3. PRACTICE A: Observational study –workpackage 3


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

MERMAIDS-ARI: 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.


MERMAIDS-PED: 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.


MERMAIDS-ARBO: Arboviral compatible febrile illness

This study includes 1500 adults >18 years old admitted to hospital with symptoms compatible with arboviral febrile illness and is focused to regions in South East Europe where the four arboviruses (TBEC, WNV, TOSC, CCHFV) endemic to Europe and with direct impact on humans have been identified, and where surveillance data shows patchy reporting. Children are not included in the study, since evidence shows that adults have the highest risk of developing more severe disease requiring health care. 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 and myalgia/arthralgia. The primary objectives are 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). Secondly, to document treatment, clinical management and outcomes of TOSV, WNV, TBEV and CCHFV infections (in adults > 18 years old) requiring admission to hospital by region, 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. Moreover, we will analyse health outcomes and burden of disease in relation to severity and demographics. This information will inform early identification and diagnostics of infectious disease outbreaks with epidemic potential and strengthen networks for diagnostics and research in Europe.


The MERMAIDS study protocols are available through the Virtual Learning Centre

Collaborating sites taking part in the WP3 studies

Key Objectives

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

  2. To prospectively study incidence, risk factors and clinical impact of infections with epidemic potential in Europe with an initial focus on acute respiratory infections, central nervous system infections, and hemorrhagic fever in hospitalised and primary care (PC) patients;

  3. To collect prospective standardised observational and natural history clinical data from hospitalised and primary care patients (3500 adults and 1000 children) with acute respiratory infection (n= 2600) and from patients with severe illness caused by central nervous system infections and undifferentiated fever (n= 1450),  and hemorrhagic fever (n=450);

  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


Herman Goossens


Deputy Coordinator:

Menno de Jong




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