Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses

Abstract

Dengue and Zika viruses are closely related mosquitoborne flaviviruses with similar transmission cycles, distribution throughout the tropics and subtropics, and disease manifestations including fever, rash, myalgia, and arthralgia. For patients with suspected dengue or Zika virus disease, nucleic acid amplification tests (NAATs) are the preferred method of diagnosis. Immunoglobulin M (IgM) antibody testing can identify additional infections and remains an important tool for the diagnosis of these diseases, but interpreting the results is complicated by cross-reactivity, and determining the specific timing of infection can be difficult. These limitations are a particular challenge for pregnant women in determining whether Zika virus infection occurred during or before the pregnancy.This report summarizes existing and new guidance on dengue and Zika virus diagnostic testing for patients with a clinically compatible illness who live in or recently traveled to an area where there is risk for infection with both viruses. CDC recommendations for screening of asymptomatic pregnant women with possible Zika virus exposure are unchanged. For symptomatic nonpregnant persons, dengue and Zika virus NAATs should be performed on serum collected ≤7 days after symptom onset. Dengue and Zika virus IgM antibody testing should be performed on NAAT-negative serum specimens or serum collected >7 days after onset of symptoms. For symptomatic pregnant women, serum and urine specimens should be collected as soon as possible within 12 weeks of symptom onset for concurrent dengue and Zika virus NAATs and IgM antibody testing. Positive IgM antibody test results with negative NAAT results should be confirmed by neutralizing antibody tests when clinically or epidemiologically indicated, including for all pregnant women. Data on the epidemiology of viruses known to be circulating at the location of exposure and clinical findings should be considered when deciding which tests to perform and for interpreting results.Patients with clinically suspected dengue should receive appropriate management to monitor and treat shock and hemorrhage. Women with laboratory evidence of possible Zika virus infection during pregnancy and their infants should be evaluated and managed for possible adverse outcomes. Dengue and Zika virus disease are nationally notifiable conditions, and cases should be reported to public health authorities.

FIGURE 1

Dengue and Zika virus testing recommendations for nonpregnant persons with a clinically compatible illness and risk for infection with both viruses* Abbreviations: IgM = immunoglobulin M; NAAT = nucleic acid amplification test; PRNT = plaque reduction neutralization test. * Specimen and test selection: Dengue and Zika virus NAATs, IgM antibody testing, and PRNTs should be performed on serum. Some NAATs also can be performed on plasma, whole blood, cerebrospinal fluid, or urine, and some antibody tests can be performed on plasma, whole blood, or cerebrospinal fluid. Laboratories might choose to perform dengue and Zika virus NAATs and IgM antibody testing simultaneously rather than sequentially, or to perform dengue virus nonstructural protein-1 testing instead of dengue virus NAAT. Indications to repeat assay(s): If the patient’s illness has epidemiologic or clinical significance (e.g., first case of local transmission in area, new transmission mode, or unusual clinical syndrome), repeat a positive NAAT on newly extracted RNA from the same specimen. For indeterminate IgM antibody test results, repeat IgM antibody testing or perform PRNT on the same specimen. In areas where PRNTs are not performed, report the indeterminate results and request a second serum specimen for IgM antibody testing. Interpretation of results: Dengue and Zika virus IgM antibodies can be detected in serum for months following infection. The specific timing of infection cannot be determined. Data on the epidemiology of viruses known to be circulating at the location of exposure and clinical findings should be considered when interpreting the results of serologic diagnostic testing.

FIGURE 2

Dengue and Zika virus testing recommendations for pregnant persons with a clinically compatible illness and risk for infection with both viruses* Abbreviations: IgM = immunoglobulin M; NAAT = nucleic acid amplification test; PRNT = plaque reduction neutralization test. * Specimen and test selection: Dengue and Zika virus NAATs, IgM antibody testing, and PRNTs should be performed on serum. Some NAATs also can be performed on plasma, whole blood, cerebrospinal fluid, or urine, and some antibody tests can be performed on plasma, whole blood, or cerebrospinal fluid. Dengue virus NAAT does not need to be performed on specimens collected >7 days after illness onset. Some laboratories might choose to perform dengue virus nonstructural protein-1 testing instead of dengue virus NAAT. Indications to repeat assay(s): If Zika virus NAAT is positive on a single specimen but IgM antibody tests are negative, repeat NAAT on newly extracted RNA from the same specimen. For indeterminate IgM antibody test results, repeat IgM antibody testing or perform PRNT on the same specimen. In areas where PRNTs are not performed, report the indeterminate results and request a second serum specimen for IgM antibody testing. Interpretation of results: Dengue and Zika virus IgM antibodies can be detected in serum for months following infection. The specific timing of infection cannot be determined. Data on the epidemiology of viruses known to be circulating at the location of exposure and clinical findings should be considered when interpreting the results of serologic diagnostic testing.