WP3’s main goal will be to provide detailed transcriptome profiling of febrile patients with bacterial or viral infections, in order to identify reliable genomic markers so as to improve diagnosis and clinical management. In order to so successfully, WP3 will need 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 is led by LSHTM – London School of Hygiene and Tropical Medicine.

WP5’s overarching aim will be 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 will be informed by data collated from the other Work-Packages (primarily WP1) but also through healthcare provider and patient surveys.

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

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

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

WP7 will then evaluate 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 will be led by Imperial College in the UK.

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

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

WP9 will be led by Imperial College, in the UK.

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

WP11 will set up the necessary underlying infrastructure and expertise for managing this data and supporting the subsequent informatics analysis carried out by the different Work-Packages. It will, furthermore, ensure continuous and reliable access to the data through a centralised and secure infrastructure housing the different data systems, on a data management repository.

WP11 will be led by Imperial College in the UK.