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ABSTRACT Arthropod‐borne flaviviruses (ABFs), transmitted by mosquitoes or ticks, are increasing due to climate change and globalization. This scoping review examines the epidemiology, clinical characteristics, diagnostics, treatment, and outcomes of ABF infection in solid organ transplant recipients (SOTRs). A database search up to January 25, 2024, focused on ABFs such as West Nile virus (WNV), dengue virus (DENV), Japanese encephalitis virus (JEV), Powassan virus (POWV), yellow fever virus (YFV), and Zika virus (ZIKV), limited to SOTRs.We identified 173 WNV cases from 84 studies, with 28 donor‐derived infections (DDIs). Common clinical features included fever (78.5%), altered mental status (65.1%), and weakness or paralysis (45.6%). Treatment involved reducing immunosuppression (IS) in 93 cases, with intravenous immunoglobulin (IVIG), interferon alfa‐2b, and ribavirin used in 75 cases. Seven cases involved graft loss or rejection post‐infection. WNV infection had a 23.7% mortality rate, with severe neurological complications in 43.9%For DENV infection, 386 cases from 47 studies were identified, including 14 DDI cases. Symptoms included fever (85%), myalgias (56.4%), and headache or retro‐orbital pain (34.6%). Severe dengue occurred in 50 cases (13.0%). IVIG was administered in six cases. Reduction in IS was reported in 116 patients. DENV mortality rate was 4.9%.Additionally, 26 cases of less common ABFs such as JEV, POWV, YFV, and ZIKV were described.In summary, ABF infections among SOTRs are associated with higher morbidity and mortality compared to the general population, emphasizing the need for improved preventive strategies, timely diagnosis, and optimized management protocols. [ABSTRACT FROM AUTHOR]

Wolbachia pipientis (= Wolbachia) has promise as a tool to suppress virus transmission by Aedes aegypti mosquitoes. However, Wolbachia can have variable effects on mosquito-borne viruses. This variation remains poorly characterized, yet the multimodal effects of Wolbachia on diverse pathogens could have important implications for public health. Here, we examine the effects of transient somatic infection with two strains of Wolbachia (wAlbB and wMel) on the alphaviruses Sindbis virus (SINV), O'nyong-nyong virus (ONNV), and Mayaro virus (MAYV) in Ae. aegypti. We found variable effects of Wolbachia including enhancement and suppression of viral infections, with some effects depending on Wolbachia strain. Both wAlbB- and wMel-infected mosquitoes showed enhancement of SINV infection rates one week post-infection, with wAlbB-infected mosquitoes also having higher viral titers than controls. Infection rates with ONNV were low across all treatments and no significant effects of Wolbachia were observed. The effects of Wolbachia on MAYV infections were strikingly strain-specific; wMel strongly blocked MAYV infections and suppressed viral titers, while wAlbB had more modest effects. The variable effects of Wolbachia on vector competence underscore the importance of further research into how this bacterium impacts the virome of wild mosquitoes including the emergent human pathogens they transmit. Author summary: In recent years, wild populations of Aedes aegypti mosquitoes in over a dozen countries have been deliberately infected with Wolbachia pipientis ("Wolbachia"); an intracellular bacterium that, in some circumstances, helps to curb the spread of mosquito-brone pathogens including dengue virus. But how does Wolbachia affect the ability of mosquitoes to become infected with and spread the many different viruses they encounter in nature? Here, we use transient somatic infections in Aedes aegypti to characterize the effects of Wolbachia on three different alphaviruses that cause illness in humans: Sindbis virus, O'nyong-nyong virus, and Mayaro virus. We find that transient Wolbachia infections have variable effects on these different pathogens, ranging from significant suppression of Mayaro virus to significant enhancement of Sindbis virus. Our research has important implications for the design of vector control strategies, and suggests further research is needed to understand how Wolbachia shapes the replication and transmission of diverse viruses in mosquitoes. [ABSTRACT FROM AUTHOR]

Recent studies on viral diseases showed that neutrophils exist in various phenotypes and functional statuses, that may play a role either in viral clearance or in immunopathology. Emerging evidence suggests that dengue virus can activate neutrophils, leading to the release of myeloperoxidase and the formation of neutrophil extracellular traps; these were shown to enhance vascular permeability and mediate dengue-associated cardiac impairment, contributing to severe dengue. Neutrophils are recruited during early dengue virus infection, and they release soluble molecules such as olfactomedin 4 and soluble urokinase plasminogen activator receptor into the circulation; these may be useful biomarkers to predict disease progression in dengue. Given that neutrophils may mediate severe dengue, attenuating the neutrophil response can be an attractive pathway to ameliorate disease severity. Dengue is a mosquito-borne viral disease which causes significant morbidity and mortality each year. Previous research has proposed several mechanisms of pathogenicity that mainly involve the dengue virus and host humoral immunity. However, innate immune cells, such as neutrophils, may also play an important role in dengue, albeit a much less defined role. In this review, we discuss the emerging roles of neutrophils in dengue and their involvement in pathologies associated with severe dengue. We also describe the potential use of several neutrophil proteins as biomarkers for severe dengue. These studies suggest that neutrophils are important players in dengue, and a better understanding of neutrophil-dengue biology is urgently needed. [ABSTRACT FROM AUTHOR]

A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2–59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18–59 years, 7–17 years, and 2–6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2–5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2–4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4–73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. For the Spanish and Portuguese translations of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is the causative agent of dengue, a mosquito-borne disease that represents a significant and growing public health burden around the world. A unique pathophysiological feature of dengue is immune-mediated enhancement, wherein preexisting immunity elicited by a primary infection can enhance the severity of a subsequent infection by a heterologous DENV serotype. A leading mechanistic explanation for this phenomenon is antibody dependent enhancement (ADE), where sub-neutralizing concentrations of DENV-specific IgG antibodies facilitate entry of DENV into FcγR expressing cells such as monocytes, macrophages, and dendritic cells. Accordingly, this model posits that phagocytic mononuclear cells are the primary reservoir of DENV. However, analysis of samples from individuals experiencing acute DENV infection reveals that B cells are the largest reservoir of infected circulating cells, representing a disconnect in our understanding of immune-mediated DENV tropism. In this study, we demonstrate that the expression of a DENV-specific B cell receptor (BCR) renders cells highly susceptible to DENV infection, with the infection-enhancing activity of the membrane-restricted BCR correlating with the ADE potential of the IgG version of the antibody. In addition, we observed that the frequency of DENV-infectible B cells increases in previously flavivirus-naïve volunteers after a primary DENV infection. These findings suggest that BCR-dependent infection of B cells is a novel mechanism immune-mediated enhancement of DENV-infection. Author summary: Dengue virus (DENV) is a mosquito-borne pathogen that infects an estimate 400 million people every year. A unique feature of DENV is immune-mediated enhancement, wherein a first (primary) DENV infection can predispose an individual to a more severe secondary infection. The leading explanation for this phenomenon is antibody dependent enhancement (ADE), wherein antibodies generated in response to a primary DENV infection bind but fail to neutralize virions introduced during a secondary infection, thereby allowing DENV to gain entry to Fc-receptor expressing cells. Accordingly, a key prediction of this model is that monocytes, macrophages, and other Fc-receptor expressing phagocytes should be the primary cellular reservoir of DENV during an acute secondary DENV infection. However, it has been noted for decades that B cells are a significant cellular reservoir of DENV, including during secondary DENV infection, representing a disconnect in our understanding of immune-mediated DENV tropism. In our study, we identified DENV-reactive B cell receptors (BCR) as a potent DENV entry receptor. This observation suggests that BCR-dependent infection of DENV-specific B cells may be a complementary mechanism of immune-mediated enhancement of DENV-infection that expands upon and complements existing models of antibody-dependent enhancement. [ABSTRACT FROM AUTHOR]

Background: Tanzania has experienced multiple dengue outbreaks between 2010 and 2019, caused by various dengue virus (DENV) strains. In 2019, there were 6917 confirmed dengue cases and 13 deaths in Tanzania. Routine diagnosis of dengue fever is unfortunately excluded, particularly during non-outbreak periods, resulting in delayed outbreak detection and control. The aim of this study was to improve early detection and control measures for DENV by investigating its circulation in human and Aedes aegypti (A.aegypti) mosquitoes during the non-outbreak periods in Dar es Salaam, Tanzania, which is an area frequently affected by dengue outbreaks. Methods: Four hundred and fifteen (415) blood samples were collected from patients attending randomly selected health facilities in five wards; Azimio, Keko, Mtoni, Mbagala and Chamazi within Temeke district. The samples were tested for DENV NS1 antigen and anti-dengue IgM and IgG antibodies by rapid test. Then, 150 out of 415 blood samples were tested for the DENV by conventional Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Two thousand two hundred and fifty (2,250) adult female A.aegypti mosquitoes were collected using a Prokopack aspirator and BG sentinel trap or obtained after rearing immature stages and tested, in pools of 15 for DENV by RT-PCR. Statistical Software, SPSS version 23, was used for data analysis. Results: Of the tested blood samples, 17% (71/415) were positive by NS1 antigen, 0.5% (2/415) by IgM, 0.5% (2/415) by IgG antibodies, and 0.5% (2/415) by IgM and IgG. None of the samples tested positive by DENV RT-PCR. Moreover, 3.3% (5/150) of tested mosquito pools had DENV by RT-PCR. Individuals aged between 21 and 40 years of age had increased risk of testing positive for DENV NS1 antigen, followed by those aged 5–20 years old, particularly those residing from Azimio ward, Keko ward, Mtoni ward and Mbagala ward, p-value ≤ 0.05. Conclusion: Findings from this study revealed evidence of DENV circulation during non-outbreak periods in Dar es Salaam, Tanzania. These findings underscore the importance of including testing for dengue infection in routine differential diagnoses of febrile cases, and also frequent dengue surveillance in mosquitos. This proactive approach will help early DENV outbreak detection and control in the country. [ABSTRACT FROM AUTHOR]

Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here, it is reported that the development of small molecule degraders of the envelope (E) protein of dengue virus. Two classes of bivalent E‐degraders are developed by linking two previously reported E‐binding small molecules, GNF‐2, and CVM‐2‐12‐2, to a glutarimide‐based recruiter of the CRL4CRBN ligase to effect proteosome‐mediated degradation of the E protein. ZXH‐2‐107 (based on GNF‐2) is an E‐degrader with ABL inhibitory activity while ZXH‐8‐004 (based on CVM‐2‐12‐2) is a selective and potent E‐degrader. These two compounds provide proof of concept that difficult‐to‐drug targets such as a viral envelope protein can be effectively eliminated using a bivalent degrader and provide starting points for the future development of a new class of direct‐acting antiviral drugs. [ABSTRACT FROM AUTHOR]

The dengue virus (DENV) is a mosquito-borne flavivirus transmitted through the infected mosquito, primarily of the Aedes genus. Over recent decades, the significant emergence of DENV infections has posed growing challenges for control efforts. Extensive research indicates that the dengue NS2B–NS3 protease, a non-structural viral protein, is the most promising target in dengue drug research. Therefore, our study synthesized two series of novel allosteric inhibitors of the NS2B–NS3 protease to explore previous allosteric inhibitors of the protease. Meanwhile, enzyme inhibitory activities of all compounds are measured and IC50 values of the optimized compounds are obtained by utilizing a fluorescence-based assay. Notably, compound A24 demonstrates the highest enzyme inhibitory activity with an IC50 value of 16 μM. Further enzyme kinetic experiments confirm that the optimized compound A24 functions as a non-competitive inhibitor of the NS2B–NS3 protease. Through molecular docking studies, compound A24 showed a binding energy of −5.6 kcal mol−1, comparable to the lead compounds, which preliminarily explains its similar inhibitory activity. In addition, compound A24 forms a stable complex with the protein primarily through hydrogen bonds and π–π interaction, with subsequent dynamics simulations confirming the stable binding mode. In conclusion, we designed and synthesized 59 novel scaffold compounds and identified compound A24 with the highest activity through pharmacological experiments and computer-aided drug design, which targets the allosteric sites and contributes significantly to the prevention of the dengue virus. [ABSTRACT FROM AUTHOR]

Dengue viral infection is caused by the Dengue virus, which spreads to humans through the bite of infected mosquitos. Dengue affects over half of the global population, with an estimated 500 million infections per year. Despite this, no effective treatment is currently available, however, several promising candidates are undergoing pre-clinical/clinical testing. The existence of four major serotypes is an important challenge in the development of drugs and vaccines to combat Dengue virus infection. Hence, the drug/vaccine thereby developed should neutralize all the four serotypes equally. However, there is no pan-serotype specific treatment for Dengue virus, thereby emphasizing the need for the identification of novel drug-like compounds that can target all serotypes of the Dengue virus equally. To this end, we employed virtual screening methodologies to find drug-like compounds that target the domain III of glycoprotein E. Most importantly, domain III of E protein is involved in viral fusion with the host membrane and is also targeted by neutralizing antibodies. Our study found two small molecule drug-like compounds (out of the 3 million compounds screened) having similar binding affinity with all four serotypes. The compounds thereby identified exhibit favourable drug like properties and can be developed as a treatment for Dengue virus. [ABSTRACT FROM AUTHOR]

Background: Dengue virus (DENV) infection, spread by Aedes aegypti mosquitoes, is a significant public health concern in tropical and subtropical regions. Among the four distinct serotypes of DENV (DENV-1 to DENV-4), DENV-2 is associated with the highest number of fatalities worldwide. However, there is no specific treatment available for dengue patients caused by DENV-2. Objective: This study aimed to identify inhibitory phytocompounds in silico in Vernonia cinerea (V. cinerea), a widely used traditional medicinal plant, for treating DENV-2 associated illnesses. Methods: The chemical structures of 17 compounds from V. cinerea were sourced from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database. These compounds underwent geometry optimization, were screened against nonstructural protein 1 (NSP1) of DENV-2, and further validated through molecular dynamics simulations (MDS). Baicalein, an established drug against DENV-2, was used for validation in molecular screening, MDS, and MM-GBSA analyses. Results: Among these compounds, Beta-amyrin, Beta-amyrin acetate, Chrysoeriol, Isoorientin, and Luteolin showed promising potential as inhibitors of the NSP1 of DENV-2, supported by the results of thermodynamic properties, molecular orbitals, electrostatic potentials, spectral data and molecular screening. Besides, these compounds adhered to the Lipinski's "rule of 5", showing no hepatotoxicity/cytotoxicity, with mixed mutagenicity, immunotoxicity, and carcinogenicity. Furthermore, final validation through MDS confirmed their potential, demonstrating stable tendencies with significant inhibitory activities against NSP1 of DENV-2 over the control drug Baicalein. Among the screened compounds, Chrysoeriol emerged as the most promising inhibitor of NSP1 of DENV-2, followed by Luteolin and Isoorientin. Conclusion: Taken together, our results suggest that Chrysoeriol is the best inhibitor of NSP1 of DENV-2, which could be evaluated as a therapeutic agent or a lead compound to treat and manage DENV-2 infections. [ABSTRACT FROM AUTHOR]

Background: 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. Methods and results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Mosquitoes in nature may acquire multiple bloodmeals (BMs) over the course of their lifetime; however, incorporation of frequent feeding behavior in laboratory vector competence studies is rarely done. We have previously shown that acquisition of a second non-infectious BM can enhance early dissemination of Zika virus (ZIKV), dengue virus, and chikungunya virus in Aedes aegypti and ZIKV in Aedes albopictus mosquitoes, yet it is unknown if other taxonomically-diverse virus-vector pairings show a similar trend under a sequential feeding regimen. Methods: To test this, we evaluated the impact of a second noninfectious BM on the vector competence of Aedes aegypti and Anopheles quadrimaculatus for Mayaro virus, Culex quinquefasciatus for West Nile virus, Aedes triseriatus for La Crosse virus, and Aedes aegypti for Oropouche virus (OROV). Female mosquitoes were fed BMs containing these viruses and half of them were given a second noninfectious BM at 3 or 4-days post infection. Mosquitoes were harvested at various time points and assayed for virus infection in bodies and disseminated infection in legs by performing reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays. Results: We found that a second noninfectious BM had no impact on midgut infection rates but increased virus dissemination for all but one of the virus-vector pairings- Ae. aegypti and OROV. Unlike the other arboviruses under consideration, which are strictly mosquito-borne, biting midges (Culicoides spp.) serve as the main vector of OROV and this virus rarely disseminated to the mosquito leg tissue in our study. Conclusions: Taken together, our findings show that sequential blood feeding enhances virus dissemination across diverse arbovirus-vector pairings, representing three mosquito genera and virus families, but a second BM was insufficient to overcome a strong midgut virus escape barrier in a nonnatural virus–vector pairing. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses co-circulating in the same endemic areas. Infection can raise cross-reactive antibodies that can be either protective or increase risk of severe disease, depending on the infection sequence, DENV serotype and elapsed time between infection. On the contrast, T cell-mediated immunity against DENV and ZIKV is considered protective. Therefore, we have developed a T cell vaccine enriched in immunodominant T cell epitopes derived from ZIKV and evaluated its immunogenicity and efficacy against ZIKV and DENV infection. Mice were vaccinated using DNA vaccine platform using the tetrafunctional amphiphilic block copolymer 704. We show that vaccination of 2 different HLA class I transgenic mice with the ZIKV non-structural (NS) poly-epitope elicits T cell response against numerous ZIKV epitopes. Moreover, vaccination induces a significant protection against ZIKV infection, in the absence of neutralizing or enhancing antibodies against ZIKV. However, vaccination does not induce a significant protection against DENV2. In contrast, immunization with a DENV1-NS poly-epitope induces a significant protection against both DENV1 and DENV2, in the absence of humoral immunity. Taken together, we have shown that T-cell based vaccination could protect against multiple flavivirus infections and could overcome the complexity of antibody-mediated enhancement. Author summary: Dengue virus (DENV) and Zika virus (ZIKV) are two closely related flaviviruses transmitted by Aedes species mosquito. In endemic regions with high circulation of ZIKV and multiple DENV serotypes, and the presence of cross-reactive or sub-neutralizing antibodies that could enhance dengue disease severity, alternative approaches to antibody-induced vaccination must be considered. This work describes a novel strategy for the development of a T-cell based vaccine composed of immunodominant T cell epitopes from ZIKV. This vaccine induces a significant protection against ZIKV infection in mice expressing different HLA class I molecules, in the absence of neutralizing antibodies. Likewise, DNA vaccination with mosaic sequence enriched in DENV T cell epitopes with identical sequences between DENV1 and DENV2 induces a significant protection against these 2 DENV serotypes, without inducing neutralizing antibodies. This study paves the way for T-cell based vaccines that could overcome the risk for antibody-mediated enhancement and protect against multiple flavivirus infections. [ABSTRACT FROM AUTHOR]

Background: Dengue is the most re-emergent infection, with approximately 100 million new cases reported annually, yet no effective treatment or vaccine exists. Here, we aim to define the microbial community structure and their functional profiles in the dengue positive patients with varying disease severity. Methodology/Principal findings: Hospital admitted 112 dengue-positive patients blood samples were analyzed by dual RNA-sequencing to simultaneously identify the transcriptionally active microbes (TAMs), their expressed genes and associated pathways. Results highlight that patients with severe dengue exhibited increased microbial diversity and presence of opportunistic species (unique and core) which includes Bacillus cereus, Burkholderia pseudomallei, Streptococcus suis, and Serratia marcescens. The functional profile analysis revealed enriched metabolic pathways such as protein degradation, nucleotide biosynthesis, ion transport, cell shape integrity, and ATP formation in severe cases, indicating the high energy demands and adaptability of these microbes. Conclusion: Our metatranscriptomic approach provides a species-level characterization of blood microbiome composition and reveals a heightened diversity of TAMs in patients with severe dengue, underscoring the need for further research into the role of blood microbiota in disease progression. Comparing the microbial signatures across the severity classes early in the disease offers unique potential for convenient and early diagnosis of dengue infection. Author summary: Dengue poses a significant public health challenge in tropical and subtropical regions. The lack of a specific treatment or broadly effective vaccine highlights the critical need for novel approaches. In this study, we investigated the transcriptionally active microbial species (TAMs) in 112 dengue-positive patients from MAX Hospital in Delhi, India, to identify their correlations with disease severity. RNA-seq analysis revealed an increased abundance of opportunistic TAMs in severe dengue patients, with some species showing significant associations with platelet counts and total leukocyte count (TLC). Our findings underscore the underappreciated importance of the blood microbiome in dengue, particularly the heightened metabolic activity of these opportunistic species in severe cases. This study offers valuable insights for early infection diagnosis for dengue management. The species-level data identified here could pave the way for systematic exploration of microbial involvement in dengue virus (DENV) infections, potentially serving as an indicator for new adjuvant treatment strategies. [ABSTRACT FROM AUTHOR]

This study investigates the kinetics of interleukine-6 (IL-6) and interleukine-10 (IL-10) levels in dengue virus (DENV) infections during the febrile stage. Viremic patients were categorized into two phases based on anti-DENV IgM presence. Among 259 patients, 71% were in Phase I and 29% in Phase II. Secondary infections, accounting for 38.2% of cases, exhibited earlier elevations of IL-6 and IL-10 than primary infections, suggesting that pre-existing immune memory primes faster cytokine release. Thrombocytopenia and elevated aspartate transaminase (AST) levels were associated with Phase II, secondary infections, and hospitalization. Elevated IL-6 and IL-10 levels correlated with low platelet counts, linking them to clinical manifestations. The key finding is that IL-6 and IL-10 levels rise earlier in secondary infections compared to primary infections, whereas elevated cytokine levels typically occur later in the febrile phase. This study highlights the importance of cytokine dynamics in DENV infections, particularly during the early stages. The observation of cytokine concentration changes, especially in viremic samples, provides insights into the progression of dengue disease. Further research with broader cytokine panels is warranted to validate and expand these findings. [ABSTRACT FROM AUTHOR]

Background: There is a dire need for the establishment of active dengue surveillance to continuously detect cases, circulating serotypes, and determine the disease burden of dengue fever (DF) in the country and region. Predicting dengue PCR results using machine learning (ML) models represents a significant advancement in pre‐emptive healthcare measures. This study outlines the comprehensive process of data preprocessing, model selection, and the underlying mechanisms of each algorithm employed to accurately predict dengue PCR outcomes. Methods: We analyzed data from 300 suspected dengue patients in Islamabad and Rawalpindi, Pakistan, from August to October 2023. NS1 antigen ELISA, IgM and IgG antibody tests, and serotype‐specific real‐time polymerase chain reaction (RT‐PCR) were used to detect the dengue virus (DENV). Representative PCR‐positive samples were sequenced by Sanger sequencing to confirm the circulation of various dengue serotypes. Demographic information, serological test results, and hematological parameters were used as inputs to the ML models, with the dengue PCR result serving as the output to be predicted. The models used were logistic regression, XGBoost, LightGBM, random forest, support vector machine (SVM), and CatBoost. Results: Of the 300 patients, 184 (61.33%) were PCR positive. Among the total positive cases detected by PCR, 9 (4.89%), 171 (92.93%), and 4 (2.17%) were infected with serotypes 1, 2, and 3, respectively. A total of 147 (79.89%) males and 37 (20.11%) females were infected, with a mean age of 33 ± 16 years. In addition, the mean platelet and leukocyte counts and the hematocrit percentages were 75,447%, 4189.02%, and 46.05%, respectively. The SVM was the best‐performing ML model for predicting RT‐PCR results, with 71.4% accuracy, 97.4% recall, and 71.6% precision. Hyperparameter tuning improved the recall to 100%. Conclusion: Our study documents three circulating serotypes in the capital territory of Pakistan and highlights that the SVM outperformed other models, potentially serving as a valuable tool in clinical settings to aid in the rapid diagnosis of DF. [ABSTRACT FROM AUTHOR]

Panama is a country with endemic Dengue virus (DENV) transmission since its reintroduction in 1993. The four serotypes have circulated in the country and the region of the Americas, however, DENV-4 confirmed autochthonous cases have not been identified since 2000, despite its circulation in neighboring countries. Here, we report DENV-4 detection in Panama in the last four-month period of 2023 with cocirculation of the other serotypes, this was associated with a peak of dengue cases during the dry season even thoughmost dengue outbreaks are described in the rainy season. Complete genomes of DENV-4 allowed us to determine that cases were caused by DENV-4 genotype IIb, the same genotype as 23 years ago, with high similarity to DENV-4 sequences circulating in Nicaragua and El Salvador during 2023. This report shows the importance ofmaintaining serotype and genotype surveillance for early detection of new variants circulating in the country. [ABSTRACT FROM AUTHOR]

Dengue fever, caused by dengue virus, poses a significant global health challenge, particularly in tropical regions where Aedes aegypti serves as the primary vector. The circadian clock in Aedes aegypti governs key behavioral and physiological processes, including activity patterns, feeding behaviors, and susceptibility to dengue virus infection. This article explores the influence of circadian rhythms on the mosquito's ability to transmit dengue virus, emphasizing how the circadian regulation of gene expression, immune responses, and lipid metabolism in the mosquito vector creates temporal windows that affect viral replication efficiency. [ABSTRACT FROM AUTHOR]

Plasmodium spp. infections and cases of malaria are a long-standing public health problem for children living in middle- and low-income countries. Dengue virus causes an emerging under-recognized disease burden. A cross sectional study was conducted between March 2020 and December 2021 to determine the status of malaria and dengue fever, and the associated factors in children living in Mwanza, Tanzania. Clinical features were recorded; blood samples were analyzed using dengue NS1 rapid diagnostics test (NS1-RDT), malaria rapid diagnostic test (MRDT) and PCR and microscopy for malaria parasites. Descriptive analysis was based on infection status; odds ratio and confidence interval were used to determine the factors associated with dengue fever and malaria. The prevalence of malaria in the 436 children included in the final analysis was 15.6%, 8.5%, and 12.1% as determined by MRDT, blood smear examination and PCR, respectively. The prevalence of dengue fever determined by the NS1-RDT was 7.8%. Body rash, muscle and joint/bone pain were associated with a positive rapid dengue test result. Retro-orbital pain characterized Plasmodium spp. and dengue virus co-infections. Clinical signs and symptoms could not readily differentiate between malaria and dengue fever patients or patients co-infected with both causative agents underscoring the urgent need for the accurate laboratory diagnostics. Additional large-scale studies are required to assess the epidemiological burden of acute febrile illness in developing countries and to produce data that will guide empirical treatment. [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]

Background: Yellow fever virus (YFV) and dengue virus (DENV) are among the major re-emerging arboviruses that pose a significant threat to public health. Their associated burden and prevalence can be substantially underestimated due to insufficient surveillance and inadequate diagnosis. This study aimed to determine evidence of dengue, yellow and related flaviviruses circulation among the rural human populations residing in Nguruman (Kajiado County) and Kerio Valley (Baringo County), two dryland ecosystems in the Kenyan Rift Valley. Methods: Serum samples obtained from febrile patients between 5 and 85 years through a hospital-based cross-sectional survey from July 2020 – May 2023, were screened for neutralizing antibodies to YFV, DENV-2 and related flaviviruses, West Nile virus (WNV) and Zika virus (ZIKV) via Plaque reduction neutralization test (PRNT). The study sites and important demographic characteristics were obtained using a structural questionnaire and the data analyzed and seroprevalence compared. A multinomial logistic regression model was done to predict risk for each of the most prevalent viruses with covariates; age, gender, and occupation. Results: Overall, 54.5% (50.1–59.0% 95% confidence interval (CI) of the samples tested positive for at least one of the four Flaviviruses. The percentage was significantly higher in Kerio Valley (64.34%, 184/286) than in Nguruman (40.2%, 78/194) (P<0.0001). YFV had the highest prevalence, followed by WNV (16.25%), ZIKV (5.2%), and DENV-2 (1%). Kerio Valley had a significantly higher YFV seroprevalence (51%) than Nguruman (6%) (P<0.0001), while DENV-2 was observed only in Nguruman with a low seropositivity of 2%. In contrast to Nguruman, where seropositivity rates were higher in males at 47.47% (P=0.049), in Kerio Valley, females showed considerably higher viral seropositivity at 60.82% than males (P<0001). Conclusion: The study suggests that there is significant circulation of Flaviviruses in both regions, posing a public health risk, that could potentially contribute to clinical disease. However, seropositivity rates vary for each specific site. Furthermore, there could be a risk of YFV, WNV, and ZIKV transmission in both sites with DENV transmission specifically noted in Nguruman. The study findings inform direct cost-effective actions (such as YF vaccines) and precise surveillance data of vector populations for improved disease risk prediction. [ABSTRACT FROM AUTHOR]

Background/Objectives: Arboviruses, transmitted by mosquitoes like Aedes aegypti, pose significant public health challenges globally, particularly in tropical regions. The rapid spread and adaptation of viruses such as Dengue, Zika, and Chikungunya have emphasized the need for innovative control methods. Essential oils from plants, such as Pectis brevipedunculata (Gardner) Sch.Bip. (Pb), have emerged as potential alternatives to conventional insecticides. Methods: In this work, we developed an eco-friendly nanogel using a low-energy, solvent-free method, incorporating the copolymer F127 and Carbopol 974p, enriched with a high concentration of essential oil from Pb (EOPb). The resulting nanogel displayed excellent physical stability, maintained under varying temperature conditions. Characterization techniques, including FTIR and DLS, confirmed the stable incorporation of EOPb within the nanogel matrix. Results: The in vitro assays against Aedes aegypti larvae revealed that at 500 μ g/mL, the mortality rates were 96.0% ± 7.0 after 24 h and 100.0% ± 0.0 after 48 h. The positive control group treated with temefos, achieved 100% mortality at both time points, validating the experimental conditions and providing a benchmark for assessing the efficacy of the nGF2002Pb nanogel. Conclusions: These results indicate that nGF2002Pb demonstrates a pronounced concentration-dependent larvicidal effect against Aedes aegypti, offering an innovative and sustainable approach to arbovirus vector control. [ABSTRACT FROM AUTHOR]

The article discusses an autochthonous dengue outbreak in Rome, Italy, in 2023, detailing the clinical and demographic characteristics of the cases. The outbreak involved three distinct dengue serotypes and affected 19 individuals, with symptoms ranging from fever to skin rash. While hospitalization was recommended for cases with warning signs, all patients eventually recovered without any severe outcomes. The study highlights the importance of early identification and monitoring of dengue cases in non-endemic areas to prevent severe forms of the disease. [Extracted from the article]

The article "Spatial clustering of dengue cases during the 2024 epidemic in Brazil" published in the Journal of Travel Medicine explores the spatial distribution of dengue cases in Brazil during the severe 2024 epidemic. The study reveals significant spatial heterogeneity in dengue incidence rates, with clusters primarily in the South and Southeast regions. Lower coverage rates of primary healthcare and family health teams were associated with higher dengue incidence, highlighting the importance of robust healthcare systems in controlling vector-borne diseases. The findings emphasize the need for targeted public health interventions, including enhanced vector control, infrastructure improvements, community health education, and strategic vaccine distribution, to reduce the burden of dengue in Brazil. [Extracted from the article]

Background Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007 to 2022. Methods We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive dengue virus (DENV)–specific reverse-transcriptase polymerase chain reaction, positive NS-1 antigen and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high-titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 World Health Organization guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. Results This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: <1–91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15–32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4–15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%) and business (11.0%). The most frequent regions of acquisition were South East Asia (50.4%), South Central Asia (14.9%), the Caribbean (10.9%) and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. Conclusions A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pre-travel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long dengue) due to travel-related dengue. [ABSTRACT FROM AUTHOR]

The article discusses the potential impact of the 2024 Olympics and Paralympic Games in Paris on the risk of dengue outbreaks in the region. It highlights the rise in dengue cases globally in 2024 and the presence of Aedes albopictus mosquitoes capable of transmitting dengue, chikungunya, and Zika viruses in mainland France. The article emphasizes the importance of surveillance, vector-control measures, and healthcare provider awareness to prevent and manage potential dengue outbreaks during and after the Olympics. Additionally, it mentions the lack of antiviral treatment for dengue and the licensing of a live-attenuated tetravalent dengue vaccine for consideration in France. [Extracted from the article]

Key Clinical Message: Although Cambodia is a dengue‐endemic country, mother‐to‐child transmission of dengue virus has yet to be documented. We report a rare case for congenital dengue diagnosed by RT‐PCR in a 4‐day‐old neonate with ascites. The neonate was initially treated for suspected perinatal infection. The management was supportive. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) gains genetic mutations during continuous transmission and evolution, making the virus more adaptive and virulent. The clade of DENV-1 genotype I has expanded and become the predominant genotype in Asia and the Pacific areas, but the underlying mechanisms are unclear. A combined analysis of nonsynonymous mutations in domain III of the envelope protein and their biological effects on virus pathogenesis and transmission was evaluated. Phylogenetic analyses found three nonsynonymous mutations (V324I, V351L, and V380I) in domain III of the envelope protein, which emerged in 1970s-1990s and stably inherited and expanded in contemporary strains after 2000. We generated reverse-mutated viruses (I324V, L351V, and I380V) based on an infectious clone of an epidemic DENV-1 strain (NIID02-20), and the results suggested that the infectivity of the contemporary epidemic virus (wild type, WT) has increased compared to the reverse mutant viruses in mammalian hosts but not mosquito vectors. The WT virus showed a higher binding affinity to host cells and increased virion stability. In addition, weaker immunogenicity and higher resistance to neutralizing antibodies of the WT virus indicated a trend of immune escape. The data suggested that nonsynonymous mutations of the E protein (V324I, V351L, and V380I) promote infectivity and immune evasion of DENV-1 genotype I, which may facilitate its onward transmission on a global scale. [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]

Dengue virus (DENV) causes millions of infections each year, and there are currently no approved antivirals. Essential oils could serve as potential candidates for developing plant-based dengue treatments. Lippia alba (Mill.) N.E. Brown essential oil (LAEO) was selected to investigate the mode of antiviral action and its effect on activated platelets. Binding affinities of 20 LAEO compounds and platelet proteins were investigated through docking analyses. LAEO showed a potent virucidal effect (IC50, 2.1 to 5.1 μg/mL) against all DENV serotypes. LAEO reduced P-selectin (from 61% to 18%) and increased survival (from 71% to 97%) in DENV-2- and DENV NS1-stimulated human platelets. Sesquiterpene hydrocarbons showed the highest binding affinities (from −7.3 to −8.0 kcal/mol) with platelet innate immune receptors such as TLR2/1, TLR4/MD-2 and αIIbβ3 integrin. The data provide a first step towards defining the potential of LAEO as a candidate for developing phytotherapeutics for dengue. [ABSTRACT FROM AUTHOR]

We identified 3 clades of dengue virus serotype 3 belonging to genotype III isolated during 2019–2020 in Jamaica by using whole-genome sequencing and phylogenomic and phylogeographic analyses. The viruses likely originated from Asia in 2014. Newly expanded molecular surveillance efforts in Jamaica will guide appropriate public health responses. [ABSTRACT FROM AUTHOR]

Dengue virus, an arbovirus of genus flavivirus, is one of the most prevalent infectious disease causing organisms in the tropical environment leading to numerous deaths every year. The envelope protein plays a crucial role in the viral genome entry into the host cell. This is achieved through structure and oligomeric status change in the dengue envelope protein. The pre-fusion and post-fusion states' structures of the dengue envelope protein are known although the pathway and intermediate structures involved in this process have remained in the dark till date. In this study, we have used targeted molecular dynamics (MD) simulation followed by conventional MD simulation and the Markov state model analysis to elucidate this pathway of change in conformation from the pre-fusion state to the post-fusion state. Intermediate conformations which may in the future serve as therapeutic targets have also been deduced from the Markov state model. This pathway determination may pave the way for the design of transition state analog inhibitors which prevent the dengue virus envelope protein from changing its conformation and thus establishing infection. The results obtained could lead to development of novel drugs to combat the viral infection. [ABSTRACT FROM AUTHOR]

Dengue fever as a mosquito-borne disease caused by dengue virus is responsible for a substantial disease burden to the world. Wolbachia as an innovative technique has been approved to inhibit the replication of dengue viruses in mosquitoes or reduce the number of wild mosquitoes. We firstly establish a birth-pulse model with sex structures to depict the nonlinear dynamics of mosquito population and then to investigate how Wolbachia can suppress or replace wild mosquitoes. The existence and stability of periodic solutions of the system are proved by analyzing its stroboscopic map. Theoretical results show that under complete maternal transmission, Wolbachia will successfully establish and completely replace wild mosquitoes. Under incomplete maternal transmission, there may be two pairs of bistable periodic solutions, including the coexistence of replacement failure and partial replacement periodic solutions, or the coexistence of replacement failure and mosquito eradication periodic solutions. For these bistable situations, if the initial proportion of Wolbachia-carrying mosquitoes is greater than the critical threshold, then the strategy of partial replacement or mosquito eradication can be succeeded. Since the initial proportion of Wolbachia mosquitoes is not always greater enough in the field, we introduce mosquito releases into the birth-pulse model, and obtain the condition for the stability of complete replacement periodic solution. Finally, we give rich numerical simulations to show the multiple attractors of the systems, the comparison of three common release strategies and the effects of Wolbachia-induced parameters on control strategies. At last section, we summarize some key suggestions on the control of mosquitoes and dengue fever in practice. This work will be helpful for public health authorities in designing proper release strategies to control the spread of dengue fever. • Birth-pulse mosquito population models with sex structures are established. • Dynamics of the systems are investigated by analyzing their stroboscopic map. • Existence for two pairs of bistable periodic solutions are proved and simulated. • Effects of three release methods and control parameters on control strategies are discussed. [ABSTRACT FROM AUTHOR]

The dengue virus is a prevalent viral infection transmitted by mosquitoes that is widespread across the globe. It results in 390 million infections each year, with over 25% of these being clinically evident and causing an illness. The severity of dengue illness is believed to be associated with the occurrence of secondary infection and high viral load. Dengue Hemorrhagic Fever (DHF) patients exhibit a greater viral load compared to Dengue Fever (DF) patients. There is currently lack of sufficient data on the projected viral load's impact on the severity of dengue infection. In the region of East Java, specifically in Jember, which is known for having high prevalence of dengue fever, there has been a lack of research conducted on the viral load of individuals infected with dengue. The objective of this study is to establish the correlation between viral load and the level of severity of dengue infection in Jember Regency. A cross-sectional observational analysis was conducted. The study included a total sample of 48 individuals, ranging in age from 1 to 65 years, who matched the specified inclusion and exclusion criteria. Bivariate analysis using the Spearman correlation test. According to the 2011 WHO-SEARO diagnostic criteria, the majority of the samples (52.1%) fell into the DF group, followed by 11 people (22.9%) in the DHF grade I group, 7 people (14.6%) in the undifferentiated fever group, and 5 people (10.4%) in the DHF grade III group. This study did not include a representative sample of individuals with DHF grade II, DHF grade IV, and expanded dengue. The Spearman correlation test revealed p-value of 0.645. The results of this bivariate study were determined to be insignificant due to the p-value was > 0.05. The severity of patients' dengue virus infection did not significantly correlate with their viral load. [ABSTRACT FROM AUTHOR]

Background and aims: Hyperglycemia, also known as diabetes, is a metabolic disorder characterized by elevated levels of glucose in the bloodstream. It can lead to the prolonged dysfunction, injury, and deterioration of several organs. In addition, dengue is a viral illness transmitted by mosquitoes that has reached epidemic proportions worldwide. In this article, we focused on the severity of comorbidities, difficulties in managing them, and preventive measures meant to lessen the risks associated with comorbidities in diabetic patients with dengue infection. Methods: We explored a number of databases, including PubMed, Scopus, Embase, Web of Science, Google Scholar, and the Cochrane Library, for this review article using various related keywords. Results: The findings of this review article indicate that elderly dengue patients with diabetes should be admitted to the hospital for close observation and early management using fluid therapy. An observed association exists between dengue hemorrhagic fever (DHF) and diabetes, indicating a possible consequence in this specific group. Additionally, patients with diabetes who contract dengue show elevated levels of inflammatory markers. Diabetes mellitus deteriorates the immune system, which exacerbates the progression of dengue fever. Cutting‐edge technology and scientific research may assist in addressing the challenges that diabetes and dengue viruses pose in low‐ and middle‐income countries. Implementing innovative diabetic care management is essential to ensuring consistency of care, improving a healthy lifestyle, and lowering patient risk factors and comorbidities. Conclusion: Dengue fever has spread to epidemic levels throughout the world. Inflammatory markers increase and the prevalence of DHF is greater in diabetes individuals with dengue infection. Given the continued growth of dengue in Asian nations, it is imperative that we concentrate our efforts and resources on providing more precise and effective treatment for this emerging issue. [ABSTRACT FROM AUTHOR]

Background: Dengue virus remains a major public health problem with one of the hallmark pathologies is the vascular leakage caused by endothelial dysfunction which can lead to Dengue Hemorrhagic Fever (DHF) manifestation. In the status quo, no specific therapy has been discovered but rather heavily relies on judicious and frequent monitoring of intravenous fluids administration. The current guideline has discussed the roles of fluid therapy during the Dengue Shock Syndrome (DSS) stage, however, administration of early fluid intervention for DHF grade I and II remains uncharted territory. In addition, the choice and timing of colloid administration remains underexplored. As one of the widely available colloids, 5% albumin has known physiological properties that potentially minimize plasma leakage. Therefore, this study aimed to evaluate the benefit of early intervention of 5% albumin in adults with DHF in the hope of preventing the lethal progression to DSS and further, shorten the length of stay (LOS) for patients. Methods: We conducted a multicenter, open-labeled, randomized controlled trial in Jakarta and Banten to compare the effect of early intervention with 5% albumin in adult patients with DHF compared to Ringer's Lactate (RL). Statistical analyses were conducted using unpaired t-test and Mann-Whitney for normally and abnormally distributed data respectively. Results: Adult patients with a diagnosis of DHF grade I and II that being hospitalized to receive the early intervention of 5% albumin had significantly lower levels of hemoconcentration 4, 12, and 24 h (p = 0.002, 0.001, 0.003, respectively), higher platelet counts 4 h (p = 0.036), higher serum albumin levels 48 h (p = 0.036), lower proteinuria 24 and 48 h post-albumin administration (p < 0.001, < 0.001, respectively), and shorter LOS (p < 0.001) when compared to the RL group. Conclusion: Early intervention of 5% albumin showed better control on vascular integrity and function compared to ringer lactate in hospitalized adults with grade I & II DHF, thus halting the progression of DHF into DSS and other related complications which leads to faster recovery and shorter length of stay. Trial registration: The study was registered to www.clinicaltrial.gov with trial registration number NCT04076254, and registration date October 31st 2016. [ABSTRACT FROM AUTHOR]

Mosquito-borne diseases such as dengue and filariasis are a growing public health concern in endemic countries. Biological approaches, such as the trans-infection of Wolbachia pipientis in mosquitoes, are an alternative vector control strategy, especially for arthropod-borne viruses such as dengue. In the present study, the effect of Wolbachia (wMel strain) on the vectorial capacity of Aedes aegypti for Dirofilaria immitis was studied. Our results showed that Wolbachia does not affect the phenotype of mosquito survival or the prevalence, number, and molting rate of third-stage larvae in both susceptible and resistant strains of Ae. aegypti. RNA-seq analysis of Malpighian tubules at 2 days post-infection with D. immitis showed the differentially expressed genes (DEGs) with and without wMel infection. No characteristic immune-related gene expression patterns were observed among the DEGs. No significant change in the amount of Wolbachia was observed in the Ae. aegypti after D. immitis infection. Our results suggest that infection of D. immitis in Ae. aegypti populations will not interfere with Wolbachia-based vector control strategies in dengue-endemic areas where cases of D. immitis are present. This study demonstrated the veterinary medical validity of a dengue control program using Wolbachia. [ABSTRACT FROM AUTHOR]

Background: Dengue is a vector-borne viral infection caused by the dengue virus transmitted to humans primarily by Aedes aegypti. The year 2024 has been a historic year for dengue in Brazil, with the highest number of probable cases ever registered. Herein, we analyze the temporal trend and spatio-temporal dynamics of dengue cases in Brazil during the first nine epidemiological weeks (EW) of 2024. Methods: This is an ecological study, including all probable cases of dengue in Brazil during the period, carried out in two steps: time series analysis to assess the temporal trend and spatial analysis to identify high-risk clusters. Results: 1,345,801 probable cases of dengue were reported. The regions with the highest increasing trend were the Northeast with an average epidemiologic week percent change (AEPC) of 52.4 (95% CI: 45.5–59.7; p < 0.001) and the South with 35.9 (95% CI: 27.7–44.5; p < 0.001). There was a statistically significant increasing trend in all states, except Acre (AEPC = -4.1; 95% CI: -16.3–10; p = 0.55), Amapá (AEPC = 1.3; 95% CI: -16.2–22.3; p = 0.9) and Espírito Santo (AEPC = 8.9; 95% CI: -15.7–40.6; p = 0.5). The retrospective space-time analysis showed a cluster within the Northeast, Central-West and Southeast regions, with a radius of 515.3 km, in which 1,267 municipalities and 525,324 of the cases were concentrated (RR = 6.3; p < 0.001). Regarding the spatial variation of the temporal trend, 21 risk areas were found, all of them located in Southeast or Central-West states. The area with the highest relative risk was Minas Gerais state, where 5,748 cases were concentrated (RR = 8.1; p < 0.001). Finally, a purely spatial analysis revealed 25 clusters, the one with the highest relative risk being composed of two municipalities in Acre (RR = 6.9; p < 0.001). Conclusions: We described a detailed temporal-spatial analysis of dengue cases in the first EWs of 2024 in Brazil, which were mainly concentrated in the Southeast and Central-West regions. Overall, it is recommended that governments adopt public policies to control the the vector population in high-risk areas, as well as to prevent the spread of dengue fever to other areas of Brazil. [ABSTRACT FROM AUTHOR]

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

Extracellular vesicles (EVs) play crucial roles in cell signaling and communication, transporting molecules that convey a message to target cells. During infectious diseases, EVs can also carry viral molecules that may contribute to viral spread, as previously reported for dengue virus (DENV). EVs from infected endothelial cells (EC) may harbor viral segments and various sets of molecules that could contribute to endothelial dysfunction during severe dengue. However, the effect of these EVs on non-infected EC (NIC) remain unknown. We characterized the EVs produced by the human EC line EA.hy 926 infected with DENV-2 and assessed their functional impact on polarized NIC. Results showed that infection induced an increased in the quantity of produced EVs, which differentially carried proteins mainly involved in proteosome activity, along with a peptide of the NS5 viral protein. Additionally, all types of Y-RNAs were found, accompanied by a set of differentially loaded microRNAs (miRs) that could regulate DENV genome. Pre-treatment of polarized NIC with small EVs (sEVs) from infected EC before DENV-2 infection caused EC activation, a decrease in viral genome replication, and a protective effect against barrier disruption during the first 24h post-infection, suggesting that sEVs could be important in the pathology or resolution of DENV and a promising therapeutic tool for infectious diseases. [ABSTRACT FROM AUTHOR]

The increased incidence of dengue poses a substantially global public health challenge. There are no approved antiviral drugs to treat dengue infections. Ivermectin, an old anti‐parasitic drug, had no effect on dengue viremia, but reduced the dengue non‐structural protein 1 (NS1) in a clinical trial. This is potentially important, as NS1 may play a causal role in the pathogenesis of severe dengue. This study established an in‐host model to characterize the plasma kinetics of dengue virus and NS1 with host immunity and evaluated the effects of ivermectin, using a population pharmacokinetic–pharmacodynamic (PK–PD) modeling approach, based on two studies in acute dengue fever: a placebo‐controlled ivermectin study in 250 adult patients and an ivermectin PK–PD study in 24 pediatric patients. The proposed model described adequately the observed ivermectin pharmacokinetics, viral load, and NS1 data. Bodyweight was a significant covariate on ivermectin pharmacokinetics. We found that ivermectin reduced NS1 with an EC50 of 67.5 μg/mL. In silico simulations suggested that ivermectin should be dosed within 48 h after fever onset, and that a daily dosage of 800 μg/kg could achieve substantial NS1 reduction. The in‐host dengue model is useful to assess the drug effect in antiviral drug development for dengue fever. [ABSTRACT FROM AUTHOR]

Dengue virus, an arbovirus of genus Flavivirus, is an infectious disease causing organisms in the tropical environment leading to numerous deaths every year. No therapeutic is available against the virus till date with only symptomatic relief available. Here, we have tried to design therapeutic compounds from scratch by fragment based method followed by pharmacophore based modelling to find suitable similar structure molecules and validated the same by MD simulation, followed by binding energy calculations and ADMET analysis. The receptor binding region of the dengue envelope protein was considered as the target for prevention of viral host cell entry and thus infection. This resulted in the final selection of kanamycin as a stable binding molecule against the Dengue virus envelope protein receptor binding domain. This study results in selection of a single molecule having high binding energy and prominent stable interactions as determined by post simulation analyses. This study aims to provide a direction for development of small molecule therapeutics against the dengue virus in order to control infection. This study may open a new avenue in the arena of structure based and fragment based therapeutic design to obtain novel molecules with therapeutic potential. [ABSTRACT FROM AUTHOR]