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1.
Biomed Environ Sci ; 37(5): 511-520, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38843924

RESUMO

Objective: This study employs the Geographically and Temporally Weighted Regression (GTWR) model to assess the impact of meteorological elements and imported cases on dengue fever outbreaks, emphasizing the spatial-temporal variability of these factors in border regions. Methods: We conducted a descriptive analysis of dengue fever's temporal-spatial distribution in Yunnan border areas. Utilizing annual data from 2013 to 2019, with each county in the Yunnan border serving as a spatial unit, we constructed a GTWR model to investigate the determinants of dengue fever and their spatio-temporal heterogeneity in this region. Results: The GTWR model, proving more effective than Ordinary Least Squares (OLS) analysis, identified significant spatial and temporal heterogeneity in factors influencing dengue fever's spread along the Yunnan border. Notably, the GTWR model revealed a substantial variation in the relationship between indigenous dengue fever incidence, meteorological variables, and imported cases across different counties. Conclusion: In the Yunnan border areas, local dengue incidence is affected by temperature, humidity, precipitation, wind speed, and imported cases, with these factors' influence exhibiting notable spatial and temporal variation.


Assuntos
Dengue , Dengue/epidemiologia , China/epidemiologia , Humanos , Análise Espaço-Temporal , Incidência , Surtos de Doenças , Regressão Espacial
3.
Health Sci Rep ; 7(6): e2170, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38845788

RESUMO

Background: In context, the dengue virus causes dengue fever, which is spread by mosquito bites. About 22,000 people every year lose their lives as a direct result of it. Dengue fever has been on the rise recently, and its spread has alarmed health officials throughout the world. Discussion: Vaccination is essential for the prevention and management of dengue cases because there is currently no particular cure against dengue virus. The current dengue epidemic calls for urgent action in the form of immunization. However, there are serious drawbacks to using existing vaccines like Dengvaxia. Besides, the Qdenga vaccine has not yet been approved by the FDA in the United States. On the other hand, positive results from a phase II randomized and controlled clinical study of the TV005 tetravalent live-attenuated dengue vaccine were recently reported in Bangladesh. Only an effective vaccination can drastically lower dengue infection and mortality rates. Conclusion: The development of safe and effective vaccination, as well as their correct dissemination, is an essential requirement for the people of Bangladesh and the rest of the globe, and we concentrated on this critical problem in this article.

4.
China CDC Wkly ; 6(20): 457-462, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38846359

RESUMO

Objective: The goal of this study is to analyze the epidemiological patterns of dengue fever across different districts and counties in Yunnan Province from 2010 to 2021. Methods: In this study, we employed joinpoint regression analysis, spatial autocorrelation analysis, and space-time scan analysis to illustrate the spatio-temporal propagation and demographic influence of dengue fever, using both graphical and tabular presentations to clearly demonstrate the findings. Results: Yunnan Province reported 14,098 cases of dengue fever during the period from 2010 to 2021. Of these, 11,513 cases were caused by local transmission, 2,566 were imported internationally, and 19 were inter-provincial imports. Seasonal trends emerged, revealing a surge in incidences during the summer and autumn months. The sex ratio of male to female cases was 1:0.88, with a significant majority of 82.00% of cases involving individuals belonging to the age group of 15-60. Commercial service workers constituted the most impacted occupational group, forming 20.96% of total cases. A spatio-temporal scan identified significant clustering of dengue fever cases across space and time, with the most pronounced cluster observed in southern Yunnan, primarily between 2015 and 2019. Conclusions: Dengue fever in Yunnan Province manifests as biennial outbreaks, underscoring the necessity for increased surveillance, particularly in counties bordering other regions.

5.
Lancet Reg Health Am ; 35: 100786, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38846808

RESUMO

Background: This study focuses on urban arboviruses, specifically dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV), which pose a significant public health challenge in Rio de Janeiro state, Southeast Brazil. In our research, we highlight critical findings on the transmission dynamics of these arboviruses in Rio de Janeiro, identifying distinct patterns of disease spread. Methods: By combining genomic data with case reports from the Brazilian Ministry of Health, we have analysed the phylogenetics, prevalence and spatial distribution of these endemic viruses within the state. Findings: Our results revealed sustained DENV transmission primarily in the northern part of the state, a significant ZIKV epidemic in 2016 affecting all mesoregions, and two major CHIKV outbreaks in 2018 and 2019, predominantly impacting the northern and southern areas. Our analysis suggests an inverse relationship between arboviral case incidence and urban density, with less populous regions experiencing higher transmission rates, potentially attributed to a complex interplay of factors such as the efficacy of vector control measures, environmental conditions, local immunity levels, and human mobility. Furthermore, our investigation unveiled distinct age and gender trends among affected individuals. Notably, dengue cases were predominantly observed in young adults aged 32, while chikungunya cases were more prevalent among individuals over 41. In contrast, cases of ZIKV were concentrated around the 33-year age group. Intriguingly, females accounted for nearly 60% of the cases, suggesting a potential gender-based difference in infection rates. Interpretation: Our findings underscore the complexity of arbovirus transmission and the need for interventions tailored to different geographical mesoregions. Enhanced surveillance and genomic sequencing will be essential for a deeper, more nuanced understanding of regional arbovirus dynamics. Identifying potential blind spots within the state will be pivotal for developing and implementing more effective public health strategies, specifically designed to address the unique challenges posed by these viruses throughout the state. Funding: This study was supported by the National Institutes of Health USA grant U01 AI151698 for the United World Arbovirus Research Network (UWARN) and the CRP-ICGEB RESEARCH GRANT 2020 Project CRP/BRA20-03.

6.
J Med Virol ; 96(6): e29726, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38828952

RESUMO

There is a lack of evidence on the optimal administration of intravenous (IV) fluids in hospitalized adult dengue patients without compensated and hypotensive shock. This study utilized a well-established cohort of dengue patients to compare risks of progressing to severe dengue (SD) over time for patients who were administered IV fluid versus others who were not. We included adult patients (n = 4781) who were hospitalized for dengue infection from 2005 to 2008. Cases were patients who developed SD (n = 689) and controls were patients who did not up until discharge (n = 4092). We estimated the hazard ratios (HRs) and risk of SD over time between groups administered different volumes of IV fluids versus the no IV fluid comparison group using Cox models with time-dependent covariates. The doubly-robust estimation approach was used to control for the propensity of fluid administration given clinical characteristics of patients. Subgroup analyses by age, sex, and dengue warning signs before IV fluid administration were conducted. High (>2000 mL/day) IV fluids volume was associated with a higher risk of development of SD for those who had warning signs (HR: 1.77 [1.05-2.97], p: 0.0713) and for those below 55 years old (HR: 1.53 [1.04-2.25], p: 0.0713). Low (<1000 mL/day) IV fluids volume was protective against SD for patients without warning signs (HR: 0.757 [0.578-0.990], p: 0.0883), no lethargy (HR: 0.770 [0.600-0.998], p: 0.0847), and females (HR: 0.711 [0.516-0.980], p: 0.0804). Over the course of hospitalization, there were no significant differences in IV fluid administration and SD risk in most subgroups, except in those who experienced lethargy and were administered IV fluid volume or quantity. Administering high volumes of IV fluids may be associated with an increased risk of SD during hospitalization for adult dengue patients without shock. Judicious use of IV fluids as supportive therapy is warranted.


Assuntos
Administração Intravenosa , Hidratação , Hospitalização , Dengue Grave , Humanos , Masculino , Feminino , Hidratação/efeitos adversos , Adulto , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Dengue Grave/terapia , Adulto Jovem , Dengue/complicações , Dengue/terapia , Idoso , Adolescente , Estudos Retrospectivos
7.
J Theor Biol ; 591: 111865, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823767

RESUMO

Dengue is a vector-borne disease transmitted by Aedes mosquitoes. The worldwide spread of these mosquitoes and the increasing disease burden have emphasized the need for a spatio-temporal risk map capable of assessing dengue outbreak conditions and quantifying the outbreak risk. Given that the life cycle of Aedes mosquitoes is strongly influenced by habitat temperature, numerous studies have utilized temperature-dependent development rates of these mosquitoes to construct virus transmission and outbreak risk models. In this study, we contribute to existing research by developing a mechanistic model for the mosquito life cycle that accurately captures its non-Markovian nature. Beginning with integral equations to track the mosquito population across different life cycle stages, we demonstrate how to derive the corresponding differential equations using phase-type distributions. This approach can be further applied to similar non-Markovian processes that are currently described with less accurate Markovian models. By fitting the model to data on human dengue cases, we estimate several model parameters, allowing the development of a global spatiotemporal dengue risk map. This risk model employs temperature and precipitation data to assess the environmental suitability for dengue outbreaks in a given area.

8.
J Formos Med Assoc ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38879404

RESUMO

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.

9.
Transfusion ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38877832

RESUMO

BACKGROUND: The large dengue (DENV) and chikungunya (CHIKV) outbreaks observed during the last decade across the world, as well as local transmissions in non-endemic areas are a growing concern for blood safety. The aim of this study was to evaluate and compare the sensitivity of nucleic acid tests (NAT) detecting DENV and CHIKV RNA. MATERIALS AND METHODS: Using DENV 1 to 4 International Standards, the limits of detection (LODs) calculated by probit analysis of two NAT assays; the cobas CHIKV/DENV assay (Roche Diagnostics) and the Procleix Dengue Virus Assay (Grifols) were compared. In addition, CHIKV-RNA LOD of the cobas CHIKV/DENV assay was evaluated. RESULTS: For dengue, the 95% LOD of the cobas assay ranged between 4.10 [CI95%: 2.70-8.19] IU/mL (DENV-2) and 7.07 [CI95%: 4.34-14.89] IU/mL (DENV-4), and between 2.19 [CI95%: 1.53-3.83] IU/mL (DENV-3) and 5.84 [CI95%: 3.84-10.77] IU/mL (DENV-1) for Procleix assay. The Procleix assay had a significant lower LOD for DENV-3 (2.19 vs. 5.89 IU/mL) when compared to the cobas assay (p = 0.005). The 95% LOD for CHIKV-RNA detection of the cobas assay was 4.76 [CI95%: 3.08-8.94] IU/mL. DISCUSSION: The two NAT assays developed for blood donor screening evaluated in this study demonstrated high and similar analytical performance. Subject to an appropriate risk-benefit assessment, they can be used to support blood safety during outbreaks in endemic areas or in non-endemic areas as an alternative to deferring blood donors during local transmission likely to affect the blood supply. The development of multiplex assays is expected to optimize laboratory organization.

10.
Int J Biol Macromol ; 272(Pt 1): 132855, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834129

RESUMO

Approximately 3.9 billion individuals are vulnerable to dengue infection, a prevalent cause of tropical diseases worldwide. Currently, no drugs are available for preventing or treating Flavivirus diseases, including Dengue, West Nile, and the more recent Zika virus. The highly conserved Flavivirus NS2B-NS3 protease, crucial for viral replication, is a promising therapeutic target. This study employed in-silico methodologies to identify novel and potentially effective anti-dengue small molecules. A pharmacophore model was constructed using an experimentally validated NS2B-NS3 inhibitor, with the Gunner Henry score confirming the model's validity. The Natural Product Activity and Species Source (NPASS) database was screened using the validated pharmacophore model, yielding a total of 60 hits against the NS2B-NS3 protease. Furthermore, the docking finding reveals that our newly identified compounds from the NPASS database have enhanced binding affinities and established significant interactions with allosteric residues of the target protein. MD simulation and post-MD analysis further validated this finding. The free binding energy was computed in terms of MM-GBSA analysis, with the total binding energy for compound 1 (-57.3 ± 2.8 and - 52.9 ± 1.9 replica 1 and 2) indicating a stronger binding affinity for the target protein. Overall, this computational study identified these compounds as potential hit molecules, and these findings can open up a new avenue to explore and develop inhibitors against Dengue virus infection.


Assuntos
Antivirais , Vírus da Dengue , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases , Serina Endopeptidases , Proteínas não Estruturais Virais , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/enzimologia , Serina Endopeptidases/química , Serina Endopeptidases/metabolismo , Antivirais/farmacologia , Antivirais/química , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Avaliação Pré-Clínica de Medicamentos , Ligação Proteica , Proteases Virais
11.
Comput Biol Med ; 178: 108707, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38870726

RESUMO

This article introduces a novel mathematical model analyzing the dynamics of Dengue in the recent past, specifically focusing on the 2023 outbreak of this disease. The model explores the patterns and behaviors of dengue fever in Bangladesh. Incorporating a sinusoidal function reveals significant mid-May to Late October outbreak predictions, aligning with the government's exposed data in our simulation. For different amplitudes (A) within a sequence of values (A = 0.1 to 0.5), the highest number of infected mosquitoes occurs in July. However, simulations project that when ßM = 0.5 and A = 0.1, the peak of human infections occurs in late September. Not only the next-generation matrix approach along with the stability of disease-free and endemic equilibrium points are observed, but also a cutting-edge Machine learning (ML) approach such as the Prophet model is explored for forecasting future Dengue outbreaks in Bangladesh. Remarkably, we have fitted our solution curve of infection with the reported data by the government of Bangladesh. We can predict the outcome of 2024 based on the ML Prophet model situation of Dengue will be detrimental and proliferate 25 % compared to 2023. Finally, the study marks a significant milestone in understanding and managing Dengue outbreaks in Bangladesh.

12.
Biochimie ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38871044

RESUMO

Proteases are key enzymes in viral replication, and interfering with these targets is the basis for therapeutic interventions. We previously introduced a hypothesis about conformational selection in the protease of dengue virus and related flaviviruses, based on conformational plasticity noted in X-ray structures. The present work presents the first functional evidence for alternate recognition by the dengue protease, in a mechanism based primarily on conformational selection rather than induced-fit. Recognition of distinct substrates and inhibitors in proteolytic and binding assays varies to a different extent, depending on factors reported to influence the protease structure. The pH, salinity, buffer type, and temperature cause a change in binding, proteolysis, or inhibition behavior. Using representative inhibitors with distinct structural scaffolds, we identify two contrasting binding profiles to dengue protease. Noticeable effects are observed in the binding assay upon inclusion of a non-ionic detergent in comparison to the proteolytic assay. The findings highlight the impact of the selection of testing conditions on the observed ligand affinity or inhibitory potency. From a broader scope, the dengue protease presents an example, where the induced-fit paradigm appears insufficient to explain binding events with the biological target. Furthermore, this protein reveals the complexity of comparing or combining biochemical assay data obtained under different conditions. This can be particularly critical for artificial intelligence (AI) approaches in drug discovery that rely on large datasets of compounds activity, compiled from different sources using non-identical testing procedures. In such cases, mismatched results will compromise the model quality and its predictive power.

13.
Infect Dis Poverty ; 13(1): 45, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867325

RESUMO

BACKGROUND: In 2023, Burkina Faso experienced the largest dengue epidemic ever in Africa. This study aimed to estimate the prevalence of symptomatic, subclinical, and asymptomatic dengue and determine the associated factors among adult contacts of dengue in the Central Region, Burkina Faso. METHODS: This cross-sectional study included contacts of dengue probable cases through cluster sampling in 2022-2023. These suspected cases that tested positive were identified from the five health facilities (Pissy CMA, Saaba CM, Kossodo CMA, Samandin CM, and Marcoussis CSPS) that reported the highest number of cases in 2021 per district. All participants underwent dengue and malaria rapid diagnostic tests (RDT). Samples positive for non-structural 1 protein antigen (AgNS1) and/or immunoglobulin M (IgM) were tested for serotype detection by reverse transcription polymerase chain reaction (RT-PCR). Binary logistic regression was done to identify the determinants of asymptomatic, subclinical, and symptomatic dengue among contacts of probable dengue cases. RESULTS: A total of 484 contacts were included, mostly in 2023 (75.2%). Most participants were females (58.6%), residing (24.3%) and passing their daytime (23.1%) in Saaba. The overall prevalence of dengue was estimated at 15.1% [95% confidence interval (CI): 12.0-18.6%], representing cases not seeking care in hospitals. Asymptomatic cases represented 2.9% (95% CI: 1.6-4.8%). Subclinical and symptomatic cases accounted for 6.0% (95% CI: 4.1-8.5%) and 6.2% (95% CI: 4.2-8.7%), respectively. Of the 58 samples tested by RT-PCR, 10 were confirmed for serotype 3 in 2023. Malaria cases were estimated at 5.6% (95% CI: 3.7-8.0%). After adjustment, participants claiming that a virus transmits dengue were likelier to have asymptomatic dengue [adjusted odds ratio (aOR) = 7.1, 95% CI: 2.4-21.0]. From the multivariable analysis, subclinical dengue was statistically associated with being included in the study in 2023 (aOR = 30.2, 95% CI: 2.0-455.5) and spending the daytime at Arrondissement 4 (aOR = 11.5, 95% CI: 1.0-131.0). After adjustment, symptomatic dengue was associated with living less than 50 m away from cultivated land (aOR = 2.8, 95% CI: 1.1-6.9) and living less than 50 m from a stretch of water (aOR = 0.1, 95% CI: 0.0-0.6). CONCLUSIONS: The overall burden of dengue among populations not seeking care in hospitals was quite high, with few asymptomatic cases. Efforts to manage dengue cases should also target non-hospital cases and raise population awareness. The 2023 epidemic could be due to dengue virus (DENV)-3.


Assuntos
Dengue , Humanos , Dengue/epidemiologia , Feminino , Masculino , Burkina Faso/epidemiologia , Adulto , Estudos Transversais , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Prevalência , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/genética , Família , Análise por Conglomerados , Criança , Pré-Escolar
14.
Gigascience ; 132024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38869150

RESUMO

Viral helicases are promising targets for the development of antiviral therapies. Given their vital function of unwinding double-stranded nucleic acids, inhibiting them blocks the viral replication cycle. Previous studies have elucidated key structural details of these helicases, including the location of substrate binding sites, flexible domains, and the discovery of potential inhibitors. Here we present a series of new Galaxy tools and workflows for performing and analyzing molecular dynamics simulations of viral helicases. We first validate them by demonstrating recapitulation of data from previous simulations of Zika (NS3) and SARS-CoV-2 (NSP13) helicases in apo and complex with inhibitors. We further demonstrate the utility and generalizability of these Galaxy workflows by applying them to new cases, proving their usefulness as a widely accessible method for exploring antiviral activity.


Assuntos
Simulação de Dinâmica Molecular , SARS-CoV-2 , SARS-CoV-2/enzimologia , Zika virus/enzimologia , Fluxo de Trabalho , RNA Helicases/química , RNA Helicases/metabolismo , Humanos , DNA Helicases/química , DNA Helicases/metabolismo , Antivirais/química , Antivirais/farmacologia , Proteases Semelhantes à Papaína de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Sítios de Ligação , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
15.
IDCases ; 36: e01996, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873641

RESUMO

Pyopericardium is a rare cause of cardiac tamponade. We present a case of a dengue fever patient who presented with cellulitis of the upper limbs, later manifesting cardiac tamponade, which was fatal. Although echocardiography on admission revealed a small pericardial effusion only, it later manifested as tamponade, causing cardiogenic shock. Staphylococcus pyopericardium was found later. Early identification could be possible with bedside point-of-care ultrasonography and echocardiography. Emergent pericardiocentesis or pig tail drain placement is life saving.

16.
Microbes Infect ; : 105378, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880233

RESUMO

Antibody dependent enhancement (ADE) of dengue virus (DENV) infection is one of the mechanisms contributing to increased severity during heterotypic, secondary infection. The complement protein C1q has been shown to reduce the magnitude of ADE in vitro. Therefore, we investigated the mechanisms of C1q modulation of ADE, focusing on processes of viral entry. Using a model of ADE of DENV-1 infection in human myeloid cell lines in the presence of monoclonal antibodies, 4G2 and 2H2, we found that C1q produced nearly a 40-fold reduction of ADE of DENV-1 in K562 cells, but had no effect in U937 cells. In K562 cells, C1q reduced adsorption of DENV-1/4G2 and exerted a dual inhibitory effect on adsorption and internalization of DENV-1/2H2. Distinct endocytic pathways in the presence of antibody corresponded to conditions where C1q produced a differential action. Also, C1q did not affect the intrinsic cell response mediated by FcγR in human myeloid cells. The modulation of ADE of DENV-1 by C1q is dependent on the FcγR expressed on immune cells and the specificity of the antibody comprising the immune complex. Understanding protective and pathogenic mechanisms in the humoral response to DENV infections is crucial for the successful design of antivirals and vaccines.

17.
J Med Virol ; 96(6): e29729, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38860590

RESUMO

Dengue, the most prevalent mosquito-borne disease worldwide, poses a significant health burden. This study integrates clinical data and transcriptomic datasets from different phases of dengue to investigate distinctive and shared cellular and molecular features. Clinical data from 29 dengue patients were collected and analyzed alongside a public transcriptomic data set (GSE28405) to perform differential gene expression analysis, functional enrichment, immune landscape assessment, and development of machine learning model. Neutropenia was observed in 54.79% of dengue patients, particularly during the defervescence phase (65.79%) in clinical cohorts. Bioinformatics analyses corroborated a significant reduction in neutrophil immune infiltration in dengue patients. Receiver operating characteristic curve analysis demonstrated that dynamic changes in neutrophil infiltration levels could predict disease progression, especially during the defervescence phase, with the area under the curve of 0.96. Three neutrophil-associated biomarkers-DHRS12, Transforming growth factor alpha, and ZDHHC19-were identified as promising for diagnosing and predicting dengue progression. In addition, the activation of neutrophil extracellular traps was significantly enhanced and linked to FcγR-mediated signaling pathways and Toll-like receptor signaling pathways. Neutrophil activation and depletion play a critical role in dengue's immune response. The identified biomarkers and their associated pathways offer potential for improved diagnosis and understanding of dengue pathogenesis and progression.


Assuntos
Biomarcadores , Dengue , Progressão da Doença , Neutrófilos , Humanos , Neutrófilos/imunologia , Dengue/imunologia , Biomarcadores/sangue , Feminino , Masculino , Adulto , Armadilhas Extracelulares/imunologia , Perfilação da Expressão Gênica , Biologia Computacional , Transcriptoma , Infiltração de Neutrófilos , Ativação de Neutrófilo , Neutropenia/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Curva ROC , Aprendizado de Máquina
18.
J Infect Dis ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842497

RESUMO

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

19.
Infect Dis Poverty ; 13(1): 43, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863070

RESUMO

BACKGROUND: The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. METHODS: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. RESULTS: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. CONCLUSIONS: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide.


Assuntos
Vírus da Dengue , Dengue , Genótipo , Filogenia , Sorogrupo , Vírus da Dengue/genética , Vírus da Dengue/classificação , Vírus da Dengue/fisiologia , China/epidemiologia , Dengue/epidemiologia , Dengue/virologia , Dengue/transmissão , Humanos , Surtos de Doenças , Filogeografia , Genoma Viral
20.
Front Genet ; 15: 1368843, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863443

RESUMO

Dengue has been one of the major public health problems in Malaysia for decades. Over 600,000 dengue cases and 1,200 associated fatalities have been reported in Malaysia from 2015 to 2021, which was 100% increase from the cumulative total of dengue cases reported during the preceding 07-year period from 2008 to 2014. However, studies that describe the molecular epidemiology of dengue in Malaysia in recent years are limited. In the present study, we describe the genetic composition and dispersal patterns of Dengue virus (DENV) by using 4,004 complete envelope gene sequences of all four serotypes (DENV-1 = 1,567, DENV-2 = 1,417, DENV-3 = 762 and DENV-4 = 258) collected across Malaysia from 2015 to 2021. The findings revealed that DENV populations in Malaysia were highly diverse, and the overall heterogeneity was maintained through repetitive turnover of genotypes. Phylogeography analyses suggested that DENV dispersal occurred through an extensive network, mainly among countries in South and East Asia and Malaysian states, as well as among different states, especially within Peninsular Malaysia. The results further suggested Selangor and Johor as major hubs of DENV emergence and spread in Malaysia.

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