3. PRACTICE A: Observational study –workpackage 3

 

Multi-centre  EuRopean study of MAjor Infectious Disease Syndromes (MERMAIDS) comprises three observational studies:

Acute respiratory infections (ARI) in adults

 

This study includes 2000 adults admitted to hospital or presenting in primary care with symptoms of a recent acute respiratory infection, across Europe. ARI pathogens are one of the most likely candidate for the next (re-) emerging pandemic. The primary objective is to identify host and pathogen related determinants of severity of community acquired acute respiratory infections (ARI) in adults. Secondary and tertiary objectives are to describe the aetiology, clinical management and outcomes of adult patients with community acquired ARI, in both primary and hospital care, across Europe; develop and validate complex, prognostic and diagnostic algorithms, from e.g. host gene expression profiles (classifier genes), pathogen profiles, demographics, co-morbidities, risk factors, and clinical parameters and to gain understanding into pathophysiological mechanisms contributing towards development of severe disease by conducting systems medicine analysis of pathogen- and patient characteristics (e.g. clinical data on disease progression, deep sequencing of pathogen genomes, patient associated microbiome etc.) in relation to RNA transcriptional profiles. This information can inform further research into more individualised prevention and targeted treatments to reduce risk of severe infections.

 

Sepsis-like syndrome in infants and ARI in children

This study includes 1000 children admitted to hospital care with a new episode of community-acquired sepsis-like syndrome (SLS) or ARI and age-matched afebrile controls attending the same centre for elective surgery or as an outpatient. SLS will include infants with severe symptoms including CNS symptoms, aseptic meningitis and encephalitis. The primary objectives are to estimate the proportion of children ≤ 6 months with sepsis-like syndrome (SLS) which is attributable to Enterovirus (EV) or Human Parechovirus (HPeV) infection and the proportions of cases of ARI in children aged 0 to 5 years old attributable to respiratory syncytial virus (RSV), influenza virus (FLU), human rhinovirus (HRV) infection or S. pneumonia. Secondary objectives are to assess associations between viral or bacterial load and between viral-viral and viral – bacterial co-detection and severity of diseases and to describe the clinical management of children admitted to hospital with these symptoms across Europe. Moreover, to document proportion of SLS associated with detection of specific subtypes of EV/HPeV in blood by region and year and the medium-term health outcome of EV/HPeV associated sepsis-like syndrome. The gene expression results from the ARI group will be compared with the adult study to establish whether common pathways exist that may explain the development of severe ARI in both adults and young children.

 

Arboviral compatible febrile illness

During the last decade a number of arboviruses have emerged in Europe and are growing public health challenges. This study will focus on four arboviruses of interest: West Nile Virus (WNV), Toscana virus (TOSV), Tick borne encephalitis virus (TBEV) and Crimean Congo haemorrhagic fever virus (CCHFV).This study includes 1500 adults (≥ 18 years old) admitted to hospital with symptoms compatible with arboviral febrile illness in regions in South East Europe where these four arboviruses are endemic, human cases have been identified and surveillance data shows patchy reporting in some areas. The study is designed to capture the symptoms commonly described in (re-) emerging infectious disease outbreaks as first symptoms on clinical presentation in primary and secondary care. The syndromes included in the study are:

  •   CNS infections
  •   Haemorrhagic symptoms
  •   Undifferentiated fever
  •   Myalgia/arthralgia

The primary objectives are to estimate the proportion of adults hospitalised admissions with a clinically compatible febrile illness who have laboratory confirmed or probable WNV, TOSV, TBEV or CCHFV infection in six different countries in South East Europe. Secondary objectives are to document treatment, clinical management and outcomes by region and severity of disease in relation to demographics. For these syndromes, where diagnostics often rely on antibody testing, follow-up sampling will be done to allow studies of the kinetics of antibody decline, which will provide essential information to interpret results of future population serosurveys, thus providing important baseline information for possible future outbreaks. This information will inform early identification and diagnostics of infectious disease outbreaks with epidemic potential and strengthen networks for diagnostics and research in Europe.

Key Objectives

  1. To identify host and pathogen related determinants of severity of community acquired acute respiratory infections (ARI) in adults

  2. To estimate the proportion of children ≤ 6 months with sepsis-like syndrome (SLS) which is attributable to Enterovirus (EV) or Human Parechovirus (HPeV) infection and the proportions of cases of ARI in children aged 0 to 5 years old attributable to respiratory syncytial virus (RSV), influenza virus (FLU), human rhinovirus (HRV) infection or S. pneumonia.

  3. To estimate the proportion of adult hospital admissions with a febrile illness in South East Europe that are attributable to four arbovirus infections: West Nile Virus (WNV), Toscana virus (TOSV), Tick borne encephalitis virus (TBEV) and Crimean Congo haemorrhagic fever virus (CCHFV)

  4. To collect geographically-representative age-stratified population serum and acute-patient samples in these cohorts.

Key tasks

1.       Develop Study Protocol, CRFs and ICFs

2.       Develop manual of operations to include sampling SOPs, data                             management plan (in collaboration with WP8), and analysis plan

3.       Obtain all ethical approvals and study registration numbers

4.       Recruitment of sites through the COMBACTE and GRACE                                   primary care networks

5.       Site set-up and training

6.       Recruitment of subjects

7.       Data collection through the Research Online Database

8.       Study oversight and quality assurance

9.       Site closure and database lock

10.     Analysis of data

11.     Produce final report

Team members

Peter Horby Coordinator
Marion Koopmans Co-leader
Peter Openshaw Co-leader
Mike Sharland Protocol team member
Menno de Jong Protocol team member
Chris Butler Protocol team member
Theo Verheij Protocol team member
Herman Goossens Protocol team member
Gail Carson Protocol team member
Emmanuelle Denis Senior Trials Manager
Kajsa-Stina Longuère Project Manager
Louise Sigfrid WP3 Team member

Contact us

Coordinator:

Herman Goossens

Herman.Goossens@uza.be

Deputy Coordinator:

Menno de Jong

m.d.dejong@amc.uva.nl

prepare@uantwerpen.be

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