What is the prognosis for dengue fever?

Prognosis of Dengue Fever

The prognosis for dengue fever is generally favorable with more than 90% of cases taking a mild course, though severe dengue can develop with mortality rates of 1-5% in cases that progress to shock and/or mucosal hemorrhages. 1

Disease Course and Classification

• Dengue infection presents as a spectrum ranging from mild febrile illness to dengue hemorrhagic fever and dengue shock syndrome 2
• The disease typically follows a triphasic course: febrile phase, critical phase, and recovery phase 1
• During the febrile phase (first 3 days), patients are typically viremic, and dengue virus RNA can be detected in serum from approximately 2 days before to 1 week after illness onset 3
• The critical phase begins around day 3-7 of illness, coinciding with defervescence, when warning signs may appear 2

Warning Signs and Severe Disease Indicators

• Danger signs requiring immediate medical attention include:

  • Persistent vomiting
  • Abdominal pain/tenderness
  • Clinical fluid accumulation
  • Mucosal bleeding
  • Lethargy/restlessness
  • Hepatomegaly
  • Hematocrit rise with concurrent thrombocytopenia 2

• Early recognition of these warning signs and appropriate management can reduce case-fatality rates to less than 0.5% 2

Prognostic Indicators by Disease Phase

Early Phase (First 3 Days)

• Platelet count ≤100 G/L (OR = 2.2; 95% CI: 1.2-3.9) and serum albumin <35 g/L (OR = 3.3; 95% CI: 1.8-6.1) are significant independent predictors of progression to severe dengue 4
• Meta-analysis with moderate-certainty evidence confirms significantly lower platelet counts (SMD -0.65,95% CI -0.97 to -0.32) in patients who later develop severe disease 5

Critical Phase (Day 4-6)

• Elevated liver enzymes: AST >400 U/L (OR = 3.0; 95% CI: 1.1-7.9) and ALT >400 U/L (OR = 6.6; 95% CI: 1.7-24.6) 4
• Persistent hypoalbuminemia <35 g/L (OR = 3.0; 95% CI: 1.5-5.9) 4
• Elevated total bilirubin >17 μmol/L (OR = 4.6; 95% CI: 2.0-10.4) 4
• AST levels are significantly higher in severe cases (SMD 0.87,95% CI 0.36 to 1.38) compared to non-severe dengue 5

Immunological Markers

• Elevated IL-10 levels up to day 7 of fever onset have been identified as a potential prognostic marker for severe dengue 6
• IFNγ may also serve as a prognostic marker, though levels vary between studies 6
• However, significant heterogeneity in methodologies and patient cohorts limits the immediate clinical application of these immunological markers 6

Monitoring and Management

• Hematocrit levels should be closely monitored during the critical phase as they begin to rise due to plasma leakage 3
• A ≥20% increase in hematocrit from baseline is considered evidence of significant plasma leakage and a criterion for identifying dengue hemorrhagic fever 3
• Presence of any warning sign warrants close monitoring and consideration for hospitalization 2
• Patients should be classified into risk groups based on clinical findings and comorbidities to determine appropriate outpatient or inpatient management 1

Pitfalls and Caveats

• The diagnosis of dengue can be challenging due to its diverse clinical presentations, ranging from mild undifferentiated fever to life-threatening conditions 7
• Cross-reactivity of antibody responses among flaviviruses can complicate serological diagnosis 7
• No single definitive diagnostic biomarker is present across the entire period of patient presentation, particularly in those experiencing secondary dengue infection 7
• Despite advances in point-of-care testing, reliable biomarkers that provide effective prognostic indicators of severe disease progression remain a challenge 7
• Inconsistent case classifications across studies contribute to substantial heterogeneity in research findings 5