Dengue Fever Virus

Diagnostic Algorithm

Clinical Background

Dengue is the most prevalent mosquito-borne viral disease in humans.

Epidemiology

• Incidence – 50-100 million cases worldwide each year
• Transmission
  • Dengue fever virus is transmitted by mosquito vectors
    • Aedes aegypti in the sub-tropical and tropical Americas
    • Aedes albopictus in Asia
  • Infection with any strain results in lifelong homologous immunity
  • Reinfection with a heterologous serotype of dengue virus enhances the infection, resulting in the most severe clinical manifestations of dengue fever, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)
  • Epidemics of dengue fever are common throughout the world

Organism

• Dengue fever is caused by 1 of 4 dengue virus serotypes (dengue 1-4)
  • Dengue virus belongs to the family Flaviviridae
  • The virus consists of a single strand of RNA surrounded by an icosahedral nucleocapsid
• Cross reactions between members of Flaviviridae are common (eg, Banzi virus; Japanese, St. Louis, and Murray Valley encephalitis viruses; Rocio virus; West Nile virus and yellow fever virus)

Clinical Presentation

• Incubation is 4-7 days
• Constitutional
  • Fever typically lasts 5-7 days
  • Headache and retroorbital pain
  • Myalgia and arthralgia
  • Prostration (incubation period of 2-6 days)
  • Severe myalgias (Breakbone fever)
• Rash
  • Typically involves flushing erythema of the face, neck and chest in the first 24-48 hours of onset of symptoms
  • Petechial, diffuse erythematous or morbilliform (occurs in 50-80% of patients)
    • Noted with “islands of sparing” (white skin in the middle of red skin)  
• Hemorrhagic manifestations – epistaxis, petechiae, gum bleeding
• Hematologic – leukopenia, thrombocytopenia
• Lymphadenopathy
• Infection can lead to DHF, resulting in renal failure and DSS
  • Majority of cases occur in children <15 years
  • Death occurs primarily in children between 5 and 15 years

Treatment

• No vaccine available, treatment is supportive

Diagnosis

• Indications for testing – flu-like illness with exanthemin endemic area or in patient with appropriate travel history
• Laboratory testing 
  • Nonspecific laboratory tests
    • CBC – frequently demonstrates leukopenia, thrombocytopenia, hemoconcentration
    • Serum transaminases – may be elevated
    • Serum electrolytes – hyponatremia
  • Laboratory diagnosis of dengue fever depends on 1 or more of the following 4 criteria
    • Viral culture – isolation of the virus from clinical specimens using cultured mosquito cells
    • Dengue-specific antibodies – detection of a fourfold or greater change in reciprocal IgG or IgM antibodies by ELISA in paired serum samples
    • EIA – demonstration of dengue virus antigen in autopsy tissue by immunohistochemistry or immunofluorescence or in serum samples
    • PCR – detection of viral genomic sequences in autopsy tissue, serum, or CSF samples

Differential Diagnosis

• Flaviviruses
  • Yellow fever
  • Japanese encephalitis
• Other viruses
  • Epstein-Barr virus
  • Cytomegaloviral infection
  • Measles
  • Rubella
  • HIV – initial infection
• Sepsis
• Bacteria
  • Salmonella typhi
  • Leptospira
  • Brucella
  • Meningococcus
• Parasites
  • Malaria
  • Babesia microti
  • Rickettsia typhi

Pharmacogenetics and Therapeutic Drug Monitoring

Screening

Monitoring

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Dengue Fever Virus Antibody, IgG 0093097 Method: Enzyme-Linked Immunosorbent Assay
Dengue Fever Virus Antibody, IgM 0093098 Method: Enzyme-Linked Immunosorbent Assay	The best evidence for current infection is significant change on two appropriately timed specimens, where both tests are done in the same laboratory at the same time

General References