Personalised Risk assessment in febrile illness to optimise Real-life Management across the European Union

(Project lifecycle: 2016 - 2021)

The Problem

The management of febrile patients is one of the most common and important problems facing healthcare providers. Distinction between bacterial infections and trivial viral infection on clinical grounds is unreliable and, as a result, innumerable patients worldwide undergo hospitalisation, invasive investigation and are treated with antibiotics for presumed bacterial infection when, in fact, they are suffering from self-resolving viral infection.

The Solution

PERFORM aimed to develop a comprehensive management plan for febrile patients, capable of being rolled out in different healthcare systems across Europe, by linking sophisticated new genomic and proteomic approaches to careful clinical phenotyping, and building on pilot data from previous studies.


By improving diagnosis and management of febrile patients, through application of sophisticated phenotypic, transcriptomic (genomic, proteomic) and bioinformatics approaches to well characterised large-scale, multi-national patient cohorts already recruited with EU funding. PERFORM identified and validated promising new discriminators of bacterial and viral infection including transcriptomic and clinical phenotype markers. The most accurate of these distinguishing between bacterial and viral infection, was evaluated in prospective cohorts of patients reflecting the different health care settings across European countries. 

The PERFORM consortium, made up of 18 world renowned organisations, from 10 different countries, actively engaged with national and European wide policy-makers and stakeholders, to maximise the project’s reach and impact.

Latest results and outputs are available on the European Commission's CORDIS website


The Work Packages

Work Package 1

Clinical Network and Biobanking

WP1 was responsible for creating the PERFORM International Clinical Network (PERFORM-ICN), by combining the clinical data and sample banks from previous EU-funded studies undertaken by members of the consortium and effectively creating the most comprehensive and well-characterised biobank in Europe.

All clinical samples for the subsequent Work-Packages were collected through WP1, including the diagnostic, genomic and proteomic studies to be conducted for Work-Packages 2-4.

WP1 was led by SERGAS – Servizo Galego de Saude, from Spain.

Work Package 2


WP2 provided high-throughput molecular diagnostics, enabling accurate patient assignment to bacterial or viral diagnostic categories. It validated candidate protein biomarkers to distinguish between bacterial and viral infection using immunoassays.

WP2 was led by the AMC – Academish Medisch Centrum bij de Universiteit van Amesterdam in the Netherlands.

Work Package 3


WP3’s main goal was to provide detailed transcriptome profiling of febrile patients with bacterial or viral infections, to identify reliable genomic markers so as to improve diagnosis and clinical management. WP3 aimed to:

  1. Obtain a genome-wide transcriptomic profile by deep sequencing a subset of febrile individuals with confirmed diagnosis of bacterial or viral infections using samples from WP1;
  2. Perform RNA expression studies in larger cohorts of febrile patients combining those with and without definitive diagnosis of infection, using samples from WP1;
  3. Validate significantly differentially expressed genes, potential genomic markers identified on transcriptome studies by alternative methods, namely nanostring and qPCR.

WP3 was led by LSHTM – London School of Hygiene and Tropical Medicine in the UK.

Work Package 4


WP4 was responsible for identifying and selecting relevant and measurable sets of protein biomarkers, based on the proteomic profiling studies undertaken for the discovery cohorts that distinguish between bacterial and viral infections, as well as the subsequent validation of said candidate biomarkers.

Data integration then allowed for the design composition of the optimal protein biomarker panel capable of distinguishing between bacterial and viral infections.

WP4 was led by RUMC – Radboud University Medical Center in the Netherlands.

Work Package 5

Comparative Health Care analysis and cost-effectiveness

WP5’s overarching aim was the development of a robust decision analytic framework capable of modelling the relative costs, risks, and benefits of introducing PERFORM’s new approach to diagnose and manage febrile children across different European health care settings. This framework was informed by data collated from the other Work-Packages (primarily WP1) but also through the healthcare provider and patient surveys.

In order to effectively measure the impact and costs of the new diagnostic approach, WP5’s model framework took into account a detailed description of current pathways, practices and associated costs across the various existing health care models, at the European level.

WP5 was led by LSHTM – London School of Hygiene and Tropical Medicine in the UK.

Work Package 6

Data Analysis and Modelling

WP6’s main role was to analyse and integrate the clinical, transcriptomic, and proteomic data to construct biomarker signatures able to distinguish between bacterial and viral infections. The focus was on developing signatures that used the minimal number of biomarkers showing optimal sensitivity and specificity.

Additionally, WP6 provided inputs and liaise closely with WP4 and WP5 to contribute to their analysis work and undertake modelling of different management strategies for febrile children.

WP6 was led by Imperial College London in the UK.

Work Package 7

Model Implementation

WP7 was responsible for receiving all transcriptomic and proteomic data from the patient cohorts and modelling the potential health-care costs achieved through the widespread inclusion of the new diagnostic approach. A clinical management algorithm was developed; encompassing the use of novel transcriptomic diagnostic tests and clinical markers.

WP7 then evaluated the performance of the algorithm using modelling data obtained from the patient cohorts including sensitivity and specificity of the combination of clinical signs, symptoms and diagnostic tests; effectively integrating the findings and results from WPs 3-6 into base management guidelines.

WP7 was led by Imperial College London in the UK.

Work Package 8

Translation of biomarkers into prototype for validation

WP8 evaluated different platforms and approaches for developing clinically applicable tests based on the transcriptomic and proteomic biomarker, facilitating future production of a rapid point of care test. The technological choices (ie molecular biology and/or immunoassay) depended on the type and the number of biomarkers identified in the discovery study, along with sensitivity, specificity, and potential for translation

WP8 was led by Biomerieux in France.

Work Package 9

Clinical Translation

WP9 closely evaluated the performance of the developed predictive models of bacterial or viral infection, through close interactions with WPs 5-8, and developed necessary guidelines for future application in different European health-care settings.

Data and contacts established through WP10, particularly regarding project stakeholders also factored in the development of new management guidelines for febrile children, taking into account the different national settings and health-care models.

WP9 was led by Imperial College London in the UK.

Work Package 10

Dissemination and Stakeholder Engagement

WP10 focussed on establishing PERFORM’s communication strategy and activities to maximise the project’s reach and potential impact across its various stakeholder communities.

It ensured results and outcomes were properly advertised and reach both international and national audiences, when relevant.

The WP leaders maintained the project’s website and other media channels.

WP10 was led by Imperial College London in the UK.

Work Package 11

Data Management

WP11’s main responsibility was to ensure that the informatics needs of the project were adequately met, given the large number of patients involved as well as the large volume and variety of data that was generated and collected across the different Work Packages.

WP11 set up the necessary underlying infrastructure and expertise for managing this data and supported the subsequent informatics analysis carried out by the different Work Packages. Additionally, it ensured continuous and reliable access to the data through a centralised and secure infrastructure housing the different data systems, on a data management repository.

WP11 was led by Imperial College London in the UK.

Work Package 12

Project Management

WP12 ensured the efficient and effective management of the entire project, across its 5-year duration. The project coordinator (Imperial) ensured that consortium partners performed in accordance to the agreed Work-Plan, and liaised with the European Commission on a periodic basis to provide relevant updates on the project’s performance.

Through WP12, PERFORM ran smoothly and efficiently; maximising its outputs across the participating partner organisations.

WP12 was led by Imperial College London in the UK.