Diagnosis of Dengue Fever

Clinical Presentation and Initial Evaluation

The Centers for Disease Control and Prevention recommends that dengue fever be suspected in patients with fever and travel history to endemic regions, with an incubation period ranging from 3-14 days, and most cases developing symptoms 4-8 days after infection 1
Dengue fever typically presents as an acute febrile illness characterized by frontal headache, retro-orbital pain, muscle and joint pain, and rash 2, 3

The World Health Organization recommends that Nucleic Acid Amplification Tests (NAATs) are the preferred diagnostic method during the first week of illness, with PCR testing on serum being most effective in the first few days of infection when patients are viremic 4, 5
The Centers for Disease Control and Prevention suggests that NS1 Antigen Detection is an excellent alternative to NAAT in the acute phase, with NS1 antigen being secreted from infected host cells as early as 1 day after symptom onset and remaining detectable up to 10 days thereafter 5
The American Society for Microbiology recommends that Serological Testing becomes more appropriate after the first week of illness, with IgM antibody capture ELISA (MAC-ELISA) being the primary serological test, and IgM antibodies typically developing during the first week of illness and remaining detectable for 2-3 months 2, 3, 5

The Centers for Disease Control and Prevention defines a Confirmed Case as a clinically compatible case that is laboratory confirmed through one of the following: isolation of dengue virus from serum and/or autopsy tissue samples, demonstration of a fourfold or greater change in antibody titers in paired samples, or detection of dengue virus antigen or viral nucleic acid 2, 3
The World Health Organization defines a Probable Case as a clinically compatible case with supportive serologic findings (IgG antibody titer ≥1280 or positive IgM antibody test on a single specimen) 2, 3

The Infectious Diseases Society of America notes that Cross-reactivity with other flaviviruses (e.g., Zika virus, West Nile virus) can complicate serological diagnosis, and Plaque reduction neutralization tests (PRNTs) provide improved specificity but are only available at select public health laboratories 5
The American College of Obstetricians and Gynecologists recommends that pregnant women receive comprehensive testing due to potential complications, including both NAAT and serology for dengue virus, as dengue infection during pregnancy may increase risk for maternal death or obstetric complications 4

The Centers for Disease Control and Prevention recommends suspecting dengue in patients presenting with fever plus at least one of the following: nausea, vomiting, rash, headache, retro-orbital pain, myalgia, arthralgia, positive tourniquet test, or leukopenia, according to the MMWR Recommendations and Reports 6
A negative IgM test on specimens collected <7 days after onset may reflect collection before antibody development and does not rule out infection, as stated in the MMWR Recommendations and Reports 6
The MMWR Recommendations and Reports suggests that some laboratories perform NAAT and IgM testing simultaneously rather than sequentially to avoid delays 6
The FDA has cleared three assays for dengue diagnosis: NAAT for use on serum and whole blood, enzyme immunoassay detecting dengue NS1 antigen in serum, and enzyme immunoassay detecting dengue IgM antibodies in serum, as reported in the MMWR Recommendations and Reports 7

Pregnant women should receive comprehensive testing with both NAAT and serology regardless of outbreak patterns due to risk of maternal death, hemorrhage, preeclampsia, eclampsia, and vertical transmission, according to the MMWR Recommendations and Reports 6
The MMWR Recommendations and Reports recommends testing for both dengue and Zika virus in pregnant women given potential for adverse outcomes with either infection 6
Other infectious etiologies to consider in differential diagnosis include: chikungunya, malaria, rubella, measles, hepatitis A, parvovirus, adenovirus, enterovirus, leptospirosis, rickettsiosis, and group A streptococcal infections, as stated in the MMWR Recommendations and Reports 6