Dengue Fever Virus

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

Indications for Testing

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

Criteria for Diagnosis

  • CDC case definition for dengue virus infections (2015)
    • Dengue fever
    • 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 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
    • PCR – detect viral genomic sequences in autopsy tissue, serum, or CSF samples
    • Cell culture for DV requires specialized mosquito cell lines not routinely available in the clinical laboratory setting

Histology

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

Differential Diagnosis

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

Epidemiology

  • Incidence – 50 million cases worldwide annually
    • ~22,000 deaths (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)
  • 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 a lifetime
  • Reinfection with a heterologous serotype of DV enhances the 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 the 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 the 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 a different DV serotype
    • In infants, most often occurs from primary DV infection when the 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

Limitations 

Usually requires paired convalescent samples 

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 the 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: August 2016