Zika Virus Persists in Infants' Brain After Birth

Troy Brown, RN

December 13, 2016

Zika virus can persist for much longer than expected in the brains of infants and fetuses and in the placentas of pregnant women, a new study from the Centers for Disease Control and Prevention (CDC) has found. The findings could explain how the virus causes catastrophic birth defects and pregnancy losses even in women who have been only mildly ill.

Julu Bhatnagar, PhD, lead of the molecular pathology team at the CDC's Infectious Diseases Pathology Branch, and colleagues report their findings in an article published online December 13 and in the January 2017 issue of Emerging Infectious Diseases.

"Our findings show that Zika virus can continue to replicate in infants' brains even after birth, and that the virus can persist in placentas for months — much longer than we expected," Dr Bhatnagar said in a CDC news release. "We don't know how long the virus can persist, but its persistence could have implications for babies born with microcephaly and for apparently healthy infants whose mothers had Zika during their pregnancies. More studies are needed to fully understand how the virus can affect babies."

The study is the first to demonstrate the replication of Zika virus RNA in brain tissues of infants born with microcephaly who subsequently died and in placentas of women who experienced pregnancy losses.

The researchers used reverse transcription polymerase chain reaction (RT-PCR) testing and in situ hybridization to test tissues from 52 case patients with clinically and epidemiologically suspected Zika virus infection. Testing included placental and umbilical cord tissue and fetal tissues (from pregnancy loss) from 44 women suspected of having prenatal Zika virus infection, and brain (including cerebral cortex, pons, medulla), kidney, liver, spleen, lung, and heart tissues from eight infants with microcephaly who died after birth. Of the 44 women, 30 experienced adverse pregnancy or birth outcomes (miscarriage, elective termination, stillbirth, or babies born with microcephaly) and 22 delivered infants who appeared healthy.

RT-PCR testing revealed Zika virus infection in brain tissues from the brains of the eight infants with microcephaly and placental/fetal tissues from 24 women.

Sixteen of those women were among the 22 women who experienced an adverse pregnancy or birth outcome. All 16, as well as the mothers of the eight infants who died from microcephaly, were infected with Zika virus during the first trimester of pregnancy.

In contrast, 8 women whose placental tissue showed evidence of Zika infection but delivered healthy-appearing infants were infected with Zika virus during the third trimester of pregnancy. All their infants tested negative for the virus after birth.

The results show that infection during the first trimester of pregnancy is more harmful for the fetus and infant than infection during the third trimester.

The investigators used in situ hybridization to test for both viral genomic RNA and replicative RNA intermediates. They localized the replicative RNA in Hofbauer cells of placenta and in neural cells and neurons in the brains of infants who had died. The authors suggest that together with other data, "these findings suggest that Hofbauer cells, which have access to fetal blood vessels, may facilitate transfer or dissemination of the virus to the fetal brain."

"[O]ur findings further support the linkage of Zika virus with microcephaly, suggest its association with adverse pregnancy outcomes, and demonstrate evidence of Zika virus replication and persistence in fetal brain and placenta," the researchers write.

"Our molecular tests for tissues extend the timeframe to detect Zika virus," Dr Bhatnagar said in the news release. "For women who contracted Zika virus during early pregnancy but were never diagnosed, these tests could help determine whether Zika virus may have caused their miscarriage, pregnancy loss, or adverse birth outcome."

The authors have disclosed no relevant financial relationships.

Emerg Infect Dis. Published online December 13, 2016. Full text

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