Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness

<strong>Background</strong> Infectious diseases play a significant role in the global burden of disease. The gold standard for the diagnosis of bacterial infection, bacterial culture, can lead to diagnostic delays and inappropriate antibiotic use. The advent of high- throughput technolog...

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Autors principals: Kelly, E, Whelan, SO, Harriss, E, Murphy, S, Pollard, AJ, O' Connor, D
Format: Journal article
Idioma:English
Publicat: Elsevier 2022
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author Kelly, E
Whelan, SO
Harriss, E
Murphy, S
Pollard, AJ
O' Connor, D
author_facet Kelly, E
Whelan, SO
Harriss, E
Murphy, S
Pollard, AJ
O' Connor, D
author_sort Kelly, E
collection OXFORD
description <strong>Background</strong> Infectious diseases play a significant role in the global burden of disease. The gold standard for the diagnosis of bacterial infection, bacterial culture, can lead to diagnostic delays and inappropriate antibiotic use. The advent of high- throughput technologies has led to the discovery of host-based genomic biomarkers of infection, capable of differentiating bacterial from other causes of infection, but few have achieved validation for use in a clinical setting. <br> <strong>Methods</strong> A systematic review was performed. PubMed/Ovid Medline, Ovid Embase and Scopus databases were searched for relevant studies from inception up to 30/03/2022 with forward and backward citation searching of key references. Studies assessing the diagnostic performance of human host genomic biomarkers of bacterial infection were included. Study selection and assessment of quality were conducted by two independent reviewers. A meta-analysis was undertaken using a diagnostic random-effects model. The review was registered with PROSPERO (ID: CRD42021208462). <br> <strong>Findings</strong> Seventy-two studies evaluating the performance of 116 biomarkers in 16,216 patients were included. Forty-six studies examined TB-specific biomarker performance and twenty-four studies assessed biomarker performance in a paediatric population. The results of pooled sensitivity, specificity, negative and positive likelihood ratio, and diagnostic odds ratio of genomic biomarkers of bacterial infection were 0.80 (95% CI 0.78 to 0.82), 0.86 (95% CI 0.84 to 0.88), 0.18 (95% CI 0.16 to 0.21), 5.5 (95% CI 4.9 to 6.3), 30.1 (95% CI 24 to 37), respectively. Significant between-study heterogeneity (I2 77%) was present. <br> <strong>Interpretation</strong> Host derived genomic biomarkers show significant potential for clinical use as diagnostic tests of bacterial infection however, further validation and attention to test platform is warranted before clinical implementation can be achieved. <br> <strong>Funding</strong> No funding received.
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spelling oxford-uuid:6542867d-63d7-4d69-8ccd-a5e9fc59b0c32023-01-30T11:02:20ZSystematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illnessJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6542867d-63d7-4d69-8ccd-a5e9fc59b0c3EnglishSymplectic ElementsElsevier2022Kelly, EWhelan, SOHarriss, EMurphy, SPollard, AJO' Connor, D<strong>Background</strong> Infectious diseases play a significant role in the global burden of disease. The gold standard for the diagnosis of bacterial infection, bacterial culture, can lead to diagnostic delays and inappropriate antibiotic use. The advent of high- throughput technologies has led to the discovery of host-based genomic biomarkers of infection, capable of differentiating bacterial from other causes of infection, but few have achieved validation for use in a clinical setting. <br> <strong>Methods</strong> A systematic review was performed. PubMed/Ovid Medline, Ovid Embase and Scopus databases were searched for relevant studies from inception up to 30/03/2022 with forward and backward citation searching of key references. Studies assessing the diagnostic performance of human host genomic biomarkers of bacterial infection were included. Study selection and assessment of quality were conducted by two independent reviewers. A meta-analysis was undertaken using a diagnostic random-effects model. The review was registered with PROSPERO (ID: CRD42021208462). <br> <strong>Findings</strong> Seventy-two studies evaluating the performance of 116 biomarkers in 16,216 patients were included. Forty-six studies examined TB-specific biomarker performance and twenty-four studies assessed biomarker performance in a paediatric population. The results of pooled sensitivity, specificity, negative and positive likelihood ratio, and diagnostic odds ratio of genomic biomarkers of bacterial infection were 0.80 (95% CI 0.78 to 0.82), 0.86 (95% CI 0.84 to 0.88), 0.18 (95% CI 0.16 to 0.21), 5.5 (95% CI 4.9 to 6.3), 30.1 (95% CI 24 to 37), respectively. Significant between-study heterogeneity (I2 77%) was present. <br> <strong>Interpretation</strong> Host derived genomic biomarkers show significant potential for clinical use as diagnostic tests of bacterial infection however, further validation and attention to test platform is warranted before clinical implementation can be achieved. <br> <strong>Funding</strong> No funding received.
spellingShingle Kelly, E
Whelan, SO
Harriss, E
Murphy, S
Pollard, AJ
O' Connor, D
Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness
title Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness
title_full Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness
title_fullStr Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness
title_full_unstemmed Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness
title_short Systematic review of host genomic biomarkers of invasive bacterial disease: Distinguishing bacterial from non-bacterial causes of acute febrile illness
title_sort systematic review of host genomic biomarkers of invasive bacterial disease distinguishing bacterial from non bacterial causes of acute febrile illness
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