Dengue Fever Virus

Dengue fever virus (DV) is the most prevalent mosquito-borne viral disease in humans.

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Flu-like illness with exanthem in endemic area
  • Patient with relevant travel history

Criteria for Diagnosis

  • CDC case definition for dengue virus infections (2015)
  • Dengue fever (DF)
    • Dengue hemorrhagic fever (DHF)
    • Dengue shock syndrome (DSS)

Laboratory Testing

  • CDC clinical and laboratory guidance for dengue fever
  • Nonspecific laboratory tests
    • CBC – frequently demonstrates leukopenia, thrombocytopenia, hemoconcentration
    • Serum transaminases – may be elevated
    • Serum electrolytes – hyponatremia not uncommon
  • Specific testing for laboratory diagnosis based on case-definition criteria
    • Dengue-specific antibodies – reciprocal IgG or IgM antibodies by enzyme-linked immunosorbent assay (ELISA) in paired serum samples
      • IgM reaches peak at 6 days – not useful in critical stage of diagnosis
      • Cross reactivity with other flaviviruses (eg, Zika) decreases test specificity
    • Polymerase chain reaction (PCR) – detect viral genomic sequences in autopsy tissue, serum, or cerebrospinal fluid (CSF) samples
    • Cell culture for dengue fever virus (DV) requires specialized mosquito cell lines not routinely available in clinical laboratory setting

Histology

Demonstration of DV antigen in autopsy tissue by immunohistochemistry or immunofluorescence, or in serum samples

Differential Diagnosis

Epidemiology

  • Incidence – ~390 million infections annually, of which ~96 million show clinical symptoms (2013 estimates reported by WHO)
    • ~22,000 deaths annually (mostly among children) associated with the disease (WHO estimate)
    • Epidemics common in tropical and subtropical areas worldwide
  • Transmission
    • Transmitted by mosquito vectors
      • Same vector as those for Zika and yellow fever viruses
      • Aedes aegypti – subtropical and tropical locations worldwide
      • Aedes albopictus – Asia; also prevalent in southeastern U.S.
    •  Transplacental transmission possible

Organism

  • Caused by 1 of 4 DV serotypes (dengue 1-4) – single-stranded RNA virus of Flaviviridae family
  • Cross-reactions between members of Flaviviridae are common (eg, Banzi virus; Japanese, St. Louis, and Murray Valley encephalitis viruses; Rocio virus; West Nile virus; yellow fever virus)
  • Infection with any strain results in lifelong homologous immunity – patients in endemic regions can be infected with up to 4 strains in lifetime
  • Reinfection with heterologous serotype of DV enhances infection – most severe clinical manifestations
    • Dengue hemorrhagic fever (DHF)
    • Dengue shock syndrome (DSS)

Clinical Presentation

  • Incubation – 4-7 days
  • Constitutional symptoms
    • Fever typically lasts 5-7 days
    • Headache and retro-orbital pain
    • Arthralgia, myalgia
      • Severe myalgia ("breakbone fever")
    • Prostration – incubation period of 2-6 days
  • Rash
    • Typically involves flushing erythema of face, neck, and chest during first 24-48 hours of symptoms
    • Petechial, diffuse erythematous or morbilliform – 50-80% of patients
      • Noted with “islands of sparing” – white skin in middle of red skin
  • Hemorrhagic manifestations – epistaxis, petechiae, gum bleeding
  • Hematologic – leukopenia, thrombocytopenia
  • Lymphadenopathy
  • DHF/DSS
    • Majority of cases found in patients with recurrent dengue fever or who are reinfected with different DV serotype
    • In infants, most often occurs from primary DV infection when mother has previous immunity
      • Majority of cases in children <15 years
      • Death primarily in children between 5-15 years
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.

Dengue Fever Virus Antibodies, IgG and IgM 0093096
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Follow-up 

For equivocal results, repeat testing in 10-14 days 

Dengue Virus (1-4) Subtype by PCR 2013294
Method: Qualitative Polymerase Chain Reaction

Limitations 

Negative result does not rule out presence of PCR inhibitors in patient specimen or of test-specific nucleic acid in concentrations below level of detection by this test

General References

Choumet V, Desprès P. Dengue and other flavivirus infections. Rev Sci Tech. 2015; 34(2): 473-8, 467-72. PubMed

Hynes NA. Dengue: A reemerging concern for travelers. Cleve Clin J Med. 2012; 79(7): 474-82. PubMed

Jain A, Chaturvedi UC. Dengue in infants: an overview. FEMS Immunol Med Microbiol. 2010; 59(2): 119-30. PubMed

Kularatne SA. Dengue fever. BMJ. 2015; 351: h4661. PubMed

Morens DM. Dengue fever and dengue hemorrhagic fever. Pediatr Infect Dis J. 2009; 28(7): 635-6. PubMed

Potts JA, Rothman AL. Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations. Trop Med Int Health. 2008; 13(11): 1328-40. PubMed

Roberts CH, Mongkolsapaya J, Screaton G. Dengue fever: a practical guide. Br J Hosp Med (Lond). 2012; 73(4): C60-4. PubMed

Simmons CP, Farrar JJ, Nguyen vV, Wills B. Dengue. N Engl J Med. 2012; 366(15): 1423-32. PubMed

Tang KF, Ooi EE. Diagnosis of dengue: an update. Expert Rev Anti Infect Ther. 2012; 10(8): 895-907. PubMed

Wright WF, Pritt BS. Update: The diagnosis and management of dengue virus infection in North America. Diagn Microbiol Infect Dis. 2012; 73(3): 215-20. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Medical Reviewers

Last Update: October 2017