Immune Responses to Dengue and Sepsis

Official title

Evaluating Immune Responses to Dengue and Sepsis in Hospitalized Patients in Cambodia

Overview

The goal of this research study is to help the investigators better understand serious dengue disease. The investigators will collect clinical information and up to four blood samples from participants with dengue, sepsis, or healthy people. The investigators will perform multiple analyses on the blood samples and compare results between dengue patients and those with sepsis and healthy people.

Detailed description

This is an observational study enrolling n=200 hospitalized individuals with dengue-like illness, n=30 individuals with sepsis, and n=10 healthy controls to evaluate immune responses in plasma leak syndromes. Sepsis and dengue patients will have blood collected at enrollment, day 1, and day 3, and dengue patients will have an additional blood draw at day 21. Healthy participants will have a single blood draw at enrollment. The blood collected will enable the evaluation of immune kinetics, including changes in neutrophils, cytokines, and adaptive responses, as dengue progresses or improves. Overall, this study will facilitate the evaluation of an understudied cell type and will provide unique data for understanding the temporal changes in the immune response to dengue virus. A better understanding of dengue pathophysiology will help identify potential therapeutic targets to improve outcomes in this disease.

Primary outcome measures

• Percentage of low density neutrophils in mild/moderate vs severe dengue [Time frame: From enrollment to study day 3]
• Mean florescence intensity of neutrophils expressing spleen tyrosine kinase [Time frame: From enrollment to study day 3.]
• Serum level of myeloperoxidase in mild/moderate versus severe dengue. [Time frame: Enrollment to study day 3]

Secondary outcome measures (9)

• Percentage of low density neutrophils in dengue versus sepsis [Time frame: From enrollment to study day 3]
• Mean florescence intensity of neutrophils expressing spleen tyrosine kinase in dengue versus sepsis [Time frame: From enrollment to study day 3.]
• Serum level of myeloperoxidase in dengue versus sepsis [Time frame: Enrollment to study day 3]
• Serum levels of interferon-gamma and interleukin-10 (pg/mL) [Time frame: Enrollment through day 3.]
• Percentage of DENV-specific activated T cells [Time frame: Enrollment through day 21.]
• DENV1-4 geometric mean titer (GMT) [Time frame: Enrollment to day 21]
• Peak dengue virus enhancing titer [Time frame: Enrollment to day 21]
• Mean fluorescence intensity of specific lymphocyte populations among groups [Time frame: Enrollment to day 3]
• Number of differentially expressed genes among groups [Time frame: Enrollment to day 3]

Eligibility criteria

Inclusion criteria

• Patients with dengue-like illness:

Patients presenting with dengue-like symptoms for a duration of maximum 72h before inclusion. Dengue-like symptoms include: presentation with oral temperature >38°C AND at least two of the following symptoms suggestive of dengue-like illness: headache, retro-orbital pain, myalgia, joint pain, rash, any bleeding symptoms, nausea or vomiting, lethargy or restlessness , abdominal pain, liver enlargement

• Sepsis patients:

Patients admitted for less than 48 hours with a primary diagnosis of sepsis as per treating team AND have blood cultures ordered AND on empiric antibiotics due to concern for bacterial infection.

• Healthy controls:

Participants with no chronic illness, no regular medications, no febrile illness in 28 days, no diagnosis of or treatment for dengue or bacterial infection in the past 6 months.

Exclusion criteria

• For biobanking purposes, children less than 2 years of age, and individuals who are pregnant, pregnant within the last 90 days, and/or breastfeeding are excluded due to restrictions on the blood volumes and the repeated sampling times.
• Individuals that do not provide informed consent will not be included for the study.
• Severe/chronic/recurrent pathological conditions: clinically significant autoimmune disease or immunodeficiency (including history of organ transplant), haematologic disorders, cardiac diseases, diabetes, cancer, HIV, chronic hepatic or renal insufficiency.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to the inclusion. For corticosteroids, this will mean a dose equivalent to 20 mg/day of prednisone or equivalent for > 2 weeks (inhaled and topical steroids allowed)
• Chronic administration of NSAIDs, including aspirin: prolonged intake (>2 weeks) within 6 months before study or any intake within the 7 days preceding sampling \[exception for low dose aspirin: maximum 250mg/daily\]
• Any underlying, chronic, or current condition that, in the opinion of the investigator, may interfere with their participation in the study.
• Expected death in the next 48-hours

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Cambodia · 3 centers

• Kampong Speu District Referral Hospital — Kampong Speu
• International Center of Excellence in Research Cambodia — Phnom Penh
• Preah Kossamak Hospital — Phnom Penh

Identifiers

NCT: NCT07040202 · 092 NECHR · Approval number

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗