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Introduction: Dengue disease represents a large and growing global threat to public health, accounting for a significant burden to health systems of endemic countries. The World Health Organization's (WHO) Strategic Advisory Group of Experts (SAGE) and the European Medicines Agency (EMA) currently recommend the use of TAK-003 dengue vaccine in high dengue burden and transmission settings for countries considering vaccination as part of their integrated management strategy for prevention and control of Dengue. Areas covered: This paper describes the main conclusions of a workshop held by the Arbovirus Committee of the Latin American Society of Pediatric Infectious Diseases (SLIPE) in November 2023, to generate consensus recommendations on the introduction of this new vaccine in the region. Considerations were made regarding the molecular epidemiology of dengue infection in the Americas and the need for more precise phylogenetic classification and correlation with clinical outcome and disease severity. Expert opinion: Introduction of dengue vaccine should be considered as an strategy for health entities in the region, with participation of social sectors, scientific societies, and ministries of health that could be able to create a successful vaccination program. [ABSTRACT FROM AUTHOR]

The establishment of a productive dengue virus (DENV) infection in the midgut epithelial cells of Aedes aegypti is critical for the viral transmission cycle. The hypothesis that DENV virions interact directly with specific mosquito midgut proteins was explored. We found that DENV serotype 2 (DENV2) pretreated with trypsin interacted with a single 31 kDa protein, identified as AAEL011180 by protein mass spectrometry. This putative receptor is a highly conserved protein and has orthologs in culicine and anopheline mosquitoes. We confirmed that impairing the expression of AAEL011180 in the midgut of Ae. aegypti females abolished the interaction with DENV2, and the virus also bound to immobilized recombinant purified receptor. Furthermore, recombinant DENV2 surface E glycoprotein bound to recombinant AAEL011180 with high affinity (38.2 nM) in binding kinetic analysis using surface plasmon resonance. The gene for this DENV2 E protein receptor (EPrRec) was disrupted, but since the gene is essential in Ae. aegypti, only heterozygote knockout (ΔEPrRec+/−) females could be recovered. Further reducing EPrRec mRNA expression in the midgut of ΔEPrRec+/− females by systemic dsRNA injection significantly reduced the prevalence of DENV2 midgut infection. EPrRec also interacts with heat shock protein 70 cognate 3 (Hsc70-3), and silencing Hsc70-3 expression in ΔEPrRec females also reduced the prevalence of DENV2 midgut infection. [ABSTRACT FROM AUTHOR]

Despite advancements in medicine and vaccination, the global death toll from dengue disease continues to rise, especially in developing countries, where modern healthcare access and prevention are limited. In the twenty-first century, dengue disease has emerged as a severe global challenge for the health sector because it severely affects more than 100 countries and causes thousands of deaths annually. This study designs an SEIR-SEI mathematical model of the dengue virus by introducing a control parameter within the mosquito population. The inclusion of this parameter enables us to determine the impact of control measures on the transmission dynamics of the dengue virus. Firstly, we ensure that all state variables are bounded and remain non-negative throughout the study. Then, we calculate the two equilibrium points, the dengue-free equilibrium (DFE) and dengue-endemic equilibrium point (DEE), of the model for further analysis. We also calculate the reproductive number R , which is a crucial threshold parameter in epidemiology. The qualitative analysis shows that the model possesses local and global stability at the DFE and DEE points if R < 1 and R > 1 , respectively. We also conduct a sensitivity analysis to identify the parameter with the most significant impact on the transmission dynamics of the dengue virus. This insight assists health policy makers in optimizing their struggles to lower the infection rates between susceptible humans and infected mosquito populations. We apply the two numerical schemes, the non-standard finite difference scheme (NSFD) and the Runga-kutta (RK4) scheme, to validate the theoretical and numerical results of the proposed SEIR-SEI dengue epidemic model. Numerical simulations are also provided in support of these results. [ABSTRACT FROM AUTHOR]

Dengue, an acute febrile disease transmitted by Aedes mosquitoes, is caused by the dengue virus (DENV), presenting a formidable challenge to global public health. By examining clues from ancient Chinese books and conducting a comprehensive review, this study elucidates the characteristics of potential dengue epidemics in China prior to 1978. This evidence indicates that China may not have experience dengue epidemics before 1840. During 1840–1949, however, it experienced a noticeable dengue occurrence and prevalence in the 1870s, 1920s, and 1940s. Then from 1949 to 1978, only sporadic reports were accounted. The disparity in the frequency of dengue occurrences across three time periods suggests that the persistent characteristic of dengue epidemics in China primarily arises from imported cases resulting from international exchanges, subsequently leading to local outbreaks influenced by global epidemic trend. This research offers a novel perspective on retrospectively examining the historical trajectory of dengue epidemics and provides valuable insights into exploration of DENV epidemic patterns. [ABSTRACT FROM AUTHOR]

Orthoflaviviruses, including zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, induce severely debilitating infections and contribute significantly to the global disease burden, yet no clinically approved antiviral treatments exist. This review offers a comprehensive analysis of small-molecule drug development targeting orthoflaviviral infections, with a focus on NS2B-NS3 inhibition. We systematically examined clinical trials, preclinical efficacy studies, and modes of action for various viral replication inhibitors, emphasizing allosteric and orthosteric drugs inhibiting NS2B-NS3 protease with in vivo efficacy and in vitro-tested competitive NS2B-NS3 inhibitors with cellular efficacy. Our findings revealed that several compounds with in vivo preclinical efficacy failed to show clinical antiviral efficacy. NS3-NS4B inhibitors, such as JNJ-64281802 and EYU688, show promise, recently entering clinical trials, underscoring the importance of developing novel viral replication inhibitors targeting viral machinery. To date, the only NS2B-NS3 inhibitor that has undergone clinical trials is doxycycline, however, its mechanism of action and clinical efficacy as viral growth inhibitor require additional investigation. SYC-1307, an allosteric inhibitor, exhibits high in vivo efficacy, while temoporfin and methylene blue represent promising orthosteric non-competitive inhibitors. Compound 71, a competitive NS2B-NS3 inhibitor, emerges as a leading preclinical candidate due to its high cellular antiviral efficacy, minimal cytotoxicity, and favorable in vitro pharmacokinetic parameters. Challenges remain in developing competitive NS2B-NS3 inhibitors, including appropriate biochemical inhibition assays as well as the selectivity and conformational flexibility of the protease, complicating effective antiviral treatment design. [ABSTRACT FROM AUTHOR]

Dengue is a highly prevalent mosquito-borne disease that is endemic in over 100 countries. It has a wider impact in terms of severity of illness and mortality risk in the absence of an effective vaccine as yet. The purpose of this study was to use meta-analysis to find out how common the dengue virus (DENV) is in India based on public data and to figure out how much of a problem. We searched, read, and reviewed about DENV in India that were available online. Forty-four cross-sectional studies were selected from the 178 records. There were reports of dengue cases in 14 out of the 28 states. Out of the patients presenting with symptoms of Dengue 27% of people were confirmed to have DENV infection with 82.29% (95% CI. 81-84%), having dengue IgM, 41.67% (95% CI: 40.16-43.43), having dengue IgG, and 23.97% (95% C.I. 14-43%), having both IgG and IgM from positive sample n=27156. Hospitalbased cross-sectional studies on suspected Dengue-like illness (DLI) found that 99.48% of people had confirmed dengue out of the patients with features of DLI, and community-based studies found that 0.52% of DLI cases had dengue. The seroprevalence rates for East, South, North, and Western regions were 35.38% (95% C.I.14-31%), 11.57% (95% C.I. 2-69%), 38.10% (95% C.I. 9-61%), and 14.87% (95% C.I. 6-38%) correspondingly. DENV is interestingly spreading across the whole country, and the disease's frequency varies a lot from place to place and from 2010-2023. However this review does not find appropriate published literature from 50% of the Indian states. The identification of IgG-class antibodies to dengue virus is indicative of prior exposure to this pathogen. Almost all immunocompetent individuals should have developed IgG antibodies against the dengue virus within three weeks of exposure. The presence of dengue virus IgM-class antibodies is indicative of an acute phase of infection. National Vector borne Disease Control Programme (NVBDCP) has some surveillance information, appropriate designed research into prevalence and risk factors for DENV infection would be required to provide adequate information for public health intervention. [ABSTRACT FROM AUTHOR]

The challenge of dengue control due to the unavailability of a specific medication stresses the importance of releasing Wolbachia-carrying mosquitoes through vector control programs. This study investigated the sustainability and frequency of Wolbachia in Wolbachia-dengue-carrying mosquitoes in two dengue hotspot localities in Selangor. A modified sticky ovitrap was used to collect adult mosquitoes in two Wolbachia-releasing areas in Selangor, Kelana Puteri and Kelana D'Putera condominiums. All mosquito samples were subjected to PCR using wsp-specific primers for Wolbachia detection. Dengue virus was detected using RT-PCR, followed by multiplex-PCR. Out of the 80 Aedes spp. collected, Ae. aegypti was the most predominant species. More than one-third of Ae. aegypti were positive for Wolbachia, with 22.9% being superinfected with both Wolbachia A and B strains. About 61.4% of the species were uninfected with Wolbachia. Ae. aegypti carrying the Wolbachia A strain was also identified, which has previously never been reported. This strain was similar to the one found naturally in Ae. albopictus. None of the Ae. aegypti and Ae. albopictus were positive for dengue virus. This study could serve as a model for local researchers or health authorities to design and plan an effective field release and monitoring of Wolbachia-infected mosquitoes. [ABSTRACT FROM AUTHOR]

We determined the dengue virus (DENV) serotypes and genotypes in archived serum samples that were collected during the 2014–2016 and 2021 dengue outbreaks in Dire Dawa City and the Somali region in Ethiopia. DENV serotype 1 (DENV-1) was predominant followed by DENV serotype 2 (DENV-2). Thirteen of the DENV-1 strains were assigned to Genotype-I, while the remaining two were found to be Genotype-III. All three DENV-2 strains were assigned the Cosmopolitan Genotype. The DENV strains responsible for the outbreaks are genetically closely related to the DENV strains that circulated in neighboring and Asian countries. The findings also showed continued local transmission of a monophyletic lineage and a co-circulation of DENV-1 and DENV-2 during the outbreaks. There is a need to strengthen DENV genomic surveillance capacity for the early detection of circulating serotypes, and prevent devastating consequences of future outbreaks due to the co-circulation of different serotypes. [ABSTRACT FROM AUTHOR]

In August 2023, we identified a case of dengue fever in Yantai City, which was imported from Xishuangbanna, China. To investigate its evolutionary history and population dynamics, we utilized the metatranscriptomic method to obtain the virus' whole genome sequence. Together with 367 selected dengue virus whole genome sequences from the NCBI database, we constructed a time-scaled Maximum Clade Credibility (MCC) tree. We found that our sequence exhibited a high homology with a sequence of DENV1 (OR418422.1) uploaded by the Guangzhou Center for Disease Control and Prevention in 2023, with an estimated divergence time around 2019 (95% HPD: 2017–2023), coinciding with the emergence of SARS-CoV-2. The DENV strain obtained in this study belongs to genotype I of DENV1. Its ancestors experienced a global epidemic around 2005 (95% HPD: 2002–2010), and its progeny strains have spread extensively in Southeast Asia and China since around 2007 (95% HPD: 2006–2011). The Bayesian skyline plot indicates that the current population of DENV1 has not been affected by SARS-CoV-2 and is expected to maintain stable transmission. Hence, it is imperative to track and monitor its epidemiological trends and genomic variations to prevent potential large-scale outbreaks in the post-SARS-CoV-2 era. [ABSTRACT FROM AUTHOR]

Dengue fever is a mosquito-borne illness that affects millions of people worldwide. Artificial intelligence (AI) is being employed in the battle against it. AI is being used to analyse dengue immune repertoires, which may yield hitherto unheard-of insights into the complexities of dengue adaptive immunity, help in the development of novel treatments, and influence the creation of vaccines. This AI-driven strategy may contribute to the creation of dengue fever therapies that are more potent. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV), transmitted by infected mosquitoes, is a major public health concern, with approximately half the world's population at risk for infection. Recent decades have increasing incidence of dengue-associated disease alongside growing frequency of outbreaks. Although promising progress has been made in anti-DENV immunizations, post-infection treatment remains limited to non-specific supportive treatments. Development of antiviral therapeutics is thus required to limit DENV dissemination in humans and to help control the severity of outbreaks. Dendritic cells (DCs) are amongst the first cells to encounter DENV upon injection into the human skin mucosa, and thereafter promote systemic viral dissemination to additional human target cells. Autophagy is a vesicle trafficking pathway involving the formation of cytosolic autophagosomes, and recent reports have highlighted the extensive manipulation of autophagy by flaviviruses, including DENV, for viral replication. However, the temporal profiling and function of autophagy activity in DENV infection and transmission by human primary DCs remains poorly understood. Herein, we demonstrate that mechanisms of autophagosome formation and extracellular vesicle (EV) release have a pro-viral role in DC-mediated DENV transmission. We show that DENV exploits early-stage canonical autophagy to establish infection in primary human DCs. DENV replication enhanced autophagosome formation in primary human DCs, and intrinsically-heightened autophagosome biogenesis correlated with relatively higher rates of DC susceptibility to DENV. Furthermore, our data suggest that viral replication intermediates co-localize with autophagosomes, while productive DENV infection introduces a block at the late degradative stages of autophagy in infected DCs but not in uninfected bystander cells. Notably, we identify for the first time that approximately one-fourth of DC-derived CD9/CD81/CD63+ EVs co-express canonical autophagy marker LC3, and demonstrate that DC-derived EV populations are an alternative, cell-free mechanism by which DCs promote DENV transmission to additional target sites. Taken together, our study highlights intersections between autophagy and secretory pathways during viral infection, and puts forward autophagosome accumulation and viral RNA-laden EVs as host determinants of DC-mediated DENV infection in humans. Host-directed therapeutics targeting autophagy and exocytosis pathways thus have potential to enhance DC-driven resistance to DENV acquisition and thereby limit viral dissemination by initial human target cells following mosquito-to-human transmission of DENV. [ABSTRACT FROM AUTHOR]

In flaviviruses such as Dengue or Zika, non-structural (NS) NS4A protein forms homo-oligomers, participates in membrane remodelling and is critical for virulence. In both viruses, mature NS4A has the same length and three predicted hydrophobic domains. The oligomers formed by Dengue NS4A are reported to be small (n = 2, 3), based on denaturing SDS gels, but no high-resolution structure of a flavivirus NS4A protein is available, and the size of the oligomer in lipid membranes is not known. Herein we show that crosslinking Zika NS4A protein in lipid membranes results in oligomers at least up to hexamers. Further, sedimentation velocity shows that NS4A in mild detergent C14-betaine appears to be in fast equilibrium between at least two species, where one is smaller, and the other larger, than a trimer or a tetramer. Consistently, sedimentation equilibrium data was best fitted to a model involving an equilibrium between dimers (n = 2) and hexamers (n = 6). Overall, the large, at least hexameric, oligomers obtained herein in liposomes and in mild detergent are more likely to represent the forms of NS4A present in cell membranes. [ABSTRACT FROM AUTHOR]

Background: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. Results: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/μL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. Conclusions: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are cellular organelles derived from the endoplasmic reticulum (ER), serving as lipid storage sites crucial for maintaining cellular lipid homeostasis. Recent attention has been drawn to their roles in viral replication and their interactions with viruses. However, the precise biological functions of LDs in viral replication and pathogenesis remain incompletely understood. To elucidate the interaction between LDs and viruses, it is imperative to comprehend the biogenesis of LDs and their dynamic interactions with other organelles. In this review, we explore the intricate pathways involved in LD biogenies within the cytoplasm, encompassing the uptake of fatty acid from nutrients facilitated by CD36-mediated membranous protein (FABP/FATP)-FA complexes, and FA synthesis via glycolysis in the cytoplasm and the TCL cycle in mitochondria. While LD biogenesis primarily occurs in the ER, matured LDs are intricately linked to multiple organelles. Viral infections can lead to diverse consequences in terms of LD status within cells post-infection, potentially involving the breakdown of LDs through the activation of lipophagy. However, the exact mechanisms underlying LD destruction or accumulation by viruses remain elusive. The significance of LDs in viral replication renders them effective targets for developing broad-spectrum antivirals. Moreover, considering that reducing neutral lipids in LDs is a strategy for anti-obesity treatment, LD depletion may not pose harm to cells. This presents LDs as promising antiviral targets for developing therapeutics that are minimally or non-toxic to the host. [ABSTRACT FROM AUTHOR]

Background: Despite maternal flavivirus infections' linkage to severe maternal and fetal outcomes, surveillance during pregnancy remains limited globally. Further complicating maternal screening for these potentially teratogenic pathogens is the overwhelming subclinical nature of acute infection. This study aimed to understand perinatal and neonatal risk for poor health outcomes associated with flaviviral infection during pregnancy in El Salvador. Methods: Banked serologic samples and clinical results obtained from women presenting for labor and delivery at a national referent hospital in western El Salvador March to September 2022 were used for this study. 198 samples were screened for dengue and Zika virus IgM, and statistical analyses analyzed demographic and clinical outcome associations with IgM positivity. Results: This serosurvey revealed a high rate of maternal flavivirus infection—24.2% of women presenting for labor and delivery were dengue or Zika virus IgM positive, suggesting potential infection within pregnancy. Specifically, 20.2% were Zika virus IgM positive, 1.5% were dengue virus IgM positive, and 2.5% were both dengue and Zika virus IgM positive. Women whose home had received mosquito abatement assistance within the last year by the ministry of health were 70% less likely to test IgM positive (aOR = 0.30, 95%CI: 0.10, 0.83). Further, statistical geospatial clustering revealed transmission foci in six primary municipalities. Pregnancy complications and poor birth outcomes were noted among the dengue and/or Zika virus maternal infection group, although these outcomes were not statistically different than the seronegative group. None of the resulting neonates born during this study were diagnosed with congenital Zika syndrome. Conclusions: The high rate of Zika virus detected among pregnant women and the lack of Zika-specific neonatal outcomes monitoring during a non-outbreak year highlights the need for continued surveillance in Central America and among immigrant mothers presenting for childbirth from these countries. As changing climatic conditions continue to expand the range of the disease vector, asymptomatic screening programs could be vital to early identification of outbreaks and clinical management of cases. [ABSTRACT FROM AUTHOR]

Dengue is a mosquito-borne pandemic viral infection, which transmits to humans from Female Aedes albopictis or Aedes agypti mosquitoes. It progressively deteriorates the health of infected individuals and poses a high threat of human morbidity and mortality. This paper proposes an intelligent healthcare system which identifies, monitors, and alerts dengue virus (DeV) infected individuals and other stakeholders in real-time and control the DeV infection outbreak using cloud computing, internet of things and fog computing paradigms. The proposed system uses Naive Bayesian Network (NBN) for diagnosing the possibly DeV infected individuals and generating real-time alerts for suggesting and alerting the concerned stakeholders for taking on-time necessary actions at the fog subsystem. The proposed system also uses Social Network Analysis at the cloud subsystem, to provide Global Positioning Systems (GPS)-based global risk assessment of the DeV infection on Google Maps (Google-based web map service) and control DeV infection outbreak. The analysis of the experimental results acknowledges the efficiency of the NBN-based DeV infection diagnosis, alert generation, and GPS-based risk assessment functionality, of the proposed system, via various statistical measures and experimental approaches. [ABSTRACT FROM AUTHOR]

The Indian subcontinent with its population density, climatic conditions, means of subsistence, socioeconomic factors as well as travel and tourism presents a fertile ground for thriving of RNA viruses. Despite being pathogens of huge significance, there is very little focus on research into the biology and pathogenesis of RNA viruses in India. Studies on epidemiology and disease burden, risk factors, the immune response to RNA viruses, circulating virus strains and virus evolution, animal models of disease, antivirals and vaccines are strikingly absent. Emerging RNA viruses such as Zika virus, Nipah virus and Crimean-Congo haemorrhagic fever virus are a matter of grave concern to India. Here we summarize the outcome of the India|EMBO symposium on “RNA viruses: immunology, pathogenesis and translational opportunities” organized at Faridabad, National Capital Region, India, on March 28–30, 2018. The meeting focused on RNA viruses (non-HIV), and both national and international experts on RNA viruses covered topics ranging from epidemiology, immune response, virus evolution and vaccine trials concerning RNA viruses. The aim of the symposium was to create a road map for RNA virus research in India. Both concrete and tentative ideas pointing towards short-term and long-term goals were presented with recommendations for follow-up at government level. [ABSTRACT FROM AUTHOR]

Objective: The aim of this research is the early detection of dengue infection on the basis of presence of high fluorescent lymphocyte (HFL) which enables the clinicians to tailor further investigations and early commencement of treatment to prevent complications and thus can reduce mortality and morbidity in dengue patients. Study Design: Prospective Research. Setting: Fauji Foundation Hospital in Rawalpindi. Period: February 2022 to July 2022. Methods: Samples of Full blood counts (FBC) received in Pathology laboratory were processed on automated Hematology analyzer Sysmex XN-series (XN-1000). All the FBCs that were of known dengue patients were excluded from the study. The FBCs with High Fluorescent Lymphocytes on White blood cell differential fluorescence (WDF) scattergram were selected and evaluated. Detection of dengue infection was done by using Dengue Virus ELISA (IgM and IgG) test. Results: Among one hundred samples with High Fluorescence Lymphocyte there were 77% were Dengue Positive. Binomial test did give a significant association of Dengue with High Fluorescence Lymphocyte (p<0.01). Conclusion: We draw the conclusion that presence of high fluorescent lymphocytes helps in the early detection of dengue positive cases. [ABSTRACT FROM AUTHOR]

Background: Thrombocytopenia is the most notable phenomenon in dengue. Activation status of platelets and interaction of platelets with endothelium contribute towards dengue disease pathogenesis. Platelets are the major cell types known to release extracellular vesicles, especially exosomes in circulation. However, the role of platelet derived exosomes (PLT-EXOs) in endothelial dysfunction during dengue infection remains unknown. Methods: In this study, we recruited 28 healthy subjects and 69 dengue patients categorized as WS- (n=31), WS+ (n=29) and SD (n=9). Platelets were isolated from platelet rich plasma of dengue patients and their activation was assessed by flow cytometry. PLT-EXOs were isolated by ultracentrifugation method. Western blot analyses were performed to characterize the exosomes. Exosome uptake experiment was carried out to see the internalization of exosomes inside endothelial cells (HUVECs). To observe the effect of exosomes on endothelial cells, exosomes were added on HUVECs and expression of adherens and tight junctional proteins were examined by immunofluorescence assay and western blot. Expression levels of vascular injury markers were measured in the culture supernatants of Exosome-HUVEC coculture and sera of dengue patients by MSDmultiplex assay Results: As compared to healthy subjects, CD41/CD61 expression was significantly reduced (p<0.0001) and CD62p expression was significantly increased (p<0.0001) on platelets in dengue patients. PLT-EXOs isolated from the dengue patients showed higher expression of CD63 and CD9 proteins than the healthy subjects. With in-vitro immunofluorescence assays, we illustrated the internalization of PLT-EXOs by the HUVECs and observed disruption of endothelial cell monolayer integrity in the presence of PLT-EXOs from WS+ and SD patients. Furthermore, the significant reduction in the expressions of ZO-2, VE-Cadherin and CD31 in endothelial cells following exposure to PLT-EXOs from the dengue patients provide direct evidence of PLT-EXOs mediated vascular permeability. PLT-EXOs stimulated the release of inflammatory markers CRP, SAA, sVCAM-1 and sICAM-1 in the supernatants of HUVEC cells. Importantly, significantly higher levels of CRP, sVCAM-1 and sICAM-1 in the sera of severe than mild dengue patients (p<0.0001) suggest their role in disease severity. Conclusions: In summary, our data suggest that PLT-EXOs promote vascular leakage via release of proinflammatory mediators and compromise vascular barrier integrity in dengue patients. [ABSTRACT FROM AUTHOR]

Aims: Dengue virus is a global pathogen that lacks an effective vaccine or therapy. Screening medicinal plants for antidengue properties provides a promising avenue to identify potent compounds. Mangroves, known for their resilience in harsh conditions, produce a diverse range of natural products with unique biochemical profiles, which hold potential for anti-dengue treatments. This study aims to evaluate the anti-dengue activity of selected mangrove plant species from Sabah against DENV2 NS2B-NS3pro, utilizing an enzymatic protease assay. Methodology and results: Six mangrove species (Avicennia marina, Bruguiera gymnorrhiza, Ceriops tagal, Rhizophora apiculata, Rhizophora mucronata and Xylocarpus granatum) were investigated, with various plant parts subjected to aqueous and ethanol extraction. The results demonstrated significant anti-dengue activity in both aqueous and ethanolic extracts of the mangroves against DENV2 NS2B-NS3pro, with IC50 values ranging from 0.95 µg/mL to 6.24 µg/mL. Notably, the ethanolic extract of R. apiculata leaves exhibited the highest inhibition, with an IC50 value of 0.95 µg/mL. Conclusion, significance and impact of study: These findings suggest that the ethanolic extracts from R. apiculata leaves hold promise as potential candidates for dengue treatment. This study underscores the importance of natural products as valuable sources for the development of novel anti-dengue treatments, highlighting the need to explore mangroves in the quest for effective therapeutic options. [ABSTRACT FROM AUTHOR]

In search of a mouse model for use in evaluating dengue vaccines, we assessed A129 mice that lacked IFN-α/β receptors, rendering them susceptible to dengue virus (DENV) infection. To our knowledge, no reports have evaluated dengue vaccine efficiency using A129 mice. A129 mice were given a single intraperitoneal (IP) or subcutaneous (SC) injection of the vaccine, Dengvaxia. After 14 days of immunization via the IP or SC injection of Dengvaxia, the A129 mice exhibited notably elevated levels of anti-DENV immunoglobulin G and neutralizing antibodies (NAb) targeting all four DENV serotypes, with DENV-4 displaying the highest NAb levels. After challenge with DENV-2, Dengvaxia and mock-immunized mice survived, while only the mock group exhibited signs of morbidity. Viral genome levels in the serum and tissues (excluding the brain) were considerably lower in the immunized mice compared to those in the mock group. The SC administration of Dengvaxia resulted in lower viremia levels than IP administration did. Therefore, given that A129 mice manifest dengue-related morbidity, including viremia in the serum and other tissues, these mice represent a valuable model for investigating novel dengue vaccines and antiviral drugs and for exploring dengue pathogenesis. [ABSTRACT FROM AUTHOR]

Dengue continues to be a major public health concern in Latin America and the Caribbean with many countries in the region having experienced drastic increases in the incidence of dengue over the past few years. Dengue virus is predominantly transmitted by the bite of an infected female Aedes aegypti mosquito via a process called horizontal transmission. However, the virus may also be transmitted from an infected female mosquito to her offspring by vertical transmission, which occurs via viral invasion of the ovary either at the time of fertilization or during oviposition. In this way, mosquitoes may become dengue virus infected before ever encountering a human host. While some researchers have reported this phenomenon and suggested it may serve as a reservoir for the dengue virus in nature, others have questioned its epidemiological significance because of the low frequency at which it has been observed. Several researchers have either altogether failed to detect it or observed its occurrence at low frequencies. However, some studies have attributed these failures to small sample sizes as well as poor sensitivities of screening methods employed. Therefore, an overview of the occurrence, significance and limitations of detection of vertical transmission of dengue virus in Aedes mosquitoes in nature within Latin America and the Caribbean will be the focus of this review. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is a major mosquito-borne human pathogen in tropical countries; however, there are currently no targeted antiviral treatments for DENV infection. Compounds 27 and 29 have been reported to be allosteric inhibitors of DENV RdRp with potent inhibitory effects. In this study, the structures of compounds 27 and 29 were optimized using computer-aided drug design (CADD) approaches. Nine novel compounds were synthesized based on rational considerations, including molecular docking scores, free energy of binding to receptor proteins, predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) parameters, structural diversity, and feasibility of synthesis. Subsequently, the anti-DENV activity was assessed. In the cytopathic effect (CPE) assay conducted on BHK-21 cells using the DENV2 NGC strain, both SW-b and SW-d demonstrated comparable or superior activity against DENV2, with IC50 values of 3.58 ± 0.29 μM and 23.94 ± 1.00 μM, respectively, compared to that of compound 27 (IC50 = 19.67 ± 1.12 μM). Importantly, both SW-b and SW-d exhibited low cytotoxicity, with CC50 values of 24.65 μmol and 133.70 μmol, respectively, resulting in selectivity indices of 6.89 and 5.58, respectively. Furthermore, when compared to the positive control compound 3′-dATP (IC50 = 30.09 ± 8.26 μM), SW-b and SW-d displayed superior inhibitory activity in an enzyme inhibitory assay, with IC50 values of 11.54 ± 1.30 μM and 13.54 ± 0.32 μM, respectively. Molecular dynamics (MD) simulations elucidated the mode of action of SW-b and SW-d, highlighting their ability to enhance π–π packing interactions between benzene rings and residue W795 in the S1 fragment, compared to compounds 27 and 29. Although the transacylsulphonamide fragment reduced the interaction between T794 and NH, it augmented the interaction between R729 and T794. In summary, our study underscores the potential of SW-b and SW-d as allosteric inhibitors targeting the DENV NS5 RdRp domain. However, further in vivo studies are warranted to assess their pharmacology and toxicity profiles. [ABSTRACT FROM AUTHOR]

Rapid and sensitive detection of Dengue virus remains a critical challenge in global public health. This study presents the development and evaluation of a Zinc Oxide nanorod (ZnO NR)-surface-integrated microfluidic platform for the early detection of Dengue virus. Utilizing a seed-assisted hydrothermal synthesis method, high-purity ZnO NRs were synthesized, characterized by their hexagonal wurtzite structure and a high surface-to-volume ratio, offering abundant binding sites for bioconjugation. Further, a comparative analysis demonstrated that the ZnO NR substrate outperformed traditional bare glass substrates in functionalization efficiency with 4G2 monoclonal antibody (mAb). Subsequent optimization of the functionalization process identified 4% (3-Glycidyloxypropyl)trimethoxysilane (GPTMS) as the most effective surface modifier. The integration of this substrate within a herringbone-structured microfluidic platform resulted in a robust device for immunofluorescence detection of DENV-3. The limit of detection (LOD) for DENV-3 was observed to be as low as 3.1 × 10−4 ng/mL, highlighting the remarkable sensitivity of the ZnO NR-integrated microfluidic device. This study emphasizes the potential of ZnO NRs and the developed microfluidic platform for the early detection of DENV-3, with possible expansion to other biological targets, hence paving the way for enhanced public health responses and improved disease management strategies. [ABSTRACT FROM AUTHOR]

Background: Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa. Methods: Relevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates. Results: Twenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide, Plasmodium falciparum and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008–2013 to 3.8% during 2014–2017 and to 5.5% during 2018–2021 (p = 0.0414). Conclusion: There was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions. Protocol registration number: CRD42022311301. [ABSTRACT FROM AUTHOR]

Dengue and chikungunya viruses are frequent causes of malarial-like febrile illness in children. The rapid increase in virus transmission by mosquitoes is a global health concern. This is the first systematic review and meta-analysis of the childhood prevalence of dengue and chikungunya in Sub-Saharan Africa (SSA). A comprehensive search of the MEDLINE (Ovid), Embase (Ovid), and Cochrane Library (Wiley) databases was conducted on 28 June 2019, and updated on 12 February 2022. The search strategy was designed to retrieve all articles pertaining to arboviruses in SSA children using both controlled vocabulary and keywords. The pooled (weighted) proportion of dengue and chikungunya was estimated using a random effect model. The overall pooled prevalence of dengue and chikungunya in SSA children was estimated to be 16% and 7%, respectively. Prevalence was slightly lower during the period 2010–2020 compared to 2000–2009. The study design varied depending on the healthcare facility reporting the disease outbreak. Importantly, laboratory methods used to detect arbovirus infections differed. The present review documents the prevalence of dengue and chikungunya in pediatric patients throughout SSA. The results provide unprecedented insight into the transmission of dengue and chikungunya viruses among these children and highlight the need for enhanced surveillance and controlled methodology. [ABSTRACT FROM AUTHOR]

Dengue is among the most important infectious diseases in the world. The main contribution of our paper is to present a mixed system of partial and ordinary differential equations. This combined model is a generalization of the two presented mathematical models (A. L. de Araujo, J. L. Boldrini and B. M. Calsavara, An analysis of a mathematical model describing the geographic spread of dengue disease, J. Math. Anal. Appl.444 (2016) 298–325) and (L. Cai, X. Li, N. Tuncer, M. Martcheva and A. A. Lashari, Optimal control of a malaria model with asymptomatic class and superinfection, Math. Biosci.288 (2017) 94–108), describing the geographic spread of dengue disease. Our model has the ability to consider the possibility of asymptomatic infection, which leads to investigate the effect of dengue asymptomatic individuals on disease dynamics and to go into the possibility of superinfection of asymptomatic individuals. In the light of considering these factors, as well as the movements of human and mature female mosquitoes, more realistic modeling of dengue disease can be achieved. We present a mathematical analysis and show the global existence of a unique non-negative solution to this model and then establish ways to control dengue disease using numerical simulations and sensitivity analysis of model parameters (which are related to the contact rates and death rate of winged mosquitoes). To show different biological behaviors, we provide several numerical results, showing the role of parameters in controlling dengue disease transmission. From our numerical simulations, it can also be concluded that local control of dengue transmission can be done at a lower cost. [ABSTRACT FROM AUTHOR]

This paper deals with dengue virus transmitted by the mosquito Aedes aegypti. A reaction–diffusion model is proposed incorporating both human and the A. aegypti population, where we divided mosquitoes into two sub-populations: the winged population and an aquatic form, with the winged mosquito population divided into the susceptible and infected classes. The threshold Q 0 depending on spatial heterogeneity is introduced for the mosquito population. Moreover, we introduce the basic reproduction number R 0 for the infected classes, as well as its analytical properties. Q 0 and R 0 are utilized to investigate the stability of the mosquito-established equilibriums. Our results show that the mosquitoes persist if Q 0 > 1 , while the transmission of dengue virus depends on the condition whether R 0 < 1 or R 0 > 1. [ABSTRACT FROM AUTHOR]

Flaviviruses have emerged as major arthropod-transmitted pathogens and represent an increasing public health problem worldwide. High-throughput screening can be facilitated using viruses that easily express detectable marker proteins. Therefore, developing molecular tools, such as reporter-carrying versions of flaviviruses, for studying viral replication and screening antiviral compounds represents a top priority. However, the engineering of flaviviruses carrying either fluorescent or luminescent reporters remains challenging due to the genetic instability caused by marker insertion; therefore, new approaches to overcome these limitations are needed. Here, we describe reverse genetic methods that include the design and validation of infectious clones of Zika, Kunjin, and Dengue viruses harboring different reporter genes for infection, rescue, imaging, and morphology using super-resolution microscopy. It was observed that different flavivirus constructs with identical designs displayed strikingly different genetic stabilities, and corresponding virions resembled wild-type virus particles in shape and size. A successful strategy was assessed to increase the stability of rescued reporter virus and permit antiviral drug screening based on quantitative automated fluorescence microscopy and replication studies. [ABSTRACT FROM AUTHOR]

Dengue is an arbovirus infection which is transmitted by Aedes mosquitoes. Its prompt detection and effective treatment is a global health challenge. Various nanoparticle-based vaccines have been formulated to present immunogen (antigens) to instigate an immune response or prevent virus spread, but no specific treatment has been devised. This review explores the role of nanomedicine-based therapeutic agents against dengue virus, taking into consideration the applicable dengue virus assays that are sensitive, specific, have a short turnaround time and are inexpensive. Various kinds of metallic, polymeric and lipid nanoparticles with safe and effective profiles present an alternative strategy that could provide a better remedy for eradicating the dengue virus. [ABSTRACT FROM AUTHOR]

Introduction: dengue cases occur frequently in Kenya, although the trend is not uniform across the country, making this infectious disease a major public health problem that is transmitted without detection. The purpose of this review study was to determine the seroprevalence of dengue virus (DENV) infection in the Kenyan population during the last ten years to reveal geographical areas with unreported dengue fever activity. For that purpose, this review describes the recent (2010 to 2020) DENV incidences, methods of detection, and the circulating genotypes in Kenya. Methods: studies were identified to summarize reported dengue fever infections and epidemic activities in Kenya using a search approach (terms "Dengue", "Dengue Virus" and "DENV" in combination with "Infection in Kenya"). All published studies between 2010 and 2020 retrieved through search engines PubMed, Google Scholar, Research4life, and ScienceDirect were screened for eligibility. Results: a total of 21 eligible articles containing 24 studies, covering five general geographic regions and 39 sampling sites, were included in this review. The results indicate a surveillance gap in dengue fever infection serosurvey in Kenya. There was transmission between epidemics in the reported areas. Seroprevalence ranged from 0.4% to 100% during outbreaks. Coast region was the most studied region with Mombasa being the most sampled site. Conclusion: about 76.6% of Kenyan Counties' DENV seroprevalence status was found to be unknown or unreported. In addition, DENV infection was unrecognized and/or unreported in most areas of the country, especially rural Kenya. This information may serve as a basis for better awareness and detection of DENV infection during outbreaks and in establishing appropriate prevention and control measures to further avoid outbreaks. [ABSTRACT FROM AUTHOR]

Background: Flavivirus comprises several important viruses, including dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). A large outbreak of DENV and ZIKV occurred in these years, leading to many cases of illness and death. However, despite the decades of efforts, there are no specific therapeutic drugs against DENV and ZIKV. Several studies had shown that histone deacetylase 6 inhibitors (HDAC6 inhibitors) possess antiviral effects on influenza A virus, hepatitis C virus, and JEV. Aim: The purpose of this study is to examine the antiviral effect of the compound J34803, a newly synthesized HDAC6 inhibitor, against DENV and ZIKV in vitro and in vivo. Methods: We investigated whether the compound J34803 inhibited viral infection by western blot and virus titer determination. The signaling pathway of inhibition was also determined by western blot. Results: The compound J34803 exhibited superior antiviral activities against DENV-2, DENV-4, and ZIKV compared to Tubastatin A (TBSA), and its antiviral mechanism may through suppressing HDAC6 and its downstream signaling pathway. Moreover, treatment with the compound J34803 could reduce viremia levels in DENV-2-and ZIKV-infected AG129 mice. Conclusion: We demonstrated that the compound J34803 had better therapeutic efficacy in virus infection as compared to TBSA and could be a potential potent therapeutic drug against emerging flaviviral infections. [ABSTRACT FROM AUTHOR]

Dengue fever, a mosquito-borne disease in tropical and subtropical climates caused by the dengue virus (DENV), has become a major social and economic burden in recent years. However, current primary detection methods are inadequate for early diagnosis of DENV because they are either time-consuming, expensive, or require training. Non-structural protein 1 (NS1) is secreted during DENV infection and is thus considered a suitable biomarker for the development of an early detection method. In the present study, we developed a detection method for the NS1 protein based on a previously reported thio-NAD cycling ELISA (i.e., ultrasensitive ELISA) and successfully achieved a LOD of 1.152 pg/mL. The clinical diagnosis potential of the detection system was also evaluated by using 85 patient specimens, inclusive of 60 DENV-positive and 25 DENV-negative specimens confirmed by the NAAT method. The results revealed 98.3% (59/60) sensitivity and 100% (25/25) specificity, which was in almost perfect agreement with the NAAT data with a kappa coefficient of 0.972. The present study demonstrates the diagnostic potential of using an ultrasensitive ELISA as a low-cost, easy-to-use method for the detection of DENV compared with NAAT and could be of great benefit in low-income countries. [ABSTRACT FROM AUTHOR]

Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. The main risks considered in this study are infections by West Nile virus, dengue virus, and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya, and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of Public Health, which is responsible for mitigating the risks associated with products of human origin and for supporting public health policy decisions, are briefly outlined. This review highlights the need for a "One Health" approach and to standardize recommendations at the international level in areas with the same viral epidemiology. [ABSTRACT FROM AUTHOR]

Introduction: Dengue virus (DENV) is the leading cause of mosquito-borne viral diseases in humans. Dengvaxia, the first licensed dengue vaccine, is recommended for DENV-seropositive individuals aged 9–45 years. In the Philippines, Dengvaxia was administered to more than 830,000 children without prior serological testing in 2016–2017. Subsequently, it was revealed that DENV-seronegative children who received Dengvaxia developed severe disease following breakthrough DENV infection. As a result, thousands of children participating in the mass vaccination campaign were at higher risk of severe dengue disease. It is vital that an assay that identifies baseline DENV-naïve Dengvaxia recipients be developed and validated. This would permit more frequent and extensive assessments and timely treatment of breakthrough DENV infections. Methods: We evaluated the performance of a candidate assay, the DENV1–4 nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay (ELISA), developed by the University of Hawaii (UH), using well-documented serum/ plasma samples including those >20 years post-DENV infection, and tested samples from 199 study participants including 100 Dengvaxia recipients from the fever surveillance programs in the Philippines. Results: The sensitivity and specificity of the assay were 96.6% and 99.4%, respectively, which are higher than those reported for pre-vaccination screening. A significantly higher rate of symptomatic breakthrough DENV infection was found among children that were DENV-naïve (10/23) than among those that were DENV-immune (7/53) when vaccinated with Dengvaxia (p=0.004, Fisher’s exact test), demonstrating the feasibility of the assay and algorithms in clinical practice. Conclusion: The UH DENV1–4 NS1 IgG ELISA can determine baseline DENV serostatus among Dengvaxia recipients not only during non-acute dengue but also during breakthrough DENV infection, and has implications for assessing the long-term safety and effectiveness of Dengvaxia in the post-licensure period. [ABSTRACT FROM AUTHOR]

Background During the American epidemic, Zika virus (ZIKV) expanded rapidly through dengue virus (DENV)-endemic regions. We analyzed the presentation of ZIKV infection in patients from the City of Orán, Argentina, and compared some of its features with dengue presentation in the same region. Methods A retrospective study was conducted at San Vicente de Paul Hospital during 2016–2018. Clinical and demographic characteristics, pre-existing immunity to DENV, viral load and type I interferon (IFN) responses were studied in 63 patients with ZIKV infection. Results Clinical manifestations of ZIKV infection were generally mild compared with dengue, although rash (p<0.001) and itching (p<0.001) were significantly more prevalent in ZIKV patients. ZIKV patients aged <15 y manifested relatively mild disease compared with older ZIKV patients, showing a decreased prevalence of headache (p=0.008), retro-orbital pain (p=0.001) and arthralgia (p=0.001). Increased Zika incidence was observed in female patients (60.3%). Serum viral load was low to undetectable in ZIKV patients and was not associated with serum anti-DENV IgG titers. Interferon-α and IFN-β serum levels did not correlate with serum viral load in ZIKV patients. Conclusions Clinical presentation of ZIKV and DENV infections is largely overlapping, presenting a challenge for diagnosis and risk assessment for uniquely at-risk populations. [ABSTRACT FROM AUTHOR]

Dengue has long been a serious health burden to the global community, especially for those living in the tropics. Despite the availability of vaccines, effective treatment for the infection is still needed and currently remains absent. In the present study, the antiviral properties of the Streptomyces sp. KSF 103 methanolic extract (Streptomyces KSF 103 ME), which consists of a number of potential antiviral compounds, were investigated against dengue virus serotype 2 (DENV-2). The effects of this extract against DENV-2 replication were determined using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Findings from the study suggested that the Streptomyces KSF 103 ME showed maximum inhibitory properties toward the virus during the virus entry stage at concentrations of more than 12.5 µg/mL. Minimal antiviral activities were observed at other virus replication stages; adsorption (42% reduction at 50 µg/mL), post-adsorption (67.6% reduction at 50 µg/mL), prophylactic treatment (68.4% and 87.7% reductions at 50 µg/mL and 25 µg/mL, respectively), and direct virucidal assay (48% and 56.8% reductions at 50 µg/mL and 25 µg/mL, respectively). The Streptomyces KSF 103 ME inhibited dengue virus replication with a 50% inhibitory concentration (IC50) value of 20.3 µg/mL and an International System of Units (SI) value of 38.9. The Streptomyces KSF 103 ME showed potent antiviral properties against dengue virus (DENV) during the entry stage. Further studies will be needed to deduce the antiviral mechanisms of the Streptomyces KSF 103 ME against DENV. [ABSTRACT FROM AUTHOR]

RNA viruses rapidly adapt to selective conditions due to the high intrinsic mutation rates of their RNA-dependent RNA polymerases (RdRps). Insertions and deletions (indels) in viral genomes are major contributors to both deleterious mutational load and evolutionary novelty, but remain understudied. To characterize the mechanistic details of their formation and evolutionary dynamics during infection, we developed a hybrid experimental-bioinformatic approach. This approach, called MultiMatch, extracts insertions and deletions from ultradeep sequencing experiments, including those occurring at extremely low frequencies, allowing us to map their genomic distribution and quantify the rates at which they occur. Mapping indel mutations in adapting poliovirus and dengue virus populations, we determine the rates of indel generation and identify mechanistic and functional constraints shaping indel diversity. Using poliovirus RdRp variants of distinct fidelity and genome recombination rates, we demonstrate tradeoffs between fidelity and Indel generation. Additionally, we show that maintaining translation frame and viral RNA structures constrain the Indel landscape and that, due to these significant fitness effects, Indels exert a significant deleterious load on adapting viral populations. Conversely, we uncover positively selected Indels that modulate RNA structure, generate protein variants, and produce defective interfering genomes in viral populations. Together, our analyses establish the kinetic and mechanistic tradeoffs between misincorporation, recombination, and Indel rates and reveal functional principles defining the central role of Indels in virus evolution, emergence, and the regulation of viral infection. [ABSTRACT FROM AUTHOR]

Dengue is the most rapidly spreading mosquito-borne disease that poses great threats to public health. We propose a compartmental model with primary and secondary infection and targeted vaccination to assess the impact of serostatus-dependent immunization on mitigating the spread of dengue virus. We derive the basic reproduction number and investigate the stability and bifurcations of the disease-free equilibrium and endemic equilibria. The existence of a backward bifurcation is proved and is used to explain the threshold dynamics of the transmission. We also carry out numerical simulations and present bifurcation diagrams to reveal rich dynamics of the model such as bi-stability of the equilibria, limit cycles, and chaos. We prove the uniform persistence and global stability of the model. Sensitivity analysis suggests that mosquito control and protection from mosquito bites are still the key measures of controlling the spread of dengue virus, though serostatus-dependent immunization is implemented. Our findings provide insightful information for public health in mitigating dengue epidemics through vaccination. [ABSTRACT FROM AUTHOR]

Background: Dengue virus infection causes major public health problems in tropical and subtropical areas. In many endemic areas, including the Lao PDR, inadequate access to laboratory facilities is a major obstacle to surveillance and study of dengue epidemiology. Filter paper is widely used for blood collection for subsequent laboratory testing for antibody and nucleic acid detection. For the first time, we demonstrate that dengue viral RNA can be extracted from dengue rapid diagnostic tests (RDT) and then submitted to real-time RT-PCR for serotyping. Methodology/Principal Findings: We evaluated the Standard Diagnostics (SD) Bioline Dengue Duo RDT, a commonly used test in dengue endemic areas. First, using the QIAamp RNA kit, dengue RNA was purified from the sample pad of the NS1 RDT loaded with virus isolates of the four serotypes, then quantified by RT-PCR. We observed greater recovery of virus, with a mean of 27 times more RNA recovered from RDT, than from filter paper. Second, we evaluated dengue NS1 RDTs from patients at Mahosot Hospital, Vientiane, (99 patients) and from rural Salavan Provincial Hospital (362 patients). There was good agreement between dengue RT-PCR from NS1 RDT with RT-PCR performed on RNA extracted from patient sera, either using RDT loaded with blood (82.8% and 91.4%, in Vientiane and Salavan, respectively) or serum (91.9% and 93.9%). There was 100% concordance between RDT and serum RT-PCR of infecting dengue serotype. Conclusions/Significance: Therefore, the collection of NS1 positive RDTs, which do not require cold storage, may be a novel approach for dengue serotyping by RT-PCR and offers promising prospects for the collection of epidemiological data from previously inaccessible tropical areas to aid surveillance and public health interventions. [ABSTRACT FROM AUTHOR]

Aim: The current study aimed to identify prevalent dengue serotypes during a major outbreak in 2021 in Pakistan. Materials & methods: From September-November 2021, 373 serum samples from different provinces were tested by RT-PCR for serotype identification, followed by partial sequence analysis of selected dengue-positive samples. Results: Out of 373 samples, 273 (73%) were positive for dengue virus infection with male predominance (61.9%). Complete predominance of DENV-2 serotype (99%) and a single case of DENV-1 was observed. Sequencing data revealed the presence of a cosmopolitan genotype within the DENV-2 Pakistani isolates. Conclusion: This study highlights the persistent predominance of DENV-2 during the 2021 outbreak, suggesting a need to improve surveillance strategies and vector breeding control programs in Pakistan. [ABSTRACT FROM AUTHOR]

Dengue is the most common viral infection spread by mosquitoes, prevalent in tropical countries. The acute dengue virus (DENV) infection is a benign and primarily febrile illness. However, secondary infection with alternative serotypes can worsen the condition, leading to severe and potentially fatal dengue. The antibody raised by the vaccine or the primary infections are frequently cross-reactive; however, weakly neutralizing, and during subsequent infection, they may increase the odds of antibody-dependent enhancement (ADE). Despite that, many neutralizing antibodies have been identified against the DENV, which are thought to be useful in reducing dengue severity. Indeed, an antibody must be free from ADE for therapeutic application, as it is pretty common in dengue infection and escalates disease severity. Therefore, this review has described the critical characteristics of DENV and the potential immune targets in general. The primary emphasis is given to the envelope protein of DENV, where potential epitopes targeted for generating serotype-specific and cross-reactive antibodies have critically been described. In addition, a novel class of highly neutralizing antibodies targeted to the quaternary structure, similar to viral particles, has also been described. Lastly, we have discussed different aspects of the pathogenesis and ADE, which would provide significant insights into developing safe and effective antibody therapeutics and equivalent protein subunit vaccines. [ABSTRACT FROM AUTHOR]

Background: Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa. Methods: Relevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates. Results: Twenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide, Plasmodium falciparum and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008–2013 to 3.8% during 2014–2017 and to 5.5% during 2018–2021 (p = 0.0414). Conclusion: There was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions. Protocol registration number: CRD42022311301. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is the most important human virus transmitted by mosquitos. Dengue pathogenesis is characterized by a large induction of proinflammatory cytokines. This cytokine induction varies among the four DENV serotypes (DENV1 to 4) and poses a challenge for live DENV vaccine design. Here, we identify a viral mechanism to limit NF-κB activation and cytokine secretion by the DENV protein NS5. Using proteomics, we found that NS5 binds and degrades the host protein ERC1 to antagonize NF-κB activation, limit proinflammatory cytokine secretion, and reduce cell migration. We found that ERC1 degradation involves unique properties of the methyltransferase domain of NS5 that are not conserved among the four DENV serotypes. By obtaining chimeric DENV2 and DENV4 viruses, we map the residues in NS5 for ERC1 degradation, and generate recombinant DENVs exchanging serotype properties by single amino acid substitutions. This work uncovers a function of the viral protein NS5 to limit cytokine production, critical to dengue pathogenesis. Importantly, the information provided about the serotype-specific mechanism for counteracting the antiviral response can be applied to improve live attenuated vaccines. [ABSTRACT FROM AUTHOR]

Dengue is one of the most critical diseases, caused by Dengue virus (DENV) serotypes (DENV-1 to DENV-4). Study aims to detect DENV in natural A. aegypti from endemic regions of Uttar Pradesh. From 2010- 2013, mosquitoes collected from Uttar Pradesh tested for Dengue virus serotypes by capsid premembrane gene-based PCR analyzed for genotypes sequencing of the C-prM junction of DENV genome. A total of 4731, 53.54% (n=2671) A. aegypti and 46 % (n=2060) A. albopictus mosquitoes were collected. Of 226 mosquito pools, 10 pools of A. aegypti and 14 pools of A. albopictus were positive for DENV by PCR. All 24 isolates identified as DENV-I; Genotype (G)-III (n=8), G-V (n=1); DENV-2; G-IV (n=4); DENV-3; G-III (n=11). The overall minimum infection rate was much higher in A. albopictus mosquitoes and presence of MIR in male mosquitoes is an indicating natural vertical transmission and important observation in geographical area indicating natural vertical transmission. [ABSTRACT FROM AUTHOR]

Dengue has become one of the vector-borne diseases that affect humans worldwide. In Latin American countries, Colombia is historically one of the most affected by epidemics of this flavivirus. The underreporting of signs and symptoms of probable cases of dengue, the lack of characterization of the serotypes of the infection, and the few detailed studies of postmortem necropsies of patients are among other conditions that have delayed progress in the knowledge of the pathogenesis of the disease. This study presents the results of fragment sequencing assays on paraffin-embedded tissue samples from fatal DENV cases during the 2010 epidemic in Colombia. We found that the predominant serotype was DENV-2, with the Asian/American genotype of lineages 1 and 2. This work is one of the few reports of the circulating genotypes of dengue during the 2010 epidemic in Colombia, one of the most lethal dates in the country's history. [ABSTRACT FROM AUTHOR]

This article presents a hybrid Au/BatiO3/WSe2-based surface plasmon resonance (SPR) biosensor for detecting the dengue virus. The sensing surface of the proposed biosensor is immobilized with different healthy and infected blood cells such as plasma, platelet, and hemoglobin. The angular interrogation method is used to investigate the detection performance of the biosensor. The design and performance analysis of the biosensor is conducted by using the finite-difference time-domain (FDTD) method. The impacts of different nanomaterials including BatiO3 and WSe2 on the performance parameters are investigated and analyzed numerically. The numerical analysis involves the use of a FDTD in a multiphysics platform to determine the effect of different nanomaterials on the performance parameters, such as sensitivity, detection accuracy and quality factor. This numerical analysis allows for the comparison of the different nanomaterials and the determination of which is most suitable for the particular application. Results from the investigation and analysis show that these nanomaterials can effectively enhance the performance of the proposed biosensor which can provide valuable insights into the effective design of the biosensor. In addition, electric field distribution and magnetic field propagation for resonance and non-resonance conditions are determined for the biosensor in which an enhanced electric field is observed at the metallic layer. This enhanced electric field is caused by the metallic layer acting as a reflector and redirecting the electric field, increasing the concentration of electric field lines in the vicinity of the metallic layer. This increased electric field concentration leads to increased sensitivity and detection accuracy of the biosensor. The proposed biosensor offers a maximum angular shift of 128.571 deg/RIU, a quality factor of 230.7 RIU−1, and a detection accuracy of 4.5 for dengue virus detection through dengue-infected blood cells. The output parameters of the proposed biosensor are compared with the reported biosensors and found to be superior to them. [ABSTRACT FROM AUTHOR]