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
CDC recommends dengue virus testing for:
- Anyone who lives in or traveled to areasexternal icon where dengue virus is transmitted and has recently experienced signs and symptoms of dengue illness.
- Signs and symptoms of dengue may include fever, headache, rash, body aches, and bleeding manifestations. Symptoms may be mild or severe. Severe dengue often requires hospitalization. Dengue can occasionally present with signs and symptoms of aseptic meningitis or encephalitis.
- Symptomatic pregnant women with possible dengue or Zika virus exposure*
Dengue virus testing is not recommended for:
- Asymptomatic patients
- Preconception screening
*Possible Zika virus exposure includes living in, traveling to, or sex without a condom with someone who lives in or has traveled to an area with risk of Zika.
Patients with symptoms consistent with dengue can be tested with both molecular and serologic diagnostic tests during the first 7 days of illness. After the first 7 days of illness, test only with serologic diagnostic tests.
To accurately diagnose dengue virus infection, perform antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) with a nucleic acid amplification test (NAAT) on a single serum specimen collected within the first 10 days of illness according to the algorithm below:
Diagnostic Tests for Dengue and Specimens
|Diagnostic Test||≤7 Days After Symptom Onset||>7 Days Post Symptom Onset||Specimen Types|
|Molecular Tests||✓||—||Serum, plasma, whole blood, cerebrospinal fluid*|
|Dengue Virus Antigen Detection (NS1)||✓||—||Serum|
|Serologic Tests||✓||✓||Serum, cerebrospinal fluid*|
|Tissue Tests||✓||✓||Fixed tissue|
* Testing cerebrospinal fluid is recommended in suspect patients with central nervous system clinical manifestations such as encephalopathy and aseptic meningitis.
Acute Phase: Initial 1-7 days after symptom onset
- The initial 1-7 days after symptom onset are referred to as the acute phase of dengue.
- During this period, dengue virus is typically present in blood or blood-derived fluids such as serum or plasma.
- Dengue virus RNA can be detected with molecular tests.
- The non-structural protein NS1 is a dengue virus protein that also can be detected using some commercial tests.
- A negative result from a molecular or NS1 test is not conclusive. For symptomatic patients during the first 1-7 days of illness, any serum sample should be tested by a NAAT or NS1 test and an IgM antibody test. Performing both molecular and IgM antibody (or NS1 and IgM antibody) tests can detect more cases than performing just one test during this time period, and usually allows diagnosis with a single sample.
Convalescent Phase: >7 days post symptom onset
- The period beyond 7 days following symptom onset is referred to as the convalescent phase of dengue.
- Patients with negative NAAT or NS1 test results and negative IgM antibody tests from the first 7 days of illness should have a convalescent sample tested for IgM antibody test.
- During the convalescent phase, IgM antibodies are usually present and can be reliably detected by an IgM antibody test.
- IgM antibodies against dengue virus can remain detectable for 3 months or longer after infection.
- Patients who have IgM antibodies against dengue virus detected in their serum specimen with an IgM antibody test and either: 1) have a negative NAAT or NS1 result in the acute phase specimen, or 2) without an acute phase specimen, are classified as having a presumptive, recent dengue virus infection.
Testing to differentiate dengue from Zika and other flaviviruses
- Cross reactivity: Cross reactivity is a limitation of dengue serologic tests. Serologic tests to detect antibodies against other flaviviruses such Japanese encephalitis, St. Louis encephalitis, West Nile, yellow fever, and Zika viruses may cross react with dengue viruses. This limitation must be considered for patients who live in or have traveled to areas where other flaviviruses co-circulate. Therefore, a patient with other recent or past flavivirus infection(s) may be positive when tested to detect IgM antibodies against dengue virus. To more precisely determine the cause of infection in IgM positive patients, the IgM-positive specimens can be tested for specific neutralizing antibodies by plaque reduction neutralization test (PRNT) (against the four dengue virus serotypes and other flaviviruses; however, PRNT does not always conclusively distinguish specific flaviviruses.
- Areas with co-circulating flaviviruses: For people living in or traveling to an area with endemic or concurrently circulating dengue, Zika, and other flaviviruses, clinicians will need to order appropriate tests to best differentiate dengue virus from other flaviviruses, and may consult with state or local public health laboratories or CDC for guidance.
- Pregnant women: If the patient is pregnant and symptomatic and lives in or has traveled to an area with risk of Zika, test for Zika in addition to dengue. Clinicians concerned that a pregnant woman has been exposed to Zika may need to attempt to differentiate between dengue and Zika by requesting PRNT.
Interpreting test results
- If a NAAT or NS1 test is positive for dengue, a current dengue diagnosis is confirmed.
- If the NAAT result is negative and the IgM antibody test is positive, the laboratory diagnosis is presumptive dengue virus infection if no other flaviviruses are circulating in the region where the patient was likely infected. Refer to CDC’s Travelers’ Health website for information.
- In the case of a positive dengue virus IgM antibody test and a negative NAAT or NS1 test from a patient’s serum specimen, if other flaviviruses such as Zika, yellow fever, Japanese encephalitis, West Nile, and St. Louis encephalitis viruses are possibly circulating in the region where the patient was likely infected, PRNT may be recommended to attempt to identify the cause of illness. PRNT adds significantly to the time and cost of testing and is usually not warranted except for pregnant women concerned about Zika infection.
- A negative PRNT on an IgM positive sample suggests a false-positive IgM result or non-confirmed case. A positive PRNT result may give a definitive specific diagnosis for dengue or other flaviviruses, but also may give a non-specific cross reactive flavivirus result.
Dengue and Zika Testing Algorithm for Symptomatic Non-Pregnant Patients
Dengue and Zika Testing Algorithm for Symptomatic Pregnant Women