Negative Predictive Value of Influenza Antigen Tests
The negative predictive value (NPV) of rapid influenza antigen tests is highly variable and context-dependent, ranging from approximately 57% to >99% depending on local influenza prevalence, but these tests should never be used to rule out influenza when community activity is high because their poor sensitivity (10-80%) makes negative results unreliable for clinical decision-making. 1, 2
Understanding NPV in the Context of Influenza Testing
The NPV represents the probability that a patient with a negative test truly does not have influenza 3. However, for rapid influenza diagnostic tests (RIDTs), this value is fundamentally limited by the test's poor sensitivity:
- Sensitivity of RIDTs ranges from only 10-80%, with studies documenting sensitivity as low as 19% in adults and 42% in general clinical practice 1, 2
- Specificity remains high at >90-95% across most studies 1
- Research has documented NPV as low as 56.8% (95% CI 40.8-72.7%) in one cross-sectional study 4
How Local Influenza Activity Determines NPV
The NPV of influenza antigen tests varies dramatically based on community influenza prevalence, making the same test result mean completely different things at different times of year: 1, 3
- **When influenza prevalence is <10%**: NPV approaches >99%, and negative tests are more reliable 3, 5
- When influenza prevalence is 10-15%: NPV drops to approximately 70-80%, making negative results less trustworthy 5
- When influenza prevalence is >20-60% (peak season): NPV becomes unreliable, and negative results cannot exclude influenza 5
The Advisory Committee on Immunization Practices explicitly states that clinicians must consider both positive and negative predictive values in the context of local influenza activity when interpreting any test result 1.
Critical Clinical Implications
Negative RIDT results should not be used to make treatment or infection-control decisions, especially when influenza viruses are known to be circulating in the community. 1
When to Ignore Negative Results:
- High-risk patients (immunocompromised, chronic medical conditions, severe illness) should receive empirical antiviral treatment despite negative rapid tests 1, 2
- Hospitalized patients with influenza-like illness during flu season should be treated regardless of negative antigen test results 2, 6
- Patients tested <12 hours from symptom onset are at higher risk for false negatives due to lower viral shedding 4
Confirmation Strategy:
If a definitive diagnosis is needed, confirm negative RIDT results with RT-PCR or viral culture, which have sensitivity of 86-100% 1, 2. This is particularly important for:
- Hospitalized patients 1, 2
- Patients with high clinical suspicion despite negative rapid test 1
- Patients with high fever and chills, which suggest influenza even with negative testing 4
Common Pitfalls to Avoid
Do not delay antiviral treatment while awaiting confirmatory testing in high-risk patients 1, 2. The American Academy of Pediatrics emphasizes that antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for test results 1, 2.
Do not use negative rapid tests to rule out influenza when clinical suspicion is high 1, 2. The poor sensitivity means that 20-80% of true influenza cases will test negative, making the NPV inadequate for excluding disease during peak season.
Do not test too early - sensitivity is lowest when testing occurs <12 hours from symptom onset 4. However, this should not delay empirical treatment in appropriate patients 1, 2.
Age-Related Considerations
RIDTs have higher sensitivity in young children compared to adults because children shed higher concentrations of influenza virus 1. This means NPV may be somewhat more reliable in pediatric populations, though it still cannot definitively rule out influenza during high community activity 1.