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1.
Pac Symp Biocomput ; 25: 487-498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31797621

RESUMO

Flaviviruses such as dengue encode a protease that is essential for viral replication. The protease functions by cleaving well-conserved positions in the viral polyprotein. In addition to the viral polyprotein, the dengue protease cleaves at least one host protein involved in immune response. This raises the question, what other host proteins are targeted and cleaved? Here we present a new computational method for identifying putative host protein targets of the dengue virus protease. Our method relies on biochemical and secondary structure features at the known cleavage sites in the viral polyprotein in a two-stage classification process to identify putative cleavage targets. The accuracy of our predictions scaled inversely with evolutionary distance when we applied it to the known cleavage sites of several other flaviviruses-a good indication of the validity of our predictions. Ultimately, our classifier identified 257 human protein sites possessing both a similar target motif and accessible local structure. These proteins are promising candidates for further investigation. As the number of viral sequences expands, our method could be adopted to predict host targets of other flaviviruses.

2.
J Environ Manage ; 253: 109748, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678687

RESUMO

On November 2015, the Fundão Tailings Dam, located at Mariana municipality in Brazil, failed. Besides the deaths and injuries, economic losses, pollution and health problems associated to heavy metals in the water, Brazilian municipalities near the accident experienced an increase in the incidence of dengue. Since dengue fever is an insect-borne disease and the mosquito develops where there is stored water, there must be a relationship between the dam accident and the incidence of the disease. The purpose of this study is to test whether there is a causal relationship between the dam accident in Mariana and the number of dengue cases, number of hospitalizations due to dengue, and dengue outbreak in the municipalities affected by the accident. We find evidence that the accident had a positive and statistically significant impact on dengue indicators (for example, the probability of a dengue outbreak increased in 19%), what makes us call attention to another negative externality of tailings dam accidents.


Assuntos
Dengue , Acidentes , Animais , Brasil , Cidades , Incidência
3.
Acta Trop ; 201: 105201, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562846

RESUMO

Zika virus (ZIKV) is a mosquito-borne flavivirus that has caused recent large outbreaks in the Americas. Given its association with severe congenital defects including microcephaly, distinguishing infections caused by ZIKV from those caused by dengue virus (DENV) is of primordial importance. The objectives of this study were to evaluate the recombinant proteins rEIII-ZIKV (Envelope protein domain III) and rNS1ß-leader-ZIKV (non-structural protein 1) for the serological diagnosis of ZIKV in the Mexican population. We also evaluated potential cross-reactivity in commercial enzyme-linked immunosorbent assays (ELISA) based on the ZIKV NS1 and DENV NS1 proteins. rEIII-ZIKV and rNS1ß-leader-ZIKV proteins were tested with sera from 30 PCR-confirmed ZIKV cases, 50 ZIKV-naive, DENV-exposed subjects with no acute febrile disease, (asymptomatic subjects, AS), and 50 ZIKV-naive and DENV naive AS. Commercial ELISA tests were evaluated with sera from 57 ZIKV and 20 DENV PCR-confirmed cases, and 50 ZIKV-naive, DENV-exposed AS. In-house ELISA assays showed that IgM antibody levels against rEIII-ZIKV and rNS1ß-ZIKV were higher in ZIKV naive, DENV-exposed AS than in acutely infected ZIKV individuals. IgG reactivity was highest for rEIII-ZIKV, and indistinguishable between acutely infected ZIKV cases and DENV exposed AS. Positivity for the Euroimmun Zika IgM assay at 7-10 days was considerably higher in DENV-naive ZIKV patients (86%) than in DENV-exposed ZIKV patients (33%), while 39% of the latter had false-negative anti-ZIKV IgG before 7 days of onset. DENV-exposed ZIKV patients presented lower anti-ZIKV IgM and higher IgG responses similar to a secondary dengue response. Forty-four percent of DENV- exposed acute ZIKV patients were DENV IgM positive with the Panbio Dengue assay, and two (15%) of the DENV-naive ZIKV patients presented false DENV IgG conversion. Given the extensive cross-reactivity to both the NS1 and EDIII proteins in current serological methods, the development of sensitive and specific serological tests to distinguish ZIKV from DENV infections is an urgent priority.

4.
J Theor Biol ; 484: 110014, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31557473

RESUMO

Superinfection exclusion is a phenomenon whereby the co-infection of a host with a secondary pathogen is prevented due to a current infection by another closely-related pathogenic strain. We construct a novel vector-host mathematical model for two pathogens that exhibit superinfection exclusion and simultaneously account for vaccination strategies against them. We then derive the conditions under which an endemic disease will prevent the establishment of another through the action of superinfection exclusion and show that vaccination against the endemic strain can enable the previously suppressed strain to invade the population. Through appropriate parameterisation of the model for dengue and yellow fever we find that superinfection exclusion alone is unlikely to explain the absence of yellow fever in many regions where dengue is endemic, and that the rollout of the recently licensed dengue vaccine, Dengvaxia, is unlikely to enable the establishment of Yellow Fever in regions where it has previously been absent.

5.
J Virol Methods ; : 113793, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794781

RESUMO

Dengue fever is a highly endemic arthropod-borne viral disease in the tropical and sub-tropical countries and is rapidly becoming a global threaten. Diagnosis has been conducted by either traditional serological methods or molecular biological techniques. However, these methods are either labor-intensive, time-consuming or with multiple steps, which are not suitable for high throughput detection of large quantity of samples. In the current study, a novel, rapid, no-wash one-step amplified luminescent proximity homogenous assay-linked immunosorbent assay (AlphaLISA) was developed and optimized for the diagnosis of dengue fever through the detection of dengue virus non-structural protein 1 (NS1). The linear range of the assay was determined to be 60,000 pg/mL to 200 pg/mL, with a lower detection limit of 127.45 pg/mL for NS1 protein. The precision of the assay was 8.24% and 4.93% for the high and low concentration. Clinical evaluation indicated that the sensitivity and specificity of the assay was 91.49% and 81.54%, respectively. This novel, rapid, no-wash one-step AlphaLISA assay is convenient and sensitive, which could be a good alternative for the screening of dengue fever in a high throughput format.

6.
PLoS Pathog ; 15(12): e1008218, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790509

RESUMO

Dengue virus (DENV) transmission by mosquitoes is a time-dependent process that begins with the consumption of an infectious blood-meal. DENV infection then proceeds stepwise through the mosquito from the midgut to the carcass, and ultimately to the salivary glands, where it is secreted into saliva and then transmitted anew on a subsequent bite. We examined viral kinetics in tissues of the Aedes aegypti mosquito over a finely graded time course, and as per previous studies, found that initial viral dose and serotype strain diversity control infectivity. We also found that a threshold level of virus is required to establish body-wide infections and that replication kinetics in the early and intermediate tissues do not predict those of the salivary glands. Our findings have implications for mosquito GMO design, modeling the contribution of transmission to vector competence and the role of mosquito kinetics in the overall DENV epidemiological landscape.

7.
PLoS One ; 14(12): e0225193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800583

RESUMO

With approximately half of the world's population at risk of contracting dengue, this mosquito-borne disease is of global concern. International travellers significantly contribute to dengue's rapid and large-scale spread by importing the disease from endemic into non-endemic countries. To prevent future outbreaks and dengue from establishing in non-endemic countries, knowledge about the arrival time and location of infected travellers is crucial. We propose a network model that predicts the monthly number of dengue-infected air passengers arriving at any given airport. We consider international air travel volumes to construct weighted networks, representing passenger flows between airports. We further calculate the probability of passengers, who travel through the international air transport network, being infected with dengue. The probability of being infected depends on the destination, duration and timing of travel. Our findings shed light onto dengue importation routes and reveal country-specific reporting rates that have been until now largely unknown. This paper provides important new knowledge about the spreading dynamics of dengue that is highly beneficial for public health authorities to strategically allocate the often limited resources to more efficiently prevent the spread of dengue.

8.
Infectio ; 23(4): 352-356, Dec. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-1040005

RESUMO

Resumen Objetivo: describir la distribución espacial y temporal de los virus del dengue, zika y Chikungunya en Colombia e identificar si existe agregación espacial, temporal y espacio-temporal. Métodos: se desarrolló un estudio descriptivo de la distribución espacial y temporal de los virus del Dengue (2006-2017), Zika (2015-2017) y Chikungunya (2014-2017) en Colombia, utilizando los principios de la estadística espacial, específicamente en el análisis exploratorio de datos espaciales. Resultados: se identificaron zonas de Colombia donde se presenta una mayor densidad y prevalencia de casos. A partir de los 1124 municipios analizados para cada evento (casos de Dengue, Zika y Chikungunya), se comprobó con significancia estadística (p<0.05) la existencia de dos conglomerados espacio-temporales, en la zona sur-occidental de la región andina y en la región de la Orinoquia. Conclusiones: Se demostró la existencia de dos conglomerados para los eventos Dengue, Zika y Chikungunya que podría establecerse como zonas de mayor riesgo de co-infección.


Abstract Objective: to describe the spatial and temporal distribution of dengue, zika and Chikungunya viruses in Colombia and to identify clusters at spatial, temporal and space-temporal levels. Methods: A descriptive study was developed about the space and time distribution of the Dengue virus (2006-2017), Zika (2015-2017) and Chikungunya (2014-2017) in Colombia, using principles of spatial statistics, namely the spatial data exploratory analysis. Results: Areas of Colombia were identified where there is a higher density and prevalence of cases and were analyzed 1124 municipalities for each event (cases of Dengue, Zika and Chikungunya). Significant clusters (P<0.05) were proven in spatial, temporal and space-temporal analysis, in the south-western zone of the Andean region and in the Orinoquia region. Conclusions: Two conglomerates were confirmed for the Dengue, Zika and Chikungunya events, that could be established as areas of higher risk of co-infection.

9.
Jpn J Infect Dis ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31787738

RESUMO

Dengue is one of the most serious mosquito-borne viral diseases occurring in humans. From their complexity of 4 serotypes, the ideal vaccine for dengue should be able to stimulate cross-neutralizing antibodies. Recently, genetic-based immune response have been studied for guiding of vaccine design for several viral pathogens. Despite a recent approval of dengue vaccine, the information of genetics-based immune response against dengue virus (DENV) are still limited. Consequently, we aimed to determine the profiles of immunoglobulin heavy chain gene from DENV2 infected patients. The immunoglobulin heavy chain variable region genes (IGHV) were amplified from peripheral blood mononuclear cells of DENV2 secondary infected patients over the acute, convalescence and recovery phases. Antibody heavy chain genes were sequenced by next-generation sequencing (NGS), and analyzed to identify correlations with neutralizing and enhancing activities of the serum samples. IGHV1-69, 3-23, and 3-30 were frequently discovered in our Thai DENV2 infected patients. Our findings provided the new data on the human B cell response during secondary DENV2 infections in Thai dengue patients that provide a supportive information for dengue vaccine design and therapeutics development.

10.
Sci Rep ; 9(1): 17926, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784616

RESUMO

Dengue is an important arboviral infection, causing a broad range symptom that varies from life-threatening mild illness to severe clinical manifestations. Recent studies reported the impairment of the central nervous system (CNS) after dengue infection, a characteristic previously considered as atypical and underreported. However, little is known about the neuropathology associated to dengue. Since animal models are important tools for helping to understand the dengue pathogenesis, including neurological damages, the aim of this work was to investigate the effects of intracerebral inoculation of a neuroadapted dengue serotype 2 virus (DENV2) in immunocompetent BALB/c mice, mimicking some aspects of the viral encephalitis. Mice presented neurological morbidity after the 7th day post infection. At the same time, histopathological analysis revealed that DENV2 led to damages in the CNS, such as hemorrhage, reactive gliosis, hyperplastic and hypertrophied microglia, astrocyte proliferation, Purkinje neurons retraction and cellular infiltration around vessels in the pia mater and in neuropil. Viral tropism and replication were detected in resident cells of the brain and cerebellum, such as neurons, astrocyte, microglia and oligodendrocytes. Results suggest that this classical mice model might be useful for analyzing the neurotropic effect of DENV with similarities to what occurs in human.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31784763

RESUMO

Dengue, the most common arbovirus, represents an increasingly significant cause of morbidity worldwide, including in travelers. After decades of research, the first dengue vaccine was licensed in 2015: CYD-TDV, a tetravalent live attenuated vaccine with a yellow fever vaccine backbone. Recent analyses have shown that vaccine performance is dependent on serostatus. In those who have had a previous dengue infection, i.e., who are seropositive, the efficacy is high and the vaccine is safe. However, in seronegative vaccinees, approximately 3 years after vaccination the vaccine increases the risk of developing severe dengue when the individual experiences a natural dengue infection.The World Health Organization recommends that this vaccine be administered only to seropositive individuals. Current efforts are underway to develop rapid diagnostic tests to facilitate prevaccination screening. Two second-generation dengue vaccine candidates, both also live attenuated recombinant vaccines in late-stage development, may not present the same limitations because of differences in the backbone used, but results of phase 3 trials need to be available before firm conclusions can be drawn.Dengue is increasingly frequent in travelers, but the only licensed dengue vaccine to date can be used only in seropositive individuals. However, the vast majority of travelers are seronegative. Furthermore, the primary series of three doses given 6 months apart renders this vaccine difficult in the travel medicine context.

12.
J Med Virol ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31784997

RESUMO

Dengue virus is an arbovirus belonging to class Flaviviridae. Its clinical manifestation ranges from asymptomatic to extreme conditions (DHF/DSS). A lot of research has been done on this ailment yet there is not any effective treatment available for the disease. This review provides the systematic understanding of all dengue proteins, role of its structural proteins (C-protein, E-protein, prM) in virus entry, assembly and secretion in host cell, and non-structural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b and NS5) in viral assembly, replication and immune evasion during dengue progression and pathogenesis. Furthermore, the review has highlighted the controversies related to only commercially available dengue vaccine i.e. dengvaxia and risk associated with it. Lastly, it provides an insight regarding various approaches for developing an effective anti-dengue treatment. This article is protected by copyright. All rights reserved.

13.
Trends Immunol ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31791719

RESUMO

A recent article by Sung et al. identified the CLEC2 platelet receptor as an important factor of lethal dengue virus infection. Formation of neutrophil extracellular traps via crosstalk with CLEC5A and TLR2 neutrophils were ascribed a causative role in DENV infection. This provides new insights for the development of candidate broad-spectrum therapies against hemorrhagic virus infections.

15.
J Biol Dyn ; 13(1): 1-25, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31793412

RESUMO

In this paper, we establish a mathematical model with two delays to reflect the intrinsic and extrinsic incubation periods of virus in dengue transmission. The basic reproduction number [Formula: see text] of the model is defined. It is proved that the disease-free equilibrium is stable when [Formula: see text] and the positive equilibrium is stable when [Formula: see text]. Next, we derive an estimation formula for the reproduction number [Formula: see text] when the human population is partially susceptible to dengue. As an application, the [Formula: see text] values of dengue transmission in Singapore in the years 2013-2015 are estimated. Our estimation method can be applied to estimating [Formula: see text] of other infectious diseases, especially when the human population is not completely susceptible to the disease.

16.
Cad Saude Publica ; 35(12): e00248118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800796

RESUMO

Dengue is a re-emerging arbovirus infection of major epidemiological importance. The detection of dengue clusters is an important epidemiological surveillance strategy, contributing to better allocation of control measures and prioritizing areas that are subject to increased risk of transmission. Studies involving human populations with low mobility are scarce, and the current study thus aims to investigate the presence of persistent dengue clusters in the city of Rio de Janeiro, Brazil, in populations with different mobility and immunity. Epidemiological data on dengue were obtained from the Brazilian Ministry of Health. Areas of increased risk were defined by the space-time scan statistical method and analysis of persistence with use of map algebra. For both study populations, the clusters that were identified did not show spatial concordance, except in years when both presented the same immunological profile. Their persistent clusters were located mostly in the West Zone of city. The clusters of the two study populations only displayed spatial concordance in years with similar immune profiles, which confirms the confounding role of immunity and supports the use of populations with high percentages of susceptible individuals when designing territory-based dengue studies. The space-time similarity between the areas of persistent risk in both populations suggests that the West Zone, a region with disorderly urban growth and low mean income, shows the highest risk of dengue transmission. The definition of persistent dengue clusters contributes to the improvement of dengue control strategies and territorial planning.

18.
Phytother Res ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802573

RESUMO

Dengue, a mosquito-borne viral disease, causes about 100 million cases of infection annually. It is a major public concern, and if left untreated or improperly diagnosed, may cause serious health problems or even death. Historically, dengue has not considered priorities for pharmaceutical companies made the available treatment options. Therefore, medicinal scientists are revealing new insights and enabling novel interventions and approaches to dengue prevention and control. Diterpenes, a class of terpenes have gained much attention due to their diverse biological effects. This review aimed at summarizing available evidences of diterpenes and their derivatives acting against dengue virus and their vectors. For this, an updated search was made in the databases: PubMed and ScienceDirect by using specific keywords. Among the 117 published reports, a total of 30 articles was included in this review. Findings suggest that a number of diterpenes and/or their derivatives act against dengue virus and their two potential vectors namely Aedes aegypti and Ae. albopictus. In conclusion, diterpenes and their derivatives may have the potential alternative therapeutic tools for the management of dengue virus and some associated diseases transmitted by Aedes mosquito.

19.
J Infect Dis ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755526

RESUMO

Dengue is a global health problem requiring an effective, safe dengue vaccine. We report the results of a phase II, randomized, open-label, single center trial in adults aged 18 to 45 years in the United States designed to explore the effects of the Chimeric Yellow Fever-Derived Tetravalent Dengue Vaccine (CYD-TDV, Dengvaxia) when administered on its designated schedule (months 0, 6 and 12) or on an accelerated dosing schedule (months 0, 2 and 6) and/or given prior to, or concomitantly with, a vaccine against Japanese Encephalitis (JE). Based on DENV serotype-specific neutralizing antibody (NAb), the accelerated dosing schedule was comparable to the 0, 6, and 12-month schedule. Giving JE vaccine concurrently with CYD-TDV did not result in an increase in overall NAb titers. Immunophenotyping of peripheral blood mononuclear cells (PBMCs) revealed an increase in activated CD8+ T cells after CYD-TDV vaccination, a phenomenon which was greatest for the JE vaccine primed. We conclude that an accelerated dosing schedule of CYD-TDV results in essentially equivalent dengue serotype-specific NAb titers as the currently used schedule and there may be an early benefit in antibody titers and activated CD8+ T cells by the administration of the JE vaccine prior to CYD-TDV vaccination. (Trial Registered at ClinicalTrials.gov: NCT01943825).

20.
Vaccine ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31706812

RESUMO

Efforts to develop a safe, effective, and affordable dengue vaccine have focused on providing simultaneous immunity against all four serotypes of the dengue virus (DENV). In the current study, Salmonella Typhimurium (ST) lysed by gene E activation was genetically constructed to deliver the envelope protein domain III (EDIII) of all four serotypes of DENV using a foreign antigen delivery and expression vector, pJHL184. Each DENV-EDIII protein expressed in the constructed strain was validated by immunoblot analysis. To assess the immunogenicity and protective efficacy of the constructs against dengue infection, BALB/c mice were injected once orally with either the individual ST-EDIII constructs or a mix of all four ST-EDIII constructs followed by intramuscular administration of the purified EDIII protein. Significantly elevated titers of EDIII-specific IgG, IgG1, and IgG2a were observed in the immunized mice (P < 0.01). Furthermore, lymphocyte proliferative activity and CD3+CD4+ T-cell subpopulations increased significantly in vitro in re-pulsed splenic T cells compared with those from non-immunized mice. In addition, a lower viral load was detected in the BG-EDIII vaccinated group after challenge with DENV-infected K562 cells. Collectively, the results demonstrate that DENV-EDIII expressed in the inactivated ST strain could induce robust humoral and cell-mediated immunity specific to the target antigen and could provide significant protective potential.

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