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

Primary outcomes

• Diagnostic accuracy compared to expert panel for bacterial versus viral. [0-7 days after initiation of symptoms]: 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)

Secondary outcomes

• Diagnostic accuracy compared to microbiology gold standard for ruling out invasive bacterial infection. [0-7 days after initiation of symptoms]: 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).
• Comparison of biomarker levels in patients with different etiologies as classified by the expert panel or healthy. [0-7 days after initiation of symptoms in cases with infection.]: 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).
• Prevalence of viruses in children with fever without source. [0-7 days after the initiation of symptoms]: 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.

Sex: All, ages: 1 Day to 3 Years, accepts healthy volunteers

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.

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