Dengue Fever (DF)
2010 Case Definition

Laboratory Criteria For Diagnosis

• Confirmatory
  • Isolation of dengue virus from or demonstration of specific arboviral antigen or genomic sequences in tissue, blood, cerebrospinal fluid (CSF), or other body fluid by polymerase chain reaction (PCR) test, immunofluorescence or immunohistochemistry, OR
  • Seroconversion from negative for dengue virus-specific serum Immunoglobulin M (IgM) antibody in an acute phase (≤5 days after symptom onset) specimen to positive for dengue-specific serum IgM antibodies in a convalescent-phase specimen collected ≥5 days after symptom onset, OR
  • Demonstration of a ≥4-fold rise in reciprocal Immunoglobulin G (IgG) antibody titer or Hemagglutination inhibition titer to dengue virus antigens in paired acute and convalescent serum samples, OR
  • Demonstration of a ≥4-fold rise in PRNT (plaque reduction neutralization test) end point titer (as expressed by the reciprocal of the last serum dilution showing a 90% reduction in plaque counts compared to the virus infected control) between dengue viruses and other flaviviruses tested in a convalescent serum sample, OR
  • Virus-specific IgM antibodies demonstrated in CSF.
• Presumptive/Probable
  • Dengue-specific IgM antibodies present in serum with a P/N ratio ≥2.

Exposure

• Travel to a dengue endemic country or presence at location with ongoing outbreak within previous two weeks of dengue-like illness, OR
• Association in time and place with a confirmed or probable dengue case.

Suspected

A clinically compatible case of DF, DHF or DSS that is epidemiologically linked to a confirmed case

Probable

A clinically compatible case of DF, DHF, or DSS with laboratory results indicative of presumptive infection

Confirmed

A clinically compatible case of DF, DHF, or DSS with confirmatory laboratory results

Comments

Asymptomatic Blood or Tissue Donor
Dengue virus-specific viral antigen or genomic sequences demonstrated in donated blood or organs during screening and confirmatory testing in the absence of symptoms in the donor.

Dengue viruses are members of the Flaviviridae and have sufficient antigenic similarity to yellow fever virus, Japanese encephalitis virus, and West Nile virus that previous infection or vaccination may raise cross-reactive serum antibodies. After a primary infection with a heterologous flavivirus, subsequent antibody testing by ELISA may produce false positive results for a different flavivirus. PRNT can often resolve cross-reactive serum antibodies in this situation and identify the infecting virus. However, high-titered cross-reactive antibody levels produced from multiple previous flavivirus infections cannot be resolved by PRNT. This demonstrates the complexity inherent in serological diagnosis and differentiation in populations living in regions where more than one flavivirus co-circulates. However, only a small proportion of the US population has evidence of previous flavivirus infection (or vaccination) so that cross-reactive flavivirus antibodies should not be a significant limitation to dengue diagnosis among most US travelers. Among US residents, most testing for dengue is done through private clinical laboratories using IgM or IgG detection techniques.

Reference testing is available from CDC’s Dengue Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, 1324 Calle Cañada, San Juan, PR 00920-3860, telephone 787-706-2399, fax 787-706-2496

Clinical Description

Dengue hemorrhagic fever (DHF) is characterized by all of the following:

• Fever lasting from 2-7 days
• Evidence of hemorrhagic manifestation or a positive tourniquet test
• Thrombocytopenia (≤100,000 cells per mm³)
• Evidence of plasma leakage shown by hemoconcentration (an increase in hematocrit ≥20% above average for age or a decrease in hematocrit ≥20% of baseline following fluid replacement therapy), OR pleural effusion, or ascites or hypoproteinemia.

Clinical Description

Dengue shock syndrome (DSS) has all of criteria for DHF plus circulatory failure as evidenced by:

• Rapid and weak pulse and narrow pulse pressure (<20mm Hg), OR
• Age-specific hypotension and cold, clammy skin and restlessness