Molecular and Cellular Basis of Severe Forms of Dengue in Sickle Cell Patients

NCT ID: NCT07000747

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 130 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-06-24
• Study Completion Date: 2026-06-24

Brief Summary

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.

Conditions

Dengue (Virus); Fever, Sandfly; Sickle Cell Disease

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients SS Group

Fifty SS patients

No interventions assigned to this group

Patients SC

Fifty SC patients

No interventions assigned to this group

Control group AA

Patients without hemoglobin disease

No interventions assigned to this group

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centre Hospitalier Universitaire de la Guadeloupe

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maryse Etienne-Julan, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CHU de la Guadeloupe

Locations

Chu de La Guadeloupe

Pointe-à-Pitre, , Guadeloupe

Site Status: RECRUITING

Countries

Guadeloupe

Central Contacts

Valérie Hamony Soter

Role: CONTACT

valerie.soter@chu-guadeloupe.fr

+590590934677

Mélanie petapermal

Role: CONTACT

melanie.petapermal@chu-guadeloupe.fr

+590590934667

Facility Contacts

Maryse etienne julan, MD

Role: primary

maryse.etienne-julan@chu-guadeloupe.fr

+590590934670

Other Identifiers

2019-A03033-54

Identifier Type: OTHER

Identifier Source: secondary_id

PAP_RIPH3_2023/09

Identifier Type: -

Identifier Source: org_study_id