Molecular and Cellular Basis of Severe Forms of Dengue in Sickle Cell Patients
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Dengue (Virus); Fever, Sandfly, Sickle Cell Disease. Basic parameters: 6 years — 25 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Guadeloupe
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Detailed description
More precisely, the objective is to determine and compare the different cellular and molecular inflammatory mediators between SS and SC patients at baseline, and to study DENV-induced activation of various blood figurative elements isolated from uninfected sickle cell patients in vitro.
Given the essential role of immune cells in the DENV cycle and in the innate and adaptive immune responses of the host, understanding the changes induced by viral infection in Peripheral Blood Mononuclear Cells (PBMC) and Monocyte-Derived Dendritic Cells (MDDC) remains a priority. The effect of DENV or DENV-Associated Molecular Patterns (PAMPs) will therefore be studied in vitro on purified cells from SC and SS patients.
The impact of MicroParticles (MPs), known to be involved in the pathogenesis of severe dengue forms and in sickle cell disease, will also be evaluated on two cell types: endothelial cells and neutrophils, the latter exhibiting exacerbated activation and production of Neutrophil Extracellular Traps (NETs).
Considering the influence of mosquito saliva components on the pathogenesis of arboviruses (including DENV) in vertebrate hosts through the amplification of inflammatory responses, a comparative analysis of cellular and molecular inflammatory mediators released following exposure of blood cells from SS and SC patients to DENV and Aedes aegypti saliva will be conducted in vitro.
Lastly, the differential blood profiles of SS and SC patients will be assessed for their impact on the vector competence of Aedes aegypti mosquitoes in transmitting DENV.
Primary outcome measures
- Lymphocyte subpopulations measured by flow cytometry at steady-state [Time frame: baseline]
Secondary outcome measures (3)
- activation status of immune cells induced by DENV [Time frame: baseline]
- Comparative Analysis of NET Formation Induced by Sickle Cell-Derived Microparticles With or Without Mosquito Saliva [Time frame: baseline]
- Impact of SS and SC Blood Profiles on Aedes aegypti Biting Behavior and Dengue Virus Transmission [Time frame: baseline]
Eligibility criteria
Inclusion criteria
- 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)
- patients followed up for SCD at the sickle cell center of Guadeloupe (University hospital of Guadeloupe, Pointe-à-Pitre)
- patients or legal representatives of minors who will provide written informed consent in accordance with the Declaration of Helsinki
- patients affiliated to national social security
- the control group (AA subjects) will be recruited among volunteers recruited by posters
Exclusion criteria
- 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)
- patients followed up for SCD at the sickle cell center of Guadeloupe (University hospital of Guadeloupe, Pointe-à-Pitre)
- patients or legal representatives of minors who will provide written informed consent in accordance with the Declaration of Helsinki
- patients affiliated to national social security
- the control group (AA subjects) will be recruited among volunteers recruited by posters
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
- Other
Study locations
Guadeloupe · 1 center
- Chu de La Guadeloupe — Pointe-à-Pitre
Identifiers
NCT: NCT07000747 · PAP_RIPH3_2023/09 · 2019-A03033-54