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

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• Communicable Diseases 4,456
• Infections 6,688
• Viremia 83
• Fever 603

Study population

Eligibility criteria

Groups and cohorts

• Fever Without Source

  Clinical diagnosis of FWS (fever of less than 7 days with no cause determined by the history and the physical exam).

• Healthy control

  Children visiting the hospital due to a non-infectious, non inflammatory etiology

Primary outcomes

1. 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

1. 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

2. 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.

3. 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

Publications

• Oved K, Cohen A, Boico O, Navon R, Friedman T, Etshtein L, Kriger O, Bamberger E, Fonar Y, Yacobov R, Wolchinsky R, Denkberg G, Dotan Y, Hochberg A, Reiter Y, Grupper M, Srugo I, Feigin P, Gorfine M, Chistyakov I, Dagan R, Klein A, Potasman I, Eden E. A novel host-proteome signature for distinguishing between acute bacterial and viral infections. PLoS One. 2015 Mar 18;10(3):e0120012. doi: 10.1371/journal.pone.0120012. eCollection 2015. PubMed 25785720 ↗
• Colvin JM, Muenzer JT, Jaffe DM, Smason A, Deych E, Shannon WD, Arens MQ, Buller RS, Lee WM, Weinstock EJ, Weinstock GM, Storch GA. Detection of viruses in young children with fever without an apparent source. Pediatrics. 2012 Dec;130(6):e1455-62. doi: 10.1542/peds.2012-1391. Epub 2012 Nov 5. PubMed 23129086 ↗
• Ambrosioni J, Bridevaux PO, Wagner G, Mamin A, Kaiser L. Epidemiology of viral respiratory infections in a tertiary care centre in the era of molecular diagnosis, Geneva, Switzerland, 2011-2012. Clin Microbiol Infect. 2014 Sep;20(9):O578-84. doi: 10.1111/1469-0691.12525. Epub 2014 Jan 24. PubMed 24382326 ↗
• L'Huillier AG, Mardegan C, Cordey S, Luterbacher F, Papis S, Hugon F, Kaiser L, Gervaix A, Posfay-Barbe K, Galetto-Lacour A. Enterovirus, parechovirus, adenovirus and herpes virus type 6 viraemia in fever without source. Arch Dis Child. 2020 Feb;105(2):180-186. doi: 10.1136/archdischild-2019-317382. Epub 2019 Aug 28. PubMed 31462437 ↗

Individual participant data

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