What is the recommended initial testing approach for diagnosing influenza A?

How to Test for Influenza A

Use RT-PCR or rapid molecular assays as the first-line diagnostic test for influenza A, collecting nasopharyngeal specimens whenever possible, and avoid relying on rapid antigen tests (RIDTs) due to their critically poor sensitivity of only 10-70%. 1, 2

Recommended Testing Approach by Clinical Setting

Hospitalized Patients

• RT-PCR or other molecular assays must be used over all other influenza tests in hospitalized patients to improve detection of influenza virus infection 1, 2
• The CDC explicitly recommends that RIDTs should not be used in hospitalized patients except when more sensitive molecular assays are unavailable 1
• Multiplex RT-PCR panels targeting multiple respiratory pathogens should be used in immunocompromised patients 2
• Processing time for standard molecular assays is 1-8 hours with high sensitivity (86-100%) and high specificity 3

Outpatient Settings

• Rapid molecular assays are preferred as first-line testing when available, with results in 15-30 minutes and sensitivity of 86-100% 3, 2
• If only RIDTs are available, positive results are reliable (specificity >90-95%), but negative results cannot rule out influenza 1, 4
• When RIDTs are used due to resource limitations, follow-up testing with RT-PCR must be performed to confirm negative RIDT results 1

Specimen Collection Priorities

• Collect nasopharyngeal specimens preferentially over throat swabs or other upper respiratory specimens to maximize detection 1, 2
• Nasopharyngeal specimens are superior to all other upper respiratory tract specimens for detecting influenza viruses 2
• If nasopharyngeal specimens are unavailable, combined nasal and throat swabs should be collected instead 2
• Collect specimens as soon as possible after illness onset, preferably within 4 days of symptom onset 2

Comparison of Available Diagnostic Tests

Rapid Molecular Assays (Preferred)

• Sensitivity: 86-100% 3, 1
• Specificity: High 3
• Time to results: 15-30 minutes 3
• Can distinguish influenza A from B but typically not subtypes 3
• Many are CLIA-waived for point-of-care use 3

Standard RT-PCR/Molecular Assays

• Sensitivity: 86-100% 3, 1
• Specificity: High 3
• Time to results: 1-8 hours 3
• Can distinguish influenza A subtypes if subtype primers are used 3
• Gold standard for hospitalized patients 1

Rapid Influenza Diagnostic Tests (RIDTs) - Not Recommended

• Sensitivity: Only 10-70% (some studies show as low as 11-42%) 3, 1
• Specificity: High (>90-95%) 3, 1
• Time to results: 10-15 minutes 3
• Cannot distinguish influenza A subtypes 3

Critical Clinical Pitfalls to Avoid

• Never rely on negative RIDT results to exclude influenza during active community transmission - the sensitivity is too low (20-70%) to rule out disease 1, 5
• Do not use negative rapid test results for treatment decisions when influenza activity is high in the community 1
• Do not delay antiviral treatment while waiting for test results in high-risk patients - start treatment empirically based on clinical suspicion 3, 2
• Understand that positive predictive value of RIDTs decreases during periods of low influenza activity 1

When Laboratory Testing Is Most Useful

• Testing is most valuable when timely results will influence clinical management or infection control measures 3
• Laboratory confirmation is particularly important in hospitalized patients to guide treatment, enable effective cohorting, and implement infection control interventions 3
• In outpatient settings during high influenza activity with typical symptoms, clinical diagnosis may be sufficient for otherwise healthy patients, though testing can reduce inappropriate antibiotic use 4, 6
• Positive results reduce additional testing to identify the cause of influenza-like illness 3

Treatment Implications

• Antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for definitive influenza test results, because early therapy provides the best outcomes 3
• Treatment efficacy is greatest when started within 24 hours of symptom onset 2, 4
• High-risk and hospitalized patients should receive presumptive antiviral treatment before receiving test results 3, 2