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

NCT03224026 | Completed

• 1 other identifier: MM-15082-Vir
• Study Type: observational
• Target: 206
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infectious Disease; Fever; Viremia

Outcome Measures

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)

  0-7 days after initiation of symptoms

Secondary Outcomes (3)

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

  0-7 days after initiation of symptoms

• 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.

• Prevalence of viruses in children with fever without source.

  0-7 days after the initiation of symptoms

Study Arms (2)

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

Eligibility Criteria

• Age: 1 Day - 3 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients below three years old which were presented with a diagnosis of fever without source to the emergency room in the Children's Hospital, Geneva University Hospitals

You may qualify if:

• 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

You may not qualify if:

• Unavailable blood
• Comorbidities predisposing to infections such as cancer, primary or secondary immunodeficiency, and iatrogenic immunosuppression
• 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.

Sponsors & Collaborators

• MeMed Diagnostics Ltd.: lead
• University Hospital, Geneva: collaborator

Study Sites (1)

Geneva University Hospitals

Geneva, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 25785720 BACKGROUND

• 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.

  PMID: 23129086 BACKGROUND

• 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.

  PMID: 24382326 BACKGROUND

• 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.

  PMID: 31462437 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum, Plasma, whole blood

MeSH Terms

Conditions

Communicable Diseases; Fever; Viremia

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Body Temperature Changes; Signs and Symptoms; Virus Diseases; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 21, 2017
• Study Start: November 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: August 1, 2018
• Last Updated: January 6, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)