Epidemiology

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Transmission/Virology

Dengue Virus is an Arbovirus (Arthropod-Borne Virus) (see Arboviruses)

• Family Flaviviridae
  • Genus Flavivirus: “flavus” means yellow in Latin (originated from Yellow Fever Virus, so named because of its propensity to cause jaundice)

Routes of Transmission

• Bite from Infected Mosquito (see Mosquito Bite)
  • Aedes Aegypti
  • Aedes Albopictus (Asian Tiger Mosquito)

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Diagnosis

Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) for Dengue Virus

• Useful
  • Testing for Chikungunya Virus and Zika Virus Should Also Be Simultaneously Performed (see Chikungunya Fever and Zika Virus): a single PCR test for all 3 infections is available from the CDC and other laboratories

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Clinical Manifestations-Asymptomatic Dengue Virus Infection

General Comments

• Most Dengue Virus Infections in Adults are Symptomatic: 86% of cases are symptomatic (Am J Trop Med Hyg, 1995) [MEDLINE]
  • However, in Children, Approximately 50% of Dengue Virus Infections are Symptomatic (Am J Epidemiol, 2002) [MEDLINE]

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Clinical Manifestations-Classic Dengue Fever (“Break-Bone Fever”)

General Comments

• Latency: symptoms usually begin 4-7 days (range: 3-14 days) after mosquito bite
  • Symptoms Occurring >14 Days After Return from a Dengue-Endemic Country Exclude the Diagnosis of Dengue Fever
• Symptoms Vary by Age, Sex, and Primary vs Secondary Dengue Virus Infection (Am J Epidemiol, 1995) [MEDLINE]
  • Frequency of Rash was Higher in Patients with Primary Dengue Virus Infection
  • Frequency of Other Symptoms and Risk of Hospitalization was Higher in Patients with Secondary Dengue Virus Infection
  • Frequency of Symptoms was Higher in Older Patients
  • Frequency of Arthralgias/Myalgias/Rash were Higher in Female Patients
• Distinction Between the Clinical Presentations of Zika Virus, Dengue Virus, and Chikungunya Virus (see Zika Virus and Chikungunya Fever) (Centers for Disease Control and Prevention, “Zika Virus-What Clinicians Need to Know?” Clinician Outreach and Communication Activity (COCA) Call 1/26/16 (Accessed 7/17) [LINK]

Dermatologic Manifestations

• Macular/Maculopapular Rash (see Papules)
  • Rash Typically Appears 2-5 Days After the Onset of Fever
  • Rash May Be Pruritic

Gastrointestinal Manifestations

• Diarrhea (see Diarrhea): occurs in 30% of cases
• Elevated Liver Function Tests (LFT’s) (see Elevated Liver Function Tests)
  • Elevated AST: frequently elevated in both pediatric and adult cases
    • AST is Usually 2-5x the Upper Limit of Normal (But May Be 5-15x the Upper Limit of Normal in Some Cases)
• Hepatomegaly (see Hepatomegaly): occurs in 20-50% of cases
• Nausea/Vomiting (see Nausea and Vomiting): occur in 50% of cases

Hematologic Manifestations

• Leukopenia (see Leukopenia)
  • Leukopenia is Common and Useful Diagnostically
• Lymphadenopathy (see Lymphadenopathy): occurs in 20-50% of cases
• Spontaneous Hemorrhage
  • Hemorrhage Occurs in 68% of Pediatric Cases (Clin Infect Dis, 2010) [MEDLINE]
    • Common Sites of Hemorrhage
      • Skin (Palpable Purpura) (see Purpura): 58% of bleeding cases
      • Epistaxis (see Epistaxis): 19% of bleeding cases
      • Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage): 4% of bleeding cases
  • Hemorrhage Occurs in 22% of Adult Cases (Am J Med, 1996) [MEDLINE]
    • Common Sites of Hemorrhage
      • Skin (Palpable Purpura) (see Purpura)
      • Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage)
• Thrombocytopenia (see Thrombocytopenia)
  • Thrombocytopenia is Observed in Most Cases: platelet count <100k is observed in 16-55% of cases (Am J Med, 1996) [MEDLINE] (J Infect Dis, 1997) [MEDLINE]

Neurologic Manifestations

• Headache (see Headache)
• Retro-Orbital Pain

Otolaryngologic Manifestations

• Conjunctival Injection
  • Epidemiology
    • Conjunctival Injection Occurs in 20-50% of Cases
• Facial Puffiness
  • Epidemiology
    • Facial Puffiness May Occur
• Nasal Congestion (see Nasal Congestion)
  • Epidemiology
    • Nasal Congestion Occurs in 33% of Cases
• Palatal Petechiae (see Palatal Petechiae)
  • Epidemiology
    • Palatal Petechiae May Occur
• Pharyngitis (see Pharyngitis)
  • Epidemiology
    • Pharyngitis Occurs in 33% of Cases

Pulmonary Manifestations

• Cough (see Cough): occurs in 33% of cases

Rheumatologic Manifestations

• Arthralgias (see Arthralgias): usually significant
• Myalgias (see Myalgias): usually significant

Other Manifestations

• Fatigue (see Fatigue)
  • Fatigue is Common
  • Fatigue Occurs After the Febrile Phase and May Last Days-Weeks (Especially in Adult Cases)
• Fever (see Fever)
  • Fever is Common and Typically Lasts 5-7 Days
  • Biphasic (“Saddleback”) Fever Curve Occurs in 5% of Cases: initial febrile phase, followed by a second febrile phase lasting 1-2 days

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Clinical Manifestations-Dengue Hemorrhagic Fever

General Comments

• Dengue Shock Syndrome is Defined by the Presence of 4 Clinical Criteria
  • Capillary Leak Syndrome
  • Hemoconcentration
  • Hemorrhage: either positive tourniquet test or spontaneous hemorrhage
  • Marked Thrombocytopenia (see Thrombocytopenia): platelet count <100k
• Distinction Between the Clinical Presentations of Zika Virus, Dengue Virus, and Chikungunya Virus (see Zika Virus and Chikungunya Fever) (Centers for Disease Control and Prevention, “Zika Virus-What Clinicians Need to Know?” Clinician Outreach and Communication Activity Call 1/26/16) [LINK]

Cardiovascular Manifestations

• Capillary Leak Syndrome
  • Capillary Leak Syndrome is the Most Specific and Life-Threatening Clinical Feature of Dengue Hemorrhagic Fever
  • Onset of Capillary Leak: between day 3-7 of illness
    • Abdominal Pain Precedes the Onset of Capillary Leak in 60% of Cases (see Abdominal Pain)
    • Constellation of Decrease in Fever + Abdominal Pain + Persistent Vomiting + Restlessness/Lethargy May Precede the Onset of Capillary Leak Syndrome/Dengue Shock Syndrome (Clin Infect Dis, 2006) [MEDLINE]
    • Onset Occurs Concomitantly with the Decrease in Fever, Severe Thrombocytopenia, and AST Elevation
  • Development of Capillary Leak: develops over 24-48 hrs
• Myocarditis/Systolic Congestive Heart Failure (see Myocarditis): may occur in some cases

Gastrointestinal Manifestations

• Abdominal Pain (see Abdominal Pain)
  • Abdominal Pain Precedes the Onset of Capillary Leak Syndrome in 60% of Cases
  • Abdominal Pain May Be Severe: may mimic an acute abdomen
• Ascites (see Ascites)
• Liver Failure (Acute Liver Failure, Acute Hepatic Necrosis, Fulminant Hepatic Necrosis, Fulminant Hepatitis) (see Fulminant Hepatic Failure): may occur in some cases after resuscitation from profound shock (suggesting that liver failure may be due to hepatic hypoerfusion, rather than a direct viral effect)
• Nausea/Vomiting (see Nausea and Vomiting)

Hematologic Manifestations

• Hemoconcentration: hematocrit may increase ≥20%
• Hemophagocytic Syndrome (Hemophagocytic Lymphohistiocytosis, HLH) (see Hemophagocytic Syndrome): case reports
• Hemorrhage: variable
  • Ecchymoses (see Ecchymosis): occur in 50% of adult cases
  • Epistaxis (see Epistaxis)
  • Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage)
  • Menorrhagia (see Menorrhagia)
  • Petechiae (see Petechiae): occur in 50% of adult cases
  • Positive Tourniquet Test: appearance of petechiae (≥10 per one square inch) after 5 min blood pressure cuff inflation to a pressure midway between the systolic and diastolic pressures
• Marked Thrombocytopenia (see Thrombocytopenia: typically <100k

Neurologic Manifestations

• Encephalopathy (see Delirium)
• Guillain-Barré Syndrome (see Guillain-Barré Syndrome)
• Motor Weakness (see xxxx)
• Peripheral Neuropathy (see Peripheral Neuropathy)
  • Mononeuropathy
  • Polyneuropathy
• Seizures (see Seizures): may occur in some cases
• Transverse Myelitis (see Transverse Myelitis)

Pulmonary Manifestations

• Pleural Effusion (see Pleural Effusion-Exudate)

Other Manifestations

• Fever (see Fever)
  • Fever Lasts 2-7 Days

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Treatment

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Prognosis

• Mortality Rate with Dengue Shock Syndrome: 12% (despite aggressive therapy) (Pediatrics, 1993) [MEDLINE]

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References

General

• Unusual neurologic manifestations occurring during dengue fever infection. Am J Trop Med Hyg. 1993;48(6):793 [MEDLINE]
• Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study. Pediatrics. 1993;92(1):111 [MEDLINE]
• Dengue fever in U.S. troops during Operation Restore Hope, Somalia, 1992-1993. Am J Trop Med Hyg. 1995;53(1):89 [MEDLINE]
• Symptoms of dengue fever in relation to host immunologic response and virus serotype, Puerto Rico, 1990-1991. Am J Epidemiol. 1995;142(11):1204 [MEDLINE]
• Dengue fever among travelers. Am J Med. 1996;101(5):516 [MEDLINE]
• Early clinical and laboratory indicators of acute dengue illness. J Infect Dis. 1997;176(2):313 [MEDLINE]
• Neurological manifestations of dengue infection. Lancet. 2000;355(9209):1053 [MEDLINE]
• Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, Thailand. Am J Epidemiol. 2002;156(1):40 [MEDLINE]
• Dengue-related deaths in Puerto Rico, 1992-1996: diagnosis and clinical alarm signals. Clin Infect Dis. 2006;42(9):1241 [MEDLINE]
• Dengue hemorrhagic fever: the sensitivity and specificity of the world health organization definition for identification of severe cases of dengue in Thailand, 1994-2005. Clin Infect Dis. 2010;50(8):1135 [MEDLINE]
• Dengue. N Engl J Med. 2012 Apr;366(15):1423-32 [MEDLINE]
• Centers for Disease Control and Prevention, “Zika Virus-What Clinicians Need to Know?” Clinician Outreach and Communication Activity (COCA) Call 1/26/16 (Accessed 7/17) [LINK]