Dengue virus (DENV) poses a growing global public health threat due to increasingly frequent and severe outbreaks. Moreover, epidemiological surveillance systems have limitations in the timely detection of outbreaks, highlighting the need for complementary tools such as Wastewater-Based Epidemiology (WBE). This study aimed to generate further information on the persistence and recovery of DENV RNA in urban wastewater to support its monitoring through WBE. Two experiments were conducted. In Experiment 1, the persistence of DENV RNA in urban wastewater incubated at 4, 25, and 35°C for 21 days was evaluated. A negative binomial mixed-effects regression model estimated temperature-specific decay coefficients of -0.67 (95 % confidence interval (CI): -0.74--0.59), -1.25 (95 % CI: -1.32--1.17), and -1.31 (95 % CI: -1.37--1.23) at 4, 25, and 35°C, respectively. The corresponding times required for a 90 % reduction in genomic copies concentration were 30.1 (95 % CI: 20.7-48.1), 5.3 (95 % CI: 4.7-6.1), and 4.8 (95 % CI: 4.3-5.4) days. In Experiment 2, the performance of four recovery methods was compared. Ultrafiltration showed the highest recovery efficacy (61 ± 8 %), followed by direct analysis (42 ± 10 %) and polyethylene glycol precipitation (7 ± 4 %). Skimmed milk flocculation yielded results below the limit of detection. In conclusion, DENV RNA persisted in urban wastewater for several days at environmentally relevant temperatures, and ultrafiltration achieved the highest recovery efficacy among the methods evaluated, supporting the application of WBE as a community surveillance tool for DENV.

Positive-strand RNA viruses remodel host endoplasmic reticulum (ER) membranes into replication organelles (ROs) that support genome replication. Members of the genus Orthoflavivirus exploit host lipid pathways, particularly the phosphatidylinositol 4-kinase (PI4K)-phosphatidylinositol 4-phosphate (PI4P)-oxysterol-binding protein (OSBP) axis, yet they display marked mechanistic divergence. Specifically, it raised a central and unresolved question: is local PI4P enrichment an indispensable determining factor for viral vesicle biogenesis, or is it merely a contributing factor to a more fundamental, underlying mechanical requirement for high membrane curvature? Zika virus (ZIKV) shows strong dependence on PI4P enrichment. ZIKV nonstructural protein 1 (NS1) binds negatively charged lipids, including PI4P, via a positively charged membrane-binding surface that includes Arg31. This interaction supports NS1-mediated ER remodeling and subsequent OSBP-mediated cholesterol delivery. In contrast, dengue virus (DENV) and West Nile virus (WNV) largely bypass strict PI4P dependence. Their RO biogenesis relies more heavily on viral membrane proteins (NS4A/NS4B), host reticulon RTN3.1A, alternative lipid-shape remodeling (including phospholipase A2-generated lysophosphatidylcholine in WNV, sterol availability, and fatty-acid synthesis. Beyond the PI4P-OSBP axis, virus-specific exploitation of lipid peroxidation (ALOX12 pathway), cholesteryl-ester-enriched lipid droplets (via SOAT1/SOAT2), nuclear lipid droplets, and glycerophospholipid/ceramide remodeling further differentiates these viruses. These distinctions have direct implications for host-targeted antivirals. PI4K and OSBP inhibitors show preferential activity against ZIKV, whereas SOAT1/2 inhibition exhibits broader anti-orthoflaviviral potential, and other targets (FASN, NAAA, ALOX12) display virus-weighted efficacy. Recognition of this mechanistic spectrum is essential for accurate interpretation of lipid-perturbation studies and for the rational design of broad-spectrum or virus-selective antiviral strategies.

Acute supraglottic edema is an uncommon but potentially fatal cause of upper-airway obstruction. Although dengue infection is associated with diverse systemic manifestations, isolated upper-airway involvement is exceedingly rare and may pose a significant diagnostic challenge. We report an elderly woman who initially presented with features of acute stroke but was subsequently found to have life-threatening airway edema as a manifestation of acute dengue infection. Neuroimaging excluded acute cerebrovascular disease. Within six hours, she rapidly developed inspiratory stridor, hypoxemia, and hypercapnic respiratory failure requiring emergency endotracheal intubation. Flexible fiberoptic laryngoscopy demonstrated diffuse supraglottic and laryngopharyngeal edema, leading to compromised airway. Initial blood investigations revealed thrombocytopenia and a positive dengue NS1 antigen (sent in view of the ongoing dengue endemic), establishing the diagnosis of acute dengue infection. Conservative management comprising mechanical ventilation, corticosteroids, antibiotics, electrolyte correction, and serial fiberoptic airway assessment resulted in complete recovery without tracheostomy. This case highlights the evolving diversity of presenting clinical features associated with dengue infections. The pathophysiology of isolated airway edema in dengue is quite unknown and is beyond the scope of this article, but prompt pharmacological management, along with airway protection, reflects the reversible nature of this symptom and the likelihood of an underlying non-IgE-mediated hypersensitivity-related pathophysiological process. Early recognition of evolving airway compromise and prompt multidisciplinary intervention are essential for favorable outcomes.

In 2023 Burkina Faso faced hyperendemic Plasmodium falciparum malaria alongside the largest dengue epidemic recorded in West Africa. Both present as undifferentiated fever, and rapid diagnostic tests (RDTs) are the practical means of distinguishing them at the point of care. We formulate a 15-dimensional ordinary differential equation model coupling malaria and dengue transmission through two vector populations (Anopheles and Aedes), in which the two screening rates are control variables competing for a single pointwise-constrained diagnostic budget. We establish well-posedness, derive the basic and invasion reproduction numbers by the next-generation matrix method, and characterise the optimal controls via the Pontryagin Maximum Principle with the Karush-Kuhn-Tucker conditions, so that the allocation depends explicitly on the shadow price of the budget. A forward-backward sweep solves the boundary value problem, cross-validated against a sequential quadratic Hamiltonian scheme. Calibration to 104 weeks of Kadiogo Province surveillance attains coefficients of determination on the log(Y+1) scale of 0.82 (malaria) and 0.72 (dengue), with R0[m]=1.14 and R0[d]=1.57. The optimal dynamic allocation outperforms every heuristic tested, including two that are themselves time-varying: it reduces disease burden by 24.6% relative to standard malaria-first practice at the baseline budget and by over 32% at double the budget, and outperforms malaria-first in every one of 200 parameter draws under ± 30% uncertainty. The gain comes from the two epidemics peaking months apart, which in an epidemic year follows from malaria opening the season near its endemic level while dengue starts from a small seed.

Background Dengue has a high disease burden, and some affected children progress to severe dengue (SD), making early identification of deterioration a clinical priority. Automated platelet indices such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) are generated at no additional cost by routine hematology analyzers. However, they are usually interpreted as static measurements and cannot distinguish peripheral platelet destruction from impaired bone marrow production. Linear mixed modeling (LMM) is well suited to correlated repeated measurements but has rarely been applied to platelet-index kinetics in pediatric dengue, particularly to distinguish dengue with warning signs (DWS) from SD. The objective of this study was to compare the longitudinal trajectories of eight automated platelet indices across dengue severity groups in hospitalized children using LMM and to assess whether platelet-index trajectories provide additional information beyond platelet count alone. Methods This prospective observational cohort included 130 children with dengue: 14 with dengue fever (DF), 80 with DWS, and 36 with SD, enrolled at a tertiary referral center. Platelet count, PCT, MPV, PDW, mean platelet component (MPC), mean platelet mass (MPM), large platelet percentage, and the composite platelet index (CPLI) were measured on study days 1, 3, 5, and 7. Study day 1 was the enrolment/admission day, which occurred within five days of fever onset. Separate LMMs were fitted for each index with fixed effects of severity group, illness day, age, sex, and a severity × day interaction, and a patient-level random intercept. Results Five indices were associated with dengue severity. Platelet count (day × severity interaction, p < 0.001), PCT (p < 0.001), large platelet percentage (p = 0.035), and CPLI (p < 0.001) showed significant severity-dependent trajectories. MPC was significantly associated with severity overall (p = 0.004), with a borderline day × severity interaction (p = 0.066). MPC showed progressive decline in SD from 26.1 g/dL (day 1) to 24.4 g/dL (day 5), signalling sustained platelet activation while remaining stable in DF. By day 3, CPLI was the only index with non-overlapping 95% confidence intervals between SD (1.46-3.74) and DWS (3.78-5.27). Large platelet percentage increased from 1.63% to 2.29% in DWS between study days 1 and 3 (absolute increase, 0.66 percentage points), compared with an increase from 1.18% to 1.28% in SD (absolute increase, 0.10 percentage points). This pattern is consistent with preserved compensatory thrombopoiesis in DWS and impaired compensation in SD. An exploratory day-1 profile of low platelet count, low CPLI, and a low large platelet percentage was observed in SD. MPV, PDW, and MPM did not discriminate by severity. Conclusions Platelet count, PCT, large platelet percentage, and CPLI showed severity-associated longitudinal trajectories in hospitalized children with dengue. The SD pattern is consistent with concurrent platelet consumption and impaired compensatory thrombopoiesis. These findings require multicenter validation, analyzer standardization, and formal prognostic evaluation before clinical application.

Climate variability is reshaping infectious disease risk through ecological, environmental, social, and health-system pathways. However, its operational implications remain insufficiently defined in fragile and conflict-affected settings. Somalia is a critical case because recurrent droughts and floods intersect with displacement, food insecurity, weak water and sanitation infrastructure, disrupted immunisation, livestock dependence, and constrained health-system capacity. This narrative review synthesises evidence on climate-sensitive infectious disease risks in Somalia, examines existing surveillance and early warning systems, identifies policy and implementation gaps, and proposes priorities for a climate-informed surveillance-to-action model for infectious disease control. The review distinguishes directly climate-sensitive infections, including cholera, malaria, dengue, and Rift Valley fever, from indirectly climate-amplified vaccine-preventable diseases, including measles, diphtheria, and polio. While Somalia has important surveillance and early warning assets, including EWARN, IDSRS/DHIS2, FEWS NET, FSNAU intelligence, WASH monitoring, livestock signals, and community-based reporting, these streams remain insufficiently integrated into district-level risk assessment and pre-financed preparedness action. Therefore, the central challenge is not the absence of warning signals but the failure to convert them into timely, disease-specific, and accountable responses. We propose a surveillance-to-action framework based on multisource signal detection, integrated district risk assessment, disease-specific trigger decisions, early preparedness actions, and feedback, accountability, and learning. Closing Somalia's warning-to-action gap requires pre-agreed disease-specific triggers, One Health coordination, flexible anticipatory financing, strengthened district surveillance capacity, and equity-centred outreach to internally displaced persons, pastoralist and nomadic communities, zero-dose children, malnourished populations, and hard-to-reach areas. Climate-informed surveillance should be understood not merely as better data collection but as an anticipatory public health function designed to act before climate shocks become infectious disease emergencies.

Monkeypox virus (MPXV) has caused two Public Health Emergencies of International Concern since 2022, with co-circulation of distinct clades (Ia, Ib, IIa, IIb) that differ in virulence and transmission patterns. Rapid discrimination of these clades is critical for outbreak control and clinical management. Here, we developed and validated a two-tube multiplex real-time quantitative PCR (qPCR) assay targeting the H3L gene, designed to first distinguish clade I from clade II, followed by subtyping into clades Ia, Ib, IIa, and IIb in separate reactions. The assay demonstrated high sensitivity, with detection limits of 100 copies/reaction for clade Ia, 10 copies/reaction for clade Ib, 10 copies/reaction for clade IIa, and 1 copy/reaction for clade IIb using standard plasmids. Excellent specificity was confirmed by the absence of cross-reactivity with nucleic acids from other human pathogens, including vaccinia virus Tiantan strain (VTT), human adenovirus (HAdV), getah virus (GETV), chikungunya virus (CHIKV), Japanese encephalitis virus (JEV), dengue virus (DENV), influenza A virus (IAV), influenza B virus (IBV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The assay exhibited high repeatability, with intra-assay coefficients of variation (CVs) ranging from 0.09 to 1.88% and inter-assay CVs from 0.23 to 2.68%. Clinical evaluation using 48 skin samples from infected crab-eating monkeys or SCID mice showed 100% concordance with singleplex qPCR for clade IIb detection. For clades Ia, Ib, and IIa, clinical validation was not feasible due to sample unavailability, and their performance was analytically confirmed using recombinant plasmids. Importantly, the clade assignment of the 48 animal specimens was not confirmed by sequencing, which represents a limitation of the current study. Furthermore, these specimens were derived from animal models rather than human patients; thus, the results represent preclinical validation, and formal clinical validation in human specimens from endemic regions is warranted. This two-tube multiplex qPCR assay provides a rapid, sensitive, and reliable tool for the analytical discrimination of all four major MPXV clades, with preliminary clinical validation for clade IIb. Its ability to distinguish emerging clades makes it a valuable asset for clinical diagnosis, epidemiological surveillance, and future outbreak preparedness, although further clinical validation in endemic regions is required.

Dengue virus (DENV), a mosquito-borne pathogen belonging to the Flaviviridae family, continues to be a major global public health concern, causing millions of infections annually across tropical and subtropical regions. The virus encodes both structural and non-structural proteins that play critical roles in its replication, assembly, and immune evasion. Despite substantial research progress, there is still no specific antiviral drug available, and current treatment remains primarily supportive. This review highlights the significance of DENV structural proteins (C, prM/M, and E) and non-structural proteins (NS1-NS5) as potential molecular targets for antiviral interventions. Green-synthesized silver, gold, and iron oxide nanoparticles have demonstrated strong inhibitory activity against DENV by targeting key viral proteins such as the envelope (E), NS3 protease/helicase, and NS5 RNA-dependent RNA polymerase. These nanoparticles interfere with viral entry, replication, and protein synthesis while exhibiting high biocompatibility and minimal cytotoxicity. Collectively, the findings discussed in this review underscore the promise of eco-friendly nanotechnology as a sustainable and effective platform for developing next-generation antiviral therapies against dengue virus.

Arboviral infections, including West Nile virus (WNV), dengue virus (DENV), chikungunya virus (CHIKV), Zika virus (ZIKV), and, to a lesser extent, Oropouche virus (OROV), pose a heterogeneous and evolving challenge for pediatric health in Europe. The increasing presence of competent vectors and international travel has resulted in both imported infections and, for selected arboviruses, documented autochthonous transmission events. Although pediatric cases are often underrecognized, children may develop severe manifestations, including neuroinvasive disease and congenital infection. Available data on pediatric arboviral infections in Europe remain limited and fragmented, complicating accurate assessment of disease burden and clinical risk. This review summarizes current evidence on the epidemiology, clinical presentation, diagnostic challenges, and prevention of selected arboviral infections in children within the European context, highlighting persistent gaps in pediatric-specific data and implications for preparedness and public health.

The persistent global threat posed by emerging and re-emerging RNA viruses, including SARS-CoV-2, influenza A(H1N1)pdm09, DENV-2, and CHIKV, highlights the critical need for novel and broad-spectrum antiviral agents. Building upon the established antiviral activity of the quinoline scaffold, this study employed a molecular hybridization strategy to design and synthesize a novel series of 1,2,3-triazole-quinoline derivatives (compounds 4a-4h). This approach strategically fused the bioactive quinoline nucleus with the pharmaceutically favorable 1,2,3-triazole ring. The new compounds were synthesized efficiently in three steps with moderate-to-high yields, and their structures were subsequently determined. Their inhibitory capacities against the four viruses and cytotoxicity across relevant cell lines were evaluated in vitro. The initial screening demonstrated that compounds 4a-4h possessed broad-spectrum antiviral activity, showing high inhibition percentages at 10 µM against SARS-CoV-2, DENV-2, and CHIKV. Notably, compounds 4c and 4e, substituted with methoxy and ethyl groups, respectively, displayed exceptional potency and safety against SARS-CoV-2, yielding high selectivity indices (SI: 1896.5 and 1265.8, respectively). Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) and molecular docking calculations suggested favorable drug-likeness profiles, including improved lipophilicity and non-P-glycoprotein substrate feasibility. The findings validate the molecular hybridization strategy, establishing this new class of compounds as promising, multi-target antiviral prototypes for further preclinical exploration against prevalent viral pathogens.

Brazil is the most hyperendemic country for dengue, with historically dominant circulation of DENV-1 and DENV-2. Bayesian phylodynamic analyses of 489 Brazilian DENV-3 genomes, including 84 newly generated sequences, reveal a recent and sustained increase in the effective population size of DENV-3 associated with the recent introduction and expansion of the 3III_B.3.2 lineage. This increase coincides with a sharp rise in the proportion of laboratory-confirmed dengue cases attributed to DENV-3 among records with available serotype information from 2024 onwards and a shift in serotype dynamics in 2025, suggesting a change in serotype distribution and a potential risk of renewed DENV-3 outbreaks, particularly in populations with limited prior exposure to this serotype.

Background/Objectives: Severe bacterial sepsis and arboviral diseases may present with overlapping manifestations of vascular leakage, hemodynamic instability, thrombocytopenia, and organ dysfunction. We examined whether etiologically distinct severe infections may converge on selected components of immunovascular dysfunction and propose the Severe Infection-Mediated Vascular Activation and Collapse (SIMVAC) model as a hypothesis-generating framework. Methods: This narrative mechanistic review integrates human clinical and physiological studies, translational biomarker evidence, experimental models, and pathogen-specific mechanistic studies, with particular attention to the relative strength of evidence across arboviruses. Results: Dengue provides the strongest arboviral mechanistic support, linking plasma leakage with NS1-mediated endothelial barrier disruption, glycocalyx degradation, tissue-specific vascular effects, and inflammatory amplification. Evidence for yellow fever, West Nile virus, and Zika supports distinct organ-specific or systemic pathways but is less complete, whereas evidence for Mayaro, Oropouche, Venezuelan equine encephalitis, and Rocio viruses remains limited or hypothesis-generating. Candidate points of convergence include glycocalyx injury, Ang-2/Tie2 and S1P dysregulation, complement activation, NETosis, and vWF/ADAMTS13 imbalance. Conclusions: SIMVAC should be regarded as a testable conceptual model rather than a validated syndrome or diagnostic tool. Prospective, pathogen-confirmed studies are required to determine whether reproducible immunovascular signatures exist across severe infections and whether they provide clinically meaningful information beyond conventional etiological and severity assessment.

Neonatal dengue infection may mimic late-onset neonatal sepsis (LOS) in endemic regions, leading to misdiagnosis and unnecessary antibiotic exposure. We describe a case series of neonates admitted to a tertiary referral hospital in a dengue-endemic area with suspected LOS who underwent standard sepsis evaluation, including blood cultures, inflammatory markers, and clinical assessment, and were subsequently tested for dengue infection by anti-dengue virus IgM using ELFA methodology on the VIDAS® platform. All patients presented with fever and hematologic abnormalities, particularly thrombocytopenia and/or leukopenia, while blood and urine cultures remained negative and procalcitonin levels were low or normal. Dengue IgM was positive in all cases, supporting the diagnosis of neonatal dengue infection. After diagnostic confirmation, antibiotics were discontinued when applicable, and all neonates had favorable clinical outcomes without complications at discharge. These findings highlight dengue as a potentially underrecognized differential diagnosis of LOS in endemic settings and suggest that arboviral testing may be considered in the diagnostic evaluation of neonates with suspected sepsis, particularly when cultures are negative and inflammatory markers are not suggestive of bacterial infection. Early recognition may help reduce unnecessary antimicrobial exposure and could support antimicrobial stewardship efforts.

Arthropod-borne viruses such as Alphaviruses and Flaviviruses are the causative agents of severe human disease, highlighted by fatal encephalitis and neurological sequelae in survivors. The lack of FDA-approved vaccines and therapeutics that can prevent or treat these infections results in a significant global disease burden. An important unmet need to address this capability gap is the need for affordable, scalable, clinically relevant human-based neuronal models to study neuroinvasive viruses and evaluate therapeutic options. Here, we described the application of a human neuronal precursor cell model, LUHMES (Lund human mesencephalic) cells, that can be differentiated into dopaminergic midbrain neurons and used to study virus infections. In this study, we demonstrated the susceptibility of LUHMES cells to infection by three arthropod-borne neurotropic viruses: Venezuelan equine encephalitis virus, dengue virus serotype 2, and West Nile virus. We also demonstrated how the model may be applied to evaluate potential therapeutic options using an FDA-approved small molecule, Omaveloxolone. Finally, we analyzed host cell responses to infection and treatment using gene expression and phospho-signaling analyses. These findings highlight the value of this model to interpret the pathogenic mechanisms of neurotropic viral infections and evaluate potential therapeutic intervention strategies in a clinically relevant in vitro human neuronal model.