II. 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. Endemic Regions (tropics and suptropics)
    1. Highest risk areas include Thailand, India, Indonesia, Brazil
  3. United States
    1. Incidence: Few hundred cases/year
    2. Travel to endemic area
    3. Regions in U.S. where patients may become infected with Dengue Fever
      1. Puerto Rico (endemic)
      2. Hawaii, Florida, Texas-Mexico border

III. 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

IV. 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): Dengue Fever
    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, Purpura)
      3. Thrombocytopenia (Platelet Count <100,000)
      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)

V. Exam: Tourniquet test

  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

VI. 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

VII. 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

VIII. 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)

IX. 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

X. Course

  1. Incubation: 3-15 days (typically 4-8 days)
  2. Usually benign and self-limited course lasting <7 days

XI. 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

XII. References

  1. Anderson (2014) Crit Dec Emerg Med 28(7): 11-9
  2. Black, Martin, DeVos (2018) Crit Dec Emerg Med 32(8): 3-12
  3. Nordurft-Froman and DeVos (2022) Crit Dec Emerg Med 36(4): 4-15
  4. Feder (2013) Am Fam Physician 88(8): 524-30 [PubMed]
  5. Huntington (2016) Am Fam Physician 94(7): 551-7 [PubMed]
  6. Mangold (2013) Pedr Emerg Care 29(5): 665-9 [PubMed]
  7. Wilder-Smith (2005) N Engl J Med 353(9): 924-32 [PubMed]

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Related Studies

Ontology: Dengue Fever (C0011311)

Definition (CHV) An acute, infectious tropical disease caused by an arbovirus transmitted by mosquitoes
Definition (CHV) An acute, infectious tropical disease caused by an arbovirus transmitted by mosquitoes
Definition (CHV) An acute, infectious tropical disease caused by an arbovirus transmitted by mosquitoes
Definition (MSH) An acute febrile disease transmitted by the bite of AEDES mosquitoes infected with DENGUE VIRUS. It is self-limiting and characterized by fever, myalgia, headache, and rash. SEVERE DENGUE is a more virulent form of dengue.
Definition (MEDLINEPLUS)

Dengue is an infection caused by a virus. You can get it if an infected mosquito bites you. Dengue does not spread from person to person. It is common in warm, wet areas of the world. Outbreaks occur in the rainy season. Dengue is rare in the United States.

Symptoms include a high fever, headaches, joint and muscle pain, vomiting, and a rash. In some cases, dengue turns into dengue hemorrhagic fever, which causes bleeding from your nose, gums, or under your skin. It can also become dengue shock syndrome, which causes massive bleeding and shock. These forms of dengue are life-threatening.

There is no specific treatment. Most people with dengue recover within 2 weeks. Until then, drinking lots of fluids, resting and taking non-aspirin fever-reducing medicines might help. People with the more severe forms of dengue usually need to go to the hospital and get fluids.

To lower your risk when traveling in dengue-prone countries

  • Wear insect repellent with DEET
  • Wear clothes that cover your arms, legs and feet
  • Close unscreened doors and windows

NIH: National Institute of Allergy and Infectious Diseases

Definition (NCI) An acute infection caused by Dengue virus. Signs and symptoms include sudden onset of fever, headache, rash, arthralgia, and myalgia. It is transmitted through mosquitoes.
Definition (CSP) acute infectious, eruptive, febrile disease caused by four antigenically related but distinct serotypes of the dengue virus; transmitted by the bite of infected Aedes mosquitoes, especially A. aegypti; classical dengue (dengue fever) is self-limiting and characterized by fever, myalgia, headache, and rash; dengue hemorrhagic fever is a more virulent form of dengue virus infection.
Concepts Disease or Syndrome (T047)
MSH D003715
ICD9 061
ICD10 A90
SnomedCT 154345006, 266194002, 38362002
LNC LA10451-5
English Dengue, Fever, Dengue, Dengue fever [classical dengue], breakbone fever, Dengue fever (diagnosis), Dengue fever virus infection, Dengue [Disease/Finding], Classical Dengues, Classical Dengue Fever, Dengue, Classical, Classical Dengue Fevers, Dengue Fever, Classical, Classical Dengue, dengue fever, Break-bone fever, Break-bone Fever, Break Bone Fever, Breakbone Fever, Fever, Breakbone, Break-Bone Fever, Fever, Break-Bone, Dengue fever, Breakbone fever, Dengue (disorder), dengue, breakbone; fever, dandy fever, dandy; fever, dengue; fever, fever; Aden, fever; breakbone, fever; dandy, fever; dengue, Aden; fever, Dengue Fever
Dutch denguekoortsvirusinfectie, dengue, Aden; koorts, breakbone; fever, dandy; fever, dengue; koorts, fever; breakbone, fever; dandy, koorts; aden, koorts; dengue, Dengue-koorts [klassieke dengue], denguekoorts, Dengue, Knokkelkoorts
French Infection par le virus de la dengue, Fièvre rouge, Dengue classique, Fièvre dengue classique, Dengue, Fièvre dengue
German Dengue-Fieber-Virusinfektion, Dengue-Fieber [Klassische Dengue], Dengue-Fieber, Denguefieber, Dengue
Italian Infezione da virus della febbre dengue, Febbre dengue, Dengue
Portuguese Infecção por vírus de dengue, Febre Quebra-Ossos, Dengue, Febre da Dengue
Spanish Infección por virus de la fiebre dengue, dengue (trastorno), dengue, fiebre dengue, fiebre quebrantahuesos, Dengue, Fiebre Dengue
Japanese デング熱ウイルス感染, デングネツウイルスカンセン, デングネツ, デング熱, H熱
Swedish Dengue
Czech dengue, Horečka dengue, Dengue, Infekce virem horečky dengue
Finnish Dengue
Korean 뎅기열[전형적 열]
Croatian DENGA
Polish Gorączka denga
Hungarian Dengue, Dengue láz vírus fertőzés, dengue láz
Norwegian Dengue, Denguefeber

Ontology: Severe Dengue (C0019100)

Definition (MSH) A virulent form of dengue characterized by THROMBOCYTOPENIA and an increase in vascular permeability (grades I and II) and distinguished by a positive pain test (e.g., TOURNIQUET PAIN TEST). When accompanied by SHOCK (grades III and IV), it is called dengue shock syndrome.
Definition (NCI) A serious condition caused by Dengue virus infection. Patients present with an acute febrile illness followed by restlessness, irritability, and bleeding. It may lead to hemorrhagic shock and death.
Concepts Disease or Syndrome (T047)
MSH D019595
ICD10 A91
SnomedCT 186599009, 186598001, 20927009
English Hemorrhagic Fever, Dengue, DHF - Dengue haemorrhag fever, Dengue hemorrhagic fever (diagnosis), Thai Hemorrhagic Fever, Fever, Philippine Hemorrhagic, Philippine Hemorrhagic Fever, Hemorrhagic Dengue, Singapore Hemorrhagic Fever, Hemorrhagic Dengues, Fever, Singapore Hemorrhagic, Fever, Thai Hemorrhagic, dengue haemorrhagic fever, dengue fever haemorrhagic, dengue hemorrhagic, dengue hemorrhagic fever, haemorrhagic dengue fever, hemorrhagic dengue fever, dengue fever hemorrhagic, Severe Dengue, Dengue Hemorrhagic Fever, Dengues, Severe, Severe Dengues, Dengue, Severe, Dengue haemorrhagic fever (disorder), Severe Dengue [Disease/Finding], Dengue hemorrhagic fever, DHF - Dengue haemorrhagic fever, DHF - Dengue hemorrhagic fever, Dengue haemorrhagic fever, Dengue hemorrhagic fever (disorder), bangkok hemorrhagic; fever, Philippine; hemorrhagic fever, dengue (virus); fever, hemorrhagic, dengue; hemorrhagic fever, dengue; hemorrhagic, Singapore; hemorrhagic fever, Thailand; hemorrhagic fever, fever; bangkok hemorrhagic, fever; dengue (virus), hemorrhagic, hemorrhagic fever; Philippine, hemorrhagic fever; Singapore, hemorrhagic fever; Thailand, hemorrhagic fever; dengue, hemorrhagic; dengue, virus; dengue, hemorrhagic fever, Bangkok; hemorrhagic fever, hemorrhagic fever; Bangkok
Dutch dengue hemorragische koorts, Bangkok; koorts, Filippijns; hemorragische koorts, Singapore; hemorragische koorts, Thailand; hemorragische koorts, dengue; hemorragische koorts, dengue; hemorragisch, dengue{virus}; koorts, hemorragisch, hemorragisch; dengue, hemorragische koorts; Filippijns, hemorragische koorts; Singapore, hemorragische koorts; Thailand, hemorragische koorts; dengue, koorts; Bangkok, koorts; dengue{virus}, hemorragisch, virus; dengue, hemorragische koorts, Bangkok; hemorragische koorts, hemorragische koorts; Bangkok, Dengue-hemorragische koorts, Hemorragische denguekoorts, Koorts, dengue-hemorragische
French Fièvre hémorragique Dengue, Fièvre hémorragique thaï, Dengue grave, Dengue hémorragique, Fièvre hémorragique des Philippines, Dengue sévère, Fièvre hémorragique de Singapour
German Dengue-Haemorrhagisches Fieber, Haemorrhagisches Dengue-Fieber, Hämorrhagisches Dengue-Fieber, Hämorrhagisches Fieber, Dengue
Italian Febbre emorragica dengue, Febbre emorragica di dengue, Forma emorragica di dengue
Portuguese Febre hemorrágica de dengue, Not Translated[Severe Dengue], Febre Hemorrágica da Dengue, Dengue Hemorrágica
Spanish Fiebre dengue hemorrágica, Fiebre hemorrágica de dengue, Not Translated[Severe Dengue], Fiebre Hemorrágica Dengue, dengue hemorrágico, fiebre hemorrágica del dengue, fiebre hemorrágica dengue (trastorno), fiebre hemorrágica dengue, fiebre quebrantahuesos hemorrágica, Dengue Hemorrágico
Swedish Dengue-blödarfeber
Japanese デングシュッケツネツ, デング性ショック症候群, デング出血性熱, 出血熱-デング, デング熱ショック症候群, デングショック症候群, デング出血熱
Czech hemoragická horečka dengue, Hemoragická horečka dengue
Finnish Verenvuotoinen dengue
Korean 뎅기출혈열
Polish Gorączka krwotoczna dengue, Gorączka krwotoczna denga, Zespół wstrząsowy dengue
Hungarian Dengue haemorrhagiás láz
Norwegian Hemoragisk denguefeber, Denguefeber, hemoragisk

Ontology: Dengue Shock Syndrome (C0376300)

Concepts Disease or Syndrome (T047)
MSH D019595
SnomedCT 409671005
Czech šokový syndrom dengue
Portuguese Síndrome de Choque da Dengue
German Dengue-Schock-Syndrom
Italian Sindrome da shock da dengue
Spanish Síndrome de Choque por Dengue, síndrome de shock por Dengue (trastorno), síndrome de shock por Dengue
Norwegian Dengue sjokksyndrom
French Syndrome de choc de la dengue, Syndrome de choc dû à la dengue, Dengue avec syndrome de choc
English Dengue shock syndrome (disorder), Dengue shock syndrome, Dengue Shock Syndrome
Dutch Dengue-shocksyndroom

Ontology: seven-day; fever, dengue (C1401762)

Concepts Disease or Syndrome (T047)
English fever; seven-day, dengue, seven-day; fever, dengue
Dutch koorts; zevendaags, dengue, zevendaags; koorts, dengue