Assess a Diagnostic Tool to Distinguish Between Bacterial and Viral Infection

This is a prospective clinical validation study of a novel in-vitro diagnostic (IVD) assay that will enroll 830 pediatric patients. The study will be conducted in two stages: In stage A 50 patients will be enrolled with the aim of verifying proper protocol execution including proper collection of patient samples, accurate data retrieval and precise etiology determination. In stage B 780 patients will be enrolled with the aim of blinded validation of the host-response based diagnostics using a fresh independent cohort of patients. Patients enrolling into the study will be managed according to the current standard of care (GCP) and per standard institutional procedures. Participation in this study requires the collection of an additional blood sample and a nasal swab sampling.

The investigated assay requires the measurement of three host-related, blood-based, protein biomarkers that are being integrated using a logistic regression formula into a single score. Based on this score, each patient is classified into one of three categories: (i) bacterial immune response (i.e., pure bacterial infections and mixed bacterial and viral co-infection), (ii) viral immune response, and (iii) marginal immune response (inconclusive or non-infectious). It is estimated that 10-20% of the infected patients will have a marginal immune response. A composite reference standard will be used in order to determine the diagnosis of each patient. Specifically, all the clinical, radiological, microbiological and laboratory data of each patient, will be recorded in a dedicated eCRF. Based on this data, the diagnosis of each patient will be determined by a panel of three independent pediatricians. Each pediatrician will be blinded to the diagnosis of his peers and to the assay results. In the current study, unanimous agreement between the experts ("consensus agreement") will be considered as the true diagnosis for the purpose of computing the assay performance.

Inclusion criteria

Patients aged 1 to 60 months whose their legal guardian agrees to sign an informed consent will be eligible for inclusion.

The infectious disease group (n = 690) should also fulfill the following criteria:

• Peak temperature ≥ 38°C (100.4°F) (AND)
• Symptoms duration ≤ 6 days (AND)
• Clinical suspicion of LRTI (OR)
• Fever without a clear source where no localizing sign of infection are present at the emergency department

The non-infectious disease control group will include:

• Patients with a non-infectious disease (n = 140)

Exclusion criteria

Patients who will meet one or more of the following criteria will be excluded from the study:

• Another episode of febrile infection during the past 3 weeks
• Congenital immune deficiency (CID)
• A proven or suspected human immunodeficiency virus (HIV)-1, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
• Active malignancy

Current treatment with immune-suppressive or immune-modulating therapies including without limitations:

• Use of high dose steroids >1 mg/kg/day prednisone or equivalent in the past two weeks
• Monoclonal antibody administration
• Intravenous immunoglobulin (IVIG)
• Cyclosporine
• G/GM-CSF
• Anti-TNF agents
• Interferon (of all kinds)

Other severe illnesses that affect life expectancy and quality of life such as:

• Moderate to severe psychomotor retardation
• Thalassemia Major
• Moderate to severe congenital metabolic disorder