What is the preferred initial diagnostic test for suspected influenza?

Preferred Initial Diagnostic Test for Suspected Influenza

Rapid molecular assays (nucleic acid amplification tests) are the preferred initial diagnostic test for suspected influenza, offering high sensitivity (86-100%) and specificity with results in 15-30 minutes, significantly outperforming rapid antigen tests. 1, 2

Test Performance Hierarchy

First-Line: Rapid Molecular Assays

• Rapid molecular assays (NAATs) provide the optimal balance of accuracy and speed for initial diagnosis, with sensitivity of 91.6% for influenza A and 95.4% for influenza B 3
• These tests detect influenza A or B viral RNA with high sensitivity and specificity, delivering results in 15-30 minutes 1
• Many rapid molecular assays are CLIA-waived, enabling point-of-care testing 1
• The Infectious Diseases Society of America specifically recommends RT-PCR or other molecular assays over rapid influenza diagnostic tests (RIDTs), particularly in hospitalized patients 2

Second-Line: Standard RT-PCR/Molecular Assays

• Standard molecular assays (including RT-PCR) offer the highest sensitivity (86-100%) and specificity when rapid results are not critical 1
• Results are available in 1-8 hours, and these tests can distinguish influenza A virus subtypes if subtype primers are used 1
• RT-PCR is the gold standard reference method for influenza diagnosis 3, 4

Avoid as Initial Test: Rapid Antigen Tests (RIDTs)

• RIDTs have critically inadequate sensitivity (20-70% overall, as low as 11-42% in some studies) and should not be used as the initial diagnostic test 2, 3
• Sensitivity for influenza A ranges from 54.4% to 71.6%, and for influenza B only 37.2% to 53.2% 5, 3, 4
• While specificity remains high (>95%), the poor sensitivity makes negative results unreliable for ruling out influenza 2, 3

Clinical Setting-Specific Recommendations

Hospitalized Patients

• Clinicians must use RT-PCR or other molecular assays over RIDTs in hospitalized patients to improve detection accuracy 2
• The CDC recommends RIDTs should not be used in hospitalized patients except when more sensitive molecular assays are unavailable 2
• Early detection enables prompt antiviral treatment and effective infection-control interventions, leading to improved patient outcomes 1

Outpatient Settings

• Use rapid molecular assays as first-line testing when available 2, 6
• If only RIDTs are available during high community influenza activity, positive results are reliable but negative results require clinical judgment and possible empirical treatment 2, 7
• For most outpatients, clinical diagnosis may be sufficient, and laboratory confirmation is not always necessary 6

Community-Acquired Pneumonia

• When influenza viruses are circulating in the community, test for influenza with a rapid influenza molecular assay (NAAT), which is preferred over rapid antigen tests 1
• This recommendation has both therapeutic and infection-control implications in the hospital setting 1

Specimen Collection Priorities

• Collect nasopharyngeal specimens preferentially over other upper respiratory tract specimens to maximize detection of influenza viruses 2
• Nasopharyngeal and nasal specimens have higher yields than throat swab specimens for both viral isolation and rapid detection 2
• Respiratory tract specimens should be collected as close to illness onset as possible for optimal testing 1

Critical Clinical Pitfalls to Avoid

Never Rely on Negative RIDTs

• Do not use negative RIDT results to exclude influenza during active community transmission—sensitivity is too low (20-70%) to rule out disease 2, 7
• If RIDTs are used due to resource limitations, follow-up testing with RT-PCR must be performed to confirm negative results 2

Timing Considerations

• Start antiviral treatment as soon as possible after illness onset without waiting for definitive test results, as early therapy provides the best outcomes 1, 2, 8
• Treatment efficacy is greatest when started within 24 hours of symptom onset 2, 8
• Rapid antigen tests are most sensitive within the first 48 hours of symptom onset, with significantly reduced sensitivity after this window 7

Test Selection Errors

• Understand that positive predictive value of RIDTs decreases during periods of low influenza activity 2
• Age affects test performance—children typically shed higher viral concentrations, resulting in better sensitivity across all test types (12.1 to 31.8 percentage points higher) 3

Practical Testing Algorithm

For hospitalized patients or those requiring definitive diagnosis:

1. Use RT-PCR or rapid molecular assays as first-line testing 2
2. Collect nasopharyngeal specimens preferentially 2
3. Do not delay antiviral treatment while awaiting results 1, 2

For outpatient settings with high community influenza activity:

1. Use rapid molecular assays if available 2, 6
2. If only RIDTs are available: positive results are reliable, but negative results require clinical judgment and possible empirical treatment 2, 7
3. Consider repeating testing or using RT-PCR confirmation if clinical suspicion remains high despite negative RIDT 7