Dengue Virus Control Research Articles

Dengue outbreaks in northern Nigeria: Evaluating the recommended Takeda vaccine and future prevention strategies.

Dengue fever, caused by the dengue virus (DENV), poses a significant public health challenge globally, with Nigeria experiencing sporadic outbreaks. A clear understanding of the dengue burden has not been achieved in Nigeria, just as in other African countries. Understanding the epidemiology and burden of dengue fever is essential for effective prevention and control strategies. This paper examines the recent dengue outbreaks in northern Nigeria, particularly in Sokoto state, and evaluates the recommended Takeda dengue vaccine (TDV) along with future prevention strategies. Despite limited surveillance and underreporting, dengue fever is endemic in Nigeria (with over 5 million cases and 5000 dengue-related deaths in 2023), with recent outbreaks indicating a growing concern. The TDV, a live attenuated tetravalent vaccine, has shown promise in preventing dengue fever, but challenges such as vaccine acceptance and accessibility need to be addressed. Global urbanization contributes to the disease's spread, which is influenced by factors such as population density, cultural beliefs, water storage practices, hygiene, and water supply accessibility. Future prevention strategies must focus on government intervention, community practices, and innovative vector control measures to mitigate the spread of DENV in Nigeria. This study will serve as a valuable reference for policymakers, researchers, and clinicians in the management and control of DENV in Nigeria and Africa as a whole.

Differences in proteome perturbations caused by the Wolbachia strain wAu suggest multiple mechanisms of Wolbachia-mediated antiviral activity

Some strains of the inherited bacterium Wolbachia have been shown to be effective at reducing the transmission of dengue virus (DENV) and other RNA viruses by Aedes aegypti in both laboratory and field settings and are being deployed for DENV control. The degree of virus inhibition varies between Wolbachia strains. Density and tissue tropism can contribute to these differences but there are also indications that this is not the only factor involved: for example, strains wAu and wAlbA are maintained at similar intracellular densities but only wAu produces strong DENV inhibition. We previously reported perturbations in lipid transport dynamics, including sequestration of cholesterol in lipid droplets, with strains wMel/wMelPop in Ae. aegypti. To further investigate the cellular basis underlying these differences, proteomic analysis of midguts was carried out on Ae. aegypti lines carrying strains wAu and wAlbA: with the hypothesis that differences in perturbations may underline Wolbachia-mediated antiviral activity. Surprisingly, wAu-carrying midguts not only showed distinct proteome perturbations when compared to non-Wolbachia carrying and wAlbA-carrying midguts but also wMel-carrying midguts. There are changes in RNA processing pathways and upregulation of a specific set of RNA-binding proteins in the wAu-carrying line, including genes with known antiviral activity. Lipid transport and metabolism proteome changes also differ between strains, and we show that strain wAu does not produce the same cholesterol sequestration phenotype as wMel. Moreover, in contrast to wMel, wAu antiviral activity was not rescued by cyclodextrin treatment. Together these results suggest that wAu could show unique features in its inhibition of arboviruses compared to previously characterized Wolbachia strains.

Clinical features and transmission risk analysis of dengue virus infections in Shenzhen, During 2014–2019

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are among the most common tropical diseases affecting humans. To analyze the risk of clinical and transmission of DF/DHF in Shenzhen, the surveillance on patients of all-age patients with dengue virus (DENV) infections was conducted. Our findings revealed that the majority of DENV-infected patients are young to middle-aged males, and the development of the disease is accompanied by abnormal changes in the percentages of neutrophils, lymphocytes, and basophils. Demographic analysis revealed that these patients is concentrated in areas such as Futian District, which may be due to the higher mosquito density and temperature than that in other area. Subsequent, mosquito infection experiments confirmed that the effect of temperature shift on DENV proliferation and transmission. Not only that, constant temperatures can enhance the spread of DENV, even increase the risk of epidemic. Thus, the role of innate immune response should be highlighted in the prediction of severe severity of DENV-infected patients, and temperature should be taken into account in the prevention and control of DENV. IntroductionDengue fever (DF) and dengue hemorrhagic fever (DHF) are among the most common tropical diseases affecting humans, and which caused by the four dengue virus serotypes (DENV 1–4). ObjectivesTo analyze the risk of clinical and transmission of DF/DHF in Shenzhen. MethodsThe surveillance on patients of all-age patients with dengue virus (DENV) infections was conducted. ResultsOur findings revealed that the majority of DENV-infected patients are young to middle-aged males, and the development of the disease is accompanied by abnormal changes in the percentages of neutrophils, lymphocytes, and basophils. Demographic analysis revealed that these patients is concentrated in areas such as Futian District, which may be due to the higher mosquito density and temperature than that in other area. Subsequent, mosquito infection experiments confirmed that the effect of temperature shift on DENV proliferation and transmission. Not only that, constant temperatures can enhance the spread of DENV, even increase the risk of epidemic. Conclusion1. Elevated levels of neutrophils, lymphocytes, basophils, and temperature are all significant risk factors for dengue transmission and pathogenesis; 2. Temperature increasing is associated with a higher risk of dengue transmission; 3. Fluctuations in temperature around 28 °C (28 ± 5 °C) would increase dengue transmission.

Dengue Lurks During Coronavirus Disease-19 Pandemic in Indonesia: A Narrative Review

BACKGROUND: Most attention and healthcare resources in Indonesia have been geared toward battling the coronavirus (CoV) disease (COVID)-19 pandemic, and less overture has been given to the looming risks of dengue that has been endemic in many areas of Indonesia. Despite related constraints, the Primary Health Cares (PHC) in Indonesia plays an important role in the face of emergency situations.
 AIM: This study aimed to review the dengue and COVID-19 infection, clinical manifestations in children and adults, clinical pathology findings, as well as the prevention strategies that could be applied in PHC.
 METHODS: This study is a narrative review based on the research articles and reports that were published between 2010 and 2020. A total of 70 articles and reports were obtained and after careful consideration, 58 articles and reports were used as references of this study.
 RESULTS: Both dengue virus (DENV) and severe acute respiratory syndrome-CoV (SARS-CoV-2) share the similarity of antigenic structure, common symptoms, and laboratory findings. The immune response in SARS-CoV-2 may cause a cytokine storm, which can increase vascular permeability and organ damage. Secondary infection of DENV with different strains may allow the occurrence of antibody-dependent enhancement. The cross-reactions between SARS-CoV-2 antibodies and DENV antigens may cause false positive on rapid dengue infection serological tests.
 CONCLUSION: PHC as the front line of health services has a fundamental role in the crisis situation. The prevention and control of DENV and SARS-CoV-2 infections are based on the mode of transmission and need compliance to the related health protocols.

Broad dengue neutralization in mosquitoes expressing an engineered antibody.

With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.

Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody

With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.

The microbiome composition of Aedes aegypti is not critical for Wolbachia-mediated inhibition of dengue virus.

BackgroundDengue virus (DENV) is primarily vectored by the mosquito Aedes aegypti, and is estimated to cause 390 million human infections annually. A novel method for DENV control involves stable transinfection of Ae. aegypti with the common insect endosymbiont Wolbachia, which mediates an antiviral effect. However, the mechanism by which Wolbachia reduces the susceptibility of Ae. aegypti to DENV is not fully understood. In this study we assessed the potential of resident microbiota, which can play important roles in insect physiology and immune responses, to affect Wolbachia-mediated DENV blocking.Methodology/FindingsThe microbiome of Ae. aegypti stably infected with Wolbachia strain wMel was compared to that of Ae. aegypti without Wolbachia, using 16s rDNA profiling. Our results indicate that although Wolbachia affected the relative abundance of several genera, the microbiome of both the Wolbachia-infected and uninfected mosquitoes was dominated by Elizabethkingia and unclassified Enterobacteriaceae. To assess the potential of the resident microbiota to affect the Wolbachia-mediated antiviral effect, we used antibiotic treatment before infection with DENV by blood-meal. In spite of a significant shift in the microbiome composition in response to the antibiotics, we detected no effect of antibiotic treatment on DENV infection rates, or on the DENV load of infected mosquitoes.Conclusions/SignificanceOur findings indicate that stable infection with Wolbachia strain wMel produces few effects on the microbiome of laboratory-reared Ae. aegypti. Moreover, our findings suggest that the microbiome can be significantly altered without affecting the fundamental DENV blocking phenotype in these mosquitoes. Since Ae. aegypti are likely to encounter diverse microbiota in the field, this is a particularly important result in the context of using Wolbachia as a method for DENV control.

Decreased Dengue Replication and an Increased Anti-viral Humoral Response with the use of Combined Toll-Like Receptor 3 and 7/8 Agonists in Macaques

BackgroundPathogenic versus protective outcomes to Dengue virus (DENV) infection are associated with innate immune function. This study aimed to determine the role of increased TLR3- and TLR7/8-mediated innate signaling after Dengue infection of rhesus macaques in vivo to evaluate its impact on disease and anti-DENV immune responses.Methodology/Principal FindingsTLR3 and TLR7/8 agonists (emulsified in Montanide) were administered subcutaneously to rhesus macaques at 48 hours and 7 days after DENV infection. The Frequency and activation of myeloid dendritic cells, plasmacytoid dendritic cells, and B cells were measured by flow cytometry while the serum levels of 14 different cytokines and chemokines were quantified. Adaptive immune responses were measured by DENV-specific antibody subtype measurements. Results showed that the combined TLR agonists reduced viral replication and induced the development of a proinflammatory reaction, otherwise absent in Dengue infection alone, without any clear signs of exacerbated disease. Specifically, the TLR-induced response was characterized by activation changes in mDC subsets concurrent with higher serum levels of CXCL-10 and IL-1Ra. TLR stimulation also induced higher titers of anti-DENV antibodies and acted to increase the IgG2/IgG1 ratio of anti-DENV to favor the subtype associated with DENV control. We also observed an effect of DENV-mediated suppression of mDC activation consistent with prior in vitro studies.Conclusions/SignificanceThese data show that concurrent TLR3/7/8 activation of the innate immune response after DENV infection in vivo acts to increase antiviral mechanisms via increased inflammatory and humoral responses in rhesus macaques, resulting in decreased viremia and melioration of the infection. These findings underscore an in vivo protective rather than a pathogenic role for combined TLR3/7/8-mediated activation in Dengue infection of rhesus macaques. Our study provides definitive proof-of-concept into the mechanism by which DENV evades immune recognition and activation in vivo.

Dengue Control: The Challenge Ahead

Dengue Control: The Challenge Ahead