Kinetics of cardiovascular and inflammatory biomarkers in paediatric dengue shock syndrome.

Glycocalyx disruption and hyperinflammatory responses are implicated in the pathogenesis of dengue-associated vascular leak, however little is known about their association with clinical outcomes of patients with dengue shock syndrome (DSS). We investigated the association of vascular and inflammatory biomarkers with clinical outcomes and their correlations with clinical markers of vascular leakage. We performed a prospective cohort study in Viet Nam.

Dengue viremia kinetics and effects on platelet count and clinical outcomes: An analysis of 2340 patients from Vietnam.

Background: Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage.

Methods: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset.

Endothelial and inflammatory pathophysiology in dengue shock: New insights from a prospective cohort study in Vietnam.

Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid).

Genome evolution of dengue virus serotype 1 under selection by in mosquitoes.

The introgression of antiviral strains of into mosquito populations is a public health intervention for the control of dengue. Plausibly, dengue virus (DENV) could evolve to bypass the antiviral effects of and undermine this approach. Here, we established a serial-passage system to investigate the evolution of DENV in mosquitoes infected with the Mel strain of .

Hyperinflammatory Syndrome, Natural Killer Cell Function, and Genetic Polymorphisms in the Pathogenesis of Severe Dengue.

Background: Severe dengue, characterized by shock and organ dysfunction, is driven by an excessive host immune response. We investigated the role of hyperinflammation in dengue pathogenesis.

Methods: Patients recruited into an observational study were divided into 3 plasma leak severity grades.

Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes.

Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).

Methods: We performed a nested case-control study from a multi-country study.

Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

 Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death.  In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures.

Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti.

The insect bacterium Wolbachia pipientis is being introgressed into Aedes aegypti populations as an intervention against the transmission of medically important arboviruses. Here we compare Ae. aegypti mosquitoes infected with wMelCS or wAlbB to the widely used wMel Wolbachia strain on an Australian nuclear genetic background for their susceptibility to infection by dengue virus (DENV) genotypes spanning all four serotypes.

C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study.

Background: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers.

Using NS1 Flavivirus Protein Microarray to Infer Past Infecting Dengue Virus Serotype and Number of Past Dengue Virus Infections in Vietnamese Individuals.

Background: In recent years, researchers have had an increased focus on multiplex microarray assays, in which antibodies are measured against multiple related antigens, for use in seroepidemiological studies to infer past transmission.

Methods: We assess the performance of a flavivirus microarray assay for determining past dengue virus (DENV) infection history in a dengue-endemic setting, Vietnam. We tested the microarray on samples from 1 and 6 months postinfection from DENV-infected patients (infecting serotype was determined using reverse-transcription polymerase chain reaction during acute, past primary, and secondary infection assessed using plaque reduction neutralization tests 6 months postinfection).

Skin dendritic cell and T cell activation associated with dengue shock syndrome.

The pathogenesis of severe dengue remains unclear, particularly the mechanisms underlying the plasma leakage that results in hypovolaemic shock in a small proportion of individuals. Maximal leakage occurs several days after peak viraemia implicating immunological pathways. Skin is a highly vascular organ and also an important site of immune reactions with a high density of dendritic cells (DCs), macrophages and T cells.

Association of Microvascular Function and Endothelial Biomarkers With Clinical Outcome in Dengue: An Observational Study.

Background: The hallmark of severe dengue is increased microvascular permeability, but alterations in the microcirculation and their evolution over the course of dengue are unknown.

Methods: We conducted a prospective observational study to evaluate the sublingual microcirculation using side-stream dark-field imaging in patients presenting early (<72 hours after fever onset) and patients hospitalized with warning signs or severe dengue in Vietnam. Clinical findings, microvascular function, global hemodynamics assessed with echocardiography, and serological markers of endothelial activation were determined at 4 time points.

Households as foci for dengue transmission in highly urban Vietnam.

Background: Dengue control programs commonly employ reactive insecticide spraying around houses of reported cases, with the assumption that most dengue virus (DENV) transmission occurs in the home. Focal household transmission has been demonstrated in rural settings, but it is unclear whether this holds true in dense and mobile urban populations. We conducted a prospective study of dengue clustering around households in highly urban Ho Chi Minh City, Vietnam.

Assessment of microalbuminuria for early diagnosis and risk prediction in dengue infections.

Background: Dengue is the most important arboviral infection of humans. Following an initial febrile period, a small proportion of infected patients develop a vasculopathy, with children at particular risk for severe vascular leakage and shock. Differentiation between dengue and other common childhood illnesses is difficult during the early febrile phase, and risk prediction for development of shock is poor.

Timing of CD8+ T cell responses in relation to commencement of capillary leakage in children with dengue.

Immune activation is a feature of dengue hemorrhagic fever (DHF) and CD8+ T cell responses in particular have been suggested as having a role in the vasculopathy that characterizes this disease. By phenotyping CD8+ T cells (CD38+/HLA-DR+, CD38+/Ki-67+, or HLA-DR+/Ki-67+) in serial blood samples from children with dengue, we found no evidence of increased CD8+ T cell activation prior to the commencement of resolution of viremia or hemoconcentration. Investigations with MHC class I tetramers to detect NS3(133-142)-specific CD8+ T cells in two independent cohorts of children suggested the commencement of hemoconcentration and thrombocytopenia in DHF patients generally begins before the appearance of measurable frequencies of NS3(133-142)-specific CD8+ T cells.