Personalised Risk Assessment in Febrile Illness to Optimise Real-life Management Across the European Union (PERFORM)

The problem to be addressed:

Fever is among the commonest symptoms for which parents consult health care providers worldwide. Distinction between life-threatening bacterial infection and viral infection is clinically difficult, and many children worldwide receive unnecessary antibiotic treatment, or undergo invasive investigations and hospitalization, whilst bacterial infection is missed in others.

Objective:

The investigators aim to validate biomarkers that will identify children with bacterial infection, viral infection and inflammatory syndromes, using whole-blood RNA expression, proteomic and metabolomics signatures. The investigators aim to assess how efficacious these biomarkers would be if they formed the basis of a diagnostic test.

Design:

The investigators will use established case-control groups of febrile children presenting to hospital, recruited across Europe as part of previous (and current) ethically-approved studies, to discover signatures of febrile illness. The investigators will validate these signatures in samples prospectively collected from children as part of this observational study.

The investigators will use prospective, observational BIVA studies to recruit febrile children with infectious and inflammatory diseases in order to validate diagnostic biomarkers. The investigators will also recruit non-febrile controls in order to discover and validate disease-specific biomarkers and to understand their biological significance.

STUDY SIZE at least 4000 febrile children;

PROCEDURES;

Informed consent using age appropriate patient/parent/guardian information sheets will be taken from parents (or from children aged 16 and over), assent will be taken from the child under the age of 16 (if appropriate).

Routine clinical and laboratory data and research samples from three timepoints (presentation, 48 hours after presentation, 28 days after admission). If patients present to hospital with fever on subsequent occasions, clinical data will be recorded and further research samples will be taken at those times.

Samples; Blood, urine, stool (in the case of gastroenteritis), nasopharyngeal/throat swab

CONTROLS:

The investigators will collect samples from age-matched control patients will not have had a febrile illness, major trauma or vaccination within the previous three weeks and who are having routine blood sampling for reasons other than investigation of infectious or inflammatory disease.

Control children may include critically ill children without infection or those with healthcare associated infections.

Inclusion criteria

• All children <18 years with fever >38ºC, or a history of fever (within 3 days), in whom the attending clinician determines the need for blood sampling or whom parents give consent for bloods taken for research purposes
• All children <18 years suspected of infection, including the full spectrum of disease severity and co-morbidities.
• Afebrile control children who are having blood tests for reasons other than for investigation of infectious or inflammatory illness.

Exclusion criteria

• Children from whom parent/legal guardian signed consent is not received
• For healthy control children only: febrile illness or vaccination within the last 3 weeks.