories. Those who were confirmed for dengue previously were excluded. Of the total, 62.6% (n = 3 276) were male with an average age of 34.6 years. Participants were briefed about the objectives of the study, and written consent was obtained to perform dengue IgG test using enzyme linked immunosorbent assay. The brief information related to age, gender and area was also taken on proforma. RESULTS: Overall 32.3% (n = 1 691) was having asymptomatic dengue infection which was 67.5% (n = 756) in Karachi followed by 39.1% (n = 391) in Islamabad, 29.9% (n = 316) in Lahore and 21% (n = 228) in Peshawar and none from Multan. More males were affected with asymptomatic dengue infection than females. The asymptomatic dengue infection was significantly higher in different cities; however, there was no significant difference with respect to age groups. CONCLUSIONS: The asymptomatic dengue infection is higher in cities i.e. Karachi, Islamabad and Lahore which are at risk of developing secondary dengue infections. There is a need of awareness among the public about secondary dengue infection.
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