Analysis of signs and symptoms in confirmed cases of severe dengue among children aged 0 to 10 years old.

OBJECTIVE: The prevalent symptoms of severe dengue in pediatric patients are divided into three subgroups: severe plasma leakage, severe bleeding, and severe organ damage. In addition, the seasonal patterns of the disease and the outcomes of cure or death from dengue were evaluated. METHODS: An epidemiological, observational, analytical, cross-sectional study was conducted with data from the Notifiable Disease Information System (SINAN - Sistema de Informação de Agravos de Notificação and DATASUS - Departamento de Informática do Sistema Único de Saúde) of the Ministry of Health from 2019 to 2020. RESULTS: During the study period, 1,857 cases of severe dengue were observed in the pediatric age group, with the most common symptoms being respiratory failure, melena, hematemesis, and altered level of consciousness. The total proportion of patients hospitalized for severe dengue was 89.6%, and 51.2% of these patients died, corroborating the importance of early detection of the disease. CONCLUSION: Severe dengue is more prevalent during the seasonal period, with hot and humid characteristics owing to the mechanism involved in the viral cycle. The most prevalent symptoms of severe dengue in pediatric patients were respiratory failure alone, gastrointestinal bleeding, and altered level of consciousness. It is important to identify signs of severity for early intervention and a better prognosis, considering that death is closely related to a delayed diagnosis.

Development and assessment of a multiepitope synthetic antigen for the diagnosis of Dengue virus infection.

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines.

Spatial distribution of arboviruses and its association with a social development index and the waste disposal in São Luís, state of Maranhão, Brazil, 2015 to 2019.

OBJECTIVE: To detect spatial and spatiotemporal clusters of urban arboviruses and to investigate whether the social development index (SDI) and irregular waste disposal are related to the coefficient of urban arboviruses detection in São Luís, state of Maranhão, Brazil. METHODS: The confirmed cases of Dengue, Zika and Chikungunya in São Luís, from 2015 to 2019, were georeferenced to the census tract of residence. The Bayesian Conditional Autoregressive regression model was used to identify the association between SDI and irregular waste disposal sites and the coefficient of urban arboviruses detection. RESULTS: The spatial pattern of arboviruses pointed to the predominance of a low-incidence cluster, except 2016. For the years 2015, 2016, 2017, and 2019, an increase of one unit of waste disposal site increased the coefficient of arboviruses detection in 1.25, 1.09, 1.23, and 1.13 cases of arboviruses per 100 thousand inhabitants, respectively. The SDI was not associated with the coefficient of arboviruses detection. CONCLUSION: In São Luís, spatiotemporal risk clusters for the occurrence of arboviruses and a positive association between the coefficient of arbovirus detection and sites of irregular waste disposal were identified.

A perspective on the worst ever dengue outbreak 2023 in Bangladesh: What makes this old enemy so deadly, and how can we combat it?

Background and Aims: Bangladesh has been going through outbreaks of dengue fever cases every year since 2000. Yet this year's (2023) episode of dengue fever has crossed every line concerning fatality. Symptoms of the fever range from high fever, headaches, and muscle aches to deadly dengue hemorrhagic fever (DHF). The present review aims to assess the current pathogenicity and associated risk factors of recent dengue outbreaks in Bangladesh. Methods: To perform this review work, we extracted relevant information from published articles available in PubMed, Scopus, and Google Scholar. We used dengue virus, dengue fever, and dengue outbreaks as keywords while searching for information. Results: This Aedes mosquito-transmitted viral fever is more common in Bangladesh because of the tropical nature and immense burden of populations, resulting in convenient conditions for the reproduction of the vector. The rapid genetic transformation of this RNA virus and the resistance of its vector against insecticides have intensified the situation. The number of hospitalized patients has increased, and the case fatality rate has risen to 0.47%. Inadequate mosquito control measures, plenty of vector breeding sites, and a lack of public awareness have worsened the situation. Routine spraying of effective insecticides in high-risk zones, regular inspection of potential mosquito breeding sites, and public awareness campaigns are the keys to limiting the spread of this virus. Also, the availability of detection kits, improved hospital settings, and trained health professionals are mandatory to keep disease fatalities under control. Conclusion: Dengue fever is a preventable disease. The successful development of a competent vaccine is now a prime need for preventing any future upsurge of the disease. Also, we recommend public awareness, vector control activities, and global collaboration to prevent spread.

Tiger prowling: Distribution modelling for northward-expanding Aedes albopictus (Diptera: Culicidae) in Japan.

The Asian tiger mosquito, Aedes albopictus, is a significant public health concern owing to its expanding habitat and vector competence. Disease outbreaks attributed to this species have been reported in areas under its invasion, and its northward expansion in Japan has caused concern because of the potential for dengue virus infection in newly populated areas. Accurate prediction of Ae. albopictus distribution is crucial to prevent the spread of the disease. However, limited studies have focused on the prediction of Ae. albopictus distribution in Japan. Herein, we used the random forest model, a machine learning approach, to predict the current and potential future habitat ranges of Ae. albopictus in Japan. The model revealed that these mosquitoes prefer urban areas over forests in Japan on the current map. Under predictions for the future, the species will expand its range to the surrounding areas and eventually reach many areas of northeastern Kanto, Tohoku District, and Hokkaido, with a few variations in different scenarios. However, the affected human population is predicted to decrease owing to the declining birth rate. Anthropogenic and climatic factors contribute to range expansion, and urban size and population have profound impacts. This prediction map can guide responses to the introduction of this species in new areas, advance the spatial knowledge of diseases vectored by it, and mitigate the possible disease burden. To our knowledge, this is the first distribution-modelling prediction for Ae. albopictus with a focus on Japan.

Potential of MALDI-TOF MS biotyping to detect deltamethrin resistance in the dengue vector Aedes aegypti.

Insecticide resistance in mosquitoes is spreading worldwide and represents a growing threat to vector control. Insecticide resistance is caused by different mechanisms including higher metabolic detoxication, target-site modification, reduced penetration and behavioral changes that are not easily detectable with simple diagnostic methods. Indeed, most molecular resistance diagnostic tools are costly and labor intensive and then difficult to use for routine monitoring of insecticide resistance. The present study aims to determine whether mosquito susceptibility status against the pyrethroid insecticides (mostly used for mosquito control) could be established by the protein signatures of legs and/or thoraxes submitted to MALDI-TOF Mass Spectrometry (MS). The quality of MS spectra for both body parts was controlled to avoid any bias due to unconformity protein profiling. The comparison of MS profiles from three inbreeds Ae. aegypti lines from French Guiana (IRF, IR03, IR13), with distinct deltamethrin resistance genotype / phenotype and the susceptible reference laboratory line BORA (French Polynesia), showed different protein signatures. On both body parts, the analysis of whole protein profiles revealed a singularity of BORA line compared to the three inbreeding lines from French Guiana origin, suggesting that the first criteria of differentiation is the geographical origin and/or the breeding history rather than the insecticide susceptibility profile. However, a deeper analysis of the protein profiles allowed to identify 10 and 11 discriminating peaks from leg and thorax spectra, respectively. Among them, a specific peak around 4870 Da was detected in legs and thoraxes of pyrethroid resistant lines compared to the susceptible counterparts hence suggesting that MS profiling may be promising to rapidly distinguish resistant and susceptible phenotypes. Further work is needed to confirm the nature of this peak as a deltamethrin resistant marker and to validate the routine use of MS profiling to track insecticide resistance in Ae. aegypti field populations.

Functional genomics screens reveal a role for TBC1D24 and SV2B in antibody-dependent enhancement of dengue virus infection.

Dengue virus (DENV) can hijack non-neutralizing IgG antibodies to facilitate its uptake into target cells expressing Fc gamma receptors (FcgR) - a process known as antibody-dependent enhancement (ADE) of infection. Beyond a requirement for FcgR, host dependency factors for this non-canonical infection route remain unknown. To identify cellular factors exclusively required for ADE, here, we performed CRISPR knockout screens in an in vitro system permissive to infection only in the presence of IgG antibodies. Validating our approach, a top hit was FcgRIIa, which facilitates binding and internalization of IgG-bound DENV but is not required for canonical infection. Additionally, we identified host factors with no previously described role in DENV infection, including TBC1D24 and SV2B, both of which have known functions in regulated secretion. Using genetic knockout and trans-complemented cells, we validated a functional requirement for these host factors in ADE assays performed with monoclonal antibodies and polyclonal sera in multiple cell lines and using all four DENV serotypes. We show that knockout of TBC1D24 or SV2B impaired binding of IgG-DENV complexes to cells without affecting FcgRIIa expression levels. Thus, we identify cellular factors beyond FcgR that are required for ADE of DENV infection. Our findings represent a first step towards advancing fundamental knowledge behind the biology of ADE that can ultimately be exploited to inform vaccination and therapeutic approaches.

Comparison of the Sensitivity and Specificity of Commercial Anti-Dengue Virus IgG Tests to Identify Persons Eligible for Dengue Vaccination.

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for 7 tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the 5 best performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9-16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the 4 best performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to Zika virus. For the detection of previous DENV infections the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation.

Guia de mensagens-chave destinadas a indivíduos, famílias e comunidades sobre ações preventivas e de controle para combater o mosquito Aedes aegypti, transmissor de dengue, chikungunya, zika e outras arboviroses na Região das Américas

O mosquito Aedes aegypti é o principal transmissor dos vírus da dengue, chikungunya e zika nas Américas. Está presente em quase todos os países (exceto o Canadá). É um mosquito doméstico (vive dentro das casas e em seus arredores) capaz de se reproduzir em qualquer lugar ou recipiente que contenha água acumulada. Este dcoumento apresentam-se aspectos gerais do mosquito Aedes aegypti e recomendações que têm o objetivo de contribuir para seu controle e assim prevenir ou reduzir o risco de transmissão de dengue, chikungunya, zika e outros arbovírus urbanos transmitidos por este vetor nas Américas.

Investigating the Clinico-Demographic Characteristics of Dengue Fever and Its Seroprevalence at a Tertiary Care Hospital in Northern India.

Background and objective Dengue virus (DENV) is a major global health threat, causing over 50,000 deaths annually. The state of Uttar Pradesh (UP) in India faces significant challenges due to the increasing number of dengue cases detected. This study aimed to assess DENV seropositivity in the Raebareli district of UP, to offer crucial insights into the region's effective control and management strategies. Materials and methods This study, after obtaining approval from the ethics committee, analyzed blood samples of individuals suspected of having dengue at a teaching hospital in rural UP between January and December 2022. To determine the disease's seroprevalence, both dengue NS1 antigen ELISA and dengue IgM Microlisa were conducted. Furthermore, RT-PCR was performed on NS1-positive samples to confirm the serotypes. The collected data were analyzed using Epi Info 7.0. Results Of the 589 suspected dengue cases, 86 (14.60%) tested positive for dengue NS1 and/or IgM. Our findings showed that males (n=330, 56.03%) and adolescents and young adults (n=301, 51.1%) from rural areas (n=523, 88.4%) were predominantly affected. Cases peaked post-monsoon, and platelet levels were notably low in NS1-positive cases. Dengue serotype 2 (DEN-2) was found in all RT-PCR-positive samples. Our results revealed a dengue seroprevalence of 14.60% (n=86), which peaked in post-monsoon months. The higher incidence among males and young adults from rural areas attending the outpatient department highlights the importance of targeted interventions and community surveillance. RT-PCR confirmed the circulation of a single serotype in the region. Conclusions This study contributes crucial insights into dengue's epidemiology and clinical profile and its findings are all the more significant now as India prepares for phase 3 trials of a quadrivalent dengue-virus vaccine in 2024. Adolescent and young adult males have an increased likelihood of acquiring the virus, and this demographic can be prioritized for vaccine trials.

Dengue virus serotypes and related factors in children with dengue hemorrhagic fever in Southern Vietnam.

INTRODUCTION: After the Coronavirus Disease 2019 pandemic, a high number of cases and severe dengue in children were reported in some provinces in the south of Vietnam. This study aimed to determine the distribution of dengue virus serotypes and their correlation with demographic factors, disease severity, clinical manifestations, and laboratory findings. METHODOLOGY: This study employed a cross-sectional design. Ninety-six dengue-infected children admitted to Can Tho Children's Hospital between October 2022 and March 2023 were included. Confirmation of dengue infection was achieved through the real-time polymerase chain reaction (RT-PCR). RESULTS: Among the identified serotypes, DENV-2 accounted for the highest proportion (71.87%), followed by DENV-1 (23.96%), and DENV-4 (4.17%). DENV-3 was not detected. No significant demographic, disease severity, or laboratory differences were observed among the identified dengue serotypes. However, DENV-2 was associated with a higher occurrence of mucous membrane hemorrhages and gastrointestinal bleeding compared to other serotypes. CONCLUSIONS: Although DENV-2 was the most prevalent serotype responsible for dengue in children in southern Vietnam, it did not lead to more severe cases compared to other serotypes. This finding is crucial for evaluating the illness's prognosis.

Simultaneous Dengue and Chikungunya Coinfection in Endemic Area in Brazil: Clinical Presentation and Implications for Public Health.

Background Dengue virus (DENV) and Chikungunya virus (CHIKV) pose significant public health threats in Brazil, where favorable conditions facilitated the proliferation of Aedes mosquitoes. Since the mid-1980s, Brazil has experienced annual outbreaks of DENV, with recent increases in confirmed cases. In addition, CHIKV, which was first reported in 2014, has spread across the country. The concurrent presence of these viruses has triggered public health alerts in endemic regions, underscoring the complexity of managing vector-borne diseases. Case Presentation: This report details a case of simultaneous DENV and CHIKV infections. A 77-year-old female patient who has diabetes and arrhythmia exhibited symptoms including fever, myalgia, and severe arthralgia. Laboratory tests confirmed the coinfection through RNA detection. The patient received supportive care, showed gradual improvement, and was eventually discharged. Conclusions Coinfection with DENV and CHIKV cases reported here developed with mild outcomes. However, one of the patients did not recover from the arthralgia after presenting diagnostic challenges, which underscores the need for accurate differentiation to manage symptoms effectively. The reported cases, amidst increasing DENV outbreaks, highlight the urgency for preparedness in the healthcare system. The Ribeirão Preto region's endemicity for DENV, coupled with the rising incidence of CHIKV, emphasizes the evolving landscape of arbovirus transmission. Studies on Aedes mosquitoes suggest potential implications for human infection dynamics, warranting further investigation into arbovirus transmission efficacy and coinfection dynamics.

Circulation of DENV-2 serotype associated with increased risk of cumulative incidence of severe dengue and dengue with warning signs: A 16-year retrospective study in Peru.

Background: Dengue poses a significant public health challenge in Peru and other endemic countries worldwide. While severe dengue is known to be associated with secondary infection at the individual level, the factors that elevate the risk of severe dengue at the population level remain poorly understood. This study leverages over 16 years of secondary data from a Peruvian dengue surveillance system to assess which type of serotype-specific circulation is associated with an increased risk of cumulative incidence of severe dengue or dengue with warning signs (SD-DWS). Methodology: This is a retrospective analysis of secondary data using the Peruvian Ministry of Health databases of dengue cases and serotyping. A mixed negative binomial regression model for repeated measures over time was employed to estimate the association between the cumulative incidence of reported SD-DWS cases per 100,000 inhabitants and serotype-specific circulation. Crude and adjusted incidence ratios (IRR) were estimated. Principal findings: The study analyzed data from 2007 to 2022 across 19 regions of Peru, totaling 304 region-years. Data from nearly 58,000 serotype identification reports and 57,966 cases of SD-DWS were analyzed. The regions with most cumulative incidence of SD-DWS per 100,000 inhabitants during 2007 to 2022 were Madre de Dios (3859), Loreto (1518), Ucayali (1492), Tumbes (1335), and Piura (722). The adjusted model revealed a higher risk of cumulative incidence of SD-DWS when there was specific circulation of DENV-123 (aIRR 7.57 CI 4.00 - 14.31), DENV-12 (aIRR 4.66 CI 2.57 - 8.44), DENV-23 (aIRR 3.55 CI 1.75 - 7.21), or when there was circulation of DENV-2 alone or co-circulating with other serotypes (aIRR 27.7 CI 15.46 -49.63). Conclusions: Circulation of DENV-2 was associated with higher average incidence rate ratios of SD-DWS. Author summary: We investigated how the circulation of different dengue virus (DENV) serotypes are associated with the incidence of severe dengue and dengue with warning signs in Peru, a country where dengue is endemic. We analyzed 16 years of data from the dengue surveillance system, including nearly 58,000 serotype identification reports and 57,966 cases of severe dengue and dengue with warning signs. We found that regions with specific circulation of DENV-2, either alone or in combination with other serotypes, had higher incidence rates of severe dengue and dengue with warning signs. Our findings highlight the importance of monitoring DENV serotype circulation to manage and prevent severe dengue, especially in regions where DENV-2 is prevalent.

Envelope-dimer epitope-like broadly protective antibodies against dengue in children following natural infection and vaccination.

Cross-reactive antibodies (Abs) to epitopes that span envelope proteins on the virion surface are hypothesized to protect against dengue. Here, we measured Abs targeting the quaternary envelope dimer epitope (EDE) as well as neutralizing and binding Abs and evaluate their association with dengue virus (DENV) infection, vaccine response, and disease outcome in dengue vaccinated and unvaccinated children (n=252) within a longitudinal cohort in Cebu, Philippines (n=2,996). Abs targeting EDE were prevalent and strongly associated with broad neutralization of DENV1-4 in those with baseline multitypic immunity. Subsequent natural infection and vaccination boosted EDE-like, neutralizing, and binding Abs. EDE-like Abs were associated with reduced dengue risk and mediated the protective effect of binding and neutralizing Abs on symptomatic and severe dengue. Thus, Abs targeting quaternary epitopes help explain broad cross protection in those with multiple prior DENV exposures, making them useful for evaluation and development of future vaccines and therapeutics.

Diabetes as risk factor to severity of dengue in naïve patients.

Background: Dengue cases can progress to severe ant life-threating forms particularly in subsequent heterologous infections. However, recent studies had explored additional risk factors, including underlying health conditions, even in individuals without prior exposure to dengue, notably, in patients with endothelial dysfunction and chronic inflammation. This study examines the link between diabetes and the development of severe dengue disease in dengue-naive patients during the 2019 dengue outbreak in São Jose do Rio Preto, Brazil. Methodology: We enrolled 529 laboratory-confirmed dengue cases, identified through DENV RT-PCR or NS1 antigen assays in a hospital cohort of acute febrile illness. Subsequently, we investigated the presence of anti-dengue and anti-Zika IgG antibodies. Samples testing positive for Zika were excluded from the analyses. Two groups were analyzed: naïve (DV-), and dengue history (DV+). Results: Initially, presence of diabetes and kidney disease, as well as being dengue-naive, were associated with a higher frequency of severe and potentially severe clinical outcomes. Multivariate analysis identified diabetes as a risk factor, while the presence of anti-dengue antibodies was considered protective. Analysis of dengue naïve samples, highlighted diabetes as an independent risk factor to severe forms of dengue disease. In DV+ patients, no condition was highlighted as a risk factor by univariate analysis or multivariate analysis. Conclusions: We investigated and confirmed diabetes as a risk factor for severe dengue disease in individuals without prior dengue or Zika exposure. Our conclusions raise significant concerns given diabetes' ever increasing global prevalence and its potential impact on patients with or previous dengue exposure. Summary: The simultaneous escalation of diabetes and dengue worldwide is striking. Notably, diabetes presents as a significant risk factor for severe dengue. This accentuates the necessity of diabetes control in dengue prevention, considering its widespread prevalence and influence on disease severity.

The impact of yeast-encapsulated orange oil in Aedes aegypti oviposition.

The yeast-encapsulated orange oil (YEOO) is a novel larvicide under development against vector mosquitoes. Despite its efficiency against Aedes aegypti (L.) in small scale experiments, its applicability in vector control can be influenced by other effects on mosquito behaviour or physiology. For this reason, the impact of YEOO particles in mosquito oviposition was evaluated in laboratory and semi-field conditions. Oviposition assays with one gravid Aedes aegypti female were carried under laboratory and semi-field conditions with natural light and temperature fluctuation. For all ovitraps, the number of eggs was manually counted in the wooden paddle and in the solution of each ovitrap. The proportion of eggs between substrates (wooden paddle and solution) varied between conditions, with females in laboratory presenting a lower preference to lay eggs in paddles when compared with studies in semi-field. This behaviour shifts in laboratory can create challenges to extrapolate results from laboratory to the field. Here, studies in both conditions indicate a similar impact of YEOO particles in Aedes aegypti oviposition. The potential treatment concentration of YEOO particles presents a strong repellent/deterrent effect (-0.559 > OAI > -0.760) within the initial 72h of application when compared with water, and weak repellent/deterrent signal (OAI = -0.220) when compared against inactivated yeast. Control ovitraps with water were more positive for egg presence than treated ovitraps, while ovitraps with YEOO particles and inactivated yeast present similar number of positive ovitraps. It is possible that the repellent/deterrent action is partially driven by the delivery system, since most times Citrus sinensis EO oviposition repellent/deterrent signal is weak, and it seem influenced by solvent/delivery used. However, it is unclear how the yeast wall that protect/surrounds the orange oil will negatively affect oviposition since live yeast are normally consider an attractant for mosquito oviposition.

Duration of Fever in Patients with Dengue: A Systematic Review and Meta-Analysis.

Dengue is an acute febrile illness endemic to tropical countries and associated with high mortality rates. Despite being a viral infection, there is rampant misuse of antibiotics in patients with dengue because of perceived delay in defervescence and fear of secondary bacterial infections. Therefore, there is a need to establish the average fever duration with a confidence interval among patients with dengue. Studies up to October 21, 2022 from two databases (PubMed and Embase) were included using the search terms related to dengue and duration of fever. All retrieved articles were screened for eligibility by two independent reviewers. Studies where the average duration of fever was available were included for systematic review. Articles with at least more than 20 patients where a mean and standard deviation for the total duration of fever was available were included for meta-analysis. A total of 643 articles were included from the two databases after duplicate deletion. After two rounds of screening, 31 articles (n = 7,905) were finally included. The mean duration of fever in the 20 articles included for meta-analysis was 5.1 (95% CI: 4.7-5.5) days. Longer duration of fever was seen in those with a higher grade of fever, those with higher disease severity, and those with concurrent bacterial infections. In the absence of risk factors for concurrent bacteremia, antimicrobials may be unnecessary in those with dengue fever duration of less than 5.5 days.

Spatiotemporal models of dengue epidemiology in the Philippines: Integrating remote sensing and interpretable machine learning.

Previous dengue epidemiological analyses have been limited in spatiotemporal extent or covariate dimensions, the latter neglecting the multifactorial nature of dengue. These constraints, caused by rigid and traditional statistical tools which collapse amidst 'Big Data', prompt interpretable machine-learning (iML) approaches. Predicting dengue incidence and mortality in the Philippines, a data-limited yet high-burden country, the mlr3 universe of R packages was used to build and optimize ML models based on remotely sensed provincial and dekadal 3 NDVI and 9 rainfall features from 2016 to 2020. Between two tasks, models differ across four random forest-based learners and two clustering strategies. Among 16 candidates, rfsrc-year-case and ranger-year-death significantly perform best for predicting dengue incidence and mortality, respectively. Therefore, temporal clustering yields the best models, reflective of dengue seasonality. The two best models were subjected to tripartite global exploratory model analyses, which encompass model-agnostic post-hoc methods such as Permutation Feature Importance (PFI) and Accumulated Local Effects (ALE). PFI reveals that the models differ in their important explanatory aspect, rainfall for rfsrc-year-case and NDVI for ranger-year-death, among which long-term average (lta) features are most relevant. Trend-wise, ALE reveals that average incidence predictions are positively associated with 'Rain.lta', reflective of dengue cases peaking during the wet season. In contrast, those for mortality are negatively associated with 'NDVI.lta', reflective of urban spaces driving dengue-related deaths. By technologically addressing the challenges of the human-animal-ecosystem interface, this study adheres to the One Digital Health paradigm operationalized under Sustainable Development Goals (SDGs). Leveraging data digitization and predictive modeling for epidemiological research paves SDG 3, which prioritizes holistic health and well-being.

3D-QSAR and molecular docking studies of peptide-hybrids as dengue virus NS2B/NS3 protease inhibitors.

Global warming and climate change have made dengue disease a global health issue. More than 50 % of the world's population is at danger of dengue virus (DENV) infection, according to the World Health Organization (WHO). Therefore, a clinically approved dengue fever vaccination and effective treatment are needed. Peptide medication development is new pharmaceutical research. Here we intend to recognize the structural features inhibiting the DENV NS2B/NS3 serine protease for a series of peptide-hybrid inhibitors (R1-R2-Lys-R3-NH2) by the 3D-QSAR technique. Comparative molecular field analysis (q2 = 0.613, r2 = 0.938, r2pred = 0.820) and comparative molecular similarity indices analysis (q2 = 0.640, r2 = 0.928, r2pred = 0.693) were established, revealing minor, electropositive, H-bond acceptor groups at the R1 position, minor, electropositive, H-bond donor groups at the R2 position, and bulky, hydrophobic groups at the R3 position for higher inhibitory activity. Docking studies revealed extensive H-bond and hydrophobic interactions in the binding of tripeptide analogues to the NS2B/NS3 protease. This study provides an insight into the key structural features for the design of peptide-based inhibitors of DENV NS2B/NS3 protease.

In-vitro assessment of cutaneous immune responses to aedes mosquito salivary gland extract and dengue virus in Cambodian individuals.

Dengue virus (DENV) poses a global health threat, affecting millions individuals annually with no specific therapy and limited vaccines. Mosquitoes, mainly Aedes aegypti and Aedes albopictus worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how Aedes mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from three different mosquito strains: Ae. aegypti USDA strain, Ae. aegypti and Ae. albopictus wild type (WT) in the presence/absence of DENV. We observed notable alterations in skin immune cell phenotypes subsequent to exposure to Aedes salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of Aedes SGE. Differences in cellular responses were observed when Aedes SGE of three distinct mosquito strains were compared. Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.