On May 31, 2016, this report was posted online as an MMWR Early Release.

Ingrid B. Rabe, MBChB1; J. Erin Staples, MD, PhD1; Julie Villanueva, PhD1; Kimberly B. Hummel, PhD1; Jeffrey A. Johnson, PhD1; Laura Rose; MTS1; Susan Hills, MBBS1; Annemarie Wasley, ScD1; Marc Fischer, MD1; Ann M. Powers, PhD1 (View author affiliations)

Summary

What is already known about this topic?

Zika virus is a mosquito-borne flavivirus closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses. Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods. However, results of Zika virus antibody testing can be difficult to interpret because of cross-reactivity with related flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus.

What is added by this report?

For persons with suspected Zika virus disease, a positive real-time reverse transcription–polymerase chain reaction (rRT-PCR) result confirms Zika virus infection, but a negative result does not exclude infection. In these cases, antibody testing can identify additional recent Zika virus infections. If immunoglobulin (Ig) M test results are positive, equivocal, or inconclusive, performing a plaque reduction neutralization test (PRNT) is needed to confirm the diagnosis. However, recent evidence suggests that a 4-fold higher titer by PRNT might not discriminate between anti-Zika virus antibodies and cross-reacting antibodies in all persons who have been previously infected with or vaccinated against a related flavivirus. Thus, a more conservative approach to interpreting PRNT results is now recommended to reduce the possibility of missing the diagnosis of either Zika or dengue virus infection.

What are the implications for public health practice?

All patients with clinically suspected dengue should receive appropriate management to reduce the risk for hemorrhagic medical complications. Pregnant women with laboratory evidence of a recent Zika virus infection or flavivirus infection should be evaluated and managed for possible adverse pregnancy outcomes and reported to the appropriate Zika virus pregnancy registry. Health care providers should consult with state or local public health authorities for assistance in interpreting test results.

Zika virus is a single-stranded RNA virus in the genus Flavivirus and is closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses (1,2). Among flaviviruses, Zika and dengue virus share similar symptoms of infection, transmission cycles, and geographic distribution. Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods. For persons with suspected Zika virus disease, a positive real-time reverse transcription–polymerase chain reaction (rRT-PCR) result confirms Zika virus infection, but a negative rRT-PCR result does not exclude infection (3–7). In these cases, immunoglobulin (Ig) M and neutralizing antibody testing can identify additional recent Zika virus infections (6,7). However, Zika virus antibody test results can be difficult to interpret because of cross-reactivity with other flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus (8). This is important because the results of Zika and dengue virus testing will guide clinical management. Pregnant women with laboratory evidence of Zika virus infection should be evaluated and managed for possible adverse pregnancy outcomes and be reported to the U.S. Zika Pregnancy Registry or the Puerto Rico Zika Active Pregnancy Surveillance System for clinical follow-up (9,10). All patients with clinically suspected dengue should have proper management to reduce the risk for hemorrhage and shock (11). If serologic testing indicates recent flavivirus infection that could be caused by either Zika or dengue virus, patients should be clinically managed for both infections because they might have been infected with either virus.

Rabe IB, Staples JE, Villanueva J, et al. Interim Guidance for Interpretation of Zika Virus Antibody Test Results. MMWR Morb Mortal Wkly Rep 2016;65. DOI: http://dx.doi.org/10.15585/mmwr.mm6521e1 .

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