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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Invasive GAS Infection

Intervention / Treatment
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* Genetic: DNA samples, GAS strains


Participation Criteria
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Eligibility Criteria
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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 : . Bacteriological isolation of S. pyogenes from a normally non-sterile site ( eg skin, upper respiratory tract ) associated with extensive soft tissue necrosis . 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.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children hospitalized for invasive GAS infection<br>Children hospitalized for invasive GAS infection | Genetic: DNA samples, GAS strains<br>* DNA samples,GAS strains<br>|
| Children with non-invasive infection<br>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<br>* DNA samples,GAS strains<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Invasive GAS infection, emm genotypes, Bacterial virulence factors, Mendelian susceptibility to infections