Validation of a Proteomic Signature and Assessment of Viremia in Children With Fever Without Source

MeMed Diagnostics Ltd.206 enrolled

Overview

The study is an observational blinded Validation study in pediatric patients below 3 years old with a diagnosis of Fever Without Source (FWS). In this study the investigators aim to validate the performance of a proteomic signature aiding the physicians to discriminate between viral and bacterial infections in febrile children. The study will also assess the prevalence of Human Enteroviruses (HEV), Human Parechoviruses (HPeV), Adenovirus (AdV) and Human Herpesvirus type 6 (HHV-6) viremia, as well as Kingella Kingae bacteremia in the study cohort.

Study Type

OBSERVATIONAL

Enrollment

206

Conditions

Infectious Disease Fever Viremia

Eligibility

Sex: ALLMin age: 1 DayMax age: 3 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Clinical diagnosis of FWS (fever of less than 7 days with no cause determined by the history or the physical exam) * Age \< 3 years old * Informed consent (IC) given by parent or legal guardian Exclusion Criteria: * Unavailable blood * Comorbidities predisposing to infections such as cancer, primary or secondary immunodeficiency, and iatrogenic immunosuppression Inclusion Criteria for healthy controls: * Age \< 3 years old * Informed consent (IC) given by parent or legal guardian * No suspicion of infectious or inflammatory disease at presentation and during the two weeks before.

Outcomes

Primary Outcomes

Diagnostic accuracy compared to expert panel for bacterial versus viral.

Sensitivity, specificity, NPV and PPV were measured for ImmunoXpert and Labscore. The proteomic signature is a combination of different markers including: tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL), interferon γ-induced protein-10 (IP-10) (pg/mL) and C-reactive protein (CRP) (mg/L). The proteomic signature is expressed as a score (no units. ranges 0-100). The Labscore is a combination of procalcitonin (ng/mL), C-reactive protein (CRP) (mg/L) and urinary dipstix (positive if presence of leucocyturia or nitrites). The Lab-score is expressed as a score (no units. ranges 0-9)

Time frame: 0-7 days after initiation of symptoms

Secondary Outcomes

Diagnostic accuracy compared to microbiology gold standard for ruling out invasive bacterial infection.

Case by case comparison between microbiology gold standard and ImmunoXpert and Labscore. The proteomic signature is a combination of different markers including: tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL), interferon γ-induced protein-10 (IP-10) (pg/mL) and C-reactive protein (CRP) (mg/L). The proteomic signature is expressed as a score (no units, ranges 0-100). The Labscore is a combination of procalcitonin (ng/mL), C-reactive protein (CRP) (mg/L) and urinary dipstix (positive if presence of leucocyturia or nitrites). The Lab-score is expressed as a score (no units, ranges 0-9).

Time frame: 0-7 days after initiation of symptoms

Comparison of biomarker levels in patients with different etiologies as classified by the expert panel or healthy.

An expert panel classified a patient as experiencing a bacterial versus viral infection. In addition healthy patients were requited. The following biomarkers were examined across the healthy versus bacterial versus viral patients: 1. The proteomic signature is a combination of different markers including: tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL), interferon γ-induced protein-10 (IP-10) (pg/mL) and C-reactive protein (CRP) (mg/L). The proteomic signature is expressed as a score (no units, ranges 0-100). 2. The Labscore is a combination of procalcitonin (ng/mL), C-reactive protein (CRP) (mg/L) and urinary dipstix (positive if presence of leucocyturia or nitrites). The Lab-score is expressed as a score (no units, ranges 0-9). 3. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL). 4. interferon γ-induced protein-10 (IP-10) (pg/mL). 5. C-reactive protein (CRP) (mg/L).

Time frame: 0-7 days after initiation of symptoms in cases with infection.

Prevalence of viruses in children with fever without source.

Prevalence of Human Enteroviruses, Human Parechoviruses, Adenovirus and Human Herpesvirus type 6 viremia and viremia from other microorganism identified by Next-Generation Sequencing (NGS) (no units) or other techniques, as well as K. kingae bacteremia in children under three years old presenting with fever without source.

Time frame: 0-7 days after the initiation of symptoms