Virus

Dengue

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Dengue, Break-bone Fever, Dandy Fever, Duengero Fever, Seven-day Fever, Dengue Hemorrhagic Fever, Dengue Fever, Aden Fever, Dengue Shock Syndrome

  • Epidemiology
  1. Worldwide
    1. Incidence: 50-100 million cases/year (with 500,000 hospitalizations and 12,500 deaths)
    2. Most common Mosquito-Borne Illness worldwide (>50% of world population at risk)
  2. United States
    1. Incidence: Few hundred cases/year
    2. Travel to endemic area
      1. Highest risk
        1. Thailand, India, Indonesia, Brazil
      2. Other regions
        1. Puerto Rico (endemic)
        2. Hawaii, Florida, Texas-Mexico border
  • Pathophysiology
  1. Transmitted by Aedes aegypti MosquitoSaliva (bites during daytime)
  2. Arbovirus in the Flavivirus genus
    1. Related to West Nile Virus and Yellow Fever virus (same Flavivirus genus)
    2. Single stranded RNA virus
  3. Infects reticuloendothelial system (RBC and platelet production organs)
    1. Liver
    2. Spleen
    3. Lymph nodes
    4. Thymus
  4. Dengue Serotypes (one Mosquito may carry multiple serotypes)
    1. DENV 1
    2. DENV 2
    3. DENV 3
    4. DENV 4
  5. Endemic areas (over 100 tropical countries with >40% of world population at risk)
    1. Southeast Asia
    2. Central America
    3. South America
    4. Caribbean
  • Symptoms
  1. Incubation
    1. Travel to endemic area within prior 14 days
    2. Abrupt flu-like symptom onset 3-15 days (typically 4-8 days) after Mosquito Bite
  2. Febrile stage (days 3-7)
    1. Undulant Fever
      1. High fever falls after Day 3
      2. Fever may rise again later
    2. Severe frontal or retro-orbital Headache
    3. Nausea or Vomiting
    4. Musculoskeletal pain ("Breakbone fever")
      1. Myalgias
      2. Arthralgias
      3. Bone pain
    5. Rash
      1. Red confluent, Morbilliform rash
        1. Petechiae may also form in areas of compression (e.g. Blood Pressure cuff)
      2. Rash starts on hands and feet, then spreads to trunk
        1. See Distal Extremity Rash
  3. Severe Dengue (1% of cases)
    1. Criteria
      1. Severe if severe plasma leakage, severe Hemorrhage or severe organ Impairment
    2. Timing
      1. Follows febrile stage in a subset of patients (2-5 days after onset), typically after fever abates
    3. Risk Factors for severe Dengue
      1. Associated with prior infection and immunity to one Dengue serotype
      2. Current, second infection with new serotype results in severe illness
    4. Herald symptoms of severe disease
      1. Abdominal Pain or tenderness
      2. Persistent Vomiting
      3. Mucosal bleeding
      4. Lethargy
      5. Hepatomegaly
      6. Heamtocrit increases with significant Thrombocytopenia
    5. Severe plasma leakage (increased vascular permeability)
      1. Third-spacing (edema, Pleural Effusion, Ascites)
    6. Dengue Hemorrhagic Fever (DHF)
      1. See Tourniquet Test as above
      2. Hemorrhage (Epistaxis, Petechiae)
      3. Thrombocytopenia
      4. Plasma, capillary leak (hypoproteinemia, effusions)
    7. Dengue Shock Syndrome (DSS) - lasts 48-72 hours, and has significant mortality risk
      1. Narrow Pulse Pressure (<20 mmHg)
      2. Hypotension
      3. Respiratory distress
      4. Abnormal Liver Function Tests (AST, ALT >1000)
      5. Altered Level of Consciousness
      6. Mortality rates approach 25-50% (however <1% with early and aggressive management)
  1. Inflate Blood Pressure cuff to midway between systolic and diastolic Blood Pressure readings
  2. Leave Blood Pressure cuff inflated for 5 minutes
  3. Release Blood Pressure cuff and wait for 2 minutes
  4. Observe for distal Petechiae
    1. At least 10-20 or more Petechiae per square inch of skin suggests capillary fragility or Thrombocytopenia
  • Diagnosis
  • Consider Dengue Fever in the returning febrile traveler if the following criteria are met (WHO)
  1. Fever AND
  2. Two of the following
    1. Severe Headache
    2. Retro-orbital pain
    3. Joint Pain
    4. Myalgia
    5. Nausea
    6. Vomiting
    7. Lymphadenopathy
    8. Rash
  • Differential Diagnosis
  1. Yellow Fever (Rare in U.S. travelers)
    1. Infects 200,000 people worldwide per year (with 30,000 deaths)
    2. Hyperbilirubinemia and Jaundice distinguish from Dengue Fever
  2. Leptospirosis
  3. Typhoid Fever
  4. Viral Hepatitis
  5. Rickettsial disease
  6. Bacterial Sepsis
  7. Malaria
  8. Leishmaniasis
  • Labs
  1. Complete Blood Count
    1. Leukopenia (common)
    2. Hematocrit and Hemoglobin increased (>10% increase predicts severe disease)
    3. Thrombocytopenia with platelets <100,000 cells/mm3 (often severe)
      1. Observe for bleeding complications
  2. Other lab findings
    1. Mild increase in liver transaminases
  3. Specific tests (confirm diagnosis, but Dengue Fever is a clinical diagnosis)
    1. Dengue IgM (after day 4) or Dengue IgG (after day 7) with 4-fold or higher increase in titers
    2. Dengue reverse transcriptase PCR (within first 5 days)
    3. Dengue non-structural protein type 1 (NS1) detection
      1. Decreased Test Specificity in those exposed to other Flavivirus (e.g. Yellow Fever)
  • Management
  1. No effective treatment or Vaccine
  2. General measures
    1. Maintain hydration
    2. Lower fever with Acetaminophen
    3. Avoid NSAIDS or Aspirin due to risk of Hemorrhage (as well as Reye Syndrome risk)
    4. Daily monitoring of Hematocrit and Platelet Count
  3. Hospitalization indications
    1. Infants, elderly and pregnant women
    2. Serious comorbidity (Diabetes Mellitus, unreliable social situation)
    3. Findings suggestive of impending severe Dengue
  4. Severe Dengue management
    1. Aggressive supportive care
    2. Intravenous Fluid initial protocol
      1. NS or LR 5-7 cc/kg/h for 1-2 hours
      2. then 3-5 ml/kg/h for 2-4 hours
      3. then 2-3 ml/kg/h
  • Course
  1. Incubation: 3-15 days (typically 4-8 days)
  2. Usually benign and self-limited course lasting <7 days
  • Prevention
  1. Limit Mosquito contact (DEET, protective clothing, bed nets)
    1. See Vector borne infection
  2. New Dengue Vaccine is available in Mexico (but not in U.S.) as of 2016