What are the recommended diagnostic tests and treatments for patients presenting with influenza-like illness?

Influenza Testing Recommendations

Primary Recommendation for Testing Strategy

For patients presenting with influenza-like illness in outpatient settings during influenza season, clinical diagnosis without laboratory confirmation is sufficient for most cases, but rapid molecular assays (not rapid antigen tests) should be used when testing is performed to guide treatment decisions, particularly in hospitalized patients, high-risk individuals, or when results will influence infection control measures. 1, 2

When to Test vs. When to Treat Empirically

Outpatient Settings

• Most outpatients with influenza-like illness do NOT require laboratory confirmation - clinical diagnosis is adequate when influenza is circulating in the community 3
• Start antiviral treatment immediately without waiting for test results in high-risk patients presenting within 48 hours of symptom onset 1, 4
• Testing may be useful when a confirmed diagnosis will change treatment decisions or for infection control purposes 1

Hospitalized Patients

• All hospitalized patients with suspected influenza should undergo diagnostic testing using molecular assays or RT-PCR, as these are more sensitive than rapid antigen tests 1, 2
• Testing should not delay initiation of antiviral therapy in severe cases 1
• During early pandemic phases (UK alert levels 1-3), comprehensive microbiological investigation is recommended for all hospitalized cases 1

Preferred Diagnostic Tests by Clinical Setting

First-Line Testing Options (Ranked by Accuracy)

1. Rapid Molecular Assays (BEST OPTION)

• Sensitivity: 86-100% for both influenza A and B 1, 5
• Specificity: >95% 5
• Processing time: <20 minutes 1
• These are the preferred tests because they combine high accuracy with rapid turnaround 1

2. RT-PCR/Nucleic Acid Amplification Tests

• Sensitivity: 86-100% 1
• Processing time: 1-8 hours 1
• Can distinguish influenza A subtypes 1
• Preferred for hospitalized patients when rapid molecular assays are unavailable 1, 2

3. Rapid Antigen Tests (LEAST PREFERRED)

• Sensitivity: Only 10-70% - unacceptably low 1, 5
• Specificity: >90% 1, 6
• Processing time: <15 minutes 1
• Critical limitation: Negative results cannot rule out influenza and should NOT guide treatment decisions 1, 6

Specimen Collection

• Collect nose and throat swabs in viral transport medium for all patients requiring virological testing 1
• Specimens should be collected before starting antiviral therapy when possible 2
• If presentation is >7 days after symptom onset, collect acute and convalescent serum samples (5-10 ml clotted blood) 7 days apart for serological testing 1

Additional Testing for Hospitalized Patients

Essential Laboratory Tests

All hospitalized patients should have: 1, 2

• Full blood count (leukocytosis with left shift suggests bacterial co-infection; lymphopenia may indicate severe viral infection) 1, 2
• Urea, creatinine, and electrolytes 1, 2
• Liver function tests 1, 2
• C-reactive protein (elevated in bacterial superinfection) 1, 2
• Creatine kinase if myositis suspected 1, 2

Imaging

• Chest radiograph should be obtained for all patients evaluated in hospital settings (emergency department or acute admissions ward) 1, 2
• Repeat chest x-ray at 6 weeks if respiratory symptoms persist 1

Testing for Bacterial Co-infection (Influenza-Related Pneumonia)

For severe pneumonia (CURB-65 score 3-5): 1

• Blood cultures (before antibiotics) 1, 2
• Pneumococcal urine antigen (20 ml urine) 1
• Legionella urine antigen (20 ml urine) 1
• Sputum Gram stain, culture, and susceptibility testing (if able to expectorate purulent samples and no prior antibiotics) 1

For non-severe pneumonia (CURB-65 score 0-2): 1

• Sputum testing only if patient fails to respond to empirical antibiotic therapy 1

Testing Strategy During Pandemic Phases

Early Pandemic (High Alert for First Cases)

• Comprehensive virological and bacteriological investigation for ALL hospitalized cases to confirm influenza, optimize treatment, and define bacterial co-pathogens 1
• Notify local Health Protection Teams immediately 1
• Access specialized laboratory networks for molecular diagnosis 1

Established Pandemic (High Caseload)

• Virological testing NOT recommended routinely - diagnosis based on clinical findings 1
• Focus microbiological investigation on severe cases unresponsive to empirical therapy 1
• Bacterial testing directed by disease severity and comorbidities 1

Critical Pitfalls to Avoid

Testing Errors

• Never rely on negative rapid antigen tests to exclude influenza - sensitivity is only 10-70%, meaning up to 90% of true cases may be missed 1, 6, 7
• Do not delay antiviral treatment while awaiting test results - treatment is most effective when started within 24 hours of symptom onset 1, 3
• Do not use clinical symptoms alone to diagnose influenza - positive predictive value of fever + cough + acute onset is only 30-53% in older adults and those with chronic disease 6

Treatment Decisions

• Positive rapid antigen tests can guide treatment, but negative tests cannot rule out influenza 1
• In high-risk patients (age <2 years, ≥65 years, immunocompromised, pregnant, chronic medical conditions), treat empirically without testing if presenting within 48 hours of symptom onset 1, 4
• Studies show only 11% of children <2 years and 23% of adults ≥65 years receive antivirals despite being high-risk groups - do not undertreated these populations 7

Specimen Handling

• Collect respiratory specimens BEFORE initiating or changing antibiotics 2
• Transport sputum samples rapidly to laboratory 1
• Ensure close liaison with laboratory regarding suspected diagnosis, sample collection, handling, and transport 1

Treatment Implications of Testing

When Testing is Positive

• Initiate oseltamivir (75 mg twice daily for 5 days in adults; weight-based dosing in children ≥2 weeks) 4
• Treatment reduces illness duration by approximately 24 hours in otherwise healthy patients 4, 3
• May decrease risk of serious complications, particularly when started within 24 hours of symptom onset 1, 3

When Testing is Negative but Clinical Suspicion High

• Treat empirically if patient is high-risk or severely ill - do not withhold antivirals based on negative rapid tests 1
• Consider repeat testing with more sensitive molecular assay or RT-PCR 1
• Continue to evaluate for alternative diagnoses and bacterial co-infection 2