June 14, 2019, Morbidity and Mortality Weekly Report: Dengue and Zika virus diagnostic testing for patients with a clinically compatible illness and risk for infection with both viruses
- Clinicians should consider dengue in a patient with a clinically compatible illness, and who lives in or recently traveled to a disease-endemic area in the 2 weeks before symptom onset.
- Patients typically present with acute onset of fever, headache, body aches, and sometimes rash spreading from the trunk.
- All patients with clinically suspected dengue should receive appropriate management to monitor for shock and reduce the risk of complications resulting from increased vascular permeability and plasma leakage and organ damage without waiting for diagnostic test results to be received.
- In the United States, because dengue is a nationally notifiable disease, all suspected cases should be reported to the local health department.
Most state health departments and many commercial laboratories perform dengue diagnostic testing.
Nucleic acid amplification tests (NAATs)
- For patients with suspected dengue virus disease, NAATs are the preferred method of laboratory diagnosis.
- NAATs should be performed on serum specimens collected 7 days or less after symptom onset.
- Laboratory confirmation can be made from a single acute-phase serum specimen obtained early (≤7 days after fever onset) in the illness by detecting viral genomic sequences with rRT-PCR or dengue nonstructural protein 1 (NS1) antigen by immunoassay.
- Presence of virus by rRT-PCR or NS1 antigen in a single diagnostic specimen is considered laboratory confirmation of dengue in patients with a compatible clinical and travel history.
- IgM antibody testing can identify additional infections and is an important diagnostic tool. However, interpreting the results is complicated by cross-reactivity with other flaviviruses, like Zika, and determining the specific timing of infection can be difficult.
- Later in the illness (≥4 days after fever onset), IgM against dengue virus can be detected with MAC-ELISA. For patients presenting during the first week after fever onset, diagnostic testing should include a test for dengue virus (rRT-PCR or NS1) and IgM.
- For patients presenting >1 week after fever onset, IgM detection is most useful, although NS1 has been reported positive up to 12 days after fever onset (Figure 3-01). In the United States, both MAC-ELISA and rRT-PCR are approved as in vitro diagnostic tests.
- IgM in a single serum sample strongly suggests a recent dengue virus infection and should be presumed confirmatory for dengue if the infection occurred in a place where other potentially cross-reactive flaviviruses (such as Zika, West Nile, yellow fever, and Japanese encephalitis viruses) are not a risk.
- PRNTs can resolve false-positive IgM antibody results caused by non-specific reactivity, and, in some cases, can help identify the infecting virus. However, in areas with high prevalence of dengue and Zika virus neutralizing antibodies, PRNT may not confirm a significant proportion of IgM positive results. PRNT testing is available through several state health departments and CDC.
- If infection is likely to have occurred in a place where other potentially cross-reactive flaviviruses circulate, both molecular and serologic diagnostic testing for dengue and other flaviviruses should be performed.
- People infected with or vaccinated against other flaviviruses (such as yellow fever or Japanese encephalitis) may produce cross-reactive flavivirus antibodies, yielding false-positive serologic dengue diagnostic test results.
IgG antibody testing
IgG detection by ELISA in a single serum sample is not useful for diagnostic testing because it remains detectable for life after a dengue virus infection.
Availability of Dengue Testing
Dengue diagnostic testing (molecular and serologic) is available from several commercial reference diagnostic laboratories, state and local public health laboratories, and CDC. Consultation on dengue diagnostic testing can be obtained from CDC at 787-706-2399.
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