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1.
J Virol Methods ; 311: 114641, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36328082

RESUMEN

Antibody-dependent enhancement (ADE) is one of the pathogenic mechanisms related to disease severity in dengue virus infection. Conventional assays for detecting ADE activity usually require several days. In this study, we established a rapid assay system to evaluate ADE activity in dengue-seropositive samples using single round infectious particles (SRIPs). Human Fc-gamma receptor-bearing cells (K562 and Mylc cells) were infected with SRIP antigen in the presence of human serum samples to measure ADE activity. Two assay protocols were introduced: (i) rapid assay with 5 h of incubation, and (ii) semi-rapid assay with 24 h of incubation. The rapid assay requires a large quantity of SRIP antigen and gives results in half a day. Although the semi-rapid assay requires slightly more than a day, it can be performed using only a small amount of SRIP. Interestingly, the range of the number of Mylc cells required for the semi-rapid assay was wider than that of K562 cells. Significant correlations were observed between the rapid and semi-rapid assays for both cell types. Although it is difficult to judge which protocol best reflects the current immune status in vivo, both assays could rapidly provide valuable information regarding the risk assessment for severe diseases.


Asunto(s)
Virus del Dengue , Dengue , Virosis , Humanos , Acrecentamiento Dependiente de Anticuerpo , Anticuerpos Antivirales
2.
Environ Res ; 216(Pt 2): 114574, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36270535

RESUMEN

This study aimed to assess the phyto-synthesizing potential of Tarenna asiatica methanol leaf extract as well as its larvicidal and pupicidal potential against Aedes aegypti larvae. According to the findings of this study, the methanol leaf extract of T. asiatica has the potential to synthesize zinc oxide nanoparticles from zinc acetate dehydrate. Standard analytical techniques such as UV-visible spectrophotometer, Fourier-transform infrared spectroscopy, X-ray Diffraction analysis, Scanning Electron Microscope, and Energy Dispersive X-Ray were used to characterize the phyto-synthesized nanoparticles. The zinc oxide nanoparticles synthesized ranged in size from 22.35 to 31.27 nm and was spherical in shape. These nanoparticles demonstrated excellent larvicidal activity against Aedes aegypti larvae in the second, third, and fourth in stars, as well as significant pupicidal activity. These findings suggest that the methanol leaf extract of T. asiatica synthesized zinc oxide nanoparticles, which could be used to develop mosquito repellents.


Asunto(s)
Aedes , Dengue , Insecticidas , Nanopartículas del Metal , Óxido de Zinc , Animales , Plata/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Metanol , Insecticidas/química , Extractos Vegetales/farmacología , Mosquitos Vectores , Larva , Dengue/prevención & control , Hojas de la Planta
3.
J Immunol ; 209(10): 2054-2067, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36344111

RESUMEN

Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poorly, particularly in secondary DENV infection. To develop a highly sensitive NS1 ELISA, we generated a large repertoire of anti-DENV NS1 mouse mAbs (n = 95) that falls into 36 mAb classes based on binding specificities. The identified mAb pair, capable of efficiently detecting NS1 from four DENV serotypes in an immunoassay, was selected based on multiparametric analysis. The selected mAbs have subnanomolar affinities for NS1 with recognition sites outside the immunodominant wing domain. The assay was converted to an ELISA kit, which showed higher analytical sensitivity (3-fold to 83-fold) for NS1 from four DENV serotypes than commercial Platelia NS1 ELISA (Bio-Rad Laboratories). Compared to RT-PCR, the developed NS1 ELISA showed 78.57% (66 of 84) sensitivity, whereas Platelia NS1 ELISA showed a sensitivity of 60.71% (51 of 84). In a subgroup of RT-PCR-positive secondary dengue samples, our ELISA showed a sensitivity of 70.18% (40 of 57), whereas Platelia ELISA detected only 47.37% (27 of 57) samples. Furthermore, unlike Platelia ELISA, our test equally detected NS1 from four serotypes; Platelia ELISA performed poorly for the DENV-2 serotype, in which only 8 of 21 (38.10%) samples were detected compared with 17 of 21 (80.95%) in our ELISA. Moreover, our ELISA showed 100% specificity in 342 challenging dengue-negative samples. The large and diverse mAb repertoire generated against DENV NS1 and the appropriate selection of mAbs allowed us to establish an ELISA that can efficiently detect NS1 Ag even in secondary dengue and without serotype level bias.


Asunto(s)
Antineoplásicos Inmunológicos , Virus del Dengue , Dengue , Ratones , Animales , Dengue/diagnóstico , Anticuerpos Monoclonales , Proteínas no Estructurales Virales , Antígenos Virales , Anticuerpos Antivirales , Sensibilidad y Especificidad , Ensayo de Inmunoadsorción Enzimática
4.
Euro Surveill ; 27(44)2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36330819

RESUMEN

France faced an unusual situation of dengue transmission in 2022, with 65 autochthonous cases spread over nine transmission events by 21 October. This exceeded the number of cases observed during the entire period 2010 to 2021. Six of these events occurred in departments that had never experienced autochthonous dengue transmission. We provide an update of dengue surveillance data in mainland France in 2022. The multiplication of transmission events calls for continuous adaption of preparedness and response to arbovirus-related risks.


Asunto(s)
Aedes , Dengue , Humanos , Animales , Dengue/epidemiología , Incidencia , Geografía , Francia/epidemiología
5.
Vaccine ; 40(50): 7343-7351, 2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36347720

RESUMEN

BACKGROUND: The World Health Organization (WHO) recommended 'pre-vaccination screening' as its preferred implementation strategy when using the licensed dengue vaccine (CYD-TDV; Dengvaxia, Sanofi), so that only individuals with previous dengue infection are vaccinated. The US Centers for Disease Control and Prevention (CDC) recommended use of CYD-TDV to prevent dengue in children with previous laboratory-confirmed dengue infection in regions where dengue is endemic. Here, we evaluate the public health impact and cost-effectiveness of a 'pre-vaccination screening' strategy in Puerto Rico. METHODS: The current analysis builds upon a previously published transmission model used to assess the benefits/risks associated with dengue vaccination. For 'pre-vaccination screening', three alternative testing methods were assessed: one using an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) dengue serotest, another with dengue serotesting using a rapid diagnostic test (RDT), and one using both sequentially (as recommended in Puerto Rico). The time horizon considered was 10 years. RESULTS: In Puerto Rico, the disability-adjusted life years (DALYs) averted for 'pre-vaccination screening' with an ELISA-based program, RDT-based program, and both sequentially would be a median 1,192 (95% CI: 716-2,232), 2,812 (95% CI: 1,579-5,019), and 1,017 (95% CI: 561-1,738), respectively. These benefits would arise from the reduction in cases: median 24,961 (95% CI: 17,480-36,782), 58,273 (95% CI: 40,729-84,796), 20,775 (95% CI: 14,637-30,374) fewer cases, respectively. The cost per DALY averted from a payer perspective would be US$12,518 (95 %CI: US$4,749-26,922), US$10,047 (95% CI: US$3,350-23,852), and US$12,334 (95% CI: US$4,965-26,444), respectively. All three strategies would be cost saving from a societal perspective. CONCLUSIONS: Our study supports the WHO and CDC 'pre-vaccination screening' guidance for CYD-TDV implementation. In Puerto Rico, regardless of the testing strategy and even with a relatively low rate of testing, it would be cost-effective from a payer perspective and cost saving from a societal perspective.


Asunto(s)
Vacunas contra el Dengue , Dengue , Humanos , Estados Unidos , Niño , Salud Pública , Análisis Costo-Beneficio , Puerto Rico , Vacunación , Dengue/prevención & control
6.
PLoS Negl Trop Dis ; 16(11): e0010877, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36342959

RESUMEN

The live attenuated tetravalent CYD-TDV vaccine (Dengvaxia) is effective but has scarcely been used due to safety concerns among seronegative recipients. Rapid diagnostic tests (RDTs) which can accurately determine individual dengue serostatus are needed for use in pre-vaccination screening. This study aimed to determine the performance of existing RDTs (which have been designed to detect levels of immunoglobulin G, IgG, associated with acute post-primary dengue) when repurposed for detection of previous dengue infection (where concentrations of IgG are typically lower). A convenience sample of four-hundred-and-six participants including 217 children were recruited during a community serosurvey. Whole blood was collected by phlebotomy and tested using Bioline Dengue IgG/IgM (Abbott) and Standard Q Dengue IgM/IgG (SD Biosensor) RDTs in the field. Serum samples from the same individuals were also tested at National Health Laboratory. The Panbio indirect IgG ELISA was used as a reference test. Reference testing determined that 370 (91.1%) participants were dengue IgG seropositive. Both assays were highly specific (100.0%) but had low sensitivity (Bioline = 21.1% and Standard Q = 4.6%) when used in the field. Sensitivity was improved when RDTs were used under laboratory conditions, and when assays were allowed to run beyond manufacturer recommendations and read at a delayed time-point, but specificity was reduced. Efforts to develop RDTs with high sensitivity and specificity for prior dengue infection which can be operationalised for pre-vaccination screening are ongoing. Performance of forthcoming candidate assays should be tested under field conditions with blood samples, as well as in the laboratory.


Asunto(s)
Vacunas contra el Dengue , Virus del Dengue , Dengue , Niño , Humanos , Dengue/diagnóstico , Anticuerpos Antivirales , Pruebas Diagnósticas de Rutina , Timor Oriental , Sensibilidad y Especificidad , Inmunoglobulina G , Vacunas Atenuadas , Inmunoglobulina M
8.
Front Public Health ; 10: 1035560, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388314

RESUMEN

Introduction: Dengue fever is a vector-borne disease with an estimate of 390 million persons getting the infection each year with a significant public health impact. It has been reported DENV patients with vitamin D deficiency led to severe form of dengue infection; while H. pylori coinfection alters vitamin D receptors leading to vitamin D deficiency. We hypothesize that DENV patient's having low vitamin D along with H. pylori coinfection could have worsen dengue severity as well as vitamin D deficiency. In this case-control study, we compared (I) the vitamin D deficiency in dengue fever cases with or without H. pylori coinfection, and (II) negative dengue fever as a control with or without H. pylori coinfection. We have also assessed the correlation between vitamin D levels and its effect on warning signs of the dengue fever. Further, we have investigated whether coinfection with H. pylori has any effect on warning signs in the dengue fever patients and the vitamin D deficiency in all serotypes of the dengue virus infected patients. Methods: In this case control study the association of the vitamin D levels with age, gender and H. pylori coinfection in dengue fever hospitalized patients was assessed using chi-square and multivariate logistic regression analysis. Results: Four hundred dengue fever patients with H. pylori coinfection were compared with 400 dengue negative controls with H. pylori coinfection. The mean age was 29.96 ± 10.5 and 29.88 ± 10.7 years among cases and controls, respectively. Most dengue fever patients with H. pylori coinfection were deficient in vitamin D compared with negative dengue controls with H. pylori coinfection. In multivariate logistic regression, the dengue cases with H. pylori coinfection were.056 times (95% CI: 0.024, 0.128, P = 0.000) more likely to have vitamin D "deficiency', while compared with the cases who did not have H. pylori coinfection. Conclusion: The present study proposes that vitamin D deficiency in dengue fever patients coinfected with H. pylori is much higher than the dengue fever negative controls coinfected with H. pylori. As hypothesized the DENV patient with H. pylori coinfection has vitamin D deficiency as well as increased dengue severity.


Asunto(s)
Coinfección , Dengue , Helicobacter pylori , Deficiencia de Vitamina D , Humanos , Adulto Joven , Adulto , Estudios de Casos y Controles , Coinfección/epidemiología , Pakistán/epidemiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Vitamina D , Dengue/complicaciones , Dengue/epidemiología
9.
Arch Argent Pediatr ; 120(6): 384-390, 2022 Dec.
Artículo en Español, Inglés | MEDLINE | ID: mdl-36374056

RESUMEN

INTRODUCTION: Dengue is a public health problem worldwide. It was originally confined to tropical and subtropical areas, but it is now present in other regions, such as Argentina. Epidemic outbreaks have been observed in the City of Buenos Aires since 2008, with few reports in children. OBJECTIVE: To analyze and compare the clinical, epidemiological, laboratory, and evolutionary characteristics of the latest 2 dengue outbreaks outside the endemic area. POPULATION AND METHODS: Time-series study. Patients under 18 years of age with probable or confirmed dengue and evaluated in a children's hospital of the City of Buenos Aires during the periods 2015-2016 and 2019-2020 were included. RESULTS: A total of 239 patients were included; 29 (12%) had a history of travel. Their median age was 132 months (interquartile range: 102- 156). All had a fever. Other symptoms included headache in 170 (71%), myalgia in 129 (54%), and rash in 122 (51%). Forty patients (17%) had comorbidities. Warning signs were observed in 79 patients (33%); 14 (6%) developed severe dengue; 115 (45%) were hospitalized; none died. DENV-1 was the most common serotype. A history of travel and hospitalization prevailed in the first period; severe dengue and prior infection, in the second period. CONCLUSIONS: No patient died due to dengue in either study period. Statistically significant differences were observed in the frequency of hospitalization; a history of travel was more common in the 2015-2016 period and severe dengue, in the 2019-2020 period.


Introducción. El dengue es un problema de salud pública a nivel mundial. Confinado en sus orígenes a las zonas tropicales y subtropicales, en la actualidad se presenta en otras regiones como Argentina. Desde el año 2008 se presenta con brotes epidémicos en la Ciudad Autónoma de Buenos Aires, con escasos reportes en niños. OBJETIVO: Analizar y comparar las características clínicas, epidemiológicas, de laboratorio y evolutivas de los dos últimos brotes de dengue fuera del área endémica. Población y métodos. Estudio de series temporales. Se incluyeron pacientes menores de 18 años con dengue probable o confirmado, evaluados en un hospital pediátrico de la Ciudad de Buenos Aires durante los períodos 2015-2016 y 2019-2020. RESULTADOS: Se incluyeron 239 pacientes, 29 (12 %) con antecedente de viaje. La mediana de edad fue de 132 meses (rango intercuartílico: 102-156). Todos tuvieron fiebre. Otros síntomas fueron: cefalea en 170 (71 %), mialgias en 129 (54 %) y exantema en 122 (51 %). Cuarenta pacientes (17 %) tenían comorbilidades. Presentaron signos de alarma 79 pacientes (33 %) y 14 (6 %) tenían dengue grave. Requirieron internación 115 pacientes (45 %) y ninguno falleció. El serotipo DENV-1 fue el más frecuente. El antecedente de viaje y la necesidad de internación predominaron en el primer período; el dengue grave y la infección previa, en el segundo. CONCLUSIONES: Ningún paciente falleció de dengue en los períodos estudiados. Se observaron diferencias estadísticamente significativas en la frecuencia de internación; el antecedente de viaje fue más frecuente en el período 2015-2016 y el dengue grave, en el 2019-2020.


Asunto(s)
Dengue , Exantema , Dengue Grave , Humanos , Niño , Adolescente , Dengue/epidemiología , Dengue/diagnóstico , Dengue Grave/epidemiología , Brotes de Enfermedades , Hospitales Pediátricos
10.
Artículo en Inglés | MEDLINE | ID: mdl-36429980

RESUMEN

Dengue fever is an acute mosquito-borne disease that mostly spreads within urban or semi-urban areas in warm climate zones. The dengue-related risk map is one of the most practical tools for executing effective control policies, breaking the transmission chain, and preventing disease outbreaks. Mapping risk at a small scale, such as at an urban level, can demonstrate the spatial heterogeneities in complicated built environments. This review aims to summarize state-of-the-art modeling methods and influential factors in mapping dengue fever risk in urban settings. Data were manually extracted from five major academic search databases following a set of querying and selection criteria, and a total of 28 studies were analyzed. Twenty of the selected papers investigated the spatial pattern of dengue risk by epidemic data, whereas the remaining eight papers developed an entomological risk map as a proxy for potential dengue burden in cities or agglomerated urban regions. The key findings included: (1) Big data sources and emerging data-mining techniques are innovatively employed for detecting hot spots of dengue-related burden in the urban context; (2) Bayesian approaches and machine learning algorithms have become more popular as spatial modeling tools for predicting the distribution of dengue incidence and mosquito presence; (3) Climatic and built environmental variables are the most common factors in making predictions, though the effects of these factors vary with the mosquito species; (4) Socio-economic data may be a better representation of the huge heterogeneity of risk or vulnerability spatial distribution on an urban scale. In conclusion, for spatially assessing dengue-related risk in an urban context, data availability and the purpose for mapping determine the analytical approaches and modeling methods used. To enhance the reliabilities of predictive models, sufficient data about dengue serotyping, socio-economic status, and spatial connectivity may be more important for mapping dengue-related risk in urban settings for future studies.


Asunto(s)
Directivas Anticipadas , Dengue , Animales , Teorema de Bayes , Algoritmos , Macrodatos , Dengue/epidemiología
11.
Int J Mol Sci ; 23(22)2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36430340

RESUMEN

Limitations in the detection of cocirculating flaviviruses such as Dengue and Zika lead us to propose the use of aptameric capture of the viral RNA in combination with RT-PCR (APTA-RT-PCR). Aptamers were obtained via SELEX and next-generation sequencing, followed by colorimetric and fluorescent characterizations. An APTA-RT-PCR assay was developed, optimized, and tested against the viral RNAs in 108 serum samples. After selection, sequence APTAZC10 was designed as a bifunctional molecular beacon (APTAZC10-MB), exhibiting affinity for the viral targets. APTA-RT-PCR was able to detect Dengue and Zika RNA in 43% and 8% of samples, respectively. Our results indicate that APTAZC10-MB and APTA-RT-PCR will be useful to improve the detection of Dengue and Zika viruses in a fast molecular assay for the improvement of infectious disease surveillance.


Asunto(s)
Dengue , Infección por el Virus Zika , Virus Zika , Humanos , Virus Zika/genética , Infección por el Virus Zika/diagnóstico , Oligonucleótidos , ARN Viral/genética , Fenómenos Magnéticos , Dengue/diagnóstico
12.
Int J Mol Sci ; 23(22)2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36430387

RESUMEN

Dengue virus belonging to the family Flaviviridae and its four serotypes are responsible for dengue infections, which extend over 60 countries in tropical and subtropical areas of the world including Pakistan. During the ongoing dengue outbreak in Pakistan (2022), over 30,000 cases have been reported, and over 70 lives have been lost. The only commercialized vaccine against DENV, Dengvaxia, cannot be administered as a prophylactic measure to cure this infection due to various complications. Using machine learning and reverse vaccinology approaches, this study was designed to develop a tetravalent modified nucleotide mRNA vaccine using NS1, prM, and EIII sequences of dengue virus from Pakistani isolates. Based on high antigenicity, non-allergenicity, and toxicity profiling, B-cell epitope, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) putative vaccine targets were predicted. Molecular docking confirmed favorable interactions between T-cell epitopes and their respective HLA alleles, while normal mode analysis validated high-affinity interactions of vaccine proteins with immune receptors. In silico immune simulations confirmed adequate immune responses to eliminate the antigen and generate memory. Codon optimization, physicochemical features, nucleotide modifications, and suitable vector availability further ensured better antigen expression and adaptive immune responses. We predict that this vaccine construct may prove to be a good vaccinal candidate against dengue virus in vitro as well.


Asunto(s)
Vacunas contra el Dengue , Virus del Dengue , Dengue , Humanos , Vacunas contra el Dengue/genética , Virus del Dengue/genética , Vacunología , Simulación del Acoplamiento Molecular , Dengue/prevención & control , Nucleótidos , ARN Mensajero/genética
13.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36430807

RESUMEN

Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.


Asunto(s)
Dengue , Células Madre Hematopoyéticas , Humanos , Células Madre Hematopoyéticas/metabolismo , Movilización de Célula Madre Hematopoyética/métodos , Médula Ósea/metabolismo , Células de la Médula Ósea/metabolismo , Dengue/metabolismo
14.
PLoS One ; 17(11): e0276725, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36399460

RESUMEN

BACKGROUND: Dengue virus can affect the cardiovascular system and men may be at higher risk of severe complications than women. We hypothesized that clinical dengue virus (DENV) infection could induce myocardial alterations of the left ventricle (LV) and that these changes could be detected by transthoracic echocardiography. METHODOLOGY/PRINCIPAL FINDINGS: We examined individuals from Acre in the Amazon Basin of Brazil in 2020 as part of the Malaria Heart Study. By questionnaires we collected information on self-reported prior dengue infection. All individuals underwent transthoracic echocardiography, analysis of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). We included 521 persons (mean age 40±15 years, 39% men, 50% urban areas) of which 253 (49%) had a history of dengue infection. In multivariable models adjusted for clinical and sociodemographic data, a history of self-reported dengue was significantly associated with lower LVEF (ß = -2.37, P < 0.01) and lower GLS (ß = 1.08, P < 0.01) in men, whereas no significant associations were found in women (P > 0.05). In line with these findings, men with a history of dengue had higher rates of LV systolic dysfunction (LVEF < 50% = 20%; GLS < 16% = 17%) than those without a history of dengue (LVEF < 50% = 7%; GLS < 16% = 8%; P < 0.01 and 0.06, respectively). CONCLUSIONS/SIGNIFICANCE: The findings of this study suggest that a clinical infection by dengue virus could induce myocardial alterations, mainly in men and in the LV, which could be detected by conventional transthoracic echocardiography. Hence, these results highlight a potential role of echocardiography for screening LV dysfunction in participants with a history of dengue infection. Further larger studies are warranted to validate the findings of this study.


Asunto(s)
Dengue , Disfunción Ventricular Izquierda , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Volumen Sistólico , Estudios de Cohortes , Función Ventricular Izquierda , Estudios Transversales , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Ecocardiografía/métodos , Dengue/complicaciones , Dengue/diagnóstico por imagen
15.
Viruses ; 14(11)2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36366548

RESUMEN

Dengue is a major vector-borne disease worldwide. Here, we examined the spatial distribution of extreme weekly dengue outbreak risk in Singapore from 2007 to 2020. We divided Singapore into equal-sized hexagons with a circumradius of 165 m and obtained the weekly number of dengue cases and the surface characteristics of each hexagon. We accounted for spatial heterogeneity using max-stable processes. The 5-, 10-, 20-, and 30-year return levels, or the weekly dengue case counts expected to be exceeded once every 5, 10, 20, and 30 years, respectively, were determined for each hexagon conditional on their surface characteristics remaining constant over time. The return levels were higher in the country's east, with the maximum weekly dengue cases per hexagon expected to exceed 51 at least once in 30 years in many areas. The surface characteristics with the largest impact on outbreak risk were the age of public apartments and the percentage of impervious surfaces, where a 3-year and 10% increase in each characteristic resulted in a 3.8% and 3.3% increase in risk, respectively. Vector control efforts should be prioritized in older residential estates and places with large contiguous masses of built-up environments. Our findings indicate the likely scale of outbreaks in the long term.


Asunto(s)
Dengue , Humanos , Anciano , Dengue/epidemiología , Singapur/epidemiología , Brotes de Enfermedades
16.
Appl Environ Microbiol ; 88(22): e0141222, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36318064

RESUMEN

The intracellular bacterium Wolbachia inhibits virus replication and is being harnessed around the world to fight mosquito-borne diseases through releases of mosquitoes carrying the symbiont. Wolbachia strains vary in their ability to invade mosquito populations and suppress viruses in part due to differences in their density within the insect and associated fitness costs. Using whole-genome sequencing, we demonstrate the existence of two variants in wAlbB, a Wolbachia strain being released in natural populations of Aedes aegypti mosquitoes. The two variants display striking differences in genome architecture and gene content. Differences in the presence/absence of 52 genes between variants include genes located in prophage regions and others potentially involved in controlling the symbiont's density. Importantly, we show that these genetic differences correlate with variation in wAlbB density and its tolerance to heat stress, suggesting that different wAlbB variants may be better suited for field deployment depending on local environmental conditions. Finally, we found that the wAlbB genome remained stable following its introduction in a Malaysian mosquito population. Our results highlight the need for further genomic and phenotypic characterization of Wolbachia strains in order to inform ongoing Wolbachia-based programs and improve the selection of optimal strains in future field interventions. IMPORTANCE Dengue is a viral disease transmitted by Aedes mosquitoes that threatens around half of the world population. Recent advances in dengue control involve the introduction of Wolbachia bacterial symbionts with antiviral properties into mosquito populations, which can lead to dramatic decreases in the incidence of the disease. In light of these promising results, there is a crucial need to better understand the factors affecting the success of such strategies, in particular the choice of Wolbachia strain for field releases and the potential for evolutionary changes. Here, we characterized two variants of a Wolbachia strain used for dengue control that differ at the genomic level and in their ability to replicate within the mosquito. We also found no evidence for the evolution of the symbiont within the 2 years following its deployment in Malaysia. Our results have implications for current and future Wolbachia-based health interventions.


Asunto(s)
Aedes , Virus del Dengue , Dengue , Wolbachia , Animales , Humanos , Wolbachia/genética , Mosquitos Vectores , Aedes/microbiología , Genómica
17.
Nat Commun ; 13(1): 6756, 2022 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-36347841

RESUMEN

Dengue virus infection can cause dengue hemorrhagic fever (DHF). Dengue NS1 is multifunctional. The intracellular dimeric NS1 (iNS1) forms part of the viral replication complex. Previous studies suggest the extracellular secreted NS1 (sNS1), which is a major factor contributing to DHF, exists as hexamers. The structure of the iNS1 is well-characterised but not that of sNS1. Here we show by cryoEM that the recombinant sNS1 exists in multiple oligomeric states: the tetrameric (stable and loose conformation) and hexameric structures. Stability of the stable and loose tetramers is determined by the conformation of their N-terminal domain - elongated ß-sheet or ß-roll. Binding of an anti-NS1 Fab breaks the loose tetrameric and hexameric sNS1 into dimers, whereas the stable tetramer remains largely unbound. Our results show detailed quaternary organization of different oligomeric states of sNS1 and will contribute towards the design of dengue therapeutics.


Asunto(s)
Virus del Dengue , Dengue , Síndrome de Noonan , Dengue Grave , Humanos , Virus del Dengue/metabolismo , Proteínas no Estructurales Virales/química
19.
Medicine (Baltimore) ; 101(43): e31322, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36316901

RESUMEN

RATIONALE: Dengue obstructive shock syndrome is a fatal complication commonly observed in the late critical phase of dengue infection and is associated with a high mortality rate. The main pathogenesis involves a dramatic increase in chest pressure, owing to severe plasma leakage and mechanical respiratory support, hampering the heart's ability to pump effectively and impeding adequate blood venous return to the heart chambers. To date, there is a paucity of clinical data about Dengue obstructive shock syndrome reported. PATIENT CONCERNS: The 2 reported patients presented with prolonged and decompensated dengue shock with critical multi-organ failures and mechanical ventilation. The patients' hemodynamics were profoundly affected by high pressure in the thoracic and abdominal cavities resulting from Dengue-induced severe plasma leakage and mechanical ventilation. DIAGNOSES: Clinical presentations, laboratory data, mini-fluid challenge test, and point-of-care (POCUS) were used to make diagnoses and guide management. INTERVENTIONS: Clinical monitoring, judicious fluid (colloids and blood products) administration guided by repeated POCUS to properly assess the adequacy of the intravascular volume, homeostasis adjustments by plasma exchange, and continuous renal replacement therapies. OUTCOMES: The patients had favorable outcomes. LESSONS: Our study highlights the clinical manifestations and management of children with dengue obstructive shock syndrome and underscores the importance of monitoring hemodynamics by consecutive POCUS at the bedside in order to make a timely diagnosis and assess intravascular fluid volume inadequacy accurately as well as closely monitor the fluid management responses.


Asunto(s)
Dengue , Respiración Artificial , Niño , Humanos , Hemodinámica , Monitoreo Fisiológico , Plasma , Dengue/complicaciones , Dengue/diagnóstico , Dengue/terapia
20.
J Infect Dev Ctries ; 16(10): 1637-1642, 2022 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-36332218

RESUMEN

INTRODUCTION: Dengue is an emerging vector-borne public health threat and characterization at the molecular level is important for proper management of the disease. The aim of the study is to examine the diversity of the dengue viral serotypes from a hilly mountainous region of Northeast India. METHODOLOGY: Thirty-six blood samples that were positive for dengue virus IgM antibodies identified by the enzyme-linked immunosorbent assay (ELISA) method were collected and quantified for the IL6 gene expression by using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: All the patients had dengue hemorrhagic fever (DHF); 12 samples had a monotypic infection and 14 samples had dual infection with various dengue virus (DENV) serotypes; one sample had triple infection with DENV-1, DENV-2, and DENV-3. CONCLUSIONS: This study identified DENV-1 as the major serotype in the state of Mizoram and it is the first report on the molecular typing of the dengue virus from the hilly mountainous state located in the Indo-Burma region bordering Myanmar and Bangladesh.


Asunto(s)
Virus del Dengue , Dengue , Humanos , Virus del Dengue/genética , Dengue/epidemiología , Serogrupo , Ensayo de Inmunoadsorción Enzimática , Tipificación Molecular , India/epidemiología , Anticuerpos Antivirales
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