BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children

Background and objectivesAdenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combine...

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Main Authors: Michal Stein, Ma’anit Shapira, Ellen Bamberger, Irena Chistyakov, Daniel Dumov, Isaac Srugo, Louis J. Bont, Adi Klein
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fped.2022.990750/full
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author Michal Stein
Michal Stein
Ma’anit Shapira
Ellen Bamberger
Ellen Bamberger
Irena Chistyakov
Daniel Dumov
Isaac Srugo
Michal Stein
Louis J. Bont
Adi Klein
Adi Klein
author_facet Michal Stein
Michal Stein
Ma’anit Shapira
Ellen Bamberger
Ellen Bamberger
Irena Chistyakov
Daniel Dumov
Isaac Srugo
Michal Stein
Louis J. Bont
Adi Klein
Adi Klein
author_sort Michal Stein
collection DOAJ
description Background and objectivesAdenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combines the expression levels of TNF-related apoptosis-induced ligand, interferon gamma-induced protein-10, and C-reactive protein exhibited a negative predictive value (NPV) of 98% in prior studies. Here we evaluate BV score's diagnostic accuracy in pediatrics with adenovirus PCR detection.MethodsThis is a sub-analysis of children aged 3 months to 20 years with adenovirus PCR-positive infection recruited prospectively in two previous cohort studies. Reference standard diagnosis (bacterial, viral or indeterminate) was based on expert adjudication. BV score ranges from 0 to 100 and provides three results based on predefined cutoffs: viral or other non-bacterial etiology (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65), and bacterial or co-infection (65 < score ≤ 100). Experts were blinded to BV results.ResultsOut of 1,779 children, 142 had an adenovirus PCR-positive nasopharyngeal swab. Median age was 1.2 years (interquartile range 0.6–1.8), 50.7% were male and 52.8% were hospitalized. 12 cases were reference standard bacterial, 115 reference standard viral and 15 were indeterminate. BV score attained sensitivity of 100.0% (no false negatives), specificity of 89.5% (95% confidence interval: 83.2–95.8), and NPV of 100.0% (92.6–100.0). Equivocal rate was 19.7%.ConclusionsBV score accurately differentiated between adenoviral and bacterial-adenoviral co-infection in this cohort of children with PCR-positive adenovirus detection. This performance supports a potential to improve appropriate antibiotic use.
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spelling doaj.art-cc10e70809f045d8b26df12a8e0521902022-12-22T03:22:43ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-11-011010.3389/fped.2022.990750990750BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive childrenMichal Stein0Michal Stein1Ma’anit Shapira2Ellen Bamberger3Ellen Bamberger4Irena Chistyakov5Daniel Dumov6Isaac Srugo7Michal Stein8Louis J. Bont9Adi Klein10Adi Klein11Pediatric Infectious Diseases Unit, Sheba Medical Center, Ramat Gan, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelLaboratory Division, Hillel Yaffe Medical Center, Hadera, IsraelPediatrics Department, Bnai Zion Medical Center, Haifa, IsraelRappaport Faculty of Medicine, Technion Institute of Technology, Haifa, IsraelPediatrics Department, Bnai Zion Medical Center, Haifa, IsraelRappaport Faculty of Medicine, Technion Institute of Technology, Haifa, IsraelPediatrics Department, Bnai Zion Medical Center, Haifa, IsraelSafra Children's Hospital, Sheba Medical Center, Ramat Gan, IsraelWilhelmina Children's Hospital, UMC Utrecht, Utrecht, NetherlandsRappaport Faculty of Medicine, Technion Institute of Technology, Haifa, IsraelPediatrics Department, Hillel Yaffe Medical Center, Hadera, IsraelBackground and objectivesAdenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combines the expression levels of TNF-related apoptosis-induced ligand, interferon gamma-induced protein-10, and C-reactive protein exhibited a negative predictive value (NPV) of 98% in prior studies. Here we evaluate BV score's diagnostic accuracy in pediatrics with adenovirus PCR detection.MethodsThis is a sub-analysis of children aged 3 months to 20 years with adenovirus PCR-positive infection recruited prospectively in two previous cohort studies. Reference standard diagnosis (bacterial, viral or indeterminate) was based on expert adjudication. BV score ranges from 0 to 100 and provides three results based on predefined cutoffs: viral or other non-bacterial etiology (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65), and bacterial or co-infection (65 < score ≤ 100). Experts were blinded to BV results.ResultsOut of 1,779 children, 142 had an adenovirus PCR-positive nasopharyngeal swab. Median age was 1.2 years (interquartile range 0.6–1.8), 50.7% were male and 52.8% were hospitalized. 12 cases were reference standard bacterial, 115 reference standard viral and 15 were indeterminate. BV score attained sensitivity of 100.0% (no false negatives), specificity of 89.5% (95% confidence interval: 83.2–95.8), and NPV of 100.0% (92.6–100.0). Equivocal rate was 19.7%.ConclusionsBV score accurately differentiated between adenoviral and bacterial-adenoviral co-infection in this cohort of children with PCR-positive adenovirus detection. This performance supports a potential to improve appropriate antibiotic use.https://www.frontiersin.org/articles/10.3389/fped.2022.990750/fullemergency medicinepediatrics, adenovirushost responsedisease etiology
spellingShingle Michal Stein
Michal Stein
Ma’anit Shapira
Ellen Bamberger
Ellen Bamberger
Irena Chistyakov
Daniel Dumov
Isaac Srugo
Michal Stein
Louis J. Bont
Adi Klein
Adi Klein
BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children
Frontiers in Pediatrics
emergency medicine
pediatrics, adenovirus
host response
disease etiology
title BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children
title_full BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children
title_fullStr BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children
title_full_unstemmed BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children
title_short BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children
title_sort bv score differentiates viral from bacterial viral co infection in adenovirus pcr positive children
topic emergency medicine
pediatrics, adenovirus
host response
disease etiology
url https://www.frontiersin.org/articles/10.3389/fped.2022.990750/full
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