Zika Diagnosis Confirmed by Placental Sample Testing

Veronica Hackethal, MD

June 22, 2017

Testing for Zika virus RNA in placental tissue can confirm Zika infection when the mother's blood tests are inconclusive, according to a study published online today in the Morbidity and Mortality Weekly Report.

"Given the complexity of Zika virus testing and interpretation, tissue specimen analysis provides another opportunity to confirm maternal Zika virus infection. A definitive maternal diagnosis of Zika virus infection provides valuable information to guide the evaluation and management of infants with possible congenital exposure," Sarah Reagan-Steiner, MD, from the National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control (CDC), Atlanta, Georgia, and colleagues write.

Overall, RNA testing confirmed the diagnosis of Zika for 47 (10%) women who gave birth to live infants in 2016, but who did not have a definitive diagnosis.

Although this proportion is relatively low, the authors emphasize that clinicians should continue to consider testing for Zika RNA when a definitive diagnosis has not been reached.

"Ensuring appropriate Zika virus testing and clinical follow-up of infants, according to published CDC guidance is critical in order to identify congenital Zika virus infection," they explain.

Because the Zika virus is present in the blood for a limited time, diagnosing Zika with blood tests presents a challenge. Tests outside of 12 weeks, when maternal antibodies start to wane, are not definitive. Also, blood tests can pick up antibodies to related flaviviruses, which can complicate the diagnosis. Zika persists for longer in placental and fetal tissue, and can confirm the diagnosis in pregnant women.

In the study, researchers used reverse transcriptase polymerase chain reaction (RT-PCR) to test for Zika RNA on tissue samples from 627 pregnancies completed in 2016. The samples came from 50 states and the District of Columbia, and included tissue from 546 live births and 81 pregnancy losses, in which the mother had possible Zika exposure during pregnancy.

Among 81 pregnancy losses, 22% (n = 18) of tissue samples were positive for Zika RNA.

Among 363 live births in which the mother's blood test was positive for unspecified flavivirus infection, 10% of placental tissue (38/363) tested positive for Zika RNA.

Among 86 live births in which the mother tested negative for Zika but had possible exposure to the virus more than 12 weeks before her blood test, 10% of placental tissue (9/86) tested positive for Zika RNA.

The authors note several limitations, including the fact that Zika RT-PCR cannot distinguish between maternal and congenital infection. Although a positive RNA test may increase the likelihood of appropriate clinical evaluation in infants born to mothers with confirmed Zika infection, a negative test does not rule out maternal Zika infection, they caution.

"[E]valuation of pregnant women and infants for Zika virus in accordance with CDC guidance is essential to direct appropriate infant clinical management and follow-up. Infant Zika virus testing and neuroimaging should not be delayed while results of placental testing are pending," they conclude.

One author reports receiving grants from Akonni Biosystems Inc, nonfinancial support from ThermoFisher, and a royalty generating collaborative agreement with Zeptometrix. The remaining authors have disclosed no relevant financial relationships.

Morb Mortal Wkly Rep. 2017;66(24):636-643. Full text

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