Innovative Multidisciplinary Strategies for Combating Severe Dengue

NCT06751836 | Recruiting DMC

• 2 other identifiers: COMBAT (2024-05758-01)101191315
• Study Type: observational
• Target: 1,400
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

DENV Without Warning Signs; DENV with Warning Signs; Severe Dengue; Healthy Controls Group - Age and Sex-matched

Keywords

Severe Dengue; Multi-omics; Predictive biomarker

Outcome Measures

Primary Outcomes (1)

• DISCOVER predictive biomarkers and AI tool for Dengue Severity

  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.

  From enrollment to the end of hospitalisation at 2 weeks

Study Arms (4)

Dengue without warning signs (DwoWS)

Laboratory confirmed Dengue without plasma leakage

Other: Infection and no infection

Dengue with warning signs (DWS)

Laboratory confirmed Dengue without plasma leakage plus abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing haematocrit with decreasing platelets

Other: Infection and no infection

Severe Dengue (SD)

Dengue with severe plasma leakage, severe bleeding, or organ failure

Other: Infection and no infection

Healthy Control

Healthy participants who have tested negative for dengue infection

Interventions

Infection and no infection OTHER

No intervention apart from the dengue infection

Dengue with warning signs (DWS); Dengue without warning signs (DwoWS); Severe Dengue (SD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

* Patients who are pregnant, immunocompromised, or undergoing chemotherapy, on steroids or immunosuppressive drugs in the last year, liver cirrhosis, or coinfection with a non-dengue pathogen. * Cases with a lab-confirmed dengue infection within the past three months will excluded from the case cohort.

You may qualify if:

• 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
• Rashes
• 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.

Sponsors & Collaborators

• Karolinska Institutet: lead
• BIO BOX GUATEMALA ONG DE INVESTIGACIÓN, SERVICIOS Y DE MEDIO AMBIENTE: collaborator
• DEVKI DEVI FOUNDATION SOCIETY, India: collaborator
• MANIPAL ACADEMY OF HIGHER EDUCATION, India: collaborator
• Artemis Medicare Services Ltd., India: collaborator

Study Sites (2)

Bio Box Guatemala Ong de Investigación, Servicios Y de Medio Ambiente

Guatemala City, Guatemala

RECRUITING

Manipal Academy of Higher Education (MAHE)

Mangalore, Karnataka, 576104, India

RECRUITING

Related Publications (1)

• Bhatt P, Varma M, Sood V, Ambikan A, Jayaram A, Babu N, Gupta S, Mukhopadhyay C, Neogi U. Temporal cytokine storm dynamics in dengue infection predicts severity. Virus Res. 2024 Mar;341:199306. doi: 10.1016/j.virusres.2023.199306. Epub 2024 Jan 6.

  PMID: 38176525 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma.

MeSH Terms

Conditions

Severe Dengue

Condition Hierarchy (Ancestors)

Dengue; Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Central Study Contacts

Ujjwal Neogi, PhD

CONTACT

+46 8524 83680; ujjwal.neogi@ki.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: December 30, 2024
• Study Start: January 3, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): October 31, 2029
• Last Updated: February 10, 2025

Record last verified: 2024-12

Locations

IN (1); GU (1)