Advancing Pandemic Preparedness: Innovative Multidisciplinary Strategies for COMBATing Severe Dengue
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,400
- 试验地点
- 2
- 主要终点
- DISCOVER predictive biomarkers and AI tool for Dengue Severity
研究概览
简要总结
The goal of this observational study is to identify biomarkers and host factors associated with dengue severity in patients from dengue-endemic regions. The main question it aims to answer is:
Can multi-omics approaches predict disease severity and identify key factors contributing to severe dengue infections?
Participants will include individuals with dengue infection, and the study will analyze their blood samples using multi-omics techniques to uncover host immune responses, disease pathogenesis, and cellular pathway interactions. The study will also assess the role of primary and secondary infections, virus serotypes, and immunological factors in disease progression. Findings aim to support disease management, improve severity prediction, and identify potential therapeutic targets to prevent severe outcomes.
详细描述
Background: Many ongoing dengue clinical trials aim to evaluate both therapeutic compounds and potential vaccine candidates. The therapeutic compounds aim to target various stages of dengue virus replication, such as viral entry, by inhibiting virus fusion, NS5 polymerase inhibitor, and NS1 antigenemia reduction, to mention a few. However, an omics-based approach to identifying the metabolic pathways that dengue utilizes to subvert the host system to derive energy from and subsequently deploy viral immune evasion strategies has yet to be established. This study will focus on exploring and understanding the pathways that the dengue virus exploits and investigate if blocking the identified pathway can cause the virus to 'starve.'
- The study will offer insight into the diverse system-level range of dengue infection markers and the dysregulated molecules involved in cellular and metabolic pathways during dengue infection.
- The identification of novel pathways affected by molecule dysregulation will unveil the association of the biomarkers with immune response and disease severity, thereby helping to improve patient triage and treatment.
- The identified biomarkers will be significant in monitoring patients, creating a platform for early intervention to mitigate severe dengue through novel therapeutic targets and management strategies.
The primary objectives of the proposed study are:
- Case-wise viral serotyping and investigation of host cytokine profile.
- System-wide blood-transcriptomics and proteomics during dengue infection and its relationship with disease severity.
- Identification of pathways influencing severity by in vitro mechanistic studies.
Study Cohorts:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group 1: Dengue without warning signs Patients presenting with the following symptoms confirmed positive for dengue infection by lab diagnosis by anti-dengue IgM or NS1 ELISA will be recruited for the study under this cohort.
- •Symptoms will be fever along with at least two of the following -
- •Myalgia, arthralgia
- •Nausea and/or vomiting
- •Leukopenia Group 2: DENV with warning signs This cohort will include patients with the above symptoms and any of the following clinical signs.
- •Abdominal pain with tenderness
- •Persistent vomiting
- •Fluid accumulation
- •Mucosal bleeding
- •Restlessness, lethargy
- •Liver enlargement >2cm
- •Laboratory findings: An increase in hematocrit levels and a rapid decrease in platelet count Group 3: Severe dengue
- •Severe plasma leakage leads to hypovolemic shock (dengue shock syndrome) and fluid accumulation with respiratory distress.
- •Severe bleeding, such as epistaxis, internal bleeding, etc., is evaluated by a clinician.
- •Severe organ involvement with any of the following symptoms
- •Liver AST or ALT ≥ 1000
- •CNS: impaired consciousness
- •Heart and other organs failure
排除标准
- 未提供
结局指标
主要结局
DISCOVER predictive biomarkers and AI tool for Dengue Severity
时间窗: From enrollment to the end of hospitalisation at 2 weeks
This project aims to identify prognostic plasma protein biomarkers for disease severity in dengue virus (DENV) using data from a clinical cohort in an endemic region experiencing a surge in DENV morbidity and mortality. It involves developing a novel consensus association-based gene/protein cooperation network to uncover key host factors driving severe disease. Additionally, the project seeks to create AI-driven prognostic tools for predicting DENV severity by integrating patient demographic and clinical data with gene and protein biomarkers, DENV serotyping, and climate information.
次要结局
未报告次要终点
研究者
Ujjwal Neogi
Senior Lecturer
Karolinska Institutet