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1.
Mem Inst Oswaldo Cruz ; 115: e200278, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33566939

RESUMEN

BACKGROUND: The impact of arbovirus cocirculation in Brazil is unknown. Dengue virus (DENV) reinfection may result in more intense viraemia or immunopathology, leading to more severe disease. The Zika virus (ZIKV) epidemic in the Americas provided pathogenicity evidence that had not been previously observed in flavivirus infections. In contrast to other flaviviruses, electron microscopy studies have shown that ZIKV may replicate in viroplasm-like structures. Flaviviruses produce an ensemble of structurally different virions, collectively contributing to tissue tropism and virus dissemination. OBJECTIVES AND METHODS: In this work, the Aedes albopictus mosquito cell lineage (C6/36 cells) and kidney epithelial cells from African green monkeys (Vero cells) were infected with samples of the main circulating arboviruses in Brazil [DENV-1, DENV-2, DENV-3, DENV-4, ZIKV, Yellow Fever virus (YFV) and Chikungunya virus (CHIKV)], and ultrastructural studies by transmission electron microscopy were performed. FINDINGS: We observed that ZIKV, the DENV serotypes, YFV and CHIKV particles are spherical. ZIKV, DENV-1, -2, -3 and -4 presented diameters of 40-50 nm, and CHIKV presented approximate diameters of 50-60 nm. Viroplasm-like structures was observed in ZIKV replication cycle. MAIN CONCLUSIONS: The morphogenesis of these arboviruses is similar to what has been presented in previous studies. However, we understand that further studies are needed to investigate the relationship between viroplasm-like structures and ZIKV replication dynamics.


Asunto(s)
Arbovirus , Fiebre Chikungunya , Dengue , Epidemias , Fiebre Amarilla , Infección por el Virus Zika , Virus Zika , Animales , Brasil/epidemiología , Fiebre Chikungunya/epidemiología , Chlorocebus aethiops , Dengue/epidemiología , Células Vero , Infección por el Virus Zika/epidemiología
2.
Rev Soc Bras Med Trop ; 54: e05192020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33533817

RESUMEN

INTRODUCTION: Dengue presents with a variable clinical course, ranging from mild illness to potentially fatal hemorrhage and shock. We aimed to evaluate the capabilities of various hematological parameters observed early in the course of illness for predicting the clinical outcomes of illness. METHODS: We retrospectively analyzed the records of children admitted in the pediatric inpatient services of the institute with dengue between 2017 and 2019. We determined the relationships between the hematological parameters observed during the first evaluation and the various clinical outcomes. RESULTS: We evaluated data from 613 patients (age range, 26 days to 17 years). Of these, 29.85% exhibited fever with warning signs, and 8.97% had severe dengue. Lower values of hemoglobin, platelet count, mean corpuscular volume, mean corpuscular hemoglobin concentration, and mean platelet volume, and higher values of total leukocyte count (TLC), hematocrit, and red cell distribution width variably correlated with numerous clinical outcomes-duration of hospital stay, development of complications, requirement of blood component transfusion, inotropic support, and mortality. Among the parameters, TLC ≥20,000/mL and initial platelet count ≤20,000/mL significantly associated with mortality, with odds ratios (95% confidence interval) of 11.81 (4.21-33.80) and 5.53 (1.90-16.09), respectively. CONCLUSIONS: Hematological parameters observed early during dengue infection may predict its clinical outcomes in infected children. Initial high TLC and low platelet count are potential predictors of fatal outcomes in the course of disease.


Asunto(s)
Dengue , Dengue Grave , Adulto , Niño , Dengue/diagnóstico , Hematócrito , Humanos , India/epidemiología , Recuento de Leucocitos , Estudios Retrospectivos , Dengue Grave/diagnóstico
3.
Mem Inst Oswaldo Cruz ; 115: e200287, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33533869

RESUMEN

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


Asunto(s)
Antígenos Virales/sangre , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Pruebas Inmunológicas/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas no Estructurales Virales/inmunología , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Dengue/sangre , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/inmunología , Humanos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Proteínas no Estructurales Virales/genética
4.
Recurso de Internet en Portugués | LIS - Localizador de Información en Salud | ID: lis-48013

RESUMEN

A estação mais quente do ano também é conhecida pela intensa propagação de vírus transmitidos pelo mosquito Aedes aegypti, como dengue, zika e chikungunya


Asunto(s)
Aedes , Dengue , Virus Zika
5.
Science ; 371(6525): 194-200, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414220

RESUMEN

Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal structures of full-length dengue virus NS1 complexed with a flavivirus-cross-reactive, NS1-specific monoclonal antibody, 2B7, at resolutions between 2.89 and 3.96 angstroms. These structures reveal a protective mechanism by which two domains of NS1 are antagonized simultaneously. The NS1 wing domain mediates cell binding, whereas the ß-ladder triggers downstream events, both of which are required for dengue, Zika, and West Nile virus NS1-mediated endothelial dysfunction. These observations provide a mechanistic explanation for 2B7 protection against NS1-induced pathology and demonstrate the potential of one antibody to treat infections by multiple flaviviruses.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas , Cristalografía por Rayos X , Dengue/prevención & control , Dengue/terapia , Endotelio/inmunología , Glicocálix/inmunología , Humanos , Ratones , Conformación Proteica en Lámina beta , Dominios Proteicos , Proteínas no Estructurales Virales/química , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
7.
BMC Infect Dis ; 21(1): 96, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33478432

RESUMEN

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


Asunto(s)
Anticuerpos Antivirales/sangre , Virus del Dengue/inmunología , Dengue/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Dengue/sangre , Virus del Dengue/aislamiento & purificación , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estudios Seroepidemiológicos , Taiwán/epidemiología , Adulto Joven
8.
BMC Infect Dis ; 21(1): 104, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482756

RESUMEN

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


Asunto(s)
Donantes de Sangre , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Dengue/epidemiología , Tamizaje Masivo/métodos , Adulto , Anticuerpos Antivirales/sangre , China/epidemiología , Dengue/sangre , Virus del Dengue/genética , Virus del Dengue/inmunología , Femenino , Humanos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Prevalencia , ARN Viral/genética , Proteínas no Estructurales Virales/genética , Adulto Joven
9.
Med Sci Monit Basic Res ; 27: e929207, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33397841

RESUMEN

As of November 25, 2020, over 60 million people have been infected worldwide by COVID-19, causing almost 1.43 million deaths. Puzzling low incidence numbers and milder, non-fatal disease have been observed in Thailand and its Southeast (SE) Asian neighbors. Elusive genetic mechanisms might be operative, as a multitude of genetic factors are widely shared between the SE Asian populations, such as the more than 60 different thalassemia syndromes (principally dominated by the HbE trait). In this study, we have plotted COVID-19 infection and death rates in SE Asian (SEA) countries against heterozygote HbE and thalassemia carrier prevalence. COVID-19 infection and death incidence numbers appear inversely correlated with the prevalence of HbE and thalassemia heterozygote populations. We posit that the evolutionary protective effect of the HbE and other thalassemic variants against malaria and the dengue virus may extend its advantage to resistance to COVID-19 infection, as HbE heterozygote population prevalence appears to be positively correlated with immunity to COVID-19. Host immune system modulations induce antiviral interferon responses and alter structural protein integrity, thereby inhibiting cellular access and viral replication. These changes are possibly engendered by HbE carrier miRNAs. Proving this hypothesis is important, as it may shed light on the mechanism of viral resistance and lead to novel antiviral treatments. This development can thus guide decision-making and action to prevent COVID-19 infection.


Asunto(s)
/genética , Resistencia a la Enfermedad/genética , Susceptibilidad a Enfermedades , Hemoglobina E/genética , Antivirales/uso terapéutico , Grupo de Ascendencia Continental Asiática , /inmunología , Dengue/genética , Heterocigoto , Humanos , Sistema Inmunológico , Interferones , Malaria/genética , Pandemias , Prevalencia , Tailandia/epidemiología , Talasemia/epidemiología , Talasemia/genética
10.
PLoS One ; 16(1): e0244937, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33406122

RESUMEN

BACKGROUND: The impact of SARS-CoV-2 in regions endemic for both Dengue and Chikungunya is still not fully understood. Considering that symptoms/clinical features displayed during Dengue, Chikungunya and SARS-CoV-2 acute infections are similar, undiagnosed cases of SARS-CoV-2 in co-endemic areas may be more prevalent than expected. This study was conducted to assess the prevalence of covert cases of SARS-CoV-2 among samples from patients with clinical symptoms compatible with either Dengue or Chikungunya viral infection in the state of Espírito Santo, Brazil. METHODS: Presence of immunoglobulin G (IgG) antibody specific to SARS-CoV-2 nucleoprotein was detected using a chemiluminescent microparticle immunoassay in samples from 7,370 patients, without previous history of COVID-19 diagnosis, suspected of having either Dengue (n = 1,700) or Chikungunya (n = 7,349) from December 1st, 2019 to June 30th, 2020. FINDINGS: Covert cases of SARS-CoV-2 were detected in 210 (2.85%) out of the 7,370 serum samples tested. The earliest undiagnosed missed case of COVID-19 dated back to a sample collected on December 18, 2019, also positive for Dengue Virus. Cross-reactivity with either Dengue virus or other common coronaviruses were not observed. INTERPRETATION: Our findings demonstrate that concomitant Dengue or Chikungunya outbreaks may difficult the diagnosis of SARS-CoV-2 infections. To our knowledge, this is the first study to demonstrate, with a robust sample size (n = 7,370) and using highly specific and sensitive chemiluminescent microparticle immunoassay method, that covert SARS-CoV-2 infections are more frequent than previously expected in Dengue and Chikungunya hyperendemic regions. Moreover, our results suggest that SAR-CoV-2 cases were occurring prior to February, 2020, and that these undiagnosed missed cases may have contributed to the fast expansion of SARS-CoV-2 outbreak in Brazil. Data presented here demonstrate that in arboviral endemic regions, SARS-CoV-2 infection must be always considered, regardless of the existence of a previous positive diagnosis for Dengue or Chikungunya.


Asunto(s)
/epidemiología , Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Adulto , Anticuerpos Antivirales/sangre , Brasil/epidemiología , Virus Chikungunya/patogenicidad , Coinfección/epidemiología , Virus del Dengue/patogenicidad , Errores Diagnósticos/tendencias , Brotes de Enfermedades , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Prevalencia , /patogenicidad
11.
Nat Commun ; 12(1): 151, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33420058

RESUMEN

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


Asunto(s)
Fiebre Chikungunya/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Dengue/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Enfermedades Endémicas/estadística & datos numéricos , Infección por el Virus Zika/epidemiología , Adolescente , Aedes/virología , Animales , Fiebre Chikungunya/prevención & control , Fiebre Chikungunya/transmisión , Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/transmisión , Enfermedades Transmisibles Emergentes/virología , Dengue/prevención & control , Dengue/transmisión , Dengue/virología , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades/prevención & control , República Dominicana/epidemiología , Enfermedades Endémicas/prevención & control , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Control de Mosquitos , Mosquitos Vectores/virología , Análisis Espacio-Temporal , Adulto Joven , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virología
12.
Parasit Vectors ; 14(1): 22, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407778

RESUMEN

BACKGROUND: Due to an increase in mosquito habitats and the lack facilities to carry out basic mosquito control, construction sites in China are more likely to experience secondary dengue fever infection after importation of an initial infection, which may then increase the number of infections in the neighboring communities and the chance of community transmission. The aim of this study was to investigate how to effectively reduce the transmission of dengue fever at construction sites and the neighboring communities. METHODS: The Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model of human and SEI model of mosquitoes were developed to estimate the transmission of dengue virus between humans and mosquitoes within the construction site and within a neighboring community, as well between each of these. With the calibrated model, we further estimated the effectiveness of different intervention scenarios targeting at reducing the transmissibility at different locations (i.e. construction sites and community) with the total attack rate (TAR) and the duration of the outbreak (DO). RESULTS: A total of 102 construction site-related and 131 community-related cases of dengue fever were reported in our area of study. Without intervention, the number of cases related to the construction site and the community rose to 156 (TAR: 31.25%) and 10,796 (TAR: 21.59%), respectively. When the transmission route from mosquitoes to humans in the community was cut off, the number of community cases decreased to a minimum of 33 compared with other simulated scenarios (TAR: 0.068%, DO: 60 days). If the transmission route from infectious mosquitoes in the community and that from the construction site to susceptible people on the site were cut off at the same time, the number of cases on the construction site dropped to a minimum of 74 (TAR: 14.88%, DO: 66 days). CONCLUSIONS: To control the outbreak of dengue fever effectively on both the construction site and in the community, interventions needed to be made both within the community and from the community to the construction site. If interventions only took place within the construction site, the number of cases on the construction site would not be reduced. Also, interventions implemented only within the construction site or between the construction site and the community would not lead to a reduction in the number of cases in the community.


Asunto(s)
Dengue/prevención & control , Dengue/transmisión , Infecciones Asintomáticas/epidemiología , China/epidemiología , Control de Enfermedades Transmisibles , Industria de la Construcción , Dengue/epidemiología , Dengue/virología , Virus del Dengue/fisiología , Brotes de Enfermedades/prevención & control , Susceptibilidad a Enfermedades/epidemiología , Susceptibilidad a Enfermedades/virología , Humanos , Incidencia , Modelos Teóricos , Control de Mosquitos , Mosquitos Vectores/crecimiento & desarrollo , Mosquitos Vectores/virología , Características de la Residencia , Lugar de Trabajo
13.
Artículo en Inglés | MEDLINE | ID: mdl-33466497

RESUMEN

Bhutan experienced its largest and first nation-wide dengue epidemic in 2019. The cases in 2019 were greater than the total number of cases in all the previous years. This study aimed to characterize the spatiotemporal patterns and effective reproduction number of this explosive epidemic. Weekly notified dengue cases were extracted from the National Early Warning, Alert, Response and Surveillance (NEWARS) database to describe the spatial and temporal patterns of the epidemic. The time-varying, temperature-adjusted cohort effective reproduction number was estimated over the course of the epidemic. The dengue epidemic occurred between 29 April and 8 December 2019 over 32 weeks, and included 5935 cases. During the epidemic, dengue expanded from six to 44 subdistricts. The effective reproduction number was <3 for most of the epidemic period, except for a ≈1 month period of explosive growth, coinciding with the monsoon season and school vacations, when the effective reproduction number peaked >30 and after which the effective reproduction number declined steadily. Interventions were only initiated 6 weeks after the end of the period of explosive growth. This finding highlights the need to reinforce the national preparedness plan for outbreak response, and to enable the early detection of cases and timely response.


Asunto(s)
Dengue , Epidemias , Número Básico de Reproducción , Bután/epidemiología , Dengue/epidemiología , Humanos
14.
Arch Virol ; 166(3): 863-870, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33495898

RESUMEN

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


Asunto(s)
Proteínas de la Cápside/genética , Virus del Dengue/genética , Dengue/epidemiología , Proteínas del Envoltorio Viral/genética , Secuencia de Aminoácidos , China/epidemiología , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades , Genotipo , Humanos , Epidemiología Molecular , Filogenia , ARN Viral/genética , Alineación de Secuencia , Análisis de Secuencia de ARN , Serogrupo
15.
Science ; 371(6525): 190-194, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414219

RESUMEN

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Células CHO , Línea Celular , Cricetulus , Reacciones Cruzadas , Dengue/prevención & control , Dengue/terapia , Modelos Animales de Enfermedad , Humanos , Ratones , Dominios Proteicos , Proteínas no Estructurales Virales/química , Viremia/terapia , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
16.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33431469

RESUMEN

Bilateral sight threatening macular and optic nerve inflammation may occur with dengue fever, necessitating the use of systemic steroids. We report a case of bilateral dengue maculopathy in an elderly woman managed with targeted intravitreal steroid therapy. A 63-year-old woman presented with acute-onset painless diminution of vision in both eyes following a dengue fever episode. She had bilateral foveal inflammatory lesions, macular oedema, small vessel occlusions at the macula and scattered retinal haemorrhages and cotton-wool spots. Following systemic evaluation, intravitreal triamcinolone acetonide injection was performed in both eyes at an interval of 3 days. The foveal lesion and macular oedema resolved quickly in both eyes with a normal foveal architecture at the end of 6-week follow-up. The visual acuity improved considerably in both eyes. Inflammatory retinopathy in dengue fever may be managed with a targeted intravitreal steroid injection approach.


Asunto(s)
Dengue/complicaciones , Glucocorticoides/administración & dosificación , Edema Macular/tratamiento farmacológico , Edema Macular/virología , Triamcinolona Acetonida/administración & dosificación , Dengue/diagnóstico , Dengue/terapia , Femenino , Humanos , Inyecciones Intravítreas , Edema Macular/diagnóstico , Persona de Mediana Edad
17.
Drug Discov Ther ; 14(6): 313-318, 2021 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-33390410

RESUMEN

The clinical profile and risk factors for mortality in dengue fever have evolved over the years. The all-cause mortality in admitted dengue patients is around 6%. We aimed to evaluate the recent change in trends of the clinical characteristics and risk factors for in-hospital mortality in adults with dengue fever. This is a retrospective study on adults with confirmed dengue fever admitted in a medical unit of a tertiary care center in North India. Medical records of confirmed dengue fever patients admitted between January 2011, and December 2016 were reviewed. Chi-squared tests with Bonferroni correction for multiple testing were used to identify risk factors for mortality. 232 records were included, of which 66.8% were males. The mean age was 31.6 ± 14 years. There were 17 deaths with an all-cause mortality rate of 7.3% with 76.5% being classified as severe dengue at admission. Among the 17 mortality cases, dyspnea (47%), tachypnea (86.7%), leucocytosis (58.8%), raised urea (80%), and elevated serum creatinine (52.9%) at presentation were significantly associated with mortality (p < 0.001). Shock at any time during the hospital stay (58.8%) was also found to be significantly associated with mortality (p < 0.001). We found that dyspnea, tachypnea, acute kidney injury, and leucocytosis at presentation was significantly associated with in-hospital mortality. Based on our results, we recommend aggressive management of patients with severe dengue and those with mild/moderate disease with the above risk factors.


Asunto(s)
Dengue/epidemiología , Leucocitosis/epidemiología , Adolescente , Adulto , Dengue/complicaciones , Dengue/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , India/epidemiología , Leucocitosis/etiología , Leucocitosis/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria , Adulto Joven
19.
Environ Res ; 192: 110303, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33069704

RESUMEN

Bangladesh is one of the most vulnerable countries to climate change impacts also struck by the COVID-19 pandemic. The lockdown measures were ineffective with no sign of flattening the curve. Therefore, the high risk of transmission is evident with an increasing number of affected people. Under this circumstance, a multiple hazards scenario can be developed in this country due to climatic hazards such as cyclones, floods, landslides, heat waves, and the outbreak of infectious diseases such as dengue, cholera, and diarrhoea. The country experiences simultaneously the global pandemic, exceptionally prolonged flood along with the recovery stage from the damages due to the cyclone (Amphan). Therefore, these multiple factors have been putting pressure on losing millions of homes, livelihoods, and agricultural crops. This study aimed to assess the potential impact of a simultaneous strike of climatic hazards and infectious disease outbreaks and their possible strategic management in Bangladesh under different scenarios. A mixed methodological approach was followed in this study including a questionnaire survey, in-depth discussion with experts, and extensive literature review to assess the multi-hazard scenario in a resource-limited setting with high population density. A set of statistical techniques were used to analyze the responses (n = 1590) from different social groups (healthcare professionals, academicians, students, Government and NGO officials, and businessman) under three scenarios. The results revealed the high possibility of aggravating the impact of COVID-19 pandemic if there is a climatic hazard such as flood, cyclone have appeared. The majority of the respondents agreed that the situation will become more devastating if there is another outbreak of diseases such as dengue, cholera, and diarrhoea. The poor and fragile healthcare system of this country cannot bear such unprecedented pressure. The lack of risk assessment and communication, lack of sectoral coordination might restrict the contingency plan of the government. Therefore, considering the unprecedented worst cases a stringent strategic plan for emergency response, short term and long-term management should have to be formulated. Resilience building through proactive planning and implementation of integrated, inclusive and sustainable strategies will be effective to ensure the health and socio-economic security for multi-hazard threats in the country.


Asunto(s)
Dengue , Bangladesh/epidemiología , Cambio Climático , Dengue/epidemiología , Humanos , Pandemias , Políticas
20.
Emerg Infect Dis ; 27(2): 348-351, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33347804

RESUMEN

An epidemic of dengue virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infections occurred in Argentina during 2020. We describe the clinical characteristics and outcomes in a cohort of patients hospitalized because of co-infection. We retrospectively identified 13 patients from different hospitals in Buenos Aires who had confirmed infection with SARS-CoV-2 and dengue virus and obtained clinical and laboratory data from clinical records. All patients had febrile disease when hospitalized. Headache was a common symptom. A total of 8 patients had respiratory symptoms, 5 had pneumonia, and 3 had rash. Nearly all patients had lymphopenia when hospitalized. No patients were admitted to an intensive care unit or died during follow up. Co-infection with SARS-CoV-2 and dengue virus can occur in patients living in areas in which both viruses are epidemic. The outcome of these patients did not seem to be worse than those having either SARS-CoV-2 or dengue infection alone.


Asunto(s)
/epidemiología , Dengue/epidemiología , Adulto , Argentina/epidemiología , Coinfección , Dengue/complicaciones , Femenino , Humanos , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
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