How do you explain a patient with positive influenza A (flu A) and influenza B (flu B) rapid tests 4 days apart, but a negative polymerase chain reaction (PCR) test?

Explaining Discordant Rapid Influenza Tests and Negative PCR

Most Likely Explanation

The positive rapid influenza tests are almost certainly false-positives, and the negative PCR result should be trusted as the definitive answer—this patient does not have influenza. 1

Understanding the Test Performance Gap

The discordance between positive rapid tests and negative PCR stems from fundamental differences in test accuracy:

• RT-PCR has 86-100% sensitivity and high specificity, making it the gold standard for influenza diagnosis and highly reliable for ruling out infection when negative 2, 3
• Rapid influenza diagnostic tests (RIDTs) have critically low sensitivity (20-70%) but high specificity (>90-95%), meaning false-negative rapid tests are common, but false-positive results should be rare 4, 1
• However, the positive predictive value of RIDTs drops substantially when influenza prevalence is low in the community, making false-positives more likely during periods of low viral circulation 4, 1

Why This Scenario is Highly Suspicious

The finding of positive Flu A followed by positive Flu B on separate tests 4 days apart is extremely unusual and should immediately raise suspicion for test malfunction, cross-reactivity, or contamination rather than true infection. 1

• Co-infection with both influenza A and B simultaneously is exceedingly rare, though documented in isolated case reports 5
• Sequential infection with different influenza types within 4 days is biologically implausible given typical viral kinetics and immune response
• This pattern strongly suggests technical issues with the rapid tests rather than true dual infection 1

Potential Causes of False-Positive Rapid Tests

Environmental Contamination

• Influenza vaccine administration in the same location as specimen collection can contaminate samples with vaccine RNA, leading to false-positive results for multiple influenza types 6
• Vaccine RNA can remain detectable in the environment for at least 66 days after administration 6
• This is particularly relevant if testing occurred near vaccination sites during flu season 6

Low Community Prevalence

• When influenza activity is low in the community, the positive predictive value of rapid tests decreases dramatically, making false-positives more likely than true positives 4, 1
• Check local surveillance data to determine current influenza prevalence in your area 1

Test Malfunction or Cross-Reactivity

• Improper test performance, expired reagents, or cross-reactivity with other respiratory pathogens could produce spurious positive results 7
• The high specificity of RIDTs (>95%) makes this less common but still possible 4

Clinical Management Algorithm

Trust the PCR result and do not initiate or continue antiviral treatment based solely on the positive rapid tests when PCR is negative. 1

Immediate Actions:

• Discontinue any influenza antiviral therapy if it was started based on the rapid test results 1
• Consider alternative diagnoses including other respiratory viral pathogens (RSV, rhinovirus, coronavirus, adenovirus) or bacterial infections 4, 1
• Evaluate whether symptoms truly match influenza or suggest another etiology 1

Diagnostic Considerations:

• The negative PCR effectively rules out influenza infection given its superior sensitivity 2, 3
• Consider testing for other respiratory pathogens if clinically indicated 1
• Review specimen collection timing—samples should ideally be collected within 4 days of symptom onset, though PCR remains highly sensitive even with delayed collection 2

Critical Pitfalls to Avoid

• Never rely on rapid test results alone for definitive diagnosis, especially when results don't make clinical sense 4
• Do not assume dual influenza infection without PCR confirmation, as this is extraordinarily rare 1, 5
• Be aware that positive rapid tests during low prevalence periods are more likely false-positives than true positives, contrary to what clinicians typically expect 4, 1
• Remember that RIDTs are designed for screening, not confirmation—the Infectious Diseases Society of America specifically recommends against using RIDTs in hospitalized patients due to poor performance 2, 3