Impact of Bacterial Expression and Immune Response in the Severity of Pertussis

NCT ID: NCT05897879

Last Updated: 2024-05-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-16
• Study Completion Date: 2026-11-16

Brief Summary

The resurgence of pertussis is associated with an evolutionary mechanism under the pressure of current acellular vaccines, with a possible impact on vaccine effectiveness and disease expression. Little is known about the mechanisms involved in the clinical variability of pertussis, including its most severe malignant form observed in infants (mortality between 50-80%). The main challenges are: (i) the lack of knowledge about the gene expression of B. pertussis strains currently circulating during human infection, incorporating evolutionary changes and vaccine-induced selective pressure; (ii) the poor understanding of the variability in clinical expression of pertussis, and (iii) the lack of biomarkers to predict disease severity or prognosis in infants.

An integrative strategy combining a clinical, microbiological, immunological and 'omic' approach from a prospective cohort of children with pertussis will be used to identify

1. 'in situ' expression profiles of B. pertussis genes and proteins incorporating recent evolutionary changes and

2. a systemic and respiratory immune signature in B. pertussis-infected children according to severity.

Results should furthermore serve as a prerequisite for the identification of severity biomarkers and new vaccine antigen candidates taking into account specific immune responses in infants.

Detailed Description

The study design is characterized by 4 work packages:

1. Collection of clinical data and biological samples (deep nasal swab, blood sample) from children with pertussis

2. Construction and validation of a microbial panel of 200 genes of interest (involved in virulence and/or potential vaccine antigens) for transcriptomic analysis

3. Transcriptomic study using the panel of interest of B. pertussis isolates from nasopharyngeal swabs preserved with an RNA stabilizer, using the Nanostring® technique

4. Study of the immune response during pertussis

Conditions

Bordetella Pertussis, Whooping Cough

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Children between 0 and 15 years with suspected pertussis

Group Type: OTHER

Nasopharyngeal swab

Intervention Type: BIOLOGICAL

For hospitalized patients :

Nasopharyngeal swab (1 aspiration or 2 swabs (1 in each nostril))

For ambulatory patients :

Deep nasal swab: 2 swabs (1 in each nostril), or 1 swab only for children for whom taking 2 swabs is complicated.

Blood samples

Intervention Type: BIOLOGICAL

For hospitalized patients : 3 to 7.5 ml For ambulatory patients: Fingertip blood sampling

Interventions

Nasopharyngeal swab

For hospitalized patients :

Nasopharyngeal swab (1 aspiration or 2 swabs (1 in each nostril))

For ambulatory patients :

Deep nasal swab: 2 swabs (1 in each nostril), or 1 swab only for children for whom taking 2 swabs is complicated.

Intervention Type: BIOLOGICAL

Blood samples

For hospitalized patients : 3 to 7.5 ml For ambulatory patients: Fingertip blood sampling

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• be between the ages of 0 and 15 years inclusive
• be suspected of having pertussis by the physician in charge, with the prescription of a diagnostic PCR (pertussis PCR, which may be a syndromic PCR, a PCR targeting IS481 and/or IS1001)
• be free of any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic insufficiency, taking immunosuppressive treatment (including taking oral corticosteroids with a dose ≥ 10 mg/d Prednisone equivalent for more than 15 days)
• Have received age-appropriate information and written assent or consent from their parents/legal guardians
• be affiliated with or benefiting from a social security plan

Exclusion Criteria

• Patient with any pathology/treatment that may influence the immune response (autoimmune/inflammatory pathology or immune deficiency not listed above, hepatic failure, taking immunosuppressive therapy (including oral corticosteroids with dose ≥ 10 mg/d prednisone equivalent for more than 15 days)
• Use of antibiotics active against pertussis in the 24 hours preceding the sampling
• Delay between the result of the diagnostic sample (pertussis PCR) and the day of inclusion > 48 hours
• Patient's condition that, in the opinion of the physician, is incompatible with the expanded/additional sampling(s) required by the study
• Infant with a weight < 2.5 kg at the time of inclusion.

• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hôpital Necker-Enfants Malades

OTHER

Sponsor Role: collaborator

Hospices Civils de Lyon

OTHER

Sponsor Role: collaborator

Hopital Universitaire Robert-Debre

OTHER

Sponsor Role: collaborator

Centre Hospitalier Intercommunal Creteil

OTHER

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: collaborator

Réseau ACTIV

UNKNOWN

Sponsor Role: collaborator

Hôpital Armand Trousseau

OTHER

Sponsor Role: collaborator

CHR - Hôpital Roger Salengo

UNKNOWN

Sponsor Role: collaborator

Hôpital Nord - APHM

UNKNOWN

Sponsor Role: collaborator

Hôpital Louis Mourier

OTHER

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role: collaborator

Hôpital de la Timone

OTHER

Sponsor Role: collaborator

University Hospital, Rouen

OTHER

Sponsor Role: collaborator

Institut Pasteur

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie Toubiana, MD

Role: STUDY_DIRECTOR

Institut Pasteur

Locations

CHU de Bordeaux

Bordeaux, , France

Site Status: NOT_YET_RECRUITING

Hôpital Louis Mourier

Colombes, , France

Site Status: RECRUITING

Centre hospitalier intercommunal de Créteil

Créteil, , France

Site Status: NOT_YET_RECRUITING

Hôpital Roger Salengo

Lille, , France

Site Status: RECRUITING

Hospices Civils de Lyon

Lyon, , France

Site Status: RECRUITING

Hôpital de la Timone Enfants, APHM

Marseille, , France

Site Status: RECRUITING

Hôpital Nord, APHM

Marseille, , France

Site Status: RECRUITING

CHU de Nantes

Nantes, , France

Site Status: NOT_YET_RECRUITING

CHU Armand Trousseau

Paris, , France

Site Status: RECRUITING

Hopital Necker

Paris, , France

Site Status: RECRUITING

Hôpital Robert Debré

Paris, , France

Site Status: NOT_YET_RECRUITING

CHU Rouen

Rouen, , France

Site Status: NOT_YET_RECRUITING

Réseau ACTIV

Saint-Maur-des-Fossés, , France

Site Status: NOT_YET_RECRUITING

CHU de Toulouse

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Julie Toubiana, MD

Role: CONTACT

julie.toubiana@pasteur.fr

+331 45 68 80 05

Facility Contacts

Emilie Pauquet, MD

Role: primary

Romain Basmaci, MD

Role: primary

Fouad Madhi, MD

Role: primary

François Dubos, MD

Role: primary

Antoine Ouziel, MD

Role: primary

Aurélie Morand, MD

Role: primary

Philippe Minodier, MD

Role: primary

David Malorey, MD

Role: primary

Mathie Lorrot, MD

Role: primary

Julie Toubiana, MD

Role: primary

Albert Faye, MD

Role: primary

Didier Pinquier, MD

Role: primary

Robert Cohen, MD

Role: primary

Camille Brehin, MD

Role: primary

Other Identifiers

2023-A00004-41

Identifier Type: OTHER

Identifier Source: secondary_id

2022-093

Identifier Type: -

Identifier Source: org_study_id