Immune Responses to Dengue and Sepsis

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.

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