Gut Leakage' in Dengue (GLiD)
Gut Leakage and Sonographic Abdominal Changes in Hospitalized Dengue Patients: an Observational Study
Dengue infections are imposing an increasing global burden of disease, particularly in tropical countries such as Bangladesh. The World Health Organization (WHO) has identified Dengue virus as a priority pathogen for the development of medical counter measures because of the high risk of it causing a Public Health Emergency of Intenational Concern (PHEIC). Warning signs for severe dengue, associated with mortality, include gastrointestinal features including abdominal pain, vomiting, and diarrhoea. Multiple alterations may occur in in the gastrointestinal tract that could lead to damaging of the gastrointestinal wall and gut leakage, the translocation of gut metabolites into the bloodstream. Study team hypothesize that gut leakage initiates inflammatory processes underlying the further development of severe dengue, including features associated with plasma leakage.
This study aims to investigate intestinal barrier dysfunction (gut leakage) in dengue infection by detecting the translocation of gut-derived bacteria and their products (Lipopolysaccharides, LPS binding protein, sCD14, I-Fatty Acid Binding Protein) into the bloodstream. Study team will recruit hospitalized adult dengue patients (18 years and older) presenting with warning signs or severe disease in a tertiary care public hospital at Chattogram, Bangladesh. Circulating biomarkers indicative of gut permeability and microbial translocation will be measured to assess their presence and association with disease severity.
Abdominal ultrasonography will be performed to characterize gastrointestinal alterations and determine their correlation with biochemical markers of gut leakage and clinical severity. In addition, study team will analyze the gut bacteriome from stool/ rectal swab of these patients to explore whether dengue infection induces compositional changes in intestinal microbiota and whether such alterations are linked to gut leakage or disease progression.
Descripción general del estudio
Estado
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Ubicaciones de estudio
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Chattogram Division
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Chittagong, Chattogram Division, Bangladesh, 4203
- Reclutamiento
- Department of Medicine, Chittagong Medical College
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Contacto:
- Rabiul Alam Md Erfan Uddin, FCPS
- Número de teléfono: +8801711129798
- Correo electrónico: rubelerfan@gmail.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Adult (≥18 years) male and non-pregnant female patients with confirmed dengue (positive NS1 antigen and/or IgM) admitted to the Department of Medicine, Chittagong Medical College Hospital will be recruited. Blood biomarkers will be collected at enrollment for all patients. Those initially classified as non-severe dengue will have no repeat sampling unless they progress to severe disease, in which case a second sample will be obtained within 24 hours. Serum ALT and blood culture will be performed on day 7 of illness. Stool samples will be collected on day 7 from 100 patients for gut microbiota analysis.
Additionally, 10 healthy adult participants (5 male, 5 female) will be recruited from patient attendants. They will undergo a single visit for baseline biomarker sampling and POCUS, serving as healthy controls for comparison.
Descripción
Inclusion Criteria:
Dengue participants
- Participant/ legally authorised representative willing and able to give informed consent for participation in the study.
- Male or Female, adults ≥18 years
- Diagnosed as a case of Dengue on the basis of clinical features and positive NS1 antigen and/or IgM dengue antibody
- Hospitalized in medicine or dengue ward in Chittagong Medical College Hospital.
- Enrolled within 24 hours of hospitalization.
Healthy participants
- Participant/ legally authorised representative willing and able to give informed consent for participation in the study.
- Male or Female, adults ≥18 years
- Clinically healthy with no acute or chronic illness
- Attendant of a dengue patient (not a patient)
Exclusion Criteria:
Dengue participants
- Unable to provide consent or participate in follow-up procedures
- Known chronic gastrointestinal (GI) disease affecting intestinal permeability (IBD, celiac disease), chronic liver disease, active chronic diarrhoea, short bowel loop syndrome, recent (<3 months) major GI surgery.
- Immunosuppression (for example chemotherapy, high-dose steroids), advanced chronic kidney disease, decompensated heart failure.
- Drugs that can alter the level of biomarkers in blood like metformin, statin, probiotics, steroid within last 48 hours of hospitalization.
- Pregnancy
Healthy participants
- Unable to provide consent
- Known chronic gastrointestinal (GI) disease affecting intestinal permeability (IBD, celiac disease), chronic liver disease, active chronic diarrhoea, short bowel loop syndrome, recent (<3 months) major GI surgery.
- Immunosuppression (for example chemotherapy, high-dose steroids), advanced chronic kidney disease, decompensated heart failure.
- Drugs that can alter the level of biomarkers in blood like metformin, statin, probiotics, steroid within last 48 hours of hospitalization.
- Pregnancy
- History of current or recent dengue or other arbo viral infection
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Severe dengue
All enrolled dengue patients will have blood biomarkers at enrolment whether they present with non-severe or severe dengue.
If participant enrolled as non-severe and do not progress to severe dengue, they will be no second test for biomarkers but if they developed clinical feature of severity, a second biomarker sample will be collected within 24 hours of developing clinical severity.
S ALT and Blood culture will be performed on day 7 of illness for all dengue patients.
Stool will be collected on day 7 of illness from 100 patients for testing gut microbiota.
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Non-severe dengue
All enrolled dengue patients will have blood biomarkers at enrolment whether they present with non-severe or severe dengue.
If participant enrolled as non-severe and do not progress to severe dengue, they will be no second test for biomarkers but if they developed clinical feature of severity, a second biomarker sample will be collected within 24 hours of developing clinical severity.
S ALT and Blood culture will be performed on day 7 of illness for all dengue patients.
Stool will be collected on day 7 of illness from 100 patients for testing gut microbiota.
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Healthy individual
These participants will undergo only one study visit for baseline biomarker sampling, baseline POCUS and will not undergo follow-up.
Their results will serve as healthy control reference values for comparison with biomarker findings in dengue patients.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
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Level of gut leakage marker in blood and gastrointestinal findings in POCUS
Periodo de tiempo: On enrollment, day of development of severity if non severe at enrolment, up to 28 days
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On enrollment, day of development of severity if non severe at enrolment, up to 28 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Document clinical events occurred in dengue patients
Periodo de tiempo: Through study completion, an average of 28 days
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Demographic: Age, gender, BMI Clinical: respiratory rate, blood pressure, heart rate, ascites, pleural effusion, any major bleeding, GCS |
Through study completion, an average of 28 days
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Document clinical events occurred in dengue patients
Periodo de tiempo: Day of enrolment/ 4th or day 7 of illness
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For mSOFA: SpO2, FiO2 |
Day of enrolment/ 4th or day 7 of illness
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Otras medidas de resultado
Medida de resultado |
Periodo de tiempo |
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Level of I-FABP Level of LPS, Level of LBP, Level of sCD14, Positive Blood culture
Periodo de tiempo: On enrollment in all cases, if clinical severity occur in initial non-severe group, 24 hours within developing severity
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On enrollment in all cases, if clinical severity occur in initial non-severe group, 24 hours within developing severity
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Alteration of gut microbiota
Periodo de tiempo: Day seven of illness
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Day seven of illness
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Organ failure
Periodo de tiempo: Through study completion, an average of 28 day
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Through study completion, an average of 28 day
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Development of shock
Periodo de tiempo: Through study completion, an average of 28 day
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Through study completion, an average of 28 day
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Detectable fluid collection in abdomen, loss of haustration, loss of normal multi-layered appearance
Periodo de tiempo: Baseline (within 24 hours of enrollment) and at the time of first development of clinical severity, assessed from enrollment until clinical severity occurs, hospital discharge, death, or up to 7 days of hospitalization, whichever occurs first.
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Baseline (within 24 hours of enrollment) and at the time of first development of clinical severity, assessed from enrollment until clinical severity occurs, hospital discharge, death, or up to 7 days of hospitalization, whichever occurs first.
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Measurement of gall bladder wall thickness, intestinal wall thickness
Periodo de tiempo: Baseline (within 24 hours of enrollment) and at the time of first development of clinical severity, assessed from enrollment until clinical severity occurs, hospital discharge, death, or up to 7 days of hospitalization, whichever occurs first.
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Baseline (within 24 hours of enrollment) and at the time of first development of clinical severity, assessed from enrollment until clinical severity occurs, hospital discharge, death, or up to 7 days of hospitalization, whichever occurs first.
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades transmitidas por vectores
- Enfermedades transmitidas por mosquitos
- Procesos Patológicos
- Infecciones
- Infecciones por virus de ARN
- Enfermedades virales
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Infecciones por arbovirus
- Infecciones por Flavivirus
- Infecciones por Flaviviridae
- Fiebres Hemorrágicas Virales
- Condiciones Patológicas, Signos y Síntomas
- Dengue
- Enfermedades intestinales
- Ascitis
- Dengue grave
Otros números de identificación del estudio
- VIR26001
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
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