Invasive Group A Streptococcus (GAS) Infection in Children: Bacterial Virulence Factors and Detection of Host Immunological and/or Genetic Factors of Predisposition to Infections (StreptoPedia)

The main objective of the study is to characterize the virulence factors of SGA and identify immunological and / or genetic factors predisposing to infections in children hospitalized with invasive GAS infection.

Study Overview

• Status: Completed
• Conditions: Invasive GAS Infection
• Intervention / Treatment: Genetic: DNA samples, GAS strains

Detailed Description

The group A streptococcus (GAS) or Streptococcus pyogenes is a strictly human pathogen , which can cause a wide variety of infections. These range from a simple asymptomatic carriage up to 20 % of children , or minor illnesses such as sore throat or impetigo, to severe conditions such as necrotizing fasciitis and toxic shock syndrome .

The pathophysiological mechanisms of invasive GAS infections are poorly understood. These mechanisms could involve not only virulence factors of the bacterium ( M protein determines the emm genotype , but also super- antigenic exotoxins SpeA , Spe C, Ssa, Sme z or other virulence genes , SilC , ... Sic ), but also in some cases, factors associated with host immunity in particular in the absence of risk factors for invasive skin infection such as cutaneous effraction ( wound , burn , chicken pox ) , corticosteroids or other immunosuppressive therapy and recent surgery .

The investigators assume that in some invasive GAS infections, especially in children without risk factors, Mendelian susceptibility to infection may be involved . This hypothesis could be tested by studying the molecular characteristics of strains isolated SGA and innate and adaptive immunity in children hospitalised for invasive GAS infection with or without identified risk factors for infection.

This study could not only lead to a better understanding of the pathophysiological mechanisms of invasive GAS infections but also to detect in children who underwent invasive GAS genetic susceptibility to infections requiring specific care . Finally, it could also identify specific strains of SGA or molecular profiles, whose detection in practice, lead to a suspicion of hereditary immune deficiency.

• Study Type: Observational
• Enrollment (Actual): 223

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Robert Debre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Children hospitalized for invasive or non invasive GAS infection

Description

Inclusion Criteria:

• Age ≥ 1 month to <15 years at the time of inclusion

• Group 1 : Children hospitalized for invasive GAS infection

  • Subgroup 1A ( N = 75 ): Children with invasive infection without known risk factor .
  • Subgroup 1B (N = 75) : Children with invasive infection with known risk factor .

GAS Invasive infections are defined by:

a) Proved infection : Bacteriological isolation of S. pyogenes from a liquid or a normally sterile site, except from a blister of a simple erysipelas, without necrosis . This is sometimes associated with a shock with multiorgan failure (streptococcal toxic shock syndrome ( STSS )) b ) Probable infection :

1. . Bacteriological isolation of S. pyogenes from a normally non-sterile site ( eg skin, upper respiratory tract ) associated with extensive soft tissue necrosis
2. . Bacteriological isolation of S. pyogenes a site or a biological sample usually non-sterile ( eg skin , upper respiratory tract ) associated with a evocative shock syndrome STSS and no other cause found .

Contributing factors for invasive infection are defined by:

cutaneous effraction (wounds , burn , chicken pox ), the use of corticosteroids or other treatment, immunosuppressive and recent surgery

• Group 2: non-invasive infection such as pharyngitis , tonsillitis, proctitis or skin infection diagnosed by a positive test for rapid diagnosis of GAS performed at the site of infection with a positive GAS culture.

Exclusion Criteria:

• Group 1: Children with a known immune deficiency unrelated to the risk factors described above.
• Group 2: Children with a known immune deficiency.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children hospitalized for invasive GAS infection	Genetic: DNA samples, GAS strains; DNA samples,GAS strains
Children with non-invasive infection; Children with non-invasive infection such as pharyngitis, tonsillitis, proctitis or skin infection diagnosed by a positive test for rapid diagnosis of GAS performed at the site of infection with a positive GAS culture	Genetic: DNA samples, GAS strains; DNA samples,GAS strains

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
virulence factors of GAS	characterize the virulence factors of GAS	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the frequency and type of hereditary immune deficiency or Mendelian susceptibility to infections associated with invasive GAS infections in children without risk factors	frequency and type of hereditary immune deficiency or Mendelian susceptibility to infections associated with invasive GAS infections	up to 3 years
describe and compare the GAS emm genotypes and virulence factors with the profiles of strains isolated with invasive GAS infection with known risk factors and with the profile of strains isolated with a non-invasive GAS infections	describe and compare the GAS emm genotypes and virulence factors profile of GAS associated with an inherited immune deficiency, or a Mendelian susceptibility to infection, with the profiles of strains isolated in children with invasive GAS infection with known risk factors (use of steroids, varicella, wounds…) and with the profile of strains isolated in children with a non-invasive GAS infections	up to 3 years
compare GAS emm genotypes and profiles of virulence strains responsible for invasive SGA infections with strains causing noninvasive infections	compare GAS emm genotypes and profiles of virulence strains responsible for invasive SGA infections with strains causing noninvasive infections	up to 3 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Albert FAYE, MD, PhD, APHP

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2014
• Primary Completion (Actual): February 10, 2018
• Study Completion (Actual): July 20, 2018

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: December 9, 2013
• First Posted (Estimate): December 12, 2013

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Invasive GAS infection; emm genotypes; Bacterial virulence factors; Mendelian susceptibility to infections
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Disease Susceptibility
• Other Study ID Numbers: P120136