What causes a discrepancy between a positive in-office rapid flu test for both Influenza A (Flu A) and Influenza B (Flu B) and a negative Polymerase Chain Reaction (PCR) test in a patient?

Discrepancy Between Positive Rapid Flu Test and Negative PCR

The most likely explanation is a false-positive rapid influenza test result, particularly if both Flu A and Flu B tested positive simultaneously, which should raise immediate suspicion for test error or cross-reactivity. 1

Understanding the Test Performance Characteristics

Rapid influenza diagnostic tests (RIDTs) have high specificity (>90-95%) but critically low sensitivity (20-70%), making false-negative rapid tests common but false-positive results less frequent. 1 However, false-positives do occur and are more likely under specific circumstances:

When False-Positive Rapid Tests Occur:

• During periods of LOW community influenza activity - the positive predictive value of RIDTs drops substantially when influenza prevalence is low in the community 1
• When influenza prevalence falls below 10%, positive predictive values can drop below 70%, meaning up to 30% of positive results may be false 2
• Dual positivity for both Flu A and Flu B simultaneously is highly unusual and should trigger suspicion for test malfunction or cross-reactivity, as co-infection with both types is extremely rare 1

Why PCR is the Gold Standard:

• RT-PCR has 86-100% sensitivity and high specificity, making it far superior to rapid antigen tests for definitive diagnosis 3, 4, 5
• PCR is the recommended confirmatory test for hospitalized patients and when definitive diagnosis is needed 3, 4
• Negative PCR results are highly reliable and can effectively rule out influenza infection 4, 5

Clinical Decision Algorithm

Step 1: Assess Community Influenza Activity

• Check local surveillance data to determine current influenza prevalence 1
• If community activity is LOW, the positive rapid test is more likely to be false-positive 1, 2

Step 2: Evaluate the Clinical Presentation

• Consider whether symptoms are truly consistent with influenza or could represent another respiratory pathogen 1
• Assess timing of specimen collection - specimens collected >4 days after symptom onset may yield less reliable results 5

Step 3: Trust the PCR Result

• The negative PCR should be considered the definitive result - PCR has superior accuracy and can reliably exclude influenza 3, 4, 5
• Do not initiate or continue antiviral treatment based solely on the positive rapid test when PCR is negative 3, 4

Step 4: Consider Alternative Diagnoses

• Investigate other respiratory pathogens that may be causing the illness 1
• Consider bacterial infections that can produce influenza-like symptoms 1

Critical Pitfalls to Avoid

• Do not treat based on a positive rapid test when PCR is negative, especially if both Flu A and B were positive on the rapid test 3, 4
• Do not assume the PCR was performed incorrectly - PCR sensitivity is 86-100% and false-negatives are rare when specimens are collected properly 3, 4, 5
• Do not ignore low community prevalence - this dramatically affects the positive predictive value of rapid tests 1, 2
• Be aware that improper specimen collection or handling could theoretically affect PCR results, but this is less common than false-positive rapid tests during low prevalence periods 3

Practical Recommendation

In this scenario, the negative PCR result should guide clinical management. Discontinue antiviral therapy if already started, and pursue alternative diagnoses for the patient's respiratory symptoms. 3, 4, 5 The simultaneous positivity for both Flu A and Flu B on the rapid test strongly suggests a technical error rather than true infection.