What is the appropriate management for a patient with a suspected false positive dengue Immunoglobulin M (IgM) result?

Management of Suspected False Positive Dengue IgM Results

For patients with suspected false positive dengue IgM results, confirmatory testing with plaque reduction neutralization tests (PRNT) should be performed when available to definitively determine if the result is truly a false positive or represents actual dengue infection.1, 2

Diagnostic Confirmation Algorithm

Step 1: Assess the Clinical and Epidemiological Context

• Consider the patient's clinical presentation, timing of symptoms, and epidemiological risk factors for dengue infection 3
• Evaluate for potential cross-reactivity with other flaviviruses or pathogens like EBV that can cause false positive dengue IgM results 4

Step 2: Perform Additional Testing Based on Timing of Symptoms

• For patients ≤7 days from symptom onset:

  • Perform dengue virus nucleic acid amplification test (NAAT) and/or NS1 antigen testing, which are more specific during the acute phase 3, 5
  • A positive NAAT or NS1 confirms acute dengue infection regardless of IgM status 2, 6
  • Negative NAAT/NS1 with positive IgM suggests possible false positive or early convalescent phase 1, 3

• For patients >7 days from symptom onset:

  • Consider performing both dengue and Zika virus IgM testing to assess for cross-reactivity 1
  • Thrombocytopenia correlates more consistently with true dengue infection, especially when NS1 is also positive 6

Step 3: Confirmatory Testing

• Perform PRNT if available - this is the gold standard for confirming dengue infection and ruling out false positives 1, 2
• Interpretation of PRNT results:
  • PRNT titer ≥10 against dengue virus with negative PRNTs against other flaviviruses confirms recent dengue virus infection 1
  • PRNT titer <10 against dengue virus confirms the IgM result was a false positive 1
  • PRNT titer ≥10 for both dengue and other flaviviruses indicates a recent flavivirus infection but cannot identify the specific virus 1

Step 4: If PRNT is Not Available

• Request a second serum specimen for repeat IgM antibody testing 1
• Consider testing for other potential causes of the patient's symptoms 3, 4
• If only one IgM test was performed and was positive, perform a second IgM test for another flavivirus (e.g., Zika) 1
• If it is not possible to perform additional tests, interpret the positive result as "presumptive recent flavivirus infection" 1

Important Considerations and Pitfalls

• Dengue IgM antibodies can persist for months after infection, making timing determination difficult 2, 7
• Cross-reactivity is common among flaviviruses and can occur with other pathogens like EBV 4, 8
• Combined testing approaches (NS1+IgM+IgG) improve diagnostic sensitivity compared to single tests 5, 9
• In areas with low dengue prevalence, the proportion of false positive IgM results increases 4
• Secondary dengue infections may have significantly lower or undetectable IgM levels 7
• Without confirmatory PRNT, positive IgM results should be interpreted cautiously as "presumptive" 2, 3

Clinical Management While Awaiting Confirmation

• For patients with clinical symptoms compatible with dengue:
  • Monitor for warning signs of severe dengue (abdominal pain, persistent vomiting, mucosal bleeding) 1, 3
  • Monitor platelet counts, as thrombocytopenia correlates well with true dengue infection 6
  • Provide appropriate supportive care based on clinical presentation 3
• For asymptomatic patients with isolated positive IgM:
  • Interpret with caution as likely false positive, especially in non-endemic areas 2, 4
  • Consider epidemiological context and exposure history 3