Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysis

Objective The objective of this study is to perform a comprehensive systematic review and meta-analysis of the accuracy of signs, symptoms and case definitions for the diagnosis of influenza.Design Systematic review and meta-analysis of diagnostic accuracy.Setting Inpatient or outpatient setting.Par...

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Main Authors: Matthew Thompson, Mark H Ebell, Barry Lutz, Ivan Rahmatullah, Cassie Hulme, Michelle Buhr, Jack Henry Kotnik, Rachel Geyer
Format: Article
Language:English
Published: BMJ Publishing Group 2025-03-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/3/e067574.full
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author Matthew Thompson
Mark H Ebell
Barry Lutz
Ivan Rahmatullah
Cassie Hulme
Michelle Buhr
Jack Henry Kotnik
Rachel Geyer
author_facet Matthew Thompson
Mark H Ebell
Barry Lutz
Ivan Rahmatullah
Cassie Hulme
Michelle Buhr
Jack Henry Kotnik
Rachel Geyer
author_sort Matthew Thompson
collection DOAJ
description Objective The objective of this study is to perform a comprehensive systematic review and meta-analysis of the accuracy of signs, symptoms and case definitions for the diagnosis of influenza.Design Systematic review and meta-analysis of diagnostic accuracy.Setting Inpatient or outpatient setting.Participants Three databases (PubMed, CINAHL and EMBASE) were searched through February 2024 for studies of clinical diagnosis of influenza using prospective data collection and a high-quality reference standard. Data were abstracted by researchers working in parallel and resolving discrepancies by discussion.Primary and secondary outcome measures Quality was assessed using QUADAS-2. Summary estimates (or ranges) of sensitivity and specificity, likelihood ratio (LR), the Youden Index and the area under the receiver operating characteristic curve were calculated.Results The final meta-analysis included 67 studies, each with between 119 and 155 866 participants. Most were judged to be low risk of bias. The signs and symptoms with the highest overall accuracy for all studies based on the Youden Index were any fever (0.32), overall clinical impression (0.28), coryza (0.25), cough and fever (0.25), and measured fever (0.25). Accuracy varied widely by age group. Only the overall clinical impression had a positive LR greater than 2.0. Cough was the most sensitive finding (0.92) with a negative LR of 0.28 in adults. The absence of any fever also had a low negative LR (0.30). The Centers for Disease Control and Prevention (CDC) definition of influenza-like illness (ILI) had good specificity but poor sensitivity in adults, while in infants, it had good sensitivity but widely varying specificity. The European CDC and WHO case definitions for ILI had modest sensitivity and specificity.Conclusions Individual signs and symptoms, their combinations, and ILI case definitions have very limited accuracy for identifying persons with influenza. More accurate surveillance and diagnosis will require the development and validation of accurate risk scores or greater use of point-of-care testing.
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spelling doaj-art-437cf754ae7742199ebffdc5280040de2025-08-20T03:23:22ZengBMJ Publishing GroupBMJ Open2044-60552025-03-0115310.1136/bmjopen-2022-067574Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysisMatthew Thompson0Mark H Ebell1Barry Lutz2Ivan Rahmatullah3Cassie Hulme4Michelle Buhr5Jack Henry Kotnik6Rachel Geyer7Department of Family Medicine, University of Washington, Seattle, Washington, USADepartment of Family Medicine, Michigan State University, East Lansing, Michigan, USADepartment of Bioengineering, University of Washington, Seattle, Washington, USAFaculty of Medicine, Universitas Airlangga, Surabaya, East Java, IndonesiaDepartment of Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USADepartment of Obstetrics and Gynecology, Emory University School of Medicine, Atlanta, Georgia, USADepartment of Bioengineering, University of Washington, Seattle, Washington, USADepartment of Family Medicine, University of Washington, Seattle, Washington, USAObjective The objective of this study is to perform a comprehensive systematic review and meta-analysis of the accuracy of signs, symptoms and case definitions for the diagnosis of influenza.Design Systematic review and meta-analysis of diagnostic accuracy.Setting Inpatient or outpatient setting.Participants Three databases (PubMed, CINAHL and EMBASE) were searched through February 2024 for studies of clinical diagnosis of influenza using prospective data collection and a high-quality reference standard. Data were abstracted by researchers working in parallel and resolving discrepancies by discussion.Primary and secondary outcome measures Quality was assessed using QUADAS-2. Summary estimates (or ranges) of sensitivity and specificity, likelihood ratio (LR), the Youden Index and the area under the receiver operating characteristic curve were calculated.Results The final meta-analysis included 67 studies, each with between 119 and 155 866 participants. Most were judged to be low risk of bias. The signs and symptoms with the highest overall accuracy for all studies based on the Youden Index were any fever (0.32), overall clinical impression (0.28), coryza (0.25), cough and fever (0.25), and measured fever (0.25). Accuracy varied widely by age group. Only the overall clinical impression had a positive LR greater than 2.0. Cough was the most sensitive finding (0.92) with a negative LR of 0.28 in adults. The absence of any fever also had a low negative LR (0.30). The Centers for Disease Control and Prevention (CDC) definition of influenza-like illness (ILI) had good specificity but poor sensitivity in adults, while in infants, it had good sensitivity but widely varying specificity. The European CDC and WHO case definitions for ILI had modest sensitivity and specificity.Conclusions Individual signs and symptoms, their combinations, and ILI case definitions have very limited accuracy for identifying persons with influenza. More accurate surveillance and diagnosis will require the development and validation of accurate risk scores or greater use of point-of-care testing.https://bmjopen.bmj.com/content/15/3/e067574.full
spellingShingle Matthew Thompson
Mark H Ebell
Barry Lutz
Ivan Rahmatullah
Cassie Hulme
Michelle Buhr
Jack Henry Kotnik
Rachel Geyer
Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysis
BMJ Open
title Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysis
title_full Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysis
title_fullStr Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysis
title_full_unstemmed Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysis
title_short Accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups: a systematic review with meta-analysis
title_sort accuracy of individual signs and symptoms and case definitions for the diagnosis of influenza in different age groups a systematic review with meta analysis
url https://bmjopen.bmj.com/content/15/3/e067574.full
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