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Original Investigation
November 27, 2000

Clinical Signs and Symptoms Predicting Influenza Infection

Author Affiliations

From the Department of Epidemiology, University of Michigan, Ann Arbor (Dr Monto); Center for Geriatrics and Gerontology, East Virginia Medical School, Norfolk (Dr Gravenstein); and Infectious Diseases and Hepatitis, Glaxo Wellcome Inc, Research Triangle Park, NC (Drs Elliott, Colopy, and Schweinle). Dr Monto has received honoraria and research support from Glaxo Wellcome Inc and Hoffmann-LaRoche Inc. Dr Gravenstein is a consultant to Glaxo Wellcome Inc and Hoffmann-LaRoche Inc and has received research support from Glaxo Wellcome Inc. Drs Elliott, Colopy, and Schweinle are employees of Glaxo Wellcome Inc and may hold Glaxo Wellcome stock or stock options.

Arch Intern Med. 2000;160(21):3243-3247. doi:10.1001/archinte.160.21.3243

Background  New antiviral drugs are available for the treatment of influenza type A and type B infections. In clinical practice, antiviral use has rarely been guided by antecedent laboratory diagnosis. Defined clinical predictors of an influenza infection can help guide timely therapy and avoid unnecessary antibiotic use.

Objective  To examine which clinical signs and symptoms are most predictive of influenza infection in patients with influenzalike illness using a large data set derived from clinical trials of zanamivir.

Methods  This analysis is a retrospective, pooled analysis of baseline signs and symptoms from phase 2 and 3 clinical trial participants. It was conducted in mainly unvaccinated (mean age, 35 years) adults and adolescents who had influenzalike illness, defined as having fever or feverishness plus at least 2 of the following influenzalike symptoms: headache, myalgia, cough, or sore throat who underwent laboratory testing for influenza. Clinical signs and symptoms were evaluated in statistical models to identify those best predicting laboratory confirmation of influenza.

Results  Of 3744 subjects enrolled with baseline influenzalike symptoms, and included in this analysis, 2470 (66%) were confirmed to have influenza. Individuals with influenza were more likely to have cough (93% vs 80%), fever (68% vs 40%), cough and fever together (64% vs 33%), and/or nasal congestion (91% vs 81%) than those without influenza. The best multivariate predictors of influenza infections were cough and fever with a positive predictive value of 79% (P<.001). The positive predictive value rose with the increase in the temperature at the time of recruitment.

Conclusion  When influenza is circulating within the community, patients with an influenzalike illness who have both cough and fever within 48 hours of symptom onset are likely to have influenza and the administration of influenza antiviral therapy may be appropriate to consider.