Dengue fever is a mosquito-borne viral illness caused by the dengue virus, primarily transmitted by Aedes aegypti mosquitoes. It remains a major public health concern in tropical and subtropical regions worldwide. Clinical presentations range from mild febrile illness to severe complications such as Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). In recent years, atypical manifestations, including cardiac involvement, have been recognised. The present case report focuses on a nine-year-old male child from a dengue-endemic area who presented with a high-grade fever, myalgia, abdominal pain, and vomiting. Laboratory findings revealed thrombocytopenia and elevated haematocrit levels, meeting the criteria for dengue with warning signs. During the course of the illness, the child was found to have Mobitz type 1 Atrioventricular (AV) block (Wenckebach phenomenon) on an Electrocardiogram (ECG). This cardiac conduction abnormality, though rare in the paediatric population, was transient and resolved spontaneously without the need for intervention. The patient was managed conservatively with close monitoring, fluid management, and supportive care, ultimately making a full recovery. A repeat ECG showed normalisation of the cardiac rhythm. The present case underscores the importance of recognising cardiac complications in dengue fever, even in children, as they may be self-limiting yet clinically significant. Early detection and vigilant monitoring of warning signs, including electrocardiographic changes, can aid in preventing potential morbidity. Clinicians should maintain a high index of suspicion for such atypical manifestations in dengue cases, especially during outbreaks.

Severe dengue is characterised by systemic inflammation, cytokine storm, vascular leakage and haemorrhagic manifestations, largely driven by the host immune response to dengue virus (DENV) infection. Despite its burden, no licensed antivirals or host-directed therapies are currently available. Our group has previously identified Annexin A1 (AnxA1) as an endogenous regulator of inflammation in dengue. Treatment with the AnxA1 peptidomimetic, Ac2-26, improved clinical outcomes in murine models of severe dengue by promoting resolution of inflammation without affecting viral control. To explore new delivery strategies, we developed a novel formulation of Ac2-26 complexed with hydroxypropyl-β-cyclodextrin (CDX-Ac2-26). In DENV-2-infected A129 mice, both intraperitoneal and oral CDX-Ac2-26 improved clinical scores and reversed thrombocytopenia. Notably, CDX-Ac2-26 reduced mast cell degranulation, MCPT-1 plasma levels and CCL2 expression in spleen, with no effect on viral titres, indicating a host-targeted mechanism and overcoming the anti-inflammatory effects of the free peptide. Intraperitoneal administration achieved the same efficacy as oral dosing with only one-third of the dose. Importantly, the combination of CDX-Ac2-26 with the antiviral nucleotide analogue sofosbuvir fully prevented disease and mortality in infected mice, highlighting a combinatorial effect between host-directed and antiviral therapies. These findings underscore the therapeutic potential of anti-inflammatory/pro-resolving strategies in severe dengue and support the development of CDX-Ac2-26 as a novel adjunctive treatment. Combining anti-inflammatory and antiviral approaches may enhance efficacy and reduce treatment-associated toxicity, offering a promising path for clinical translation.

Animal models illuminate dengue immunopathogenesis to guide vaccine and therapeutic developments.

Bridging the gap towards a novel antiviral therapeutic against dengue virus with major flavonoids from Scutellaria baicalensis.

First report of laboratory-confirmed Zika virus infection in human from South Karnataka, India: A case study.

Development of an ELISA using recombinant Dengue NS1 constructs to measure antibody titers and predict dengue disease outcome in a pediatric population in India.

Mitochondrial COI gene based population genetic structure and diversity of Aedes aegypti populations across diverse climatic regions of India.

Forecasting the incidence of dengue fever in Fujian province under varying climate change and demographic scenarios.

Clinical interpretation of dengue severity: Why time and sex are not enough

Introduction: Dengue fever is becoming a global health emergency, being the most widespread mosquito-borne viral disease, putting half the world population at risk of infection. Dengue virus (DENV), the causative agent of the disease, is classified into four serotypes (DENV-1 – DENV-4), each associated with fever and dengue shock syndrome. Currently, no antiviral drugs are approved for the disease; treatments are based on supportive care. This study follows a comprehensive structure-based virtual screening approach to screen a collection of approved antimalarial drugs for binding efficiency and inhibitory potential against DENV RNA-dependent RNA polymerase (DENV RdRp). Method: We retrieved thirty-one (31) approved antimalarial drugs from published literature. This was followed by downloading the three-dimensional structures (3D) of each drug from the PubChem website and the crystal structure of the protein (PDB ID: 2J7W) from the Protein Data Bank. We computed the root mean square deviation (RMSD) to validate the docking study. The molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) evaluation were performed using the Maestro Schrodinger software user interface. The Maestro’s molecular visualisation tool was utilised to perform a post-docking analysis for each of the top drug candidates Result: The computed RMSD for the redocked cocrystallized ligand was 2.0 Å. The docking scores for the top 5 drug candidates were Chloroquine (-4.109 kcal/mol), 3-hydroxyquinine (-4.01 kcal/mol), Tetracycline (-6.494 kcal/mol), Artesunate (-4.4 kcal/mol) and Chlorproguanil (-4.021 kcal/mol). The MMGBSA (dG bind) for the top five drug candidates were Chloroquine (-40.66 kcal/mol), 3-hydroxyquinine (-36.95 kcal/mol), Tetracycline (-36.69 kcal/mol), Artesunate (-35.17 kcal/mol), and Chlorproguanil (-34.18 kcal/mol). The post-docking analysis revealed considerable intermolecular interactions between the drug candidates and protein. Conclusion: Several clinically approved antimalarial agents, including chloroquine, 3-hydroxyquinine, tetracycline, and artesunate, demonstrated favourable binding affinities and stable interactions with catalytically essential residues of the enzyme (DENV RdRp). These interactions suggest potential inhibitory effects on viral replication consistent with previous in vitro and in vivo observations. Future studies should integrate molecular dynamics simulations, enzymatic inhibition assays, and animal model testing to confirm their antiviral efficacy and clarify the molecular basis of NS5 inhibition.

Dengue, a mosquito-borne illness caused by the Flavivirus and second only to COVID-19 in global impact, affects over 112 countries. With four distinct serotypes, current research emphasizes understanding genetic diversity and improving treatment and diagnostics. This study explores the relationship between stress hormones (cortisol and adrenaline) and DENV-1 sequence homology in dengue-positive patients. Among 165 subjects, hematological indices, NS1 antigen levels, and serotypes were analyzed. Hormone levels were quantified using ELISA, and viral load via RT-PCR. Amplicon sequencing and bioinformatics tools aided viral characterization. Statistical analyses included the Mann-Whitney U, Kruskal-Wallis, and Spearman's correlation tests for non-parametric comparisons. The results revealed that cortisol and adrenaline levels were lower in dengue-positive patients, while patients infected with serotype DENV-2 showed comparatively higher epinephrine levels. DENV-1 was the most prevalent strain, accounting for 80% of cases. Hematological markers, including hemoglobin and red blood cell counts, showed comparable ranges. Phylogenetic reconstruction of DENV-1 whole-genome sequencing indicated multiple introductions into Pakistan from different countries, rather than a single source. The DENV-1 strain was found to predominantly affect males in Karachi. Notably, comparisons across different DENV serotypes did not reveal statistically significant differences in stress hormone response, indicating only descriptive trends. Spearman's correlation analysis showed weak, non-significant associations between viral load and cortisol (r = 0.184, p = 0.170) and between viral load and epinephrine (r = 0.165, p = 0.224). Statistically significant but negative correlation was observed only between viral load and hemoglobin (r = -0.228, p = 0.005). These findings enhance our understanding of the complex interactions between dengue serotypes and their impact on infection progression, particularly in relation to stress hormones and viral load. However, as most associations were exploratory and not statistically significant. The descriptive trends identified here highlight the need for larger, longitudinal studies to better define the relationship between stress hormones, viral load, and dengue severity.

Data on infectious complications associated with biologic therapies in tropical settings are scarce. French Guiana, an Amazonian French overseas territory, combines an important burden of infectious diseases with a high use of biologic therapies. Our objective was to assess the incidence, spectrum, and risk factors for infections in patients treated with biotherapies for inflammatory and autoimmune diseases in French Guiana. We performed a multicentre retrospective study of adult patients receiving biotherapies between January 2021 and December 2023 in the French Guiana University Hospital (including its main site in Cayenne, its three local hospitals and 15 remote health centres). The primary outcome was the occurrence of any infectious event. Secondary outcomes included the severity of infection and identification of clinical and epidemiological risk factors. 146 patients (mean age 44.1 years, 61.6% female) were included. 48.0% of patients included had at least one infectious event. Most infections were mild (90.4%) and significantly associated with concomitant immunosuppressants (35.7%) or with remote health centres follow-up (11.4%). The tropical context revealed a distinct epidemiology, with five cases of dengue fever, two cases of scabies and one histoplasmosis. The majority (55%) of events occurred under first-generation biotherapies (notably rituximab and anti-TNF agents). The most frequent type of infection was cutaneous (27.2%), particularly in patients with a dermatological indication. Biotherapies appear generally well tolerated in this tropical setting, but patients living in remote areas or with concomitant immunosuppressant therapies remain vulnerable. Specific awareness should be dedicated to secondary cutaneous infections in patients treated for dermatological indications. Not applicable.

Introduction Aedes albopictus is the primary vector of major arboviral diseases such as dengue fever, chikungunya fever, and Zika virus disease, and its control is highly dependent on chemical insecticides. However, the long-term use of pyrethroid insecticides has led to the development of insecticide resistance in Ae. albopictus , which severely undermines the efficacy of vector control programs. Methods Ae. albopictus populations were collected from five sites in Guangdong and Hainan provinces, China. Beta-cypermethrin resistance levels were determined via bioassays, with resistance ratios at the median lethal concentration (RR 50 ) calculated. Target-site resistance was evaluated via kdr mutation detection in the voltage-gated sodium channel (VGSC) gene. Transcriptome sequencing identified differentially expressed genes (DEGs), and 16S rRNA sequencing characterized gut microbiome alterations. Correlation analysis and Cedecea neteri dietary supplementation assays verified the role of gut microbiota in resistance. Results The results showed that all four populations (except the CP population) exhibited varying degrees of resistance to beta-cypermethrin, with resistance ratios at the median lethal concentration (RR 50 ) ranging from 2.84 to 29.18. Detection of kdr mutations revealed three mutations (F1534C, F1534L, F1534S) at codon 1534 of the voltage-gated sodium channel (VGSC) gene in all field populations, with mutation frequencies ranging from 49.4% to 100.0%, and a low-frequency V1016G mutation at codon 1016. Transcriptome analysis identified a total of 2,566 commonly upregulated genes and 994 commonly downregulated genes across the resistant populations. Gut microbiome analysis revealed a significant alteration in the intestinal microbial community structure of resistant populations; specifically, the relative abundance of the genus Cedecea differed significantly between resistant and susceptible populations and correlated strongly with the expression of most differentially expressed genes. Furthermore, dietary supplementation with Cedecea neteri significantly increased the survival rate of Ae. albopictus exposed to β-cypermethrin (73.86% vs 40.00%; P < 0.0001). Discussion From the perspectives of target-site mutations, gene expression regulation, and gut microbe interactions, this study providing a foundation for further studies on resistance mechanisms in Ae. albopictus , thereby providing a theoretical foundation for further dissection of resistance mechanisms and optimization of vector control strategies.

Hematologic aberrations, such as thrombocytopenia and leukopenia, commonly occur in patients with dengue fever and occur in tandem with malignant hematologic disorders; therefore, these two diseases frequently overlap for differential diagnostic purposes in endemic areas. A case report is presented for a 35-year-old male patient who had been diagnosed with dengue fever based on the history of low-grade fever, myalgias, retro-orbital pain, and dysuria for the past ten days, as well as positive NS1 and IgM from outside laboratory analysis. Because the patient had persistent cytopenias that were beyond the expected duration of the course of dengue fever, he underwent further evaluation. A peripheral blood smear revealed more than 35% of the cells to be blasts with Sudan Black B positivity, and a bone marrow aspirate showed hypercellularity with greater than 60% of myeloblasts present. This allowed for confirmation of acute myeloid leukemia diagnosis. The patient was started on the standard “7+3” regimen of cytarabine and daunorubicin; however, he rapidly deteriorated and died within 7 days. Patients with dengue fever who develop persistent cytopenias should evaluate for the presence of hematologic malignancies.

Background: Thrombocytopenia, which raises the risk of bleeding and indicates the severity of the illness, frequently complicates acute febrile illness (AFI), a leading cause of paediatric admissions. Infections including dengue, malaria, typhoid, and scrub typhus frequently produce this dual presentation, although autoimmune diseases, hematological abnormalities, or drug-induced reasons can also cause it. Management is difficult because to overlapping symptoms and poor diagnostics, particularly in endemic areas. For the purpose of directing treatment and averting complications, early detection of thrombocytopenia in children with fever is essential. To enhance diagnostic techniques, treatment plans, and medical responses in high-burden environments, targeted study on clinical profiles and outcomes is required. Aim and Objectives: This study aims to evaluate the clinical profile and outcomes of children aged 1 month to 18 years admitted with acute febrile illness and thrombocytopenia at a tertiary care center in Puducherry. The objectives are to describe clinical presentations, identify infectious and non-infectious etiologies, and correlate the severity of thrombocytopenia with disease outcomes. Materials and Methods: In this cross-sectional study, 266 children with acute febrile illness and thrombocytopenia, ages 1 month to 18 years, were enrolled in the paediatrics department of a tertiary care hospital in Puducherry between June 2023 and June 2024. A thorough history, clinical examination, and pertinent tests (CBC, peripheral smear, renal/liver function tests, malaria RDT, dengue serology, scrub typhus IgM, Widal, blood cultures, chest X-ray, MRI for probable encephalitis) were carried out following informed consent and assent. Transfusions were administered for severe thrombocytopenia or bleeding, and platelet counts were tracked until they returned to normal. Malaria, dengue, scrub typhus, enteric fever, leukemia/ITP, septicemia, viral encephalitis, and undetected fever were among the diagnoses. Results and Discussion: The clinical profile and results of paediatric patients with acute fever and thrombocytopenia are highlighted in this study. The most common causes were scrub typhus and dengue fever, highlighting the significance of regional epidemiology in directing diagnosis. The majority of patients had minor thrombocytopenia, a good prognosis, a high rate of recovery, and little need for transfusions. Severe thrombocytopenia, however, was linked to extended hospital admissions and sporadic organ malfunction, highlighting the necessity of continuous observation and critical treatment in these situations. In endemic areas, serological tests—specifically, dengue IgM and scrub typhus IgM— proved useful in making diagnoses. The significance of a thorough organ function assessment was highlighted by anomalies in severe instances, even when liver and renal functions were generally conserved. Overall, from the results it is clear that it is difficult to treat paediatric febrile thrombocytopenia and emphasize the need for immediate therapies, systematic diagnostic techniques, and additional research into risk stratification models and new biomarkers to enhance outcomes.

Aedes aegypti, the main urban vector of dengue fever, poses a major public health problem in Nouakchott, Mauritania. This study analyzed the host-seeking and sugar-feeding behaviors of Ae. aegypti. Mosquitoes were collected using a vacuum cleaner in four districts between December 2023 and October 2024. Biting activity on humans was studied in May 2024, exclusively in the districts of Ksar, Tevragh Zeina and Arafat, between 5:00 a.m. and 9:00 p.m. A negative binomial model was performed to analyze the effect of location and time on the human biting rate (HBR) of mosquitoes. In Nouakchott, except in the Arafat district, Ae. aegypti bites occur mainly outdoors, between 8:00 a.m. and 1:00 p.m., with a peak between 11:00 a.m. and noon (HBR = 20 bites/person), and between 5:00 p.m. and 7:00 p.m., with a peak between 6:00 p.m. and 7:00 p.m. (HBR = 11 bites/person). Inside homes, Ae. aegypti biting activity remains low everywhere (HBR ≤ 1.5 bites/person/hour). Molecular analysis of the origin of the blood meals showed that the females collected in Nouakchott were exclusively anthropophilic. Molecular analysis of the sugar sources revealed a great diversity with sweet potato being among the most common. These results highlight the need for targeted outdoor interventions and larval control measures to reduce the risk of dengue transmission in Nouakchott.

Dengue virus infection is a global threat to public health due to its widespread morbidity and mortality. The incidence of dengue has grown dramatically around the world in recent decades. The aim of this study is to detect and characterize dengue fever virus infection among patients with febrile illness attending healthcare facilities in Ebonyi State, Nigeria. Those reporting with febrile conditions were recruited for the study excluding patients under two years of age. The study was carried out at the major primary health care centres and hospitals within Ebonyi State and the phlebotomy unit of each of the hospitals was used as the sample collection point. The study adopted a cross-sectional survey and a wellstructured questionnaire was used to obtain information from the patients. ELISA technique was used to presumptively detect the presence of dengue virus in the patient’s serum sample and then subsequently analysed molecularly using nested PCR technique to identify the different serotypes of the dengue virus. Other major febrile causing agents were also assessed to determine the level of co-infection with dengue virus. The other febrile agents assessed in this study are, Plasmodium falciparum, hepatitis C virus (HCV), hepatitis B virus (HBV) and enteric fever.

Early prediction of dengue shock syndrome (DSS) is crucial for effective patient triage and management. However, the lack of consensus regarding the precise definition of the laboratory warning sign (WS) -"an increase in hematocrit concurrent with a rapid decrease in platelet count"- has made it difficult to utilize this WS for predicting DSS. A matched case - control study was conducted among adult dengue patients (aged ≥16 years) hospitalized within the first four days of illness between November 2022 and August 2023, with each DSS case was matched with three non-DSS ones. There were 448 patients (112 DSS and 336 non-DSS) included in this study. An increase in hematocrit concurrent with a rapid decrease in platelet count was observed 1-2 days prior to the development of DSS. The cut-off value of an increase in hematocrit by ≥5% concurrent with a decrease in platelet count by ≥50% as compared with those of the previous day was found to be a predictor of DSS, with a sensitivity of 60.71% and a specificity of 83.04%. A DSS scoring system developed using these two cut-off values, along with the number of clinical WSs, can be used to predict the risk of DSS in adult patients. It achieved an area under the receiver operating characteristic curve (AUC) of 0.93 (95% CI: 0.90-0.96), sensitivity of 86.6%, and specificity of 87.8%. The Score enables triage of patients into low-, intermediate-, and high-risk groups for appropriate monitoring and management. The WS "an increase in hematocrit concurrent with a rapid decrease in platelet count" can be defined as "an increase in hematocrit ≥5% concurrent with a decrease in platelet count ≥50% compared to the previous day". The DSS score, developed from traditional WSs, serves as a good predictor of DSS in adult patients.

Clinical Spectrum and Predictors of Severe Dengue Among Hospitalized Children in a Tertiary Care Hospital in Bangladesh

Dengue secreted non-structural protein 1 (sNS1) contributes to the vascular permeability symptom of severe dengue hemorrhagic fever. Previous flavivirus sNS1 structures suggest that they predominantly exist as loose tetramers. Here, we report two stable tetramer structures (3.1-3.6 Å) together with loose tetramers. Formation of the stable tetramers involves a dramatic rearrangement of their N-terminal regions compared to the loose tetramers. We observe a higher molecular weight complex (HMWC) comprising dimeric sNS1 and heat shock proteins, which exhibits much lower endothelial hyperpermeability activity than the tetramer-enriched samples. We also determine high-resolution structures of the sNS1 complex with heparin, an analogue of the attachment factor heparan sulfate, showing that heparin binds to a conserved basic groove on the outer surface of the dimer, at the intra-dimer interface. Pre-incubation of sNS1 with heparin reduces its endothelial hyperpermeability activity. Our findings provide important structural information for future sNS1-based drug or vaccine design.