Diagnostic Significance of Influenza Symptoms and Signs, and Their Variation by Type/Subtype, in Outpatients Aged ≥ 15 Years: Novi Sad, Serbia

This study assessed the diagnostic performance of influenza-related symptoms and signs and their combinations, as well as differences in patient characteristics based on the type/subtype of influenza, in outpatients at a primary healthcare surveillance system. Our prospective analysis included cases aged ≥ 15 years from two influenza seasons (2022/23 and 2023/24) in Novi Sad, Serbia. Influenza cases were confirmed using polymerase chain reaction (PCR) testing. The mean age of participants with laboratory-confirmed influenza was significantly lower than that of those without influenza (<i>p</i> < 0.0001): 37.90 vs. 54.92 years in 2022/23, and 40.21 vs. 54.17 years in 2023/24. Among the examined symptoms and signs, the highest sensitivity in the 2022/23 season was demonstrated for fever (87.95%, CI: 78.96-94.07), while in the 2023/24 season it was cough (100.00%, CI: 88.06-100.00). In the 2022/23 season, the positive predictive values (PPVs) were highest for fever (34.93%), chills (31.95%), myalgia (30.30%), and malaise (28.57%), but they dropped significantly in 2023/24 for all observed symptoms and signs (ranging from 1.91% to 9.17%). Compared to the World Health Organization's case definition for influenza-like illness (ILI), the case definition provided by the European Centre for Disease Prevention and Control demonstrated higher sensitivity but lower specificity across both seasons. Participants who tested positive between December and February were more likely to have influenza A(H1N1)pdm09 or A(H3N2), whereas those who tested positive between February and April were more likely to have influenza B. This study underscores the importance of seasonal timing, symptom evaluation, and case definitions in improving influenza diagnosis in primary care.