What is the best diagnostic approach for influenza?

Best Diagnostic Approach for Influenza

For most outpatient cases during influenza season, clinical diagnosis based on fever and cough is sufficient without laboratory testing, but when testing is needed, rapid molecular assays (not rapid antigen tests) are the preferred diagnostic method due to their superior sensitivity (86-100%) and 15-30 minute turnaround time. 1, 2

Clinical Diagnosis Framework

Start with clinical diagnosis during influenza season - the combination of abrupt onset fever and cough provides 71-83% positive predictive value in children and 70-77% in adults, making laboratory confirmation unnecessary for most outpatient cases. 3 However, clinical diagnosis performs poorly in older adults (only 30% positive predictive value in patients ≥60 years) and hospitalized adults (only 44-51% present with typical symptoms), so maintain a high index of suspicion in these populations. 3

Begin antiviral treatment immediately without waiting for test results in high-risk patients presenting within 48 hours of symptom onset - early therapy provides the best outcomes, with greatest benefit when started within 24 hours. 4, 1, 2

When Laboratory Testing Is Indicated

Laboratory confirmation should be obtained in these specific situations where results will change management:

• All hospitalized patients with suspected influenza - molecular assays are mandatory in this setting for accurate diagnosis and infection control 1, 2
• High-risk individuals where confirmation will guide antiviral therapy decisions 1
• When results will influence infection control measures or cohorting decisions 4, 1
• Patients where bacterial co-infection testing is needed 1

Do not test routinely in otherwise healthy outpatients during peak influenza season when clinical diagnosis is adequate. 3

Diagnostic Test Selection Algorithm

First-Line: Rapid Molecular Assays

Use rapid molecular assays as your primary diagnostic test - these provide 86-100% sensitivity, >95% specificity, and results in 15-30 minutes, making them ideal for point-of-care testing. 4, 1, 2 They are CLIA-waived and can distinguish influenza A from B (but typically not subtypes). 2

Second-Line: Standard RT-PCR/Molecular Assays

For hospitalized patients or when rapid molecular assays are unavailable, use standard RT-PCR with 1-8 hour turnaround time, 86-100% sensitivity, and ability to distinguish influenza A subtypes if subtype primers are used. 4, 1, 2

Never Use: Rapid Antigen Tests (RIDTs)

Avoid rapid antigen tests due to critically low sensitivity of 10-70% (some studies show as low as 11-42% in clinical practice), making them unreliable for ruling out influenza despite high specificity >90-95%. 1, 2, 5, 6 If RIDTs are the only option available due to resource limitations, positive results are reliable, but negative results must be confirmed with RT-PCR. 2

Specimen Collection Priorities

Collect nasopharyngeal specimens preferentially over throat swabs - they have significantly higher yields for both viral isolation and rapid detection. 2 Collect specimens as close to illness onset as possible and before starting antiviral therapy when feasible. 4, 1

For hospitalized patients with severe pneumonia, also collect specimens for bacterial co-infection testing including blood cultures, pneumococcal urine antigen, and Legionella urine antigen. 1

Critical Pitfalls to Avoid

• Never rely on negative rapid antigen test results to exclude influenza during active community transmission - the 20-70% sensitivity is too low to rule out disease 2
• Do not wait for laboratory confirmation before starting antivirals in high-risk patients when influenza is suspected clinically 1, 3
• Do not dismiss influenza in older adults or immunocompromised patients who lack typical symptoms - they frequently present atypically 3
• Do not use rapid antigen tests in hospitalized patients except when more sensitive molecular assays are completely unavailable 2
• Do not start antibiotics empirically for uncomplicated influenza without evidence of bacterial co-infection 3

Special Considerations

Interpret all test results in context of local influenza activity - positive and negative predictive values vary with community prevalence. 4, 3 During periods of low influenza activity, even tests with high specificity will have decreased positive predictive value. 2

Consider multiplex molecular assays (1-2 hour turnaround) when testing for other respiratory pathogens is clinically indicated, as they can detect influenza A/B plus other viral or bacterial targets simultaneously with high sensitivity and specificity. 4