What is the recommended approach to diagnose influenza?

How to Diagnose Influenza

For outpatients during influenza season, diagnose influenza clinically based on fever and cough, and reserve laboratory testing for situations where confirmation would change management decisions; for hospitalized patients, use RT-PCR or other molecular assays as the preferred diagnostic method. 1

Clinical Diagnosis Approach

Outpatient Setting

Clinical diagnosis is sufficient during influenza season when patients present with characteristic symptoms. 2

• The hallmark presentation includes abrupt onset of fever (>38°C), cough, chills, myalgias, and malaise, with a positive predictive value of approximately 70-77% during influenza season 2
• The combination of fever and cough provides a positive predictive value of 71-83% in children, though lower in adults 2
• Consider influenza in any patient with respiratory symptoms or fever during influenza season, even without classic presentation 1

When Clinical Diagnosis Fails

Be aware that clinical diagnosis performs poorly in specific populations:

• Older adults (≥60 years) have a positive predictive value of only 30% 2
• Among hospitalized adults with laboratory-confirmed influenza, only 44-51% presented with typical influenza-like illness symptoms 1, 2
• Patients with chronic cardiopulmonary disease may not present with typical symptoms 1

Laboratory Testing Strategy

Indications for Laboratory Testing

Order laboratory testing when results would influence clinical management decisions, particularly for:

• Hospitalized patients with suspected influenza 1, 2
• Patients where confirmation would affect antiviral therapy decisions 2
• Immunocompromised patients 1
• Situations requiring infection control decisions 1

Test Selection by Clinical Setting

For outpatients:

• Use rapid influenza diagnostic tests (RIDTs) to improve detection of influenza virus infection 1
• Rapid molecular assays (nucleic acid amplification tests) are preferred over RIDTs when available 1

For hospitalized patients:

• Use RT-PCR or other molecular assays as the primary diagnostic method 1
• RT-PCR is the most sensitive and specific test, with results available in 2-6 hours 2
• Use multiplex RT-PCR assays targeting a panel of respiratory pathogens in immunocompromised patients 1

Do NOT use in hospitalized patients (except when molecular assays unavailable):

• RIDTs have low sensitivity (20-70%) and should be avoided 1
• Immunofluorescence assays should be avoided 1
• If RIDTs or immunofluorescence are used, confirm negative results with RT-PCR 1

Specimen Collection

Optimal Specimen Types

Collect specimens as soon as possible, preferably within 4 days of symptom onset: 1

For outpatients (in order of preference):

1. Nasopharyngeal specimens (highest yield) 1
2. Combined nasal and throat swabs if nasopharyngeal unavailable 1
3. Mid-turbinate nasal swabs over throat swabs alone 1
4. Use flocked swabs over non-flocked swabs 1

For hospitalized patients without severe lower respiratory disease:

• Collect nasopharyngeal, mid-turbinate nasal, or combined nasal-throat specimens 1

For hospitalized patients with respiratory failure on mechanical ventilation:

• Collect endotracheal aspirate or bronchoalveolar lavage fluid specimens 1
• Repeat collection from upper and lower respiratory tract if initial results are negative but clinical suspicion remains high 1

What NOT to Collect

Do not collect or test:

• Specimens from nonrespiratory sites (blood, plasma, serum, CSF, urine, stool) 1
• Serum specimens for serological diagnosis for clinical management purposes 1
• Serologic testing requires paired acute/convalescent sera 2-3 weeks apart and is only for epidemiologic investigations 1

Understanding Test Performance

Rapid Diagnostic Tests (RIDTs)

RIDTs have significant limitations:

• High specificity (>90%) but low to moderate sensitivity (20-70%) 1
• Sensitivity can be as low as 42% in clinical practice and 19% in adults 1
• Higher sensitivity in young children (70-90%) compared to adults (40-60%) because children shed higher viral concentrations 1, 3
• Most sensitive within first 48 hours of symptom onset 3

RT-PCR and Molecular Assays

RT-PCR is the gold standard:

• Most sensitive and specific test available 2
• Results available in 2-6 hours 2
• Can detect both viable and non-viable viral particles 2

Timing Considerations

Test performance depends on timing:

• Collect specimens as close to illness onset as possible (ideally ≤48 hours) 1
• Nasopharyngeal and nasal specimens have higher yields than throat swabs 1
• Positive tests can occur up to 7 days after live attenuated influenza vaccine 1

Common Pitfalls to Avoid

Critical mistakes in influenza diagnosis:

1. Relying solely on typical symptoms in older adults or immunocompromised patients who may present atypically 2
2. Waiting for laboratory confirmation before initiating antiviral therapy in high-risk patients when influenza is suspected 2
3. Using RIDTs in hospitalized patients when molecular assays are available 1
4. Accepting negative RIDT results as definitive during influenza season when clinical suspicion is high 1, 2, 3
5. Using throat swabs alone instead of nasopharyngeal or combined specimens 1
6. Testing too early or too late in the course of illness, as viral shedding patterns affect sensitivity 3
7. Dismissing influenza outside peak season, as sporadic cases occur year-round 2
8. Using antibiotics empirically for uncomplicated influenza without evidence of bacterial co-infection 2

Interpretation in Context

Always interpret test results considering:

• Local influenza activity and surveillance data 1, 2
• Clinical and epidemiologic information 1
• Positive and negative predictive values vary with disease prevalence 2
• Negative rapid tests should be confirmed with RT-PCR when clinical suspicion is high 1, 2