What are the diagnostic criteria and treatment options for dengue fever?

Diagnosis of Dengue Fever

Dengue fever should be diagnosed using nucleic acid amplification tests (NAATs) on serum collected within 7 days of symptom onset, or NS1 antigen detection as an alternative, with positive results confirming acute infection. 1

Clinical Diagnostic Criteria

Dengue testing should be considered in patients with:

• Fever plus one or more of the following:
  • Nausea/vomiting (present in 52% of cases)
  • Rash (similar to measles)
  • Headache
  • Retro-orbital pain
  • Myalgia/arthralgia ("breakbone fever")
  • Positive tourniquet test
  • Leukopenia
  • Warning signs of severe disease 2, 1

Epidemiological Considerations

• Recent travel to or residence in endemic areas (tropical/subtropical regions)
• Sexual contact with someone who lives in or recently traveled to endemic areas 2

Diagnostic Testing Algorithm

For patients ≤7 days after symptom onset:

1. First-line testing: Dengue virus NAAT on serum (preferred method)
2. Alternative: NS1 antigen detection test (FDA-cleared)
   • Positive results confirm acute dengue infection 1

For patients >7 days after symptom onset:

1. Primary testing: IgM antibody detection
   • IgM antibodies appear 3-5 days after symptom onset and remain detectable for 2-3 months
   • Negative IgM results in specimens collected 7 days to 12 weeks after symptom onset rule out recent infection 1

For positive IgM results without positive NAAT/NS1:

• Perform plaque reduction neutralization tests (PRNTs) against dengue and other endemic flaviviruses
• PRNT titer ≥10 against dengue virus and negative PRNTs against other flaviviruses confirms recent dengue infection 1

Laboratory Findings Supporting Diagnosis

• Thrombocytopenia (platelet count <100,000/mm³)
• Leukopenia
• Elevated hematocrit (indicating hemoconcentration)
• Elevated liver enzymes (present in 70% of hospitalized patients) 1, 3

Diagnostic Challenges and Pitfalls

Cross-reactivity Issues

• Dengue IgM antibodies may cross-react with other flaviviruses (e.g., Zika virus)
• In areas with co-circulation of multiple flaviviruses, PRNT may not reliably distinguish between infections 1

Secondary Infection Considerations

• In secondary dengue infections, the IgM antibody response may be diminished or absent
• Rapid increase in neutralizing antibodies against multiple flaviviruses makes diagnostic testing more complex 1

Timing Considerations

• False negatives may occur if specimens are collected too early for antibody detection
• Testing during the appropriate window is critical for accurate diagnosis 1

Treatment Approach

Once diagnosed, management should include:

• Outpatient management for patients who:

  • Have no comorbidities
  • Can maintain oral hydration
  • Have normal urine output
  • Show no bleeding manifestations 1

• Hospitalization for patients with high-risk factors:

  • Pregnancy
  • Advanced age
  • Obesity
  • Diabetes
  • Hypertension
  • Kidney or heart disease
  • Hemoglobinopathies 1

• Supportive care:

  • Oral hydration or intravenous fluids (5-10 ml/kg/hour, adjusted based on clinical response)
  • Acetaminophen/paracetamol for fever and pain
  • Avoid NSAIDs and aspirin due to bleeding risk 1

• Close monitoring for warning signs:

  • Abdominal pain or tenderness
  • Persistent vomiting
  • Clinical fluid accumulation (pleural effusion, ascites)
  • Mucosal bleeding
  • Lethargy or restlessness
  • Liver enlargement
  • Increasing hematocrit with rapid decrease in platelet count 1

With proper diagnosis and management, mortality from dengue can be reduced to less than 0.5% even in hospitalized patients 1.