II. Epidemiology
- Worldwide
- Incidence: 50-100 million cases/year (with 500,000 hospitalizations and 12,500 deaths)
- Most common Mosquito-Borne Illness worldwide (>50% of world population at risk)
- Endemic Regions (tropics and suptropics)
- Highest risk areas include Thailand, India, Indonesia, Brazil
- United States
- Incidence: Few hundred cases/year
- Travel to endemic area
- Regions in U.S. where patients may become infected with Dengue Fever
- Puerto Rico (endemic)
- Hawaii, Florida, Texas-Mexico border
III. Pathophysiology
- Transmitted by Aedes aegypti MosquitoSaliva (bites during daytime)
-
Arbovirus in the Flavivirus genus
- Related to West Nile Virus and Yellow Fever virus (same Flavivirus genus)
- Single stranded RNA virus
- Infects reticuloendothelial system (RBC and Platelet production organs)
- Dengue Serotypes (one Mosquito may carry multiple serotypes)
- DENV 1
- DENV 2
- DENV 3
- DENV 4
- Endemic areas (over 100 tropical countries with >40% of world population at risk)
- Southeast Asia
- Central America
- South America
- Caribbean
IV. Symptoms
- Incubation
- Travel to endemic area within prior 14 days
- Abrupt flu-like symptom onset 3-15 days (typically 4-8 days) after Mosquito Bite
- Febrile stage (days 3-7): Dengue Fever
- Undulant Fever
- High fever falls after Day 3
- Fever may rise again later
- Severe frontal or retro-orbital Headache
- Nausea or Vomiting
- Musculoskeletal pain ("Breakbone fever")
- Myalgias
- Arthralgias
- Bone pain
- Rash
- Red confluent, Morbilliform rash
- Petechiae may also form in areas of compression (e.g. Blood Pressure cuff)
- Rash starts on hands and feet, then spreads to trunk
- Red confluent, Morbilliform rash
- Undulant Fever
- Severe Dengue (1% of cases)
- Criteria
- Severe if severe plasma leakage, severe Hemorrhage or severe organ Impairment
- Timing
- Follows febrile stage in a subset of patients (2-5 days after onset), typically after fever abates
- Risk Factors for severe Dengue
- Associated with prior infection and Immunity to one Dengue serotype
- Current, second infection with new serotype results in severe illness
- Herald symptoms of severe disease
- Abdominal Pain or tenderness
- Persistent Vomiting
- Mucosal bleeding
- Lethargy
- Hepatomegaly
- Heamtocrit increases with significant Thrombocytopenia
- Severe plasma leakage (increased vascular permeability)
- Third-spacing (edema, Pleural Effusion, Ascites)
- Dengue Hemorrhagic Fever (DHF)
- See Tourniquet Test as above
- Hemorrhage (Epistaxis, Petechiae, Purpura)
- Thrombocytopenia (Platelet Count <100,000)
- Plasma, capillary leak (hypoproteinemia, effusions)
- Dengue Shock Syndrome (DSS) - lasts 48-72 hours, and has significant mortality risk
- Narrow Pulse Pressure (<20 mmHg)
- Hypotension
- Respiratory distress
- Abnormal Liver Function Tests (AST, ALT >1000)
- Altered Level of Consciousness
- Mortality rates approach 25-50% (however <1% with early and aggressive management)
- Criteria
V. Exam: Tourniquet test
- Inflate Blood Pressure cuff to midway between systolic and diastolic Blood Pressure readings
- Leave Blood Pressure cuff inflated for 5 minutes
- Release Blood Pressure cuff and wait for 2 minutes
- Observe for distal Petechiae
- At least 10-20 or more Petechiae per square inch of skin suggests capillary fragility or Thrombocytopenia
VI. Diagnosis: Consider Dengue Fever in the returning febrile traveler if the following criteria are met (WHO)
- Fever AND
- Two of the following
- Severe Headache
- Retro-orbital pain
- Joint Pain
- Myalgia
- Nausea
- Vomiting
- Lymphadenopathy
- Rash
VII. Differential Diagnosis
-
Yellow Fever (Rare in U.S. travelers)
- Infects 200,000 people worldwide per year (with 30,000 deaths)
- Hyperbilirubinemia and Jaundice distinguish from Dengue Fever
- Leptospirosis
- Typhoid Fever
- Viral Hepatitis
- Rickettsial Disease
- Bacterial Sepsis
- Malaria
- Leishmaniasis
VIII. Labs
-
Complete Blood Count
- Leukopenia (common)
- Hematocrit and Hemoglobin increased (>10% increase predicts severe disease)
-
Thrombocytopenia with Platelets <100,000 cells/mm3 (often severe)
- Observe for bleeding complications
- Other lab findings
- Mild increase in liver transaminases
- Specific tests (confirm diagnosis, but Dengue Fever is a clinical diagnosis)
- Dengue IgM (after day 4) or Dengue IgG (after day 7) with 4-fold or higher increase in titers
- Dengue reverse transcriptase PCR (within first 5 days)
- Dengue non-structural Protein type 1 (NS1) detection
- Decreased Test Specificity in those exposed to other Flavivirus (e.g. Yellow Fever)
IX. Management
- No effective treatment or Vaccine
-
General measures
- Maintain hydration
- Lower fever with Acetaminophen
- Avoid NSAIDS or Aspirin due to risk of Hemorrhage (as well as Reye Syndrome risk)
- Daily monitoring of Hematocrit and Platelet Count
- Hospitalization indications
- Infants, elderly and pregnant women
- Serious comorbidity (Diabetes Mellitus, unreliable social situation)
- Findings suggestive of impending severe Dengue
- Severe Dengue management
- Aggressive supportive care
- Intravenous Fluid initial protocol
- NS or LR 5-7 cc/kg/h for 1-2 hours
- then 3-5 ml/kg/h for 2-4 hours
- then 2-3 ml/kg/h
X. Course
- Incubation: 3-15 days (typically 4-8 days)
- Usually benign and self-limited course lasting <7 days
XI. Prevention
XII. References
- Anderson (2014) Crit Dec Emerg Med 28(7): 11-9
- Black, Martin, DeVos (2018) Crit Dec Emerg Med 32(8): 3-12
- Nordurft-Froman and DeVos (2022) Crit Dec Emerg Med 36(4): 4-15
- Feder (2013) Am Fam Physician 88(8): 524-30 [PubMed]
- Huntington (2016) Am Fam Physician 94(7): 551-7 [PubMed]
- Mangold (2013) Pedr Emerg Care 29(5): 665-9 [PubMed]
- Wilder-Smith (2005) N Engl J Med 353(9): 924-32 [PubMed]