Assess a Diagnostic Tool to Distinguish Between Bacterial and Viral Infection
Condition: Lower Respiratory Tract Infection; Unspecified Fever
MeSH terms: Infections; Communicable Diseases; Respiratory Tract Infections; Fever
Study type: Observational

Summary: 
      In the past 70 years antibiotics have served as the first line of defense against infectious
      diseases. However, antibiotics are only effective against bacterial infections and are not
      the solution for infections caused by viruses such as common colds or flu. Despite their
      contribution to healthcare, antibiotics are currently recognized as the most misused drugs in
      the world with global overuse estimated at 40%-70%, mostly due to the ineffectiveness of
      current diagnostic solutions to distinguish between bacterial and viral infections.
      Antibiotics misuse often causes preventable adverse events that impact patient care and lead
      to the emergence of antibiotic-resistant bacteria, one of the major threats to global health
      today. To address these challenges, MeMed has been developing the ImmunoDx™, a novel
      technology that relies on the best available detection system for differentiating between
      viruses and bacteria - the body's own immune system. The ImmunoDx™ technology employs a
      simple blood test that provides the physician, within two-hours, the information he needs to
      decide whether to treat the patient with antibiotics or not. This technology has been tested
      on over 1000 patients of different ages and diseases and was found to be highly accurate and
      safe. The current study is a non-interventional study and the participants do not receive any
      investigational drug nor any experimental examination or procedure. Therefore, the collected
      data in this study will not affect the diagnosis, prognosis, or treatment of the
      participants. Participation includes the collection of a teaspoon of blood and collection of
      a specimen using a nasal swab. These procedures are common in the clinical practice and are
      widely performed and possess no significant risk. By participating in the study, the subjects
      impact the development of the ImmunoDx™ technology, which is expected to enable a future
      faster and more accurate diagnosis of infectious diseases as well as more appropriate
      prescription of antibiotics. This will open the way to improve treatment decisions in
      millions of patients around the world.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study population will include eligible subjects aged 1 to 60 months of age from both
        genders that attend the hospital or the emergency department (ED) due to a suspected LRTI,
        FWS or due to a non-infectious disease. These subjects are expected to fall into one of the
        following categories:

          1. Patients with an acute bacterial infection

          2. Patients with an acute viral infection

          3. Patients with an acute mixed co-infection (bacterial and viral)

          4. Patients with an undetermined disease etiology

          5. Patients with a non-infectious disease (control group; n=140) We estimate that
             approximately 75% of the patients will fall into categories number 1-3 (i.e.,
             bacterial, viral or mixed infections).
      
Biospecimen description: 
      One blood sample and one nasal swab will be collected per patient