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

NCT05897879 | Recruiting

• 2 other identifiers: 2022-0932023-A00004-41
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 14

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. 1.'in situ' expression profiles of B. pertussis genes and proteins incorporating recent evolutionary changes and
2. 2.a systemic and respiratory immune signature in B. pertussis-infected children according to severity.

Conditions

Bordetella Pertussis, Whooping Cough

Keywords

vaccination

Outcome Measures

Primary Outcomes (3)

• Measurement of expression level of Bp genes during infection by Nanostring transcriptomic analysis of Bp isolates from the nasopharynx of children with pertussis.

  To identify in a standardized way the microbial "in situ" expression profiles of currently circulating Bp genes during infection in children ;

  3 years

• Measurement of plasma cytokine and chemokine concentrations by SIMOA digital ELISA

  To determine systemic and respiratory immune responses in children during pertussis.

  3 years

• Phenotyping of immune cells by cytometry with a 20-color flow cytometry panel

  To determine systemic and respiratory immune responses in children during pertussis.

  3 years

Secondary Outcomes (3)

• Measurement of expression level of Bp genes which is modified by recent gene developments related to vaccine pressure by Nanostring transcriptomic analysis of Bp isolates

  3 years

• Measurement of high expression level of Bp genes in all clinical forms of pertussis by Nanostring transcriptomic analysis of Bp isolates

  3 years

• Measurement of expression level of Bp genes which is associated with severe pertussis by Nanostring transcriptomic analysis of Bp isolates

  3 years

Study Arms (1)

Children between 0 and 15 years with suspected pertussis

OTHER

Biological: Nasopharyngeal swab; Biological: Blood samples

Interventions

Nasopharyngeal swab 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.

Children between 0 and 15 years with suspected pertussis

Blood samples BIOLOGICAL

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

Children between 0 and 15 years with suspected pertussis

Eligibility Criteria

• Age: Up to 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• Patient's condition that, in the opinion of the physician, is incompatible with the expanded/additional sampling(s) required by the study

Sponsors & Collaborators

• Institut Pasteur: lead
• Hôpital Necker-Enfants Malades: collaborator
• Hospices Civils de Lyon: collaborator
• Hopital Universitaire Robert-Debre: collaborator
• Centre Hospitalier Intercommunal Creteil: collaborator
• Nantes University Hospital: collaborator
• Réseau ACTIV: collaborator
• Hôpital Armand Trousseau: collaborator
• CHR - Hôpital Roger Salengo: collaborator
• Hôpital Nord - APHM: collaborator
• Hôpital Louis Mourier: collaborator
• University Hospital, Toulouse: collaborator
• University Hospital, Bordeaux: collaborator
• Hôpital de la Timone: collaborator
• University Hospital, Rouen: collaborator

Study Sites (14)

CHU de Bordeaux

Bordeaux, France

NOT YET RECRUITING

Hôpital Louis Mourier

Colombes, France

RECRUITING

Centre hospitalier intercommunal de Créteil

Créteil, France

NOT YET RECRUITING

Hôpital Roger Salengo

Lille, France

RECRUITING

Hospices Civils de Lyon

Lyon, France

RECRUITING

Hôpital de la Timone Enfants, APHM

Marseille, France

RECRUITING

Hôpital Nord, APHM

Marseille, France

RECRUITING

CHU de Nantes

Nantes, France

NOT YET RECRUITING

CHU Armand Trousseau

Paris, France

RECRUITING

Hopital Necker

Paris, France

RECRUITING

Hôpital Robert Debré

Paris, France

NOT YET RECRUITING

CHU Rouen

Rouen, France

NOT YET RECRUITING

Réseau ACTIV

Saint-Maur-des-Fossés, France

NOT YET RECRUITING

CHU de Toulouse

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Whooping Cough

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Julie Toubiana, MD

  Institut Pasteur

  STUDY DIRECTOR

Central Study Contacts

Julie Toubiana, MD

CONTACT

+331 45 68 80 05; julie.toubiana@pasteur.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: June 9, 2023
• Study Start: November 16, 2023
• Primary Completion: November 16, 2025
• Study Completion (Estimated): November 16, 2026
• Last Updated: May 24, 2024

Record last verified: 2024-05

Locations

FR (14)