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There are a limited number of effective vaccines against dengue virus (DENV) and significant efforts are being made to develop potent anti-virals. Previously, we described that platelet-chemokine CXCL4 negatively regulates interferon (IFN)-α/β synthesis and promotes DENV2 replication. An antagonist to CXCR3 (CXCL4 receptor) reversed it and inhibited viral replication. In a concurrent search, we identified CXCR3-antagonist from our compound library, namely 7D, which inhibited all serotypes of DENV in vitro. With a half-life of ~2.85 h in plasma and no significant toxicity, 7D supplementation (8 mg/kg-body-weight) to DENV2-infected IFNα/β/γR−/−AG129 or wild-type C57BL6 mice increased synthesis of IFN-α/β and IFN-λ, and rescued disease symptoms like thrombocytopenia, leukopenia and vascular-leakage, with improved survival. 7D, having the property to inhibit Sirt-1 deacetylase, promoted acetylation and phosphorylation of STAT3, which in-turn increased plasmablast proliferation, germinal-center maturation and synthesis of neutralizing-antibodies against DENV2 in mice. A STAT3-inhibitor successfully inhibited these effects of 7D. Together, these observations identify compound 7D as a stimulator of IFN-α/β/λ synthesis via CXCL4:CXCR3:p38:IRF3 signaling, and a booster for neutralizing-antibody generation by promoting STAT3-acetylation in plasmablasts, capable of protecting dengue infection. Synopsis: Effective vaccines and anti-viral drugs against dengue are limited. Our study identifies a small molecule, namely 7D as a stimulator of IFNα/β/λ synthesis, and also booster for neutralizing-antibody generation, capable of protecting dengue infection in 3 different mice models. Schematic describes the CXCL4-mediated activation of CXCR3:p38:IRF3 signaling, in turn suppression of IRF3 phosphorylation and IFNα/β/λ synthesis in monocytes and macrophages. Conversely, 7D supplementation reverses the above signaling and improves IFNα/β/λ synthesis. Besides, 7D increases acetylation and phosphorylation of STAT3, in turn promotes proliferation of plasmablasts and plasma cells, in turn increases IgG synthesis via suppression of deacetylase activity of Sirt-1. 7D is a potent anti-viral drug against dengue. Effective vaccines and anti-viral drugs against dengue are limited. Our study identifies a small molecule, namely 7D as a stimulator of IFNα/β/λ synthesis, and also booster for neutralizing-antibody generation, capable of protecting dengue infection in 3 different mice models. [ABSTRACT FROM AUTHOR]

Background: Dengue fever is one of the most prevalent mosquito-borne diseases in Cambodia. Until now, no specific vaccine nor antiviral treatment exists the virus causing Dengue fever. Consequently, its prevention relies only on vector control strategies. However, efficient vector control in turn relies on a good knowledge of the biology of the vector species. Therefore, this study aims to provide the first review of the distribution, ecology, meteorological impacts, trophic behavior, vector competence, vector control and insecticide resistance of dengue vector species in Cambodia. Methods: A systematic search of the Google Scholar and PubMed databases was conducted for relevant published articles. Of the 610 published articles originally identified, 70 articles were ultimately selected for inclusion in this review. We also included new data from unpublished research conducted in Cambodia between 2017 and 2023 related to dengue vector bionomics. Results: Eleven Aedes (Stegomyia) mosquito species have been recorded in Cambodia, including a new species described in 2024. Four species are associated with dengue virus transmission, among which Aedes aegypti and Ae. albopictus are the main vectors and Ae. malayensis and Ae. scutellaris are considered to be potential vectors. Aedes aegypti and Ae. albopictus are present in all provinces of Cambodia. Aedes albopictus shows a preference for forest, rural and suburban areas, while Ae. aegypti is mostly found in urban and suburban areas. The distribution of these two species is also influenced by meteorological factors, seasonality and the availability of breeding habitats and blood meals. Both species are predominant during the rainy season, and their respective density is impacted by precipitation and temperature. Aedes aegypti is characterized as anthropophilic, while Ae. albopictus exhibits zooanthropophilic behavior, and both species have been observed to be predominantly diurnal. In addition, they were found to be highly resistant to the insecticides used in Cambodia for their control, such as temephos for larvae and deltamethrin and permethrin for adult mosquitoes. Conclusions: This review provides extensive and important knowledge on dengue vectors in Cambodia. This knowledge is derived not only from published research articles but also from many recent studies in Cambodia on the bionomics of dengue vector species. The review provides valuable information for use by public health authorities on dengue virus transmission and to develop better vector control strategies in the country. [ABSTRACT FROM AUTHOR]

Codon optimality refers to the effect that codon composition has on messenger RNA (mRNA) stability and translation level and implies that synonymous codons are not silent from a regulatory point of view. Here, we investigated the adaptation of virus genomes to the host optimality code using mosquito-borne dengue virus (DENV) as a model. We demonstrated that codon optimality exists in mosquito cells and showed that DENV preferentially uses nonoptimal (destabilizing) codons and avoids codons that are defined as optimal (stabilizing) in either human or mosquito cells. Human genes enriched in the codons preferentially and frequently used by DENV are upregulated during infection, and so is the tRNA decoding the nonoptimal and DENV preferentially used codon for arginine. We found that adaptation during single-host passaging in human or mosquito cells results in the selection of synonymous mutations towards DENV's preferred nonoptimal codons that increase virus fitness. Finally, our analyses revealed that hundreds of viruses preferentially use nonoptimal codons, with those infecting a single host displaying an even stronger bias, suggesting that host–pathogen interaction shapes virus-synonymous codon choice. Synopsis: Analyses of viral genome adaptation to the host optimality code, reveal that hundreds of human-infecting viruses preferentially use non-optimal codons and suggest that host-pathogen interactions can shape virus synonymous codon choice. Dengue virus (DENV) preferentially uses non-optimal codons and avoids codons that are defined as optimal in either human or mosquito cells. Codon optimality mechanism exists in mosquito cells. Human genes enriched in the codons preferentially and frequently used by DENV are up-regulated during DENV infection, as well as tRNAs decoding the non-optimal codon that DENV preferentially uses. Hundreds of human-infecting viruses preferentially use non-optimal codons suggesting that host-pathogen interaction shapes virus synonymous codon choice. Analyses of viral genome adaptation to the host optimality code, reveal that hundreds of human-infecting viruses preferentially use non-optimal codons and suggest that host-pathogen interactions can shape virus synonymous codon choice. [ABSTRACT FROM AUTHOR]

Background: While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity. Methods: Primary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF = 8) or dengue haemorrhagic fever (DHF = 8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF. Results: Significantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p = 0.01, median = 45.69 pg/ml), but lower levels when NS1 was co-cultured with HDL (p = 0.05, median = 4.617 pg/ml). MDMs of those with past DHF produced higher levels of IL-1β when NS1 was co-cultured with PAF (p = 0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF. Conclusions: As RPLP2 is important in DENV replication, regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions. [ABSTRACT FROM AUTHOR]

The last decade has seen major advances and growth in internet-based surveillance for infectious diseases through advanced computational capacity, growing adoption of smart devices, increased availability of Artificial Intelligence (AI), alongside environmental pressures including climate and land use change contributing to increased threat and spread of pandemics and emerging infectious diseases. With the increasing burden of infectious diseases and the COVID-19 pandemic, the need for developing novel technologies and integrating internet-based data approaches to improving infectious disease surveillance is greater than ever. In this systematic review, we searched the scientific literature for research on internet-based or digital surveillance for influenza, dengue fever and COVID-19 from 2013 to 2023. We have provided an overview of recent internet-based surveillance research for emerging infectious diseases (EID), describing changes in the digital landscape, with recommendations for future research directed at public health policymakers, healthcare providers, and government health departments to enhance traditional surveillance for detecting, monitoring, reporting, and responding to influenza, dengue, and COVID-19. [ABSTRACT FROM AUTHOR]

Background: Dengue disease is caused by dengue virus, which is transmitted by Aedes mosquitoes in tropical and subtropical regions worldwide. Although most infected individuals have benign febrile illness or no apparent symptoms, a small percentage develop severe dengue, a potentially fatal condition that occurs after a febrile stage. Many studies have identified factors predicting dengue severity among different populations and time courses. To help find practical approaches applicable in remote settings, we focused on the investigation of early factors associated with severe dengue in Thai–Myanmar cross-border region. Methods: This retrospective case-control study was performed to determine factors contributing to severe dengue in the pediatric population. We reviewed the hospital records of patients with dengue infection aged 0–19 years who were admitted to Maesot General Hospital, situated near the Thai–Myanmar cross-border region, between 2017 and 2022. Medical data during the first 5 days of illness and outcomes were collected and analyzed. Results: This study included 144 patients with a serologically confirmed diagnosis of dengue infection, with 43 severe and 101 non-severe cases. Among biological factors, being an infant and belonging to an ethnic group in Myanmar showed a significant association with severe dengue in the univariable analysis. Multivariable logistic regression revealed that the presence of mucosal bleeding (adjusted OR 5.39, 95% CI 1.06–27.52, P = 0.043), a change in hematocrit ≥ 10% (adjusted OR 3.68, 95% CI 1.15–11.74, P = 0.028), and serum albumin < 35 g/L (adjusted OR 8.10, 95% CI 2.55–25.72, P < 0.001) during the first 5 days of illness were significantly associated with developing severe dengue. Conclusions: This study supports the use of certain WHO warning signs and hematocrit change during febrile phase to predict pediatric severe dengue in low-resource settings. Potential factors such as very young age and ethnic groups warrant further exploration to identify risks contributing to severe dengue infection. [ABSTRACT FROM AUTHOR]

Dengue is an infectious disease caused by infection of dengue virus (DENV) transmitted by Aedes aegypti and Aedes albopictus. In Indonesia, dengue commonly occurs with an increasing incidence rate annually. It is known that early detection of dengue infection is one of the keys to controlling this disease outbreak. Rapid and accurate early detection to diagnose dengue can be achieved by molecular tests, one of which is through a real-time PCR method. However, real-time PCR assay for dengue developed based on Indonesian DENV sequences has not been available. Therefore, we developed in-house dengue real-time PCR (SYBR- and TaqMan-based) assays and evaluated those assays in routine clinical testing in the community. These assays target the 3′ UTR region of the four DENV serotypes and was found to be specific for DENV. The most sensitive assay was the TaqMan assay with the LOD95% of 482 copy/ml, followed by the SYBR assay with the LOD95% of 14,398 copy/ml. We recruited dengue suspected patients from three primary health care services in West Java, Indonesia to represent the community testing setting. Dengue infection was examined using the two in-house real-time PCR assays along with NS1, IgM, and IgG rapid diagnostic tests (RDT). In total, as many as 74 clinical specimens of dengue suspected patients were included in this study. Among those patients, 21 were positive for TaqMan assay, 17 were positive for SYBR assay, nine were positive for NS1 test, six were positive for both IgG and IgM tests, and 22 were positive for IgG test only. Compared with our in-house TaqMan assay, the sensitivity of NS1 test, IgM test, and IgG test were 42.86%, 14.29%, and 28.57% respectively. Among these three RDT tests, NS1 showed 100% specificity. Thus, our study confirmed that NS1 test showed high specificity, indicating that a positive result of NS1 can be confidently considered a dengue case. However, NS1, IgM, and IgG tests with RDT are not enough to diagnose a dengue case. We suggest applying the high sensitivity and specificity rRT-PCR test as the gold standard for early detection and antibody test as a follow-up test for rRT-PCR negative cases. [ABSTRACT FROM AUTHOR]

Background: Despite dengue virus (DENV) outbreak in Gabon a decade ago, less is known on the potential circulation of DENV serotypes in the country. Previous studies conducted in some areas of the country, are limited to hospital-based surveys which reported the presence of some cases of serotype 2 and 3 seven years ago and more recently the serotype 1. As further investigation, we extend the survey to the community of Moyen Ogooué region with the aim to assess the presence of the dengue virus serotypes, additionally to characterize chikungunya (CHIKV) infection and describe the symptomatology associated with infections. Method: A cross-sectional survey was conducted from April 2020 to March 2021. The study included participants of both sexes and any age one year and above, with fever or history of fever in the past seven days until blood collection. Eligible volunteers were clinically examined, and blood sample was collected for the detection of DENV and CHIKV using RT-qPCR. Positive samples were selected for the target sequencing. Results: A total of 579 volunteers were included. Their mean age (SD) was 20 (20) years with 55% of them being female. Four cases of DENV infection were diagnosed giving a prevalence of 0.7% (95%CI: 0.2–1.8) in our cohort while no case of CHIKV was detected. The common symptoms and signs presented by the DENV cases included fatigue, arthralgia myalgia, cough, and loss of appetite. DENV-1was the only virus detected by RT-qPCR. Conclusion: Our results confirm the presence of active dengue infection in the region, particularly DENV-1, and could suggest the decline of DENV-2 and DENV-3. Continuous surveillance remains paramount to comprehensively describe the extent of dengue serotypes distribution in the Moyen-Ogooué region of Gabon. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In dengue-endemic areas, transmission control is limited by the difficulty of achieving sufficient coverage and sustainability of interventions. To maximize the effectiveness of interventions, areas with higher transmission could be identified and prioritized. The aim was to identify burden clusters of Dengue virus (DENV) infection and evaluate their association with microclimatic factors in two endemic towns from southern Mexico. Information from a prospective population cohort study (2·5 years of follow-up) was used, microclimatic variables were calculated from satellite information, and a cross-sectional design was conducted to evaluate the relationship between the outcome and microclimatic variables in the five surveys. Spatial clustering was observed in specific geographic areas at different periods. Both, land surface temperature (aPR 0·945; IC95% 0·895–0·996) and soil humidity (aPR 3·018; IC95% 1·013–8·994), were independently associated with DENV burden clusters. These findings can help health authorities design focused dengue surveillance and control activities in dengue endemic areas. [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]

Background: Dengue virus (DENV) is endemic to many parts of the world and has serious health and socioeconomic effects even in high-income countries, especially with rapid changes in the climate globally. We explored the literature on dengue vector control methods used in high-income, city settings and associations with dengue incidence, dengue prevalence, or mosquito vector densities. Methods: Studies of any design or year were included if they reported effects on human DENV infection or Aedes vector indices of dengue-specific vector control interventions in high-income, city settings. Results: Of 24 eligible sources, most reported research in the United States (n = 8) or Australia (n = 5). Biocontrol (n = 12) and chemical control (n = 13) were the most frequently discussed vector control methods. Only 6 sources reported data on the effectiveness of a given method in reducing human DENV incidence or prevalence, 2 described effects of larval and adult control on Aedes DENV positivity, 20 reported effectiveness in reducing vector density, using insecticide, larvicide, source reduction, auto-dissemination of pyriproxyfen and Wolbachia, and only 1 described effects on human-vector contact. Conclusions: As most studies reported reductions in vector densities, rather than any effects on human DENV incidence or prevalence, we can draw no clear conclusions on which interventions might be most effective in reducing dengue in high-income, city areas. More research is needed linking evidence on the effects of different DENV vector control methods with dengue incidence/prevalence or mosquito vector densities in high-income, city settings as this is likely to differ from low-income settings. This is a significant evidence gap as climate changes increase the global reach of DENV. The importance of community involvement was clear in several studies, although it is impossible to tease out the relative contributions of this from other control methods used. Author summary: Dengue virus is present in many parts of the world and has serious health and socioeconomic effects even in high-income countries, especially with rapid changes in the climate globally. In this study, we explored the literature on dengue vector control methods used in high-income, city settings and associations with number of human dengue infections, and the density of mosquitoes. We found 24 papers with relevant results. Most of these described studies in the United States or Australia. Most were about various forms of biological or chemical control of the mosquitoes. Few papers discussed effects on human dengue infection. We were unable to draw any clear conclusions on how effective mosquito control methods were as we could identify little research on this subject in this specific setting. More research is needed on this topic, particularly as climate change will make more areas of the world vulnerable to dengue infection. [ABSTRACT FROM AUTHOR]

Background: Dengue fever caused by dengue virus is a tropical disease and is among the deadliest vector-borne diseases. The humid and hot summers of Pakistan support the probation of the vectors responsible for the transmission of viral and other parasitic diseases. Methodology: A retrospective study, from 2012- 2019, of dengue infected individuals from the Punjab province of Pakistan was carried out to analyze epidemiology, clinical and laboratory findings of subjects with dengue virus infection. Data was derived from National Institute of Health (NIH) followed by Dengue control program of Pakistan, covering the incidence rate in 36 districts of Punjab and Islamabad Capital Territory (ICT) respectively. Patients data including the presence of dengue specific antigen or/and antibodies such as NS1 and IgG/IgM were observed. The study also included the analysis of demographic data, geographic data, and the month-wise distribution of dengue cases to examine seasonal trends. Results: We analyzed 25,682 dengue infected individuals. The statistical analysis revealed a significant association between genders in which male population was more affected by dengue than females. It was also noted that the middle age group was the most affected age group while the highest number of cases were reported in October. Rawalpindi and Lahore were the most affected cities in Punjab province while Islamabad represented the highest number of cases during the recent outbreak in 2019. The IgM and IgG antibodies were highly prevalent among the infected patients. Conclusion: Dengue is endemic in Pakistan, circulating throughout the year. Highest number of cases were observed in the month of October, September and November respectively. Association between climate change and vector-borne diseases need to be investigated in Pakistan as they significantly influence the timing and intensity of dengue and other disease outbreaks. Further exploration of hematological parameters is required to better diagnose and treat the disease. For the effective control of dengue outbreaks, awareness campaigns on sewage management and vector control along with social factors are strongly recommended for better control and eradication of the disease. [ABSTRACT FROM AUTHOR]

Background: Dengue fever is a well-studied vector-borne disease in tropical and subtropical areas of the world. Several methods for predicting the occurrence of dengue fever in Taiwan have been proposed. However, to the best of our knowledge, no study has investigated the relationship between air quality indices (AQIs) and dengue fever in Taiwan. Results: This study aimed to develop a dengue fever prediction model in which meteorological factors, a vector index, and AQIs were incorporated into different machine learning algorithms. A total of 805 meteorological records from 2013 to 2015 were collected from government open-source data after preprocessing. In addition to well-known dengue-related factors, we investigated the effects of novel variables, including particulate matter with an aerodynamic diameter < 10 µm (PM10), PM2.5, and an ultraviolet index, for predicting dengue fever occurrence. The collected dataset was randomly divided into an 80% training set and a 20% test set. The experimental results showed that the random forests achieved an area under the receiver operating characteristic curve of 0.9547 for the test set, which was the best compared with the other machine learning algorithms. In addition, the temperature was the most important factor in our variable importance analysis, and it showed a positive effect on dengue fever at < 30 °C but had less of an effect at > 30 °C. The AQIs were not as important as temperature, but one was selected in the process of filtering the variables and showed a certain influence on the final results. Conclusions: Our study is the first to demonstrate that AQI negatively affects dengue fever occurrence in Taiwan. The proposed prediction model can be used as an early warning system for public health to prevent dengue fever outbreaks. [ABSTRACT FROM AUTHOR]

Dengue, caused by the dengue virus (DENV), affects millions of people worldwide every year. This virus has two distinct life cycles, one in the human and another in the mosquito, and both cycles are crucial to be controlled. To control the vector of DENV, the mosquito Aedes aegypti, scientists employed many techniques, which were later proved ineffective and harmful in many ways. Consequently, the attention shifted to the development of a vaccine; researchers have targeted the E protein, a surface protein of the virus and the NS1 protein, an extracellular protein. There are several types of vaccines developed so far, such as live attenuated vaccines, recombinant subunit vaccines, inactivated virus vaccines, viral vectored vaccines, DNA vaccines, and mRNA vaccines. Along with these, scientists are exploring new strategies of developing improved version of the vaccine by employing recombinant DNA plasmid against NS1 and also aiming to prevent the infection by blocking the DENV life cycle inside the mosquitoes. Here, we discussed the aspects of research in the field of vaccines until now and identified some prospects for future vaccine developments. [ABSTRACT FROM AUTHOR]

Background Dengue is caused by a positive-stranded RNA virus called dengue virus, which is spread by Aedes mosquito species. It is a fast-growing acute febrile disease with potentially lethal consequences that is a global public health problem, mostly in tropical and subtropical countries. In Ethiopia, dengue fever is understudied, although the virus is still being transmitted and viral infection rates are rising. This systematic review and meta-analysis was aimed at estimating the pooled prevalence of DENV infection in Ethiopia. Methods A literature search was done on the PubMed, Hinari and Google Scholar databases to identify studies published before July, 2023. Random effects and fixed effects models were used to estimate the pooled prevalence of all three markers. The Inconsistency Index was used to assess the level of heterogeneity. Results A total of 11 studies conducted on suspected individuals with dengue fever and acutely febrile participants were included in this review. The majority of the studies had a moderate risk of bias and no study had a high risk of bias. A meta-analysis estimated a pooled IgG prevalence of 21% (95% CI: 19–23), a pooled IgM prevalence of 9% (95%CI: 4–13) and a pooled DENV-RNA prevalence of 48% (95% CI: 33–62). There is evidence of possible publication bias in IgG but not in the rest of the markers. Conclusion Dengue is prevalent among the dengue fever suspected and febrile population in Ethiopia. Healthcare providers, researchers and policymakers should give more attention to dengue fever. [ABSTRACT FROM AUTHOR]

Dengue viruses (DENV) are endemic in the US territories of Puerto Rico, American Samoa, and the US Virgin Islands, with focal outbreaks also reported in the states of Florida and Hawaii. However, little is known about the intensity of dengue virus transmission over time and how dengue viruses have shaped the level of immunity in these populations, despite the importance of understanding how and why levels of immunity against dengue may change over time. These changes need to be considered when responding to future outbreaks and enacting dengue management strategies, such as guiding vaccine deployment. We used catalytic models fitted to case surveillance data stratified by age from the ArboNET national arboviral surveillance system to reconstruct the history of recent dengue virus transmission in Puerto Rico, American Samoa, US Virgin Islands, Florida, Hawaii, and Guam. We estimated average annual transmission intensity (i.e., force of infection) of DENV between 2010 and 2019 and the level of seroprevalence by age group in each population. We compared models and found that assuming all reported cases are secondary infections generally fit the surveillance data better than assuming all cases are primary infections. Using the secondary case model, we found that force of infection was highly heterogeneous between jurisdictions and over time within jurisdictions, ranging from 0.00003 (95% CrI: 0.00002–0.0004) in Florida to 0.08 (95% CrI: 0.044–0.14) in American Samoa during the 2010–2019 period. For early 2020, we estimated that seropositivity in 10 year-olds ranged from 0.09% (0.02%–0.54%) in Florida to 56.3% (43.7%–69.3%) in American Samoa. In the absence of serological data, age-specific case notification data collected through routine surveillance combined with mathematical modeling are powerful tools to monitor arbovirus circulation, estimate the level of population immunity, and design dengue management strategies. Author summary: Viruses transmitted by Aedes mosquitoes are a substantial public health burden globally. In the US, the increasing number of outbreaks in recent decades and the co-circulation of the four dengue viruses present a risk of experiencing sequential infections, which can result in more severe disease. However, reported cases only represent a proportion of all infections, so the intensity of dengue circulation in US jurisdictions and the level of population immunity are largely unknown. Combining dengue surveillance data stratified by age with mathematical models enables direct estimation of transmission intensity and previous exposure. We found that dengue virus transmission intensity was highest in American Samoa and Puerto Rico. The US Virgin Islands also showed patterns of endemic transmission, while Hawaii and Guam present more sporadic outbreak profiles. These estimates can help improve risk assessment in these locations and guide interventions to the populations who most need them. [ABSTRACT FROM AUTHOR]

Dengue fever has remained a continuing global medical threat that impacts half of the world's population. Developing a highly effective dengue vaccine, with live-attenuated tetravalent vaccines as leading candidates, remains essential in preventing this disease. For the development of live virus vaccines (LVVs), potency measurements play a vital role in quantifying the active components of vaccine drug substance as well as drug product during various stages of research, development, and post-licensure evaluations. Traditional plaque-based assays are one of the most common potency test methods, but they generally take up to weeks to complete. Less labor and time-intensive potency assays are thus called for to aid in the acceleration of vaccine development, especially for multivalent LVVs. Here, we introduce a fully automated, 96-well format µPlaque assay that has been optimized as a high-throughput tool to evaluate process and formulation development of a live-attenuated tetravalent dengue vaccine. To the best of our knowledge, this is the first report of a miniaturized viral plaque method for dengue with full automation via an integrated robotic system. Compared to the traditional manual plaque assay, this newly developed method substantially reduces testing time by approximately half and allows for the evaluation of over ten times more samples per run. The fully automated workflow, from cell culture to plaque counting, significantly minimizes analyst hands-on time and improves assay repeatability. The study presents a pioneering solution for the rapid measurement of LVV viral titers, offering promising prospects for advancing vaccine development through high-throughput analytics. [ABSTRACT FROM AUTHOR]

Dengue fever has remained a continuing global medical threat that impacts half of the world’s population. Developing a highly effective dengue vaccine, with live-attenuated tetravalent vaccines as leading candidates, remains essential in preventing this disease. For the development of live virus vaccines (LVVs), potency measurements play a vital role in quantifying the active components of vaccine drug substance as well as drug product during various stages of research, development, and post-licensure evaluations. Traditional plaquebased assays are one of the most common potency test methods, but they generally take up to weeks to complete. Less labor and time-intensive potency assays are thus called for to aid in the acceleration of vaccine development, especially for multivalent LVVs. Here, we introduce a fully automated, 96-well format µPlaque assay that has been optimized as a high-throughput tool to evaluate process and formulation development of a live-attenuated tetravalent dengue vaccine. To the best of our knowledge, this is the first report of a miniaturized viral plaque method for dengue with full automation via an integrated robotic system. Compared to the traditional manual plaque assay, this newly developed method substantially reduces testing time by approximately half and allows for the evaluation of over ten times more samples per run. The fully automated workflow, from cell culture to plaque counting, significantly minimizes analyst hands-on time and improves assay repeatability. The study presents a pioneering solution for the rapid measurement of LVV viral titers, offering promising prospects for advancing vaccine development through highthroughput analytics. [ABSTRACT FROM AUTHOR]

Background: Montelukast has shown potential as a candidate treatment for dengue. This study aimed to evaluate the efficacy and safety of montelukast in preventing dengue with warning signs. Methods: This multicenter, randomized, double-blind, placebo-controlled trial enrolled adult participants with NS1 antigenemia in Thailand. The participants were randomly assigned to receive either oral montelukast (10 mg) or a placebo for 10 days or until all symptoms resolved. Results: Between January 2021 and June 2023, 358 participants were enrolled and randomly assigned (1:1) to receive either montelukast or placebo. The incidence rate of warning signs in the montelukast group and the placebo group were 9.5% and 7.8% per day, respectively. There was no difference between the two groups (HR 1.36; 95%CI 0.94–1.96, P = 0.105). No statistically significant differences were observed in the incidence rate of severe dengue, hemoconcentration, thrombocytopenia, admission, or recovery from dengue. Neither dengue shock, nor mortality occurred. The montelukast group exhibited a decreased incidence rate of transaminase elevations (0.7% vs 1.4% per day, HR: 0.48, 95%CI 0.25–0.90, P = 0.023). Conclusion: Oral montelukast does not reduce the incidence of warning signs among patients with dengue. Nevertheless, the observed decrease in transaminase elevations warrants further investigation to evaluate the potential effect of montelukast. Clinical Trials Registration: Clinicaltrials.gov, NCT04673422, registered on 9 December 2020 Author summary: Although there is no specific treatment for dengue to date, montelukast shows promise as a potential therapeutic agent. An open-label study previously showed a 71% reduction in dengue shock among patients with dengue who were administered montelukast. However, concerns were raised regarding the clinical study's lack of a power analysis or predefined statistical difference. Because of its affordability, relatively safe profile, and widespread availability, exploring its role in preventing dengue complications holds great significance. This study is a double-blind clinical trial with pragmatic design assessing the efficacy of montelukast in dengue. In contrast to the previous open-label study, montelukast does not reduce the incidence of warning signs among patients with dengue. Nevertheless, a reduction in the incidence of transaminase elevations was observed. In conclusion, montelukast should not be used for the prevention of warning signs in patients with dengue. However, the observed decrease in transaminase elevations warrants further investigation to evaluate the potential effect of montelukast. [ABSTRACT FROM AUTHOR]

Background: The timely identification of severe dengue in peadiatric patients is of utmost importance, as any delay in diagnosis could lead to an irreversible state of shock potentially leading to fatal consequences. The primary aim of our study was to characterize dengue severity in paediatric patients based on initial symptoms, signs, and laboratory investigation of their presentation in the emergency department. Methodology: We conducted a retrospective data retrieval from the medical records of 254 paediatric patients who had been diagnosed with confirmed cases of dengue fever. The clinical characteristics were compared between severe and non-severe dengue. Multiple logistic regression analysis was utilised to elucidate the variables that exhibited associations with severe dengue. Results: A total of 254 paediatric patients were included, among whom 15.4% (n = 39) were diagnosed with severe dengue. Multiple logistic regression analysis identified lethargy, systolic blood pressure (SBP) below 90 mmHg, capillary refilled time (CRT) longer than 2 seconds, ascites, and hepatomegaly were independently associated with severe dengue. Conclusion: In paediatric patients, severe dengue is associated with specific clinical indicators, including lethargy, low systolic blood pressure, prolonged capillary refill time (CRT), and the presence of ascites and hepatomegaly. Identifying these clinical features early is crucial for primary care physicians, as it enables accurate diagnosis and timely intervention to manage severe dengue effectively. Author summary: Cheras is a suburban area located in the Klang Valley region of Malaysia. In recent years, the population of Cheras has grown rapidly due to urbanization and economic development in the surrounding areas. Cheras has a relatively high population density (N = 135,823, 8,489 / km2) with a mix of high-rise apartment buildings, landed residential properties, and commercial areas. The area is well-connected to other parts of the Klang Valley via major highways and public transportation, which also contributes to the population density. The present study documented clinical and laboratory profiles of 254 paediatric patients with dengue who presented in the emergency department between November 2018 to November 2019 at the only hospital in Cheras, a prevalent dengue area. Patients had an average age of 13 years old, and the male-to-female ratio was nearly balanced. More than 15% had severe dengue manifestation. We found the independent clinical risk factors for severe dengue in paediatric patients include lethargy, systolic blood pressure (SBP) below 90 mmHg, capillary refilled time (CRT) longer than 2 seconds, ascites, and hepatomegaly. Early recognition of these manifestations will assist primary care physicians in making correct diagnosis with timely intervention and management. The presence of dengue in a high-density population and rapidly growing zone warrants further holistic actions to reduce its impact on children's health. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is a public health challenge across the tropics and subtropics. Currently, there is no licensed prophylactic or antiviral treatment for dengue. The novel DENV inhibitor JNJ-1802 can significantly reduce viral load in mice and non-human primates. Here, using a mechanistic viral kinetic model calibrated against viral RNA data from experimental in-vitro infection studies, we assess the in-vitro inhibitory effect of JNJ-1802 by characterising infection dynamics of two DENV-2 strains in the absence and presence of different JNJ-1802 concentrations. Viral RNA suppression to below the limit of detection was achieved at concentrations of >1.6 nM, with a median concentration exhibiting 50% of maximal inhibitory effect (IC50) of 1.23x10-02 nM and 1.28x10-02 nM for the DENV-2/RL and DENV-2/16681 strains, respectively. This work provides important insight into the in-vitro inhibitory effect of JNJ-1802 and presents a first step towards a modelling framework to support characterization of viral kinetics and drug effect across different host systems. Author summary: Dengue poses a major challenge to global public health, with almost half of the world's population at risk of infection each year. However, currently, no licensed specific prophylactic or antiviral treatment for dengue exists. JNJ-1802, a novel dengue inhibitor under development by Janssen Pharmaceutica, is one of the most advanced candidate dengue antivirals and has recently been shown to significantly reduce viral load in pre-clinical animal studies. Here we use mathematical models, fitted to viral RNA data obtained from experimental infection studies in Vero cells, to quantify the in-vitro inhibitory effect of JNJ-1802 on the viral kinetics of two strains of dengue serotype 2. For both strains, we find the effect of JNJ-1802 on viral replication is strongly concentration-dependent, with viral suppression to below the limit of detection achieved at concentrations of 1.6 nM and above. This work is an important first step in quantifying the potential of JNJ-1802 as a dengue antiviral, and demonstrates how interdisciplinary research can help inform drug development and help inform dosing regimens. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study of Aedes vectors to assess the risk of dengue transmission and arbovirus outbreaks in Sargodha district, Pakistani Punjab. Pupae and 3rd and 4th instar larvae of the predominant vectors, Aedes aegypti and A. albopictus mosquitoes, were collected from houses and containers using different tools. Containers were catalogued according to type, location, sun exposure, lid status, water type, and water status. Breeding Preference Ratio (BPR) and larval indices were calculated. Sixty-seven of 1782 houses and 28 of 1494 containers were found infested. Among positive containers, discarded tires had the highest BPR (2.22), followed by barrels and polythene sheets (1.72). The highest absolute counts of Aedes mosquitos were found in plastic drums, whereas other species of mosquitos were highly detected also in jerry cans. The water containers with the highest infestation rates were indoors, in shady locations, only partially covered, and held clean or rain water. Awan and Farooq colonies were identified as high-risk areas, based on a high House Index (5.97 and 4.93, respectively). Our survey suggests that local authorities should promptly address the issue of growing vector populations, particularly in the Awan colony (to be referred as Priority class II area), in order to stem the risk of future epidemics. The number of mosquitoes can be substantially reduced by better handling specific breeding sites and educating people to properly store water. [ABSTRACT FROM AUTHOR]

Background: Strengthening the mosquito control measures undertaken by residents of an area where dengue fever is present can significantly decrease the spread of this disease. The aim of this study was to explore the effects of the source of information and knowledge of dengue fever on the mosquito control behavior of residents of areas at high risk of this disease to determine effective ways of enhancing this behavior. Methods: A survey was conducted via face-to-face interviews or questionnaires between March and May 2021 in three regions of the province of Yunnan, China. The survey included basic information about the respondents, the source(s) of their dengue fever information, the level of their dengue fever knowledge, and the measures they had implemented to control mosquitoes. Principal component analysis was used to extract the main components of the sources of information. Correlation analysis and structural equation analysis were used to explore the impact of the sources of information and residents' dengue fever knowledge on their mosquito control behavior. Results: Publicity achieved through mass media, including official WeChat accounts, magazines/newspapers, poster leaflets, television/radio and the Internet, had a direct effect on dengue fever knowledge and mosquito control behavior, and indirectly affected mosquito control behavior through dengue fever knowledge. Organized publicity campaigns, including information provided by medical staff and through community publicity, had a direct effect on dengue fever knowledge and indirectly affected mosquito control behavior through dengue fever knowledge. The residents' level of dengue fever knowledge had a significant, positive, direct effect on their mosquito control behavior. Conclusions: Mosquito control is an important measure for the prevention and control of outbreaks of dengue fever. An effective source of information can improve the level of dengue fever knowledge among residents and thus enhance their mosquito control behavior. [ABSTRACT FROM AUTHOR]

Background: The mosquito Aedes aegypti is an urban vector of dengue and other arboviruses. During epidemics of these viruses, pyrethroid insecticides are used for the control of adult mosquitoes. The worldwide resistance of Ae. aegypti to these insecticides is a cause of failure of vector control campaigns. The primary target of pyrethroids is the voltage-gated sodium channel. Point mutations in the gene coding for this channel, called knockdown resistance (kdr) mutations, are associated with pyrethroid resistance. Two kdr mutations, V1016I and F1534C, have increased in frequency in natural populations of Ae. aegypti in the Americas during the last decade. Their association with pyrethroid resistance has been largely demonstrated in field populations throughout the Americas, and in in vitro assays. Diagnostics for kdr polymorphism allow early detection of the spread of insecticide resistance, which is critical for timely decisions on vector management. Given the importance of resistance management, high-throughput methods for kdr genotyping are valuable tools as they can be used for resistance monitoring programs. These methods should be cost-effective, to allow regional-scale surveys. Despite the extensive presence of Ae. aegypti and incidence of dengue in Argentina, the presence, abundance, and distribution of kdr mutations in populations of this mosquito have yet to be reported for the country. Methods: Aedes aegypti samples were collected as immature stages or adults from Buenos Aires Metropolitan Area and northern localities of Tartagal (Salta Province) and Calilegua (Jujuy Province). Immature stages were maintained in the laboratory until they developed into adults. A high-resolution melting assay, based on an analysis of melting temperatures, was developed for the simultaneous genotyping of V1016I and F1534C kdr mutations. We used this method to infer the presence and frequencies of kdr alleles in 11 wild populations from Argentina. Results: We demonstrated the presence of kdr mutations in Ae. aegypti in Argentina in regions where this species is under different selection pressures due to the use of pyrethroids. The populations under analysis are located in geographically distant regions of the species' distribution in Argentina: the northern provinces of Salta and Jujuy and the Buenos Aires Metropolitan Area. Higher frequencies of resistant-associated alleles were detected in the northern region. We report a multiplex high-throughput assay based on a high-resolution melting polymerase chain reaction method for the simultaneous genotyping of V1016I and F1534C kdr mutations. This assay was shown to be cost-effective, and thus provides an interesting molecular tool for kdr genotyping in A. aegypti control campaigns. Conclusions: We report, to the best of our knowledge for the first time, the presence of kdr mutations in populations of Ae. aegypti from geographically distant locations of Argentina that differ with respect to their epidemiological situation and history of mosquito control. We have developed a high-throughput method for the genotyping of kdr mutations in Ae. aegypti from the Americas. Given its affordability and short running time, this method can be used in control campaigns to monitor the presence and spread of kdr alleles. The information provided here is relevant for the rational design of control strategies in the context of integrated vector management. [ABSTRACT FROM AUTHOR]

Among several vector control methods commonly used, environmental management is one of the control measures to mitigate dengue in such vulnerable communities. Since there is no curative treatment for dengue yet, targeted environmental and ecosystem management is increasingly relevant. Hence, this review was conducted to identify the effectiveness of environmental management intervention strategy to reduce dengue cases. We searched PUBMED, CENTRAL, SCOPUS, Web of Science, CIJE, WHO ICTRP, and ClinicalTrials.gov up to January 2021. A total of 521 articles were screened. Only 16 studies were included in this review. There were 6 studies that applied all three types of environmental management interventions (manipulation, modification and behavior), 8 studies applied two types of interventions (manipulation and behavior) and 2 studies applied one type of intervention (manipulation or behavior). All included studies reported reduction of Aedes entomological indices. The studies showed reduction in dengue cases and density of Aedes population through environmental interventions. It is recommended for the health authority to incorporate environmental management intervention in dengue control activities and enhanced the community involvement to ensure sustainability with high impact on dengue reduction. [ABSTRACT FROM AUTHOR]

Background: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. Methods: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). Results: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002–2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. Conclusions: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping. [ABSTRACT FROM AUTHOR]

Background: Dengue is a public health problem in the Indo-Pacific countries. There are concerns over the facilitators and barriers to community engagement in health service research aimed at dengue control. The objective of his study was to identify and synthesize facilitators and barriers to community engagement in health service research aimed at dengue control. Methodology: The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) checklist was used to perform this review. Health-related databases including PubMed, Ovid, and Google Scholar were searched for relevant studies. A consolidated framework with five domains was developed after undertaking a six-phase reflective thematic assessment of the data. Results: Thirteen studies were identified, spanning eight low-and middle-income countries of the Indo-Pacific region including Cambodia, India, Indonesia, Myanmar, Philippines, Sri Lanka, Thailand, and Vietnam. The studies in this review covered the period from 2002 to 2021. A broad range of study designs and objectives were revealed across these 13 studies. An array of communities such as the local government, project-related health staff, local health services staff, community leaders, local communities/residences/general public, heads of households, community health volunteers, school teachers, and schoolchildren participated in these dengue related studies. The five Consolidated Framework for Implementation Research (CFIR) domains of 'intervention characteristics', 'inner setting', 'outer setting',' individual characteristics', and 'program implementations' were used to identify and describe barriers and facilitators. Conclusions: The findings indicate a range of barriers and facilitators to community engagement in dengue control in the selected LMIC in the Indo-Pacific countries. Future health services research on dengue control approaches should be carefully planned, methodologically constructed, aligned with community engagement principles, and involve considerable community participation at all stages of the research. [ABSTRACT FROM AUTHOR]

Background: Worldwide invasion and expansion of Aedes albopictus, an important vector of dengue, chikungunya, and Zika viruses, has become a serious concern in global public health. Chemical insecticides are the primary means currently available to control the mosquito populations. However, long-term and large-scale use of insecticides has selected for resistance in the mosquito that is accompanied by a genetic load that impacts fitness. Results: A number of laboratory strains representing different resistance mechanisms were isolated and identified from laboratory-derived, deltamethrin-resistant Ae. albopictus recovered in previous work. Resistance levels and fitness costs of the strains were evaluated and compared to characterize the evolution of the resistance genotypes and phenotypes. The heterozygous F1534S mutation (1534F/S) in the voltage gated sodium channel (vgsc) gene product (VGSC), first detected in early stages of resistance evolution, not only confers high-level resistance, but also produces no significant fitness costs, leading to the rapid spread of resistance in the population. This is followed by the increase in frequency of homozygous F1534S (1534S/S) mosquitoes that have significant fitness disadvantages, prompting the emergence of an unlinked I1532T mutation with fewer side effects and a mating advantage better adapted to the selection and reproductive pressures imposed in the experiments. Metabolic resistance with no significant fitness cost and mediating a high-tolerance resistance phenotype may play a dominant role in the subsequent evolution of resistance. The different resistant strains had similar vector competence for dengue virus type-2 (DENV-2). Furthermore, a comparative analysis of vectorial capacity revealed that increased survival due to deltamethrin resistance balanced the negative fitness cost effects and contributed to the risk of dengue virus (DENV) transmission by resistant populations. The progressive evolution of resistance results in mosquitoes with both target-site insensitivity and metabolic resistance with lower fitness costs, which further leads to resistant populations with both high resistance levels and vectorial capacity. Conclusions: This study reveals a possible mechanism for the evolution of deltamethrin resistance in Aedes albopictus. These findings will help guide practical strategies for insecticide use, resistance management and the prevention and control of mosquito-borne disease. [ABSTRACT FROM AUTHOR]

Badung district has recorded the highest dengue fever (DF) in Bali Province. This research presents the distribution of DF in Badung district and analyses its association with climate and visitors. The monthly data of DF, climate and number of visitors during January 2013 to December 2017 were analysed using Poisson Regression. A total of 10,689 new DF cases were notified from January 2013 to December 2017. DF in 2016 was recorded as the heaviest incidence. Monthly DF cases have positive association with average temperature (0.59 (95% CI: 0.56–.62)), precipitation (5.7 x 10−4 (95% CI: 3.8 x 10−4 − 7.6 x 10−4)), humidity (.014 (95% CI: 0.003–.025)) and local visitors (7.40 x 10−6 95% CI: 5.88 x 10−6 : 8.91 x 10−6). Negative association was shown between DF cases with foreign visitors (−2.18 x 10−6 (95% CI: −2.50 x 10−6 : −1.87 x 10−6)). This study underlines the urgency to integrate climate and tourism for DF surveillance. [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: Dengue virus serotypes (DENV-1 to -4) can be transmitted vertically in Aedes aegpti mosquitoes. Whether infection with the wMel strain of the endosymbiont Wolbachia can reduce the incidence of vertical transmission of DENV from infected females to their offspring is not well understood. Methods: A laboratory colony of Vietnamese Ae. aegypti, both with and without wMel infection, were infected with DENV-1 by intrathoracic injection (IT) to estimate the rate of vertical transmission (VT) of the virus. VT in the DENV-infected mosquitoes was calculated via the infection rate estimation from mosquito pool data using maximum likelihood estimation (MLE). Results: In 6047 F1 Vietnamese wild-type Ae. aegypti, the MLE of DENV-1 infection was 1.49 per 1000 mosquitoes (95% confidence interval [CI] 0.73–2.74). In 5500 wMel-infected Ae. aegypti, the MLE infection rate was 0 (95% CI 0–0.69). The VT rates between mosquito lines showed a statistically significant difference. Conclusions: The results reinforce the view that VT is a rare event in wild-type mosquitoes and that infection with wMel is effective in reducing VT. [ABSTRACT FROM AUTHOR]

Dengue fever is a rapidly spreading mosquito-borne contagion. However, the effects of extreme rainfall events on dengue occurrences have not been widely evaluated. With their immense precipitation and high winds, typhoons may have distinct effects on dengue occurrence from those during other heavy rain events. Frequented by typhoons and situated in the tropical climate zone, southern Taiwan is an appropriate study area due to its isolated geographic environment. Each subject to distinct orographic effects on typhoon structure and typhoon-induced precipitation, 9 typhoon trajectories around Taiwan have not been observed until now. This study analyzes typhoon-induced precipitation and examines historical typhoon events by trajectory to determine the effects of typhoons on dengue occurrences in different urban contexts of Tainan and Kaohsiung in high-epidemic southern Taiwan. We employed data from 1998 to 2019 and developed logistic regression models for modeling dengue occurrence while taking 28-day lag effects into account. We considered factors including typhoon trajectory, occurrence, and typhoon-induced precipitation to dengue occurrences. Our results indicate that typhoon trajectories are a significant risk factor for dengue occurrence. Typhoons affect dengue occurrence differently by trajectory. One out of four northbound (along the Taiwan Strait) and four out of five westbound (across Taiwan) typhoons were found to be positively correlated with dengue occurrences in southern Taiwan. We observe that typhoon-induced precipitation is not associated with dengue occurrence in southern Taiwan, which suggests that wind destruction during typhoon events may serve as the primary cause for their positive effects by leaving debris suitable for mosquito habitats. Our findings provide insights into the impact of typhoons by trajectory on dengue occurrence, which can improve the accuracy of future dengue forecasts in neighboring regions with similar climatic contexts. [ABSTRACT FROM AUTHOR]

The Dengue Virus (DENV) non-structural protein 3 (NS3) is a multi-functional protein critical in the viral life cycle. The DENV NS3 is comprised of a serine protease domain and a helicase domain. The helicase domain itself acts as a molecular motor, either translocating in a unidirectional manner along single-stranded RNA or unwinding double-stranded RNA, processes fueled by the hydrolysis of nucleoside triphosphates. In this brief review, we summarize our contributions and ongoing efforts to uncover the thermodynamic and mechanistic functional properties of the DENV NS3 as an NTPase and helicase. [ABSTRACT FROM AUTHOR]

Background: Severe dengue often leads to poor clinical outcomes and high mortality; as a result, it is of vital importance to find prognostic factors associated with the severe form of dengue. Obesity is known to deteriorate many infectious diseases due to impaired immune responses. Several studies have suggested that obese patients with dengue infection tend to have more severe manifestations with poorer prognosis. However, a firm conclusion could not be drawn due to the varied results of these studies. Here, we aimed to conduct a systematic review and meta-analysis to investigate the association between obesity and dengue severity. Methods: A literature search for relevant studies was conducted in PubMed, Embase, Ovid Medline and Cochrane from inception to September 9, 2022. The two main keywords were "dengue" and "obesity". Mantel-Haenszel method and random effects model was used to analyze the pooled odds ratio with 95% confidence intervals. Results: A total of 15 article involving a total of 6,508 patients were included in the meta-analysis. Included patients in most studies were hospitalized pediatric patients. Only one study included adulthood data. Three cohort studies, four case-control studies, and one cross-sectional studies found a significant association between obesity and dengue severity. In contrast, three cohort studies, three case-control studies, and one cross-sectional study reported no significant relationship between obesity and dengue severity. Our analysis results showed that patient with obesity is 50% (OR = 1.50; 95%CI: 1.15–1.97) more likely to develop severe manifestation of dengue. Conclusion: This meta-analysis revealed that overweight could be a clinical predictor for severe disease for pediatric patients with dengue infection. [ABSTRACT FROM AUTHOR]

Background and Aim: Dengue fever, transmitted by Aedes mosquitoes, is a significant public health concern in tropical and subtropical regions. With the end of the COVID-19 pandemic and the reopening of the borders, dengue fever remains a threat to mainland China, Zhejiang province of China is facing a huge risk of importing the dengue virus. This study aims to analyze and predict the current and future potential risk regions for Aedes vectors distribution and dengue prevalence in Zhejiang province of China. Method: We collected occurrence records of DENV and DENV vectors globally from 2010 to 2022, along with historical and future climate data and human population density data. In order to predict the probability of DENV distribution in Zhejiang province of China under future conditions, the ecological niche of Ae. aegypti and Ae. albopictus was first performed with historical climate data based on MaxEnt. Then, predicted results along with a set of bioclimatic variables, elevation and human population density were included in MaxEnt model to analyze the risk region of DENV in Zhejiang province. Finally, the established model was utilized to predict the spatial pattern of DENV risk in the current and future scenarios in Zhejiang province of China. Results: Our findings indicated that approximately 89.2% (90,805.6 KM2) of Zhejiang province of China is under risk, within about 8.0% (8,144 KM2) classified as high risk area for DENV prevalence. Ae. albopictus were identified as the primary factor influencing the distribution of DENV. Future predictions suggest that sustainable and "green" development pathways may increase the risk of DENV prevalence in Zhejiang province of China. Conversely, Fossil-fueled development pathways may reduce the risk due to the unsuitable environment for vectors. Conclusions: The implications of this research highlight the need for effective vector control measures, community engagement, health education, and environmental initiatives to mitigate the potential spread of dengue fever in high-risk regions of Zhejiang province of China. [ABSTRACT FROM AUTHOR]

The state of Ceará, in the Northeast Region of Brazil, presents the simultaneous circulation of Zika (ZIKV), dengue (DENV) and chikungunya (CHIKV) viruses. In 2017 there were a high number of cases of these three arboviruses, especially CHIKV. Here, we detected the presence of arboviruses ZIKV, DENV and CHIKV and their coinfections in women in endemic regions of the city of Fortaleza, Ceará in a post-Zika epidemic year. Sociodemographic and environmental characteristics associated with arbovirus positivity were also analyzed. Women (n = 1289) between 15 and 39 years old were included. RT-qPCR was performed for virus detection and IgM antibody positivity was also analyzed. One hundred and six (8.3%) participants were positive for one or more arboviruses. Monoinfections (76; 5.9%) were distributed between 22 (1.7%) for ZIKV, 39 (3.1%) for DENV and 15 (1.2%) for CHIKV. Co-infections were detected in 30 (2.3%) of the positive participants and one case with triple infection was found. IgM positivity was found in 2.4% of ZIKV RT-qPCR, 9.6% of DENV and 16.3% of CHIKV. RT-qPCR positivity for arboviruses was associated with low socioeconomic class and presence of a water box sealing in the household. A higher positivity to the three viruses occurred in the month with the lowest wind velocity, which was also preceded by the highest peak of rain and humidity. We identified the simultaneous circulation and co-infection of ZIKV, DENV and CHIKV in Fortaleza in a post-Zika epidemic year. We also highlight the need for continuous epidemiological surveillance combined with molecular diagnostic tools. [ABSTRACT FROM AUTHOR]

Background: Reduction of the Aedes aegypti population is the priority effort to control dengue virus transmission including the use of larvivorous fish. Biologically, the predatory efficiency of fish will slow down when the water acidity and temperature change from normal conditions. This study aimed to determine the predatory efficiency of three species of larvivorous fish against the Ae. aegypti larvae in different water temperatures. Methods: Three well-known species of larvivorous fish namely Poecilia reticulata, Betta splendens, and Aplocheilus panchax were placed into 12 cm diameter jars with three water temperature ranges namely 20–21 ºC, 27–28 ºC, and 34– 35 ºC, and allowed to three days acclimatization. As many as one hundred 4 th -instars larvae of Ae. aegypti were gradually entered into each jar, and a longitudinal observation was made at 5, 10, 30, 60, 120, 240, 360, 480, 600, and 720 minutes. The predated larvae were recorded. Results: In normal temperature ranges, the predatory efficiency of the larvivorous fish was 75%, 72.3%, and 32.8% for B. splendens. Aplocheilus panchax, and P. reticulata, respectively. The predation abilities decreased due to temperature changes. Betta splendens and A. panchax indicated the best predatory efficiency against Ae. aegypti larvae in different temperature conditions. Conclusion: Betta splendens is the best larvivorous fish in the lower to normal, but A. panchax is the best in the normal to higher temperature ranges. This finding should be considered by public health workers in selecting larvivorous fish to control the Dengue vectors. [ABSTRACT FROM AUTHOR]

The non-structural protein 5 (NS5) is the most conserved protein among flaviviruses, a family that includes the dengue virus. It functions both as an RNA-dependent RNA polymerase and an RNA-methyltransferase and is therefore essential for the replication of viral RNA. The discovery that dengue virus NS5 protein (DENV-NS5) can also localize to the nucleus has resulted in renewed interest in its potential roles at the host-virus interface. In this study, we have used two complementary computational approaches in parallel – one based on linear motifs (ELM) and another based on tertiary structure of the protein (DALI) – to predict the host proteins that DENV-NS5 might interact with. Of the 42 human proteins predicted by both these methods, 34 are novel. Pathway analysis of these 42 human proteins shows that they are involved in key host cellular processes related to cell cycle regulation, proliferation, protein degradation, apoptosis, and immune responses. A focused analysis of transcription factors that directly interact with the predicted DENV-NS5 interacting proteins was performed, followed by the identification of downstream genes that are differentially expressed after dengue infection using previously published RNA-seq data. Our study provides unique insights into the DENV-NS5 interaction network and delineates mechanisms whereby DENV-NS5 could impact the host-virus interface. The novel interactors identified in this study could be potentially targeted by NS5 to modulate the host cellular environment in general, and the immune response in particular, thereby extending the role of DENV-NS5 beyond its known enzymatic functions. [ABSTRACT FROM AUTHOR]

Dengue fever, which is spread by Aedes mosquitoes, has claimed many lives in Kerala, with the Thiruvananthapuram district bearing the brunt of the toll. This study aims to demarcate the dengue risk zones in Thiruvananthapuram district using the analytical hierarchy process (AHP) and the fuzzy-AHP (F-AHP) methods. For the risk modelling, geo-environmental factors (normalized difference vegetation index, land surface temperature, topographic wetness index, land use/land cover types, elevation, normalized difference built-up index) and demographic factors (household density, population density) have been utilized. The ArcGIS 10.8 and ERDAS Imagine 8.4 software tools have been used to derive the risk zone maps. The area of the risk maps is classified into five zones. The dengue risk zone maps were validated using dengue case data collected from the Integrated Disease Surveillance Programme portal. From the receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) values, it is proved that the F-AHP method (AUC value of 0.971) has comparatively more prediction capability than the AHP method (AUC value of 0.954) in demarcating the dengue risk zones. Also, based on the comparison of the risk zone map with actual case data, it was confirmed that around 82.87% of the dengue cases occurred in the very high and high-risk zones, thus proving the efficacy of the model. According to the dengue risk map prepared using the F-AHP model, 9.09% of the area of Thiruvananthapuram district is categorized as very high risk. The prepared dengue risk maps will be helpful for decision-makers, staff with the health, and disaster management departments in adopting effective measures to prevent the risks of dengue spread and thereby minimize loss of life. [ABSTRACT FROM AUTHOR]

Background: Arbovirus diseases such as dengue, Zika, and chikungunya are a public health threat in tropical and subtropical areas. In the absence of a vaccine or specific treatment, vector management (in this case the control of the primary vector Aedes aegypti) is the best practice to prevent the three diseases. A good understanding of vector behaviour, ecology, human mobility and water use can help design effective vector control programmes. This study collected baseline information on these factors for identifying the arbovirus transmission risk and assessed the requirements for a large intervention trial in Colombia. Methods: Baseline surveys were conducted in 5,997 households, randomly selected from 24 clusters (neighbourhoods with on average 2000 houses and 250 households inspected) in the metropolitan area of Cucuta, Colombia. The study established population characteristics including water management and mobility as well as larval-pupal indices which were estimated and compared in all clusters. Additionally, the study estimated disease incidence from two sources: self-reported dengue cases in the household survey and cases notified by the national surveillance system. Results: In all 24 study clusters similar social and demographic characteristics were found but the entomological indicators and estimated disease incidence rates varied. The entomological indicators showed a high vector infestation: House Index = 25.1%, Container Index = 12.3% and Breteau Index = 29.6. Pupae per person Index (PPI) as an indicator of the transmission risk showed a large range from 0.22 to 2.04 indicating a high transmission risk in most clusters. The concrete ground tanks for laundry –mostly outdoors and uncovered- were the containers with the highest production of Ae. aegypti as 86.3% of all 17,613 pupae were identified in these containers. Also, the annual incidence of dengue was high: 841.6 self-reported cases per 100,000 inhabitants and the dengue incidence notified by the National surveillance system was 1,013.4 cases per 100,000 in 2019. Only 2.2% of the households used container water for drinking. 40.3% of the study population travelled during the day (when Aedes mosquitoes bite) outside their clusters. Conclusions: The production of Ae. aegypti mosquitoes occurred almost exclusively in concrete ground tanks for laundry (lavadero), the primary intervention target. The baseline study provides necessary evidence for the design and implementation of a cluster randomized intervention trial in Colombia. [ABSTRACT FROM AUTHOR]

Background: The mosquito Aedes aegypti transmits two of the most serious mosquito-borne viruses, dengue virus (DENV) and Zika virus (ZIKV), which results in significant human morbidity and mortality worldwide. The quickly shifting landscapes of DENV and ZIKV endemicity worldwide raise concerns that their co-circulation through the Ae. aegypti mosquito vector could greatly exacerbate the disease burden in humans. Recent reports have indicated an increase in the number of co-infection cases in expanding co-endemic regions; however, the impact of co-infection on viral infection and the detailed molecular mechanisms remain to be defined. Methods: C6/36 (Aedes albopictus) cells were cultured in Dulbecco's modified Eagle medium/Mitsuhashi and Maramorosch Insect Medium (DMEM/MM) (1:1) containing 2% heat-inactivated fetal bovine serum and 1× penicillin/streptomycin solution. For virus propagation, the cells were infected with either DENV serotype 2 (DENV2) strain 16681 or ZIKV isolate Thailand/1610acTw (MF692778.1). Mosquitoes (Ae. aegypti UGAL [University of Georgia Laboratory]/Rockefeller strain) were orally infected with DENV2 and ZIKV through infectious blood-feeding. Results: We first examined viral replication activity in cells infected simultaneously, or sequentially, with DENV and ZIKV, and found interspecies binding of viral genomic transcripts to the non-structural protein 5 (NS5). When we challenged Ae. aegypti mosquitos with both DENV2 and ZIKV sequentially to probe similar interactions, virus production and vector susceptibility to infection were significantly enhanced. Conclusions: Our results suggest that DENV2 and ZIKV simultaneously establishing infection in the Ae. aegypti mosquito vector may augment one another during replication. The data also implicate the homologous NS5 protein as a key intersection between the flaviviruses in co-infection, highlighting it as a potential target for vector control. [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]

Background: Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems. Methods: To identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell (PBMC) transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia. Results: After a secondary infection, progression to uncomplicated dengue featured transcriptional profiles associated with increased cell proliferation and metabolism, and an expansion of ICOS+CD4+ and CD8+ effector memory T cells. These responses were virtually absent in cases progressing to severe DHF, that instead mounted an innate-like response, characterised by inflammatory transcriptional profiles, high circulating levels of inflammatory chemokines and with high frequencies of CD4low non-classical monocytes predicting increased odds of severe disease. Conclusions: Our results suggests that effector memory T cell activation might play an important role ameliorating severe disease symptoms during a secondary dengue infection, and in the absence of that response, a strong innate inflammatory response is required to control viral replication. Our research also identified discrete cell populations predicting increased odds of severe disease, with potential diagnostic value. [ABSTRACT FROM AUTHOR]

More than a hundred thousand dengue cases are diagnosed in India annually, and about half of the country's population carries dengue virus-specific antibodies. Dengue propagates and adapts to the selection pressures imposed by a multitude of factors that can lead to the emergence of new variants. Yet, there has been no systematic analysis of the evolution of the dengue virus in the country. Here, we present a comprehensive analysis of all DENV gene sequences collected between 1956 and 2018 from India. We examine the spatio-temporal dynamics of India-specific genotypes, their evolutionary relationship with global and local dengue virus strains, interserotype dynamics and their divergence from the vaccine strains. Our analysis highlights the co-circulation of all DENV serotypes in India with cyclical outbreaks every 3–4 years. Since 2000, genotype III of DENV-1, cosmopolitan genotype of DENV-2, genotype III of DENV-3 and genotype I of DENV-4 have been dominating across the country. Substitution rates are comparable across the serotypes, suggesting a lack of serotype-specific evolutionary divergence. Yet, the envelope (E) protein displays strong signatures of evolution under immune selection. Apart from drifting away from its ancestors and other contemporary serotypes in general, we find evidence for recurring interserotype drift towards each other, suggesting selection via cross-reactive antibody-dependent enhancement. We identify the emergence of the highly divergent DENV-4-Id lineage in South India, which has acquired half of all E gene mutations in the antigenic sites. Moreover, the DENV-4-Id is drifting towards DENV-1 and DENV-3 clades, suggesting the role of cross-reactive antibodies in its evolution. Due to the regional restriction of the Indian genotypes and immunity-driven virus evolution in the country, ~50% of all E gene differences with the current vaccines are focused on the antigenic sites. Our study shows how the dengue virus evolution in India is being shaped in complex ways. Author summary: Dengue is a mosquito-borne disease with four closely related serotypes of the virus (DENV-1-4). Further, cross-reacting dengue antibodies from a previous infecting dengue serotype can protect or enhance infection from other serotypes. This can force the emergence of new dengue variants that find ways to escape the immune action or take advantage of it. In endemic countries like India, high rates of previous dengue infection can drive the evolution of dengue serotypes in complex ways. We compare all published dengue virus sequences to understand how new variants of dengue are emerging in India. Dengue cases and corresponding viruses display triennial surges. Further, the dengue envelope protein for each serotype shows recurring divergence and reversal towards its ancestral strain over a three-year window. Such fluctuations are also correlated among the dengue serotypes in India and could arise from the changing levels of cross-reactive antibodies. This, combined with the regional exchange of the virus among Asia-Pacific countries, has led to the emergence of India-specific DENV lineages, including a new DENV-4 (Id) variant. This has also contributed to significant variations in the epitope regions of the current dengue viruses in India compared to the vaccines with implications for their efficacy. [ABSTRACT FROM AUTHOR]

Previous studies suggested that dengue was associated with an increased risk of several autoimmune diseases. However, this association still needs to be explored due to the limitations of these studies. A population-based cohort study was conducted using national health databases in Taiwan and included 63,814 newly diagnosed, laboratory-confirmed dengue patients between 2002 and 2015 and 1:4 controls (n = 255,256) matched by age, sex, area of residence and symptom onset time. Multivariate Cox proportional hazard regression models were used to investigate the risk of autoimmune diseases after dengue infection. Dengue patients had a slightly higher risk of overall autoimmune diseases than non-dengue controls (aHR 1.16; P = 0.0002). Stratified analyses by specific autoimmune diseases showed that only autoimmune encephalomyelitis remained statistically significant after Bonferroni correction for multiple testing (aHR 2.72; P < 0.0001). Sixteen (0.025%) dengue patients and no (0%) controls developed autoimmune encephalomyelitis in the first month of follow-up (HR >9999, P < 0.0001), but the risk between groups was not significantly different thereafter. Contrary to previous studies, our findings showed that dengue was associated with an increased short-term risk of a rare complication, autoimmune encephalomyelitis, but not associated with other autoimmune diseases. Author summary: Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Antibodies produced during dengue infection can cross-react with several self-antigens to the tissues of the body and contribute to thrombocytopenia, coagulopathy, and vascular leakage in severe dengue. Autoimmunity might occur after dengue infection and cause some autoimmune diseases. Previous studies suggested some autoimmune diseases might be associated with dengue infection. Contrary to previous studies, our findings showed that dengue was associated with an increased short-term risk of a rare complication, autoimmune encephalomyelitis, but not associated with other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background Dengue infections caused by the four antigenically distinct dengue virus serotypes (DENV1, DENV2, DENV3, DENV4) of the family Flaviviridae are the most major arboviral diseases in humans in terms of geographic spread, morbidity, and mortality. Objective: The study was conducted to assess serum lactate in cases of dengue and correlate it with severity in dengue infection. Methodology: A prospective observational study was carried out among indoor patients admitted to the general medicine department of the tertiary care hospital SMIMER Surat. The study's duration was 15 to 18 months. Result: our study found out of total 154 cases; majority of cases were belonged from 83(53.90%) cases were from less than 30 years. male was contributed 96 (62.34%), majority of cases had duration of fever 39(25.32%), 66 (42.66%) case had high LDH, comparison of serum lactate dehydrogenase with severity of dengue mean lactate dehydrogenase of dengue without severity was mean was 148.45 and SD 11.81, while in severe dengue mean serum lactate dehydrogenase 388.23 and SD 99.47 with p value 0.001 which was statically significant. Conclusion According to this study, it is preferable to monitor serial lactate levels as opposed to using a single lactate number. [ABSTRACT FROM AUTHOR]

Dengue is among the fastest-spreading vector-borne infectious disease, with outbreaks often overwhelm the health system and result in huge morbidity and mortality in its endemic populations in the absence of an efficient warning system. A large number of prediction models are currently in use globally. As such, this study aimed to systematically review the published literature that used quantitative models to predict dengue outbreaks and provide insights about the current practices. A systematic search was undertaken, using the Ovid MEDLINE, EMBASE, Scopus and Web of Science databases for published citations, without time or geographical restrictions. Study selection, data extraction and management process were devised in accordance with the 'Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies' ('CHARMS') framework. A total of 99 models were included in the review from 64 studies. Most models sourced climate (94.7%) and climate change (77.8%) data from agency reports and only 59.6% of the models adjusted for reporting time lag. All included models used climate predictors; 70.7% of them were built with only climate factors. Climate factors were used in combination with climate change factors (10.3%), both climate change and demographic factors (10.3%), vector factors (5.1%), and demographic factors (5.1%). Machine learning techniques were used for 39.4% of the models. Of these, random forest (15.4%), neural networks (23.1%) and ensemble models (10.3%) were notable. Among the statistical (60.6%) models, linear regression (18.3%), Poisson regression (18.3%), generalized additive models (16.7%) and time series/autoregressive models (26.7%) were notable. Around 20.2% of the models reported no validation at all and only 5.2% reported external validation. The reporting of methodology and model performance measures were inadequate in many of the existing prediction models. This review collates plausible predictors and methodological approaches, which will contribute to robust modelling in diverse settings and populations. Author summary: Dengue is considered as a major public health challenge and a life-threatening disease affecting people worldwide. Over the past decades, numerous forecast models have been developed to predict dengue incidence using various factors based on different geographical locations. Dengue transmission appears to be highly sensitive to climate variability and change, however quantitative models used to assess the relationship between climate change and dengue often differ due to their distribution assumptions, the nature of the relationship and the spatial and/or temporal dynamics of the response. We performed a systematic review to examine current literature surrounding existing quantitative models based on development methodology, predictor variable used and model performance. Our analysis demonstrates several shortcomings in current modelling practice, and advocates for the use of real time primary predictor data, the incorporation of non-climatic parameters as predictors and more comprehensive reporting of model development techniques and validation. This review collates methodological approaches adopted in the modelling practices in the field across current literature. This will provide an evidence-based framework for upgrading future modelling practice to develop more accurate predictive models with robust techniques. In turn, this also provided an opportunity for the effective distribution of limited public health resources to prepare for demand. [ABSTRACT FROM AUTHOR]

Current knowledge of dengue virus (DENV) transmission provides only a partial understanding of a complex and dynamic system yielding a public health track record that has more failures than successes. An important part of the problem is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions based on a relatively small portion of the human population; i.e., people who are convenient to study because they manifest clinically apparent disease. Approaching dengue from the perspective of people with overt illness has produced an extensive body of useful literature. It has not, however, fully embraced heterogeneities in virus transmission dynamics that are increasingly recognized as key information still missing in the struggle to control the most important insect-transmitted viral infection of humans. Only in the last 20 years have there been significant efforts to carry out comprehensive longitudinal dengue studies. This manuscript provides the rationale and comprehensive, integrated description of the methodology for a five-year longitudinal cohort study based in the tropical city of Iquitos, in the heart of the Peruvian Amazon. Primary data collection for this study was completed in 2019. Although some manuscripts have been published to date, our principal objective here is to support subsequent publications by describing in detail the structure, methodology, and significance of a specific research program. Our project was designed to study people across the entire continuum of disease, with the ultimate goal of quantifying heterogeneities in human variables that affect DENV transmission dynamics and prevention. Because our study design is applicable to other Aedes transmitted viruses, we used it to gain insights into Zika virus (ZIKV) transmission when during the project period ZIKV was introduced and circulated in Iquitos. Our prospective contact cluster investigation design was initiated by detecttion of a person with a symptomatic DENV infection and then followed that person's immediate contacts. This allowed us to monitor individuals at high risk of DENV infection, including people with clinically inapparent and mild infections that are otherwise difficult to detect. We aimed to fill knowledge gaps by defining the contribution to DENV transmission dynamics of (1) the understudied majority of DENV-infected people with inapparent and mild infections and (2) epidemiological, entomological, and socio-behavioral sources of heterogeneity. By accounting for factors underlying variation in each person's contribution to transmission we sought to better determine the type and extent of effort needed to better prevent virus transmission and disease. [ABSTRACT FROM AUTHOR]

Dengue is a rapidly spreading viral disease transmitted to humans by Aedes mosquitoes. Due to global urbanization and climate change, the number of dengue cases are gradually increasing in recent decades. Hence, an early prediction of dengue continues to be a major concern for public health in countries with high prevalence of dengue. Creating a robust forecast model for the accurate prediction of dengue is a complex task and can be done through various data modelling approaches. In the present study, we have applied vector auto regression, generalized boosted models, support vector regression, and long short-term memory (LSTM) to predict the dengue prevalence in Kerala state of the Indian subcontinent. We consider the number of dengue cases as the target variable and weather variables viz., relative humidity, soil moisture, mean temperature, precipitation, and NINO3.4 as independent variables. Various analytical models have been applied on both datasets and predicted the dengue cases. Among all the models, the LSTM model was outperformed with superior prediction capability (RMSE: 0.345 and R2:0.86) than the other models. However, other models are able to capture the trend of dengue cases but failed in predicting the outbreak periods when compared to LSTM. The findings of this study will be helpful for public health agencies and policymakers to draw appropriate control measures before the onset of dengue. The proposed LSTM model for dengue prediction can be followed by other states of India as well. [ABSTRACT FROM AUTHOR]