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| ID | Type | Description | Link |
|---|---|---|---|
| Approval number | Other Identifier | National Ethics Committee for Health Research Cambodia |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. | ||
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of low density neutrophils in mild/moderate vs severe dengue | Low density neutrophils will be isolated from the PBMC layer of centrifuged blood and characterized via flow cytometry. The percentages of low density neutrophils will be compared between dengue groups. | From enrollment to study day 3 |
| Mean florescence intensity of neutrophils expressing spleen tyrosine kinase | The mean florescence intensity (MFI) of neutrophils expressing spleen tyrosine kinase will be measured via flow cytometry and compared between mild/moderate vs severe dengue. | From enrollment to study day 3. |
| Serum level of myeloperoxidase in mild/moderate versus severe dengue. | The serum level of myeloperoxidase will be measured in pg/mL and compared between participants with mild/moderate versus severe dengue. | Enrollment to study day 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of low density neutrophils in dengue versus sepsis | Low density neutrophils will be isolated from the PBMC layer of centrifuged blood and characterized via flow cytometry. The percentage of low density neutrophils will be compared in dengue versus sepsis. | From enrollment to study day 3 |
| Mean florescence intensity of neutrophils expressing spleen tyrosine kinase in dengue versus sepsis |
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Inclusion Criteria:
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
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.
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:
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Patients will be enrolled from Kampong Speu District Referral Hospital (Kampong Speu), Preah Kossamak Hospital (Phnom Penh), and the International Center of Excellence in Research Cambodia.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chanthap Lon, MD | Contact | +855 12976 799 | lonc@icercambodia.org | |
| Camila D Odio, MD | Contact | camila.odio@nih.gov |
| Name | Affiliation | Role |
|---|---|---|
| Tineke Cantaert, PhD | Institut Pasteur du Cambodge | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kampong Speu District Referral Hospital | Recruiting | Kampong Speu | Cambodia |
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| ID | Term |
|---|---|
| D003715 | Dengue |
| D018805 | Sepsis |
| D007239 | Infections |
| ID | Term |
|---|---|
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| D001102 | Arbovirus Infections |
| D014777 | Virus Diseases |
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Mean florescence intensity (MFI) of neutrophils expressing spleen tyrosine kinase will be measured via flow cytometry and compared between those with dengue versus sepsis. Other markers of neutrophil maturation, activation, and degranulation will be measured by flow cytometry and compared among dengue groups and between dengue and sepsis. |
| From enrollment to study day 3. |
| Serum level of myeloperoxidase in dengue versus sepsis | Serum level of myeloperoxidase will be measured in pg/mL and compared between participants with dengue versus sepsis. Other biomarkers of neutrophil activation such as calprotectin, resistin, and lactoferrin will be measured and compared among groups. | Enrollment to study day 3 |
| Serum levels of interferon-gamma and interleukin-10 (pg/mL) | Serum levels of interferon-gamma and interleukin-10 (pg/mL) will be measured and compared between dengue groups and sepsis overtime. Other cytokines may also be measured and compared among groups. | Enrollment through day 3. |
| Percentage of DENV-specific activated T cells | Activation induced marker assays will be used to compare dengue virus (DENV)-specific T cell activation over time in mild/moderate versus severe dengue. | Enrollment through day 21. |
| DENV1-4 geometric mean titer (GMT) | DENV1-4 GMT overtime will be compared between mild/moderate and severe dengue groups. These will also be correlated with disease outcome and GMT at convalescence. | Enrollment to day 21 |
| Peak dengue virus enhancing titer | Peak dengue virus enhancing titer overtime will be compared between mild/moderate and severe dengue groups. These will also be correlated with disease outcome and GMT at convalescence. | Enrollment to day 21 |
| Mean fluorescence intensity of specific lymphocyte populations among groups | Mean fluorescence intensity of specific lymphocyte populations will be compared mild/moderate versus severe dengue and dengue versus sepsis. | Enrollment to day 3 |
| Number of differentially expressed genes among groups | The number of differentially expressed genes will be compared between mild/moderate and severe dengue and dengue versus sepsis based on thresholds for statistical significance (e.g., adjusted p-value < 0.05) and magnitude of change (e.g., absolute log2 fold change > 1). | Enrollment to day 3 |
| International Center of Excellence in Research Cambodia | Recruiting | Phnom Penh | Cambodia |
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| Preah Kossamak Hospital | Recruiting | Phnom Penh | Cambodia |
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| D018177 | Flavivirus Infections |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006482 | Hemorrhagic Fevers, Viral |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |