TAK-003 is a dengue vaccine introduced in dengue-endemic countries and considered for travelers. Although not yet approved in Japan, inquiries from travelers are increasing. With limited evidence about vaccine use for travelers, consolidated expert opinions would aid in vaccination decision-making. Therefore, this study examined the opinions on TAK-003 and the need for decision-support information and materials among travel medicine providers before its launch in Japan. Participants recruited from the Japanese Society of Travel and Health were assessed on their intention to receive TAK-003 themselves when visiting dengue-endemic areas, and their intention to recommend it to travelers, with responses provided separately for short- and long-term travels. Participants who did not recommend TAK-003 provided reasons using multiple-choice questions. All participants were asked about their need for supporting information to aid in vaccination decision-making. Among the 154 respondents, over half intended to receive (55% for short-term, 75% for long-term) and recommend (53% for short-term, 75% for long-term) the vaccination. The primary reasons for not recommending it were concerns about efficacy and safety, which were also the most requested support information. These findings suggest that many travel medicine providers have positive opinions on TAK-003 as a travel vaccine and need decision-support information and materials.

Arboviruses constitute the largest known group of viruses and are responsible for various infections that impose significant socioeconomic burdens worldwide, particularly due to their link with insect-borne diseases. The increasing incidence of dengue fever in non-endemic regions underscores the urgent need for innovative strategies to combat this public health threat. Wolbachia, a bacterium, presents a promising biological control method against mosquito vectors, offering a novel approach to managing dengue fever. We systematically investigated biomedical databases (PubMed, Web of Science, Google Scholar, Science Direct, and Embase) using "AND" as a Boolean operator with keywords such as "dengue fever," "dengue virus," "risk factors," "Wolbachia," and "outbreak." We prioritized articles that offered significant insights into the risk factors contributing to the outbreak of dengue fever and provided an overview of Wolbachia's characteristics and functions in disease management, considering studies published until December 25, 2024. Field experiments have shown that introducing Wolbachia-infected mosquitoes can effectively reduce mosquito populations and lower dengue transmission rates, signifying its potential as a practical approach for controlling this disease.

Dengue, a formidable life-threatening malady, currently exerts a profound impact upon the Western Pacific and Southeast-Asian developing and underdeveloped nations. The intricacies inherent in addressing dengue are manifold, requiring a concerted effort not only towards vector control but also the implementation of efficacious host treatments to forestall the progression of the disease into severe manifestations, such as hemorrhage and shock. The only vaccine available for dengue in the market is DENGVAXIA, with several other vaccine candidates which are currently in the clinical developmental stages. However, DENGVAXIA, owing to incidences of adverse events in among children, was withdrawn in Philippines. This warrants the development of new safer vaccine candidates. The existent control strategies, regrettably, demonstrate inadequacy in effectively mitigating the rampant dissemination of this ailment. Moreover, the diagnostic and therapeutic modalities exhibit potential for refinement, specifically through precision diagnostics and tailored therapeutic interventions, to enhance the precision and efficacy of dengue management. This comprehensive review endeavors to provide an in-depth elucidation of the utilization of nanotechnology-based approaches synergistically integrated with conventional methodologies in the overarching domains of dengue control, diagnosis, and treatment.

Dengue Fever continues to pose a global threat due to the widespread distribution of its vector mosquitoes, Aedes aegypti and Aedes albopictus. While the WHO-approved vaccine, Dengvaxia, and antiviral treatments like Balapiravir and Celgosivir are available, challenges such as drug resistance, reduced efficacy, and high treatment costs persist. This study aims to identify novel potential inhibitors of the Dengue virus (DENV) using an integrative drug discovery approach encompassing machine learning and molecular docking techniques.

Utilizing a dataset of 21,250 bioactive compounds from PubChem (AID: 651640), alongside a total of 1,444 descriptors generated using PaDEL, we trained various models such as Support Vector Machine, Random Forest, k-nearest neighbors, Logistic Regression, and Gaussian Naïve Bayes. The top-performing model was used to predict active compounds, followed by molecular docking performed using AutoDock Vina. The detailed interactions, toxicity, stability, and conformational changes of selected compounds were assessed through protein-ligand interaction studies, molecular dynamics (MD) simulations, and binding free energy calculations.

We implemented a robust three-dataset splitting strategy, employing the Logistic Regression algorithm, which achieved an accuracy of 94%. The model successfully predicted 18 known DENV inhibitors, with 11 identified as active, paving the way for further exploration of 2683 new compounds from the ZINC and EANPDB databases. Subsequent molecular docking studies were performed on the NS2B/NS3 protease, an enzyme essential in viral replication. ZINC95485940, ZINC38628344, 2',4'-dihydroxychalcone and ZINC14441502 demonstrated a high binding affinity of -8.1, -8.5, -8.6, and -8.0 kcal/mol, respectively, exhibiting stable interactions with His51, Ser135, Leu128, Pro132, Ser131, Tyr161, and Asp75 within the active site, which are critical residues involved in inhibition. Molecular dynamics simulations coupled with MMPBSA further elucidated the stability, making it a promising candidate for drug development.

Overall, this integrative approach, combining machine learning, molecular docking, and dynamics simulations, highlights the strength and utility of computational tools in drug discovery. It suggests a promising pathway for the rapid identification and development of novel antiviral drugs against DENV. These in silico findings provide a strong foundation for future experimental validations and in-vitro studies aimed at fighting DENV.

Dengue remains a global threat to public health, however, its disease burden among children and adolescents has always been poorly quantified. Therefore, we aimed to systematically estimate the global, regional, and national burden and temporal trends of dengue infection in children and adolescents from 1990 to 2021.

Data on the number and rate of incidence and disability-adjusted life-years (DALYs) of dengue infection among children and adolescents under 20 years were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) of the age-standardised incidence rate (ASIR) and age-standardised DALYs rate (ASDR), by age, sex, and different countries and regions, were calculated to quantify the temporal trends of dengue burden. The association between development levels (measured using the socio-demographic index [SDI]) and dengue burden was also determined.

From 1990 to 2021, the global burden of dengue incidence and its associated DALYs was consistently higher in children and adolescents than in the entire population. Globally, among children and adolescents, there were 21,641,016 incident cases in 2021, an increase of 64.43% compared to 13,241,719 in 1990. The ASIR per 100,000 population increased from 587.81 in 1990 to 812.16 in 2021, with an EAPC of 1.39% (95% confidence interval [CI], 1.13%-1.65%). Besides, the number of dengue-associated DALYs among children and adolescents increased by 16.36%, from 910,458.60 in 1990 to 1,059,428.31 in 2021. The increase in DALYs was less pronounced than incidence, with the ASDR per 100,000 population increasing from 40.17 in 1990 to 41.50 in 2021, and the EAPC was only 0.67% (95% CI, 0.40%-0.95%). The incidence and DALYs burden of dengue in children and adolescents was highest in middle SDI regions, followed by low-middle SDI regions, with the lowest burden in high SDI regions. Furthermore, Tropical Latin America had an extremely high ASIR (6040.29 per 100,000 population in 2021), and Southeast Asia had an extremely high ASDR (298.20 per 100,000 population in 2021), much higher than other regions around the world.

The global dengue burden in children and adolescents is high and has been increasing from 1990 to 2021, even though the distribution patterns vary across different countries and territories. This study first reported the global disease burden and temporal trends of children and adolescents, which has significant implications for policymakers and public health officials, as it underscores the need for age- and region-specific strategies to mitigate the growing global burden of dengue.

National Natural Science Foundation of China.

Background & objectives Dengue virus causes frequent outbreaks and epidemics with high morbidity and mortality. It is important to monitor the trends of the dengue virus and its serotypes. We carried out the present work to study the prevalence of the dengue virus and its serotypes in clinically suspected cases of dengue in Rajasthan. Methods A total of 1,47,777 individuals reporting as pyrexia of unknown origin or clinically suspected of dengue infection were included in this study. The presence of dengue NS1 antigen and dengue IgM was tested by ELISA. Nucleic acid extraction and PCR was done for detection of dengue virus RNA. Serotyping of representative dengue PCR-positive samples was done by real time PCR. Results Of the 1,47,777 dengue suspected cases, 28092 (19.01%) were positive for dengue by NS1antigen or IgM ELISA. Year-wise percentage positivity from 2015 to 2022 was 30.42, 16.49, 17.81, 20.15, 20.50, 9.25, 24.55 and 15.16 per cent, respectively. Males of age >15 yr were found to be more commonly affected. The number of dengue cases was significantly higher during the post-monsoon period throughout the eight-year study period. All four dengue serotypes circulated during the study period. DENV-2 and DENV-3 were the predominant serotypes during 2015 to 2017, while DENV-1 and DENV-2 were predominant during 2018 to 2022. Interpretation & conclusion The findings of this study suggest that the dengue positivity in Rajasthan was the highest in post-monsoon season among adult males. The serotype prevalent varied from time to time and was helpful in understanding the changing epidemiology of DENV.

Dengue is the most rapidly spreading vector-borne disease worldwide, with over half the global population at risk for an infection. Antibody-dependent enhancement (ADE) is associated with increased disease severity and may also be attributable to the deterioration of disease in vaccinated people. Two dengue vaccines are approved momentarily, with more in development. The increasing use of vaccines against dengue, combined with the development of more, makes a thorough understanding of the processes behind ADE more important than ever. Above that, due to the lack of treatment options, this method of prevention is of great importance. This review aims to explore the impact of ADE in dengue vaccinations, with the goal of enhancing potential vaccination strategies in the fight against dengue.

The escalating impact of dengue infection on health and mortality is a critical global issue. Therefore, it is of interest to assess the current trends of dengue infection in India. We searched through a wide range of internet databases to gather comprehensive studies on the incidence, prevalence, sero-prevalence, cost effectiveness and mortality rate of dengue infection in India from 2014 to 2023 (10 years) in a total of 127 studies. Analysis shows significant heterogeneity (diversity) in reported outcomes (p-values < 0.001). Thus, public health strategies should include early detection of dengue infection in our country.

Dengue is a significant global public health concern that poses a threat to Africa. Particularly, African countries are at risk of viral introductions through air travel connectivity with areas of South America and Asia that experience frequent explosive outbreaks. Limited reporting and diagnostic capacity hinder a comprehensive assessment of continent-wide transmission dynamics and deployment of surveillance strategies in Africa. This study aimed to identify African airports at high risk of receiving dengue infected passengers from Asia, Latin America and other African countries with high dengue incidence.

The risk of dengue introduction into Africa from countries of high incidence in Africa, Latin America and within Africa was estimated based on origin-destination air travel flows and epidemic activity at origin. We produced a novel proxy for local dengue epidemic activity using a composite index of theoretical climate-driven transmission suitability and population density, which we used, along with travel information in a risk flow model, to estimate importation risk.

We find that countries in East Africa face higher estimated risk of importation from Asia and other East African countries, whereas for West African countries, larger risk of importation is estimated from within the region. Some countries with high risk of importation experience low local transmission suitability which likely hampers the chances that importations lead to local transmission and establishment. Conversely, Mauritius, Uganda, Ivory Coast, Senegal, and Kenya are identified as countries susceptible to dengue introductions during periods of persistent transmission suitability.

Our work improves data driven allocation of surveillance resources, in regions of Africa that are at high risk of dengue introduction and establishment, including from regional circulation. This will be critical in detecting and managing imported cases and can improve local response to dengue outbreaks.

Rockefeller Foundation, National Institute of Health, EDCTP3 and Horizon Europe Research and Innovation, World Bank Group, Medical Research Foundation, Wellcome Trust, Google.org, Oxford Martin School Pandemic Genomics programme, John Fell Fund.

The 4 serotypes of dengue virus (DENV1-4) can each cause potentially deadly dengue disease, and are spreading globally from tropical and subtropical areas to more temperate ones. Nepal provides a microcosm of this global phenomenon, having met each of these grim benchmarks. To better understand DENV transmission dynamics and spread into new areas, we chose to study dengue in Nepal and, in so doing, to build the onsite infrastructure needed to manage future, larger studies.

During the 2022 dengue season, we enrolled 384 patients presenting at a hospital in Kathmandu with dengue-like symptoms; 79% of the study participants had active or recent DENV infection (NS1 antigen and IgM). To identify circulating serotypes, we screened serum from 50 of the NS1+ participants by RT-PCR and identified DENV1, 2, and 3 - with DENV1 and 3 codominant. We also performed whole-genome sequencing of DENV, for the first time in Nepal, using our new on-site capacity. Sequencing analysis demonstrated the DENV1 and 3 genomes clustered with sequences reported from India in 2019, and the DENV2 genome clustered with a sequence reported from China in 2018.

These findings highlight DENV's geographic expansion from neighboring countries, identify China and India as the likely origin of the 2022 DENV cases in Nepal, and demonstrate the feasibility of building onsite capacity for more rapid genomic surveillance of circulating DENV. These ongoing efforts promise to protect populations in Nepal and beyond by informing the development and deployment of DENV drugs and vaccines in real time.

Dengue, a mosquito-borne viral disease, has occurred in many cities in China, and it tends to spread to higher latitudes (Huang et al., 2023). Xi'an, situated in central-west China, has witnessed an increase imported cases in the past few years, raising concerns of local dengue transmission. It is crucial to investigate the population density of Aedes albopictus and its insecticides resistance to enhance early warning of dengue fever.

Eight sampling sites in eight counties (YT, BL, WY, CH, YL, LN, LT, ZZ) of Xi'an city were surveyed by larval dipping and human-baited double net trap biweekly from June 2021 to September 2022. The Breteau Index (BI, number of positive containers per 100 houses) and Container Index (CI, the percentage of containers containing larvae or pupae) were used to assess larval density, and the human-baited double net trap (HDN, the number of Ae. albopictus females collected per person per hour) to indicate human bating rate (HBR). Meanwhile, the association between the meteorological factors and mosquito density was analyzed. The Ae. albopictus adult insecticides resistance was evaluated by the World Health Organization (WHO) standard resistance bioassay. Adult females were exposed to insecticide-impregnated paper for 1 h, then transferred to the recovery tube, and mortality rate was calculated after 24 h. According to the Implementation Plan for National Vector Surveillance (2016), resistance status was classified into three levels based on mortality: <80% mortality as resistant, between 80% and 98% mortality as possibly resistant, and >98% mortality as sensitive.

From June 2021 to September 2022, a total of 1,065 houses were surveyed for water holding containers, and 99 of 430 water holding containers were checked to be positive for Ae. albopictus larvae and pupae. A total of 1,048 Ae. albopictus females were collected. The average BI, CI and HBR were 10.39, 21.41, and 11.20 female/man/hour in 2021 and 8.86, 20.86, and 11.63 f/m/h in 2022, respectively. The findings showed that the BI exceeded 5 in most months and reached above 20 in specific months. The CI varied in different months and monitoring sites, with the highest CI in August 2021 and July 2022. The discarded tires had the highest positivity rate, with up to 40.32% testing positive for Ae. albopictus larvae. The monthly average temperature showed a positive correlation with CI (r = 0.77), and the monthly BI was positively associated with CI (r = 0.93). The BI, CI, and HBR were significantly higher in the rainy season than other seasons. The bioassay results showed that the mortality rate of Ae. albopictus at the YT monitoring site was 76.92%, indicating resistance to deltamethrin. The mortality rate of Ae. Albopictus at BL, WY, CH, YL, LN, LT, and ZZ sampling sites were varying from 81.25%∼100%, suggesting possibly resistant or still sensitive to beta-cypermethrin, alpha-cypermethrin, malathion, chlorpyrifos, and propoxur.

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

Aedes albopictus is an important vector for pathogens such as dengue, Zika, and chikungunya viruses. While insecticides is the mainstay for mosquito control, their widespread and excessive use has led to the increased resistance in Ae. albopictus globally. Gut symbiotic bacteria are believed to play a potential role in insect physiology, potentially linking to mosquitoes' metabolic resistance against insecticides.

We investigated the role of symbiotic bacteria in the development of resistance in Ae. albopictus by comparing gut symbiotic bacteria between deltamethrin-sensitive and deltamethrin-resistant populations. Adults were reared from field-collected larvae. Sensitive and resistant mosquitoes were screened using 0.03% and 0.09% deltamethrin, respectively, on the basis of the World Health Organization (WHO) tube bioassay. Sensitive and resistant field-collected larvae were screened using 5 × LC50 (lethal concentration at 50% mortality) and 20 × LC50 concentration of deltamethrin, respectively. Laboratory strain deltamethrin-sensitive adults and larvae were used as controls. The DNA of gut samples from these mosquitoes were extracted using the magnetic bead method. Bacterial 16S rDNA was sequenced using BGISEQ method. We isolated and cultured gut microorganisms from adult and larvae mosquitoes using four different media: Luria Bertani (LB), brain heart infusion (BHI), nutrient agar (NA), and salmonella shigella (SS).

Sequencing revealed significantly higher gut microbial diversity in field-resistant larvae compared with field-sensitive and laboratory-sensitive larvae (P < 0.01). Conversely, gut microorganism diversity in field-resistant and field-sensitive adults was significantly lower compared with laboratory-sensitive adults (P < 0.01). At the species level, 25 and 12 bacterial species were isolated from the gut of field resistant larvae and adults, respectively. The abundance of Flavobacterium spp., Gemmobacter spp., and Dysgonomonas spp. was significantly higher in the gut of field-resistant larvae compared with sensitive larvae (all P < 0.05). Furthermore, the abundance of Flavobacterium spp., Pantoea spp., and Aeromonas spp. was significantly higher in the gut of field-resistant adults compared with sensitive adults (all P < 0.05). The dominant and differentially occurring microorganisms were also different between resistant larval and adult mosquitoes. These findings suggest that the gut commensal bacteria of Ae. albopictus adults and larvae may play distinct roles in their deltamethrin resistance.

This study provides an empirical basis for further exploration of the mechanisms underlying the role of gut microbial in insecticide resistance, potentially opening a new prospect for mosquito control strategies.

Dengue fever represents a significant medical and socio-economic burden in (sub)tropical regions, yet antivirals for treatment or prophylaxis are lacking. JNJ-A07 was described as highly active against the different genotypes within each serotype of the disease-causing dengue virus (DENV). Based on clustering of resistance mutations it has been assumed to target DENV non-structural protein 4B (NS4B). Using a photoaffinity labeling compound with high structural similarity to JNJ-A07, here we demonstrate binding to NS4B and its precursor NS4A-2K-NS4B. Consistently, we report recruitment of the compound to intracellular sites enriched for these proteins. We further specify the mechanism-of-action of JNJ-A07, which has virtually no effect on viral polyprotein cleavage, but targets the interaction between the NS2B/NS3 protease/helicase complex and the NS4A-2K-NS4B cleavage intermediate. This interaction is functionally linked to de novo formation of vesicle packets (VPs), the sites of DENV RNA replication. JNJ-A07 blocks VPs biogenesis with little effect on established ones. A similar mechanism-of-action was found for another NS4B inhibitor, NITD-688. In summary, we unravel the antiviral mechanism of these NS4B-targeting molecules and show how DENV employs a short-lived cleavage intermediate to carry out an early step of the viral life cycle.

The 4 serotypes of dengue virus (DENV1-4) can each cause potentially deadly dengue disease, and are spreading globally from tropical and subtropical areas to more temperate ones. Nepal provides a microcosm of this global phenomenon, having met each of these grim benchmarks. To better understand DENV transmission dynamics and spread into new areas, we chose to study dengue in Nepal and, in so doing, to build the onsite infrastructure needed to manage future, larger studies.

During the 2022 dengue season, we enrolled 384 patients presenting at a hospital in Kathmandu with dengue-like symptoms; 79% of the study participants had active or recent DENV infection (NS1 antigen and IgM). To identify circulating serotypes, we screened serum from 50 of the NS1 + participants by RT-PCR and identified DENV1, 2, and 3 - with DENV1 and 3 codominant. We also performed whole-genome sequencing of DENV, for the first time in Nepal, using our new on-site capacity. Sequencing analysis demonstrated the DENV1 and 3 genomes clustered with sequences reported from India in 2019, and the DENV2 genome clustered with a sequence reported from China in 2018.

These findings highlight DENV's geographic expansion from neighboring countries, identify China and India as the likely origin of the 2022 DENV cases in Nepal, and demonstrate the feasibility of building onsite capacity for more rapid genomic surveillance of circulating DENV. These ongoing efforts promise to protect populations in Nepal and beyond by informing the development and deployment of DENV drugs and vaccines in real time.

Artificial intelligence (AI) is a rapidly evolving field that can impel research in communicable diseases with respect to climate projections, ecological indicators and environmental impact, at the same time revealing new, previously overlooked events. A number of zoonotic and vector-borne diseases already show signs of expanding their northern geographical ranges and appropriate risk assessment and decision support are urgently needed. The deployment of AI-enabled monitoring systems tracking animal populations and environmental changes is of immense potential in the study of transmission under different climate scenarios. In addition, AI's capability to identify new treatments should not only accelerate drug and vaccine discovery but also help predicting their effectiveness, while its contribution to genetic pathogen speciation would assist the evaluation of spillover risks with regard to viral infections from animals to human. Close collaboration between AI experts, epidemiologists and other stakeholders is not only crucial for responding to challenges interconnected with a variety of variables effectively, but also necessary to warrant responsible AI use. Despite its wider successful implementation in many fields, AI should be seen as a complement to, rather than a replacement of, traditional public health measures.

Dengue, the world's fastest-growing vector-borne disease, has skyrocketed in the 21st century. Dengue has harmed human health since its first known cases among Spanish soldiers in the Philippines to its 21st-century outbreaks in Southeast Asia, the Pacific, and the Americas. In light of the current circumstances, it is imperative to investigate its origin and prevalence, enabling the implementation of effective interventions to curb the upsurge.

Our study examines the history of dengue outbreaks, and evolving impact on public health, aiming to offer valuable insights for a more resilient public health response worldwide. In this comprehensive review, we incorporated data from renowned databases such as PubMed, Google Scholar, and Scopus to provide a thorough analysis of dengue outbreaks.

Recent dengue outbreaks are associated with rapid urbanization, international travel, climatic change, and socioeconomic factors. Rapid urbanization and poor urban design and sanitation have created mosquito breeding places for dengue vectors. Also, international travel and trade have spread the pathogen. Climate change in the past two decades has favored mosquito habitats and outbreaks. Socioeconomic differences have also amplified the impact of dengue outbreaks on vulnerable communities. Dengue mitigation requires vector control, community engagement, healthcare strengthening, and international cooperation.

Climate change adaptation and urban planning are crucial. Although problems remain, a comprehensive vector control and community involvement plan may reduce dengue epidemics and improve public health in our interconnected world.

Dengue is a global public health threat, with about half of the world's population at risk of contracting this mosquito-borne viral disease. Climate change, urbanization, and global travel accelerate the spread of dengue virus (DENV) to new areas, including southern parts of Europe and the US. Currently, no dengue-specific small-molecule antiviral for prophylaxis or treatment is available. Here, we report the discovery of JNJ-1802 as a potent, pan-serotype DENV inhibitor (EC50's ranging from 0.057 to 11 nM against the four DENV serotypes). The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in human hepatocytes, the absence of major in vitro pharmacology safety alerts, and a dose-proportional increase in efficacy against DENV-2 infection in mice were all supportive of its selection as a development candidate against dengue. JNJ-1802 is being progressed in clinical studies for the prevention or treatment of dengue.

The objectives of this study were to compare dengue virus (DENV) cases, deaths, case-fatality ratio [CFR], and meteorological parameters between the first and the recent decades of this century (2000-2010 vs. 2011-2022) and to describe the trends, seasonality, and impact of change of temperature and rainfall patterns on transmission dynamics of dengue in Bangladesh. For the period 2000-2022, dengue cases and death data from Bangladesh's Ministry of Health and Family Welfare's website, and meteorological data from the Bangladesh Meteorological Department were analyzed. A Poisson regression model was performed to identify the impact of meteorological parameters on the monthly dengue cases. A forecast of dengue cases was performed using an autoregressive integrated moving average model. Over the past 23 yr, a total of 244,246 dengue cases were reported including 849 deaths (CFR = 0.35%). The mean annual number of dengue cases increased 8 times during the second decade, with 2,216 cases during 2000-2010 vs. 18,321 cases during 2011-2022. The mean annual number of deaths doubled (21 vs. 46), but the overall CFR has decreased by one-third (0.69% vs. 0.23%). Concurrently, the annual mean temperature increased by 0.49 °C, and rainfall decreased by 314 mm with altered precipitation seasonality. Monthly mean temperature (Incidence risk ratio [IRR]: 1.26), first-lagged rainfall (IRR: 1.08), and second-lagged rainfall (IRR: 1.17) were significantly associated with monthly dengue cases. The increased local temperature and changes in rainfall seasonality might have contributed to the increased dengue cases in Bangladesh.

Background and Objectives: Dengue is an important public health concern that warrants an examination of the longer-term global trends of its disease burden. The aim of this study was to assess the trends in dengue incidence and mortality worldwide over the last three decades. Materials and Methods: A descriptive epidemiological study was carried out, investigating the trends in the incidence and mortality of dengue from 1990 to 2019. The dengue incidence and mortality data were obtained from the Global Burden of Disease study database. Trends were examined using joinpoint regression analysis. Results: Globally, there were 56.7 million new cases of dengue reported in 2019: the disease was diagnosed in 27.4 million males and 29.3 million females. A total of 36,055 (18,993 males and 17,032 females) related deaths were reported worldwide in 2019. In both sexes, about 60% of new cases were recorded in the South-East Asia region (16.3 million in males and 17.4 million in females). Globally, the incidence of dengue exhibited an increasing tendency from 1990 to 2019 in both sexes (equally, by 1.2% per year). A significantly decreasing trend in the mortality of dengue was recorded only in females (by -0.5% per year), while an increasing trend was observed in males (by +0.6% per year). Conclusions: The rise in the number of new dengue cases and deaths in the world in the last several decades suggests a need for implementing more effective prevention and management measures.

Dengue is one of Pakistan's major health concerns. In this study, we aimed to advance our understanding of the levels of knowledge, attitudes, and practices (KAPs) in Pakistan's Dengue Fever (DF) hotspots. Initially, at-risk communities were systematically identified via a well-known spatial modeling technique, named, Kernel Density Estimation, which was later targeted for a household-based cross-sectional survey of KAPs. To collect data on sociodemographic and KAPs, random sampling was utilized (n = 385, 5 % margin of error). Later, the association of different demographics (characteristics), knowledge, and attitude factors-potentially related to poor preventive practices was assessed using bivariate (individual) and multivariable (model) logistic regression analyses. Most respondents (>90 %) identified fever as a sign of DF; headache (73.8 %), joint pain (64.4 %), muscular pain (50.9 %), pain behind the eyes (41.8 %), bleeding (34.3 %), and skin rash (36.1 %) were identified relatively less. Regression results showed significant associations of poor knowledge/attitude with poor preventive practices; dengue vector (odds ratio [OR] = 3.733, 95 % confidence interval [CI ] = 2.377-5.861; P < 0.001), DF symptoms (OR = 3.088, 95 % CI = 1.949-4.894; P < 0.001), dengue transmission (OR = 1.933, 95 % CI = 1.265-2.956; P = 0.002), and attitude (OR = 3.813, 95 % CI = 1.548-9.395; P = 0.004). Moreover, education level was stronger in bivariate analysis and the strongest independent factor of poor preventive practices in multivariable analysis (illiterate: adjusted OR = 6.833, 95 % CI = 2.979-15.672; P < 0.001) and primary education (adjusted OR = 4.046, 95 % CI = 1.997-8.199; P < 0.001). This situation highlights knowledge gaps within urban communities, particularly in understanding dengue transmission and signs/symptoms. The level of education in urban communities also plays a substantial role in dengue control, as observed in this study, where poor preventive practices were more prevalent among illiterate and less educated respondents.

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

Immunoinformatics is an emerging interdisciplinary field which integrates immunology, bioinformatics, and computational biology to study the immune system. In this study, we apply immunoinformatics approaches to explore the dengue proteome in order to design a multi-epitope vaccine construct.

We used existing databases and algorithms to predict potential epitopes on dengue proteins and used a bioinformatics approach to identify the most promising epitopes. We then used molecular modelling to develop a multi-epitope construct which could be used as a potential vaccine. The results of this study demonstrate that immunoinformatics is a powerful tool for exploring and designing potential vaccines for infectious diseases like dengue.

Here, we found four CD4+ epitopes NLKYSVIVTVHTGDQ, ANPIVTDKEKPVNIE, LDPVVYDAKFEKQL, and VGAIALDFKPGTSGS that were used to design vaccine construct. The vaccine construct docked with TLR5. RMSD values suggest that docked complex of TLR5 and vaccine construct have putative stable interaction to induce immunogenic effects on host.

Furthermore, our study provides a proof of concept for the use of immunoinformatics approaches in DENV vaccine design. This vaccine can be effective in treating patients infected with DENV virus.

Wolbachia is a widespread bacterial endosymbiont that can inhibit vector competency when stably transinfected into the mosquito, Aedes aegypti, a primary vector of the dengue virus (DENV) and other arboviruses. Although a complete mechanistic understanding of pathogen blocking is lacking, it is likely to involve host immunity induction and resource competition between Wolbachia and DENV, both of which may be impacted by microbiome composition. The potential impact of Wolbachia transinfection on host fitness is also of importance given the widespread release of mosquitos infected with the Drosophila melanogaster strain of Wolbachia (wMel) in wild populations. Here, population-level genomic data from Ae. aegypti was surveyed to establish the relationship between the density of wMel infection and the composition of the host microbiome.

Analysis of genomic data from 172 Ae. aegypti females across six populations resulted in an expanded and quantitatively refined, species-level characterization of the bacterial, archaeal, and fungal microbiome. This included 844 species of bacteria across 23 phyla, of which 54 species were found to be ubiquitous microbiome members across these populations. The density of wMel infection was highly variable between individuals and negatively correlated with microbiome diversity. Network analyses revealed wMel as a hub comprised solely of negative interactions with other bacterial species. This contrasted with the large and highly interconnected network of other microbiome species that may represent members of the midgut microbiome community in this population.

Our bioinformatic survey provided a species-level characterization of Ae. aegypti microbiome composition and variation. wMel load varied substantially across populations and individuals and, importantly, wMel was a major hub of a negative interactions across the microbiome. These interactions may be an inherent consequence of heightened pathogen blocking in densely infected individuals or, alternatively, may result from antagonistic Wolbachia-incompatible bacteria that could impede the efficacy of wMel as a biological control agent in future applications. The relationship between wMel infection variation and the microbiome warrants further investigation in the context of developing wMel as a multivalent control agent against other arboviruses. Video Abstract.

Up to 40% of the world population live in areas where mosquitoes capable of transmitting the dengue virus, including Aedes aegypti, coexist with humans. Understanding how mosquito egg development and oviposition are regulated at the molecular level may provide new insights into novel mosquito control strategies. Previously, we identified a protein named eggshell organizing factor 1 (EOF1) that when knocked down with RNA interference (RNAi) resulted in non-melanized and fragile eggs that did not contain viable embryos.

In this current study, we performed a comprehensive RNAi screen of putative A. aegypti eggshell proteins to identify additional proteins that interact with intracellular EOF1. We identified several proteins essential for eggshell formation in A. aegypti and characterized their phenotypes through a combination of molecular and biochemical approaches. We found that Nasrat, Closca, and Polehole structural proteins, together with the Nudel serine protease, are indispensable for eggshell melanization and egg viability. While all four proteins are predominantly expressed in ovaries of adult females, Nudel messenger RNA (mRNA) expression is highly upregulated in response to blood feeding. Furthermore, we identified four additional secreted eggshell enzymes that regulated mosquito eggshell formation and melanization. These enzymes included three dopachrome-converting enzymes (DCEs) and one cysteine protease. All eight of these eggshell proteins were essential for proper eggshell formation. Interestingly, their eggshell surface topologies in response to RNAi did not phenocopy the effect of RNAi-EOF1, suggesting that additional mechanisms may influence how EOF1 regulates eggshell formation and melanization.

While our studies did not identify a definitive regulator of EOF1, we did identify eight additional proteins involved in mosquito eggshell formation that may be leveraged for future control strategies.

By 2100, greenhouse gases are predicted to reduce ozone and cloud cover over the tropics causing increased exposure of organisms to harmful ultraviolet-B radiation (UVBR). UVBR damages DNA and is an important modulator of immune function and disease susceptibility in humans and other vertebrates. The effect of UVBR on invertebrate immune function is largely unknown, but UVBR together with ultraviolet-A radiation impairs an insect immune response that utilizes melanin, a pigment that also protects against UVBR-induced DNA damage. If UVBR weakens insect immunity, then it may make insect disease vectors more susceptible to infection with pathogens of socioeconomic and public health importance. In the tropics, where UVBR is predicted to increase, the mosquito-borne dengue virus (DENV), is prevalent and a growing threat to humans. We therefore examined the effect of UVBR on the mosquito Aedes aegypti, the primary vector for DENV, to better understand the potential implications of increased tropical UVBR for mosquito-borne disease risk. We found that exposure to a UVBR dose that caused significant larval mortality approximately doubled the probability that surviving females would become infected with DENV, despite this UVBR dose having no effect on the expression of an effector gene involved in antiviral immunity. We also found that females exposed to a lower UVBR dose were more likely to have low fecundity even though this UVBR dose had no effect on larval size or activity, pupal cuticular melanin content, or adult mass, metabolic rate, or flight capacity. We conclude that future increases in tropical UVBR associated with anthropogenic global change may have the benefit of reducing mosquito-borne disease risk for humans by reducing mosquito fitness, but this benefit may be eroded if it also makes mosquitoes more likely to be infected with deadly pathogens.

Early identification of plasma leakage may guide treatment decisions in dengue patients. This study evaluated the value of point-of-care ultrasound (POCUS) to detect plasma leakage and predict hospitalization or referral to a higher level of care in suspected dengue patients under routine conditions at a primary care facility in Colombia.

We conducted a cohort study between April 2019 and March 2020 in a primary care hospital in Cali, Colombia. We prospectively included and followed 178 patients who were at least 2 years old with fever of less than 10 days and clinician-suspected dengue. A trained general practitioner performed a standardized POCUS protocol. Images were quality-rated and overread by an expert radiologist, and her results and those of the general practitioner were compared using the Kappa index. Logistic regression was used to identify factors associated with plasma leakage at enrollment and explore its prognostic value regarding hospital admission or referral to a higher level of care.

Half (49.6%) POCUS images were of suitable quality to be interpreted. The proportion of plasma leakage reported by the radiologist was 85.1% (95% CI: 78.6-90.2%) and 47.2% by the study physician (Kappa = 0.25, 95% CI: 0.15-0.35). The most frequent ultrasound findings were ascites (hepatorenal 87.2%, splenorenal 64%, or pelvic 21.8%) and gallbladder wall thickening (10.5%). Plasma leakage was higher in subjects with thrombocytopenia (aOR = 4, 95% CI: 1.3-12.1) and lower in patients 30-59 years old (aOR = 0.1, 95% CI: 0.0-0.4) than in those 18 years old or younger. POCUS evidence of plasma leakage (aOR = 8.2, 95% CI: 2.2-29.9), thrombocytopenia (aOR = 6.3, 95% CI: 2.4-16.0) and pulse pressure (aOR = 1.1, 95% CI: 1.07-1.2) were associated with hospital admission or referral to a higher level of care.

Ultrasound is useful to detect plasma leakage in primary care and, challenges remain to guarantee high-quality images and diagnostic accuracy, for which a standardized dengue POCUS protocol and training program is needed.

Dengue fever is hyperendemic in several Southeast and South Asian countries, including India, with all four serotypes (DENV 1-4) circulating at different periods and in different locations. Sustainable and improved virological and entomological surveillance is the only tool to prevent dengue and other vector-borne diseases.

The present study has been carried out to detect and characterize the circulating dengue virus (DENV) in field-collected Aedes mosquitoes in Bhopal, Central India.

Aedes mosquitoes were collected from 29 localities within Bhopal city during October 2020 to September 2022. DENV infection was assessed in the individual head and thorax regions of Aedes mosquitoes using reverse transcriptase PCR. Positive samples were sequenced, and the circulating serotypes and genotypes were determined using phylogenetic analysis.

DENV RNA was detected in 7 Aedes aegypti and 1 Aedes albopictus, with infection rates of 0.59 and 0.14%, respectively. Phylogenetic analysis revealed all the isolates belonged to DENV serotype 2 and distinctly clustered with the non-Indian lineage (cosmopolitan genotype 4a), which was not recorded from the study area earlier. The time to most common recent ancestor (TMRCA) of these sequences was 7.4 years old, with the highest posterior density (HPD) of 3.5-12.2 years, indicating that this new lineage emerged during the year 2014. This is the first report on the DENV incrimination in both Ae. aegypti and Ae. albopictus mosquitoes collected from Bhopal, Central India.

The observed emergence of the non-Indian lineage of DENV-2 in Bhopal, which again is a first report from the area, coincides with the gradual increase in DENV cases in Bhopal since 2014. This study emphasizes the importance of DENV surveillance and risk assessment in this strategically important part of the country to decipher its outbreak and severe disease-causing potential.

Dengue fever (DF) is a mosquito-borne viral disease caused by the dengue virus (DENV). In recent years, Hangzhou has undergone a DF epidemic, particularly in 2017, with an outbreak of 1,128 patients. The study aimed to investigate the genetic diversity and molecular evolution among the DF clinical isolates during and after the outbreak to aid in mapping its spread.

To understand the genetic diversity, 74 DENV-2 strains were isolated from DF epidemic cases between 2017 and 2019. Combining whole genome sequencing (WGS) technology, additional phylogenetic, haplotype, amino acid (AA) substitution, and recombination analyses were performed.

The results revealed that strains from 2017 were closely related to those from Singapore, Malaysia, and Thailand, indicating an imported international transmission. Local strains from 2018 were clustered with those recovered from 2019 and were closely associated with Guangzhou isolates, suggesting a within-country transmission after the significant outbreak in 2017. Compared to DENV-2 virus P14337 (Thailand/0168/1979), a total of 20 AA substitutions were detected. Notably, V431I, T2881I, and K3291T mutations only occurred in indigenous cases from 2017, and A1402T, V1457I, Q2777E, R3189K, and Q3310R mutations were exclusively found in imported cases from 2018 to 2019. The recombination analysis indicated that a total of 14 recombination events were observed.

This study may improve our understanding of DENV transmission in Hangzhou and provide further insight into DENV-2 transmission and the local vaccine choice.

More than half of the global population is predicted to be living in areas susceptible to dengue transmission with the vast majority in Asia. Dengue fever is of public health concern, particularly in the southern region of Thailand due to favourable environmental factors for its spread. The risk of dengue infection at the population level varies in time and space among sub-populations thus, it is important to study the risk of infection considering spatio-temporal variation.

This study presents a joint spatio-temporal epidemiological model in a Bayesian setting using Markov chain Monte Carlo (MCMC) simulation with the CARBayesST package of R software. For this purpose, monthly dengue records by district from 2002 to 2018 from the southern region of Thailand provided by the Ministry of Public Health of Thailand and eight environmental variables were used.

Results show that an increasing level of temperature, number of rainy days and sea level pressure are associated with a higher occurrence of dengue fever and consequently higher incidence risk, while an increasing level of wind speed seems to suggest a protective factor. Likewise, we found that the elevated risks of dengue in the immediate future are in the districts of Phipun, Phrom Kili, Lan Saka, Phra Phrom and Chaloem Phakiat. The resulting estimates provide insights into the effects of covariate risk factors, spatio-temporal trends and dengue-related health inequalities at the district level in southern Thailand.

Possible implications are discussed considering some anthropogenic factors that could inhibit or enhance dengue occurrence. Risk maps indicated which districts are above and below baseline risk, allowing for the identification of local anomalies and high-risk boundaries. In the event of near future, the threat of elevated disease risk needs to be prevented and controlled considering the factors underlying the spread of mosquitoes in the Southeast Asian region.

Dengue fever is an infectious disease of global health concern. This study aimed to describe the epidemiology and field experience of a locally transmitted outbreak of dengue fever in Muscat Governorate, Oman from mid-March to mid-April 2022, and the multi-sectoral approach to control the outbreak.

Data were collected from an electronic e-notification system, active surveillance and contact investigations.

Of 250 suspected and probable cases, 169 were confirmed as dengue fever with DENV-2 serotype. Of these, 108 (63.9%) were male and 94 (55.6%) were Omani. The mean age was 39 years (standard deviation 13 years). Fever was the most common symptom and occurred in 100% of cases. Haemorrhagic manifestations occurred in 10% (n=17) of cases. Hospitalization was required for 93 cases (55.1%). The field investigation included 3444 houses and other suspected sites. Breeding sites for Aedes aegypti were identified in 565 (18.5%) sites visited. Interventions to control the outbreak included environmental and entomological assessment of the affected houses and surrounding areas (400 m radius of each house).

Outbreaks are expected to continue, with the possibility of severe cases due to antibody-dependent enhancement. More data are required to understand the genetics, geographical spread and behaviour of A. aegypti in Oman.

Climate change is an important driver of the increased spread of dengue from tropical and subtropical regions to temperate areas around the world. Climate variables such as temperature and precipitation influence the dengue vector's biology, physiology, abundance, and life cycle. Thus, an analysis is needed of changes in climate change and their possible relationships with dengue incidence and the growing occurrence of epidemics recorded in recent decades.

This study aimed to assess the increasing incidence of dengue driven by climate change at the southern limits of dengue virus transmission in South America.

We analyzed the evolution of climatological, epidemiological, and biological variables by comparing a period of time without the presence of dengue cases (1976-1997) to a more recent period of time in which dengue cases and important outbreaks occurred (1998-2020). In our analysis, we consider climate variables associated with temperature and precipitation, epidemiological variables such as the number of reported dengue cases and incidence of dengue, and biological variables such as the optimal temperature ranges for transmission of dengue vector.

The presence of dengue cases and epidemic outbreaks are observed to be consistent with positive trends in temperature and anomalies from long-term means. Dengue cases do not seem to be associated with precipitation trends and anomalies. The number of days with optimal temperatures for dengue transmission increased from the period without dengue cases to the period with occurrences of dengue cases. The number of months with optimal transmission temperatures also increased between periods but to a lesser extent.

The higher incidence of dengue virus and its expansion to different regions of Argentina seem to be associated with temperature increases in the country during the past two decades. The active surveillance of both the vector and associated arboviruses, together with continued meteorological data collection, will facilitate the assessment and prediction of future epidemics that use trends in the accelerated changes in climate. Such surveillance should go hand in hand with efforts to improve the understanding of the mechanisms driving the geographic expansion of dengue and other arboviruses beyond the current limits. https://doi.org/10.1289/EHP11616.

Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66-0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.

This research aims to predict dengue fever cases in Malaysia using machine learning techniques. A dataset consisting of weekly dengue cases at the state level in Malaysia from 2010 to 2016 was obtained from the Malaysia Open Data website and includes variables such as climate, geography, and demographics. Six different long short-term memory (LSTM) models were developed and compared for dengue prediction in Malaysia: LSTM, stacked LSTM (S-LSTM), LSTM with temporal attention (TA-LSTM), S-LSTM with temporal attention (STA-LSTM), LSTM with spatial attention (SA-LSTM), and S-LSTM with spatial attention (SSA-LSTM). The models were trained and evaluated on a dataset of monthly dengue cases in Malaysia from 2010 to 2016, with the task of predicting the number of dengue cases based on various climate, topographic, demographic, and land-use variables. The SSA-LSTM model, which used both stacked LSTM layers and spatial attention, performed the best, with an average root mean squared error (RMSE) of 3.17 across all lookback periods. When compared to three benchmark models (SVM, DT, ANN), the SSA-LSTM model had a significantly lower average RMSE. The SSA-LSTM model also performed well in different states in Malaysia, with RMSE values ranging from 2.91 to 4.55. When comparing temporal and spatial attention models, the spatial models generally performed better at predicting dengue cases. The SSA-LSTM model was also found to perform well at different prediction horizons, with the lowest RMSE at 4- and 5-month lookback periods. Overall, the results suggest that the SSA-LSTM model is effective at predicting dengue cases in Malaysia.

Dengue encephalitis is considered as a severe but unusual clinical presentation of dengue infection. Limited molecular information is available on the neurotropism of dengue virus (DENV), highlighting the need for further research. During a dengue outbreak in Vietnam in 2013, two DENV-3 strains were isolated, in which one was isolated from cerebrospinal fluid (CSF) samples from a dengue encephalitis patient and another strain was isolated from a patient with classical dengue fever in Hai Phong, Vietnam. DENV serotype-3 (DENV-3) isolated from these samples belonged to genotype III, marking the first report of this genotype in the country at that time. Genetic variation between both strains was elucidated by using a full genome sequencing by next-generation sequencing (NGS). The infectivity of the isolated DENV-3 strains was further characterized using human and mouse neuronal cell lines. Phylogenetic analysis of the isolates demonstrated high homogeneity between the CSF-derived and serum-derived DENV-3, in which the full genome sequences of the CSF-derived DENV-3 presented a Thr-1339-Ile mutation in the nonstructural 2A (NS2A) protein. The CSF-derived DENV-3 isolate grew preferentially in human neuronal cells, with a significant proportion of cells that were positive for nonstructural 1 (NS1), nonstructural 4B (NS4B), and nonstructural 5 (NS5) antigens. These results suggest that NS2A may be a crucial region in the neuropathogenesis of DENV-3 and its growth in human neuronal cells. Taken together, our results demonstrate that a CSF-derived DENV-3 has unique infectivity characteristics for human neuronal cells, which might play a crucial role in the neuropathogenesis of DENV infection.

Driven by globalization, urbanization and climate change, the distribution range of invasive vector species has expanded to previously colder ecoregions. To reduce health-threatening impacts on humans, insect vectors are extensively studied. Population genomics can reveal the genomic basis of adaptation and help to identify emerging trends of vector expansion. By applying whole genome analyses and genotype-environment associations to populations of the main dengue vector Aedes aegypti, sampled along an altitudinal gradient in Nepal (200-1300 m), we identify putatively adaptive traits and describe the species' genomic footprint of climate adaptation to colder ecoregions. We found two differentiated clusters with significantly different allele frequencies in genes associated to climate adaptation between the highland population (1300 m) and all other lowland populations (≤800 m). We revealed nonsynonymous mutations in 13 of the candidate genes associated to either altitude, precipitation or cold tolerance and identified an isolation-by-environment differentiation pattern. Other than the expected gradual differentiation along the altitudinal gradient, our results reveal a distinct genomic differentiation of the highland population. Local high-altitude adaptation could be one explanation of the population's phenotypic cold tolerance. Carrying alleles relevant for survival under colder climate increases the likelihood of this highland population to a worldwide expansion into other colder ecoregions.

Dengue virus (DENV) was detected in Senegal in 1979 for the first time. Since 2017, unprecedented frequent outbreaks of DENV were noticed yearly. In this context, epidemiological and molecular evolution data are paramount to decipher the virus diffusion route. In the current study, we focused on a dengue outbreak which occurred in Senegal in 2018 in the context of a large religious gathering with 263 confirmed DENV cases out of 832 collected samples, including 25 life-threatening cases and 2 deaths. It was characterized by a co-circulation of dengue serotypes 1 and 3. Phylogenetic analysis based on the E gene revealed that the main detected serotype in Touba was DENV-3 and belonged to Genotype III. Bayesian phylogeographic analysis was performed and suggested one viral introduction around 2017.07 (95% HPD = 2016.61-2017.57) followed by cryptic circulation before the identification of the first case on 1 October 2018. DENV-3 strains are phylogenetically related, with strong phylogenetic links between strains retrieved from Burkina Faso and other West African countries. These phylogenetic data substantiate epidemiological data of the origin of DENV-3 and its spread between African countries and subsequent diffusion after religious mass events. The study also highlighted the usefulness of a mobile laboratory during the outbreak response, allowing rapid diagnosis and resulting in improved patient management.

Dengue haemorrhagic fever is a severe form of acute dengue infection characterized by leakage of plasma through capillaries into body spaces resulting in circulatory insufficiency leading to shock. Despite varying degrees of liver involvement occurring in acute dengue infection, intrahepatic cholestasis is very rare in the literature with only two cases reported so far. We report a challenging case of a middle-aged woman with DHF complicated by acute liver failure, coagulopathy, acute renal failure and prolonged intrahepatic cholestasis. She was successfully managed in the intensive care unit with supportive therapy, Cytosorb® and therapeutic plasma exchange.

A 54-year-old Sri Lankan obese woman with multiple comorbidities presented with fever, headache, vomiting and generalized malaise for 3 days and was diagnosed with dengue haemorrhagic fever. Despite the standard dengue management, she clinically deteriorated due to development of complications such as, acute liver injury, intrahepatic cholestasis and acute renal injury. Acute liver failure was evidenced by transaminitis, lactic acidosis, coagulopathy with pervaginal bleeding and severe encephalopathy necessitating elective intubation and mechanical ventilation. She was immediately transferred to intensive care facilities where she underwent supportive management for liver failure, continuous renal replacement therapy coupled with cytosorb and therapeutic plasma exchange with which she made a remarkable recovery.

Acute liver failure with a prolonged phase of intrahepatic cholestasis is a very rare complication of acute dengue illness which is sparsely documented in medical literature so far. This patient was managed successfully with supportive therapy, aided by cytoSorb hemo-adsorption and therapeutic plasma exchange.