Paediatric European Group A Streptococcal United Study. (PEGASUS)

PEGASUS: Paediatric European Group A Streptococcal United Study.

Introduction Since 2022 there are reports of a rapid increase in invasive group A streptococcal infections (iGAS) in children in some but not all European countries. Detailed information on this increase is lacking. Furthermore, an increase in other invasive infections as well as the emergence of novel pathogens and disease entities is seen, such as MIS-C and severe hepatitis of unknown origin.

Aims To set up a European research network and describe the incidence, risk factors, clinical phenotypes, microbiology and resistance, treatment, and outcomes of iGAS in children across Europe. The network will subsequently be utilized for early alerting regarding the rise of other invasive and emerging infections in children. It will enable swift data collection pertaining to patient characteristics, presentation, progression, and treatment.

Methods International, retrospective cohort and observational surveillance study of children 0-18y attending the ED or admitted to the hospital with iGAS. Clinical and microbiological data, national vaccination schedules, and COVID non-pharmaceutical interventions (NPIs) will be collected and compared between countries. Subsequently, the network will be employed to raise alarms regarding the surge of other invasive infections or emerging infections in children. Anonymous data about these novel infections will be collected, similar to the data from iGAS (clinical characteristics and microbiological data). The study is a non-profit study.

Significance Our study will describe variation in the clinical phenotypes of iGAS, will aid in the understanding of its association with COVID NPIs and allow for comparison between countries. Furthermore, it will aid in early recognition of invasive and emergent infectious diseases in children and the reduction of outbreaks.

Study Overview

• Status: Recruiting
• Conditions: Invasive Group A Beta-Haemolytic Streptococcal Disease
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Dorine Borensztajn, MD, PhD, MSc; Phone Number: +31880855262; Email: dm.borensztajn@nwz.nl

Study Locations

• Netherlands
  • NH
    • Alkmaar, NH, Netherlands, 1815 JD
      • Recruiting
      • Noordwest Ziekenhuisgroep
      • Contact: Dorine Borensztajn, MD, PhD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Definitions

Confirmed iGAS infection:

• Clinical presentation consistent with iGAS* AND
• Isolation of group A streptococcus by culture or PCR or antigen detection test from a normally sterile body site

Probable iGAS infection:

• Clinical presentation consistent with STSS or necrotizing fasciitis * AND
• Isolation of group A streptococcus by culture or PCR or antigen detection test from a non-sterile body site AND

• No evidence of other pathogen explaining the clinical presentation

  • Clinical presentation consistent with iGAS:

Clinically severe illness, such as sepsis, septic shock, STSS, pneumonia, meningitis, arthritis, osteomyelitis, myositis or necrotizing fasciitis

Description

• All children (1 month-18 years)
• attending the Emergency Department and/or admitted to the participating hospital - with iGAS infection or other invasive or emergent infectious disease.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
children with invasive group A streptococcal disease; children with invasive group A streptococcal disease or other invasive or emergent infectious disease	Other: No intervention; no intervention, this is an observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
What is the incidence of iGAS in children before, during and after COVID NPIs in different European countries?	2018-2025
Is there a change in clinical phenotypes and outcome during these periods?	2018-2025

Secondary Outcome Measures

Outcome Measure	Time Frame
Is there a change in emm types and other virulence factors during these periods	2018-2025
Are there differences in antimicrobial resistance between periods and between 4. Are there differences in antimicrobial resistance between periods and between countries	2018-2025
Can we identify risk factors for iGAS infection (e.g., preceding infections, age)?	2018-2025
Can we explain differences between countries (e.g., differences in vaccination strategies, NPIs or emm types)	2018-2025
Can we use this research network for early alarming on other invasive and emergent infectious diseases in children	2018-2025

Collaborators and Investigators

• Sponsor: Noordwest Ziekenhuisgroep
• Collaborators: Karolinska Institutet; Medical University of Graz; Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Imperial College London; University of Padova; Newcastle University; National and Kapodistrian University of Athens; University of Liverpool; Leiden University Medical Center; University Medical Centre Ljubljana; Wroclaw Medical University; Hospital Universitario 12 de Octubre; University Hospital Munich; Hospital Universitario La Paz; Maasstad Hospital; Hospital Clínico Universitario de Santiago de Compostela; Riga Stradins University; HagaZiekenhuis; Gregorio Marañón Hospital; Mitera Hospital; European Society for Paediatric Infectious Diseases; Children's hospital Iceland

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 21, 2023
• First Submitted That Met QC Criteria: September 21, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 1.2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No