What are the recommended tests and management for diagnosing and treating dengue fever?

Diagnostic Testing and Management for Dengue Fever

For patients with suspected dengue fever, nucleic acid amplification tests (NAATs) should be performed on serum collected within 7 days of symptom onset, followed by IgM antibody testing for NAAT-negative specimens or specimens collected after 7 days of symptom onset. 1

Clinical Criteria for Testing

Testing for dengue should be considered for patients with:

• Clinically compatible illness (fever plus one or more of: nausea, vomiting, rash, headache, retro-orbital pain, myalgia, arthralgia, positive tourniquet test, leukopenia, or dengue warning signs)
• Recent travel to or residence in an area with risk for dengue infection 1

Diagnostic Algorithm

For specimens collected ≤7 days after symptom onset:

1. First-line testing: Dengue virus NAAT on serum or whole blood

   • Alternative: NS1 antigen detection (high sensitivity of 89-94%) 1, 2
   • A positive result confirms acute dengue infection

2. If NAAT is negative: Perform dengue virus IgM antibody testing

   • Note: Early in infection (days 1-3), IgM antibodies may not be detectable 3

For specimens collected >7 days after symptom onset:

1. First-line testing: Dengue virus IgM antibody testing

   • A positive result indicates recent dengue infection
   • Note: By day 7, IgM antibody detection sensitivity increases to 78-94% 3

2. For confirmation of positive IgM results: Perform plaque reduction neutralization test (PRNT)

   • PRNT titer ≥10 against dengue virus with negative PRNTs against other flaviviruses confirms recent dengue infection 1

Interpretation of Results

Test Results	Interpretation
Positive dengue NAAT	Acute dengue infection
Negative dengue NAAT, positive IgM antibody	Recent dengue infection (timing cannot be determined)
Positive IgM antibody with PRNT ≥10 for dengue and <10 for other flaviviruses	Confirmed recent dengue infection
Negative NAAT and negative IgM antibody (specimens >7 days)	No evidence of dengue infection

Management Approach

While no specific antiviral treatment exists for dengue, proper clinical management is crucial to reduce mortality:

1. Monitor for warning signs of severe disease:

   • Abdominal pain or tenderness
   • Persistent vomiting
   • Clinical fluid accumulation
   • Mucosal bleeding
   • Lethargy/restlessness
   • Liver enlargement >2 cm
   • Laboratory: Increase in hematocrit concurrent with rapid decrease in platelet count

2. Fluid management:

   • For patients without warning signs: Oral rehydration
   • For patients with warning signs or severe dengue: Intravenous fluid therapy and close monitoring of vital signs and fluid balance 1

3. Blood component therapy may be needed for severe cases with significant bleeding

Important Caveats

• Clinical criteria alone are insufficient to distinguish dengue from other febrile illnesses 2
• A negative NAAT result does not exclude dengue infection, especially if collected late in the course of illness 1
• In areas where multiple flaviviruses circulate, cross-reactivity in antibody tests can complicate diagnosis 1
• Combining multiple test methods (NAAT, NS1 antigen, and IgM antibody) increases diagnostic sensitivity to 93% 4
• During the early phase of illness (days 1-3), IgM antibodies are typically undetectable, making NAAT or NS1 antigen detection the preferred diagnostic methods 3

Special Considerations for Pregnant Women

Pregnant women with suspected dengue require particular attention due to increased risk of maternal death and obstetric complications:

• Test with both NAAT and IgM antibody testing concurrently
• Manage aggressively for possible dengue complications including hemorrhage, preeclampsia, and eclampsia 1