What to do in case of a suspected false positive dengue (Dengue virus) antigen test?

Managing Suspected False Positive Dengue Antigen Test Results

In cases of suspected false positive dengue antigen test results, confirmatory testing with dengue and Zika virus nucleic acid amplification tests (NAATs) and plaque reduction neutralization tests (PRNTs) should be performed to establish the correct diagnosis. 1

Diagnostic Approach for Suspected False Positive Results

Initial Assessment

• Evaluate clinical presentation and epidemiological context:
  • Recent travel to endemic areas
  • Presence of typical dengue symptoms (fever, headache, retro-orbital pain, myalgia, arthralgia, rash)
  • Local outbreaks of dengue or other flaviviruses

Confirmatory Testing Algorithm

1. For specimens collected ≤7 days after symptom onset:

   • Perform dengue and Zika virus NAATs on serum 1
   • Consider dengue virus NS1 antigen testing as an alternative to NAAT 1
   • If NAAT is positive for dengue, this confirms acute dengue infection
   • If NAAT is negative, proceed with IgM antibody testing for both dengue and Zika virus

2. For specimens collected >7 days after symptom onset:

   • Perform dengue and Zika virus IgM antibody testing 1
   • If either IgM test is positive, perform confirmatory PRNTs against dengue, Zika, and other endemic flaviviruses

3. PRNT Interpretation:

   • PRNT titer ≥10 against dengue virus with negative PRNTs against Zika virus: confirms recent dengue virus infection 1
   • PRNT titer ≥10 for both dengue and Zika virus: indicates recent flavivirus infection but cannot identify specific virus 1
   • Negative PRNT titers against both viruses: rules out infection with either virus 1

Causes of False Positive Dengue Antigen Tests

• Cross-reactivity with other flaviviruses (West Nile, St. Louis encephalitis, Japanese encephalitis, yellow fever) 1, 2
• Previous flavivirus infections or yellow fever vaccination 2
• Cross-reactivity with other infections (e.g., parvovirus B19) 3
• Nonspecific reactivity of the test 1

Special Considerations

• Timing matters: NS1 antigen tests perform best in the first 3 days of illness (sensitivity 71-100%), with decreasing sensitivity thereafter 4
• Test performance varies: NS1 antigen test specificity ranges from 22.2% to 89.0% depending on the test kit and setting 5
• Combined testing improves accuracy: Using both NS1 antigen and IgM antibody tests together improves overall sensitivity 6
• Repeat testing: If the initial test result doesn't match clinical presentation, consider collecting a second sample 2-7 days later 2

Management Recommendations

1. If false positive is suspected but cannot be immediately confirmed:

   • Monitor for warning signs of severe dengue (abdominal pain, persistent vomiting, mucosal bleeding, lethargy, liver enlargement)
   • Maintain adequate hydration
   • Avoid NSAIDs and aspirin until dengue is ruled out

2. After confirmatory testing:

   • If dengue is confirmed: continue appropriate clinical management
   • If dengue is ruled out: investigate for alternative diagnoses (other arboviruses, malaria, leptospirosis, typhoid fever)

3. Documentation:

   • Document the false positive result and confirmatory testing to prevent future diagnostic confusion

Pitfalls to Avoid

• Don't rely solely on rapid diagnostic tests: While convenient, RDTs have limitations in sensitivity and specificity 7
• Don't ignore epidemiological context: The prevalence of circulating viruses affects the predictive value of tests 3
• Don't forget about other flaviviruses: Cross-reactivity is common among flaviviruses 1, 2
• Don't dismiss clinical presentation: Laboratory results should be interpreted in the context of symptoms and exposure history

By following this structured approach to suspected false positive dengue antigen tests, clinicians can establish accurate diagnoses and provide appropriate patient management while avoiding unnecessary treatments or hospitalizations.