Molecular and Cellular Basis of Severe Forms of Dengue in Sickle Cell Patients
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age6-25
SponsorCentre Hospitalier Universitaire de la Guadeloupe
About this trial
Dengue virus (DENV) belongs to the genus of Flavivirus transmitted by the mosquito Aedes aegypti and is responsible for an infectious disease associated with different forms and severities such as dengue hemorrhagic fever or shock syndrome. Several recent reports have shown that sickle cell patients exhibited an increased risk of developing severe forms of dengue episodes compared to non-sickle cell subjects. Furthermore, among major sickle cell syndromes, these studies suggest that SC patients are at the highest risk of death during these infectious episodes although this sickle cell syndrome is generally associated with a more moderate expression of sickle cell disease. However, the mechanisms involved remain unknown to date.
The aim of the present study is to identify the molecular and cellular basis of this increased severity of dengue in SC patients. We hypothesize an exacerbation during DENV infection of the inflammatory response in SC patients compared to SS patients.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
patients with SS or SC SCD or controls with hemoglobin AA
diagnosis of SCD performed by electrophoresis or HPLC in a reference laboratory for hemoglobinopathies
patients older than 6 years and younger than 25 at inclusion
clinically in a steady state at inclusion (without complication during the last month and without transfusion in the three last months)
Disqualifiers
patients with SS or SC SCD or controls with hemoglobin AA
diagnosis of SCD performed by electrophoresis or HPLC in a reference laboratory for hemoglobinopathies
patients older than 6 years and younger than 25 at inclusion
clinically in a steady state at inclusion (without complication during the last month and without transfusion in the three last months)
Trial population
patients from 6 to 25 years, with sicke cell disease in a steady state at inclusion
Trial design
Design model
Other
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
130 Participants
are grouped into 3 trial groupsGroup A: Patients SS Group
Group B: Patients SC
Group C: Control group AA
Trial outcomes
Primary outcomes
1
Lymphocyte subpopulations measured by flow cytometry at steady-state
Comparison of circulating lymphocyte subpopulations in terms of activation and expression of markers of inflammation (cytokines, microparticles) and neutrophil proteome of SS and SC sickle cell patients at steady-state.
Time frame
baselineSecondary outcomes
1
activation status of immune cells induced by DENV
Quantification and comparison of activation state of immune cells (PBMC/monocytes) isolated from SS and SC sickle cell patients induced in vitro by DENV and/or DENV PAMPS (such as NS1 viral protein) in the presence or absence of mosquito saliva
Time frame
baseline2
Comparative Analysis of NET Formation Induced by Sickle Cell-Derived Microparticles With or Without Mosquito Saliva
Comparison of the induction properties of Neutrophil Extracellular Traps (NETs) in vitro by microparticles isolated from SS and SC patients in the presence or absence of mosquito saliva
Time frame
baseline3
Impact of SS and SC Blood Profiles on Aedes aegypti Biting Behavior and Dengue Virus Transmission
Evaluation of the influence of SS and SC blood profiles on the biting behavior of Aedes aegypti and its ability to transmit DENV.
Time frame
baselineSponsors and contacts
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Source ClinicalTrials.gov