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Zika virus pits pregnant women against time, knowledge gaps




The Zika in Infants and Pregnancy (ZIP) study, recently launched by the NIH, will provide a prospective look at birth outcomes in 10,000 women aged 15 years and older who will be followed throughout their pregnancies to determine if they become infected with Zika virus, and if so, how infection impacts birth outcomes.

The international, multi-site study will help clarify the timing of risk, Dr. Spong said, and is intended to elucidate pregnancy risks in symptomatic vs. asymptomatic women. The study will also help indicate whether nutritional, socioeconomic status, and other cofactors such as Dengue infection are implicated. Once born, all children in the study will be observed for a year. “Even if they have no abnormalities, after birth there could be developmental delays, or more subtle consequences later on in the child’s life,” Dr. Meaney-Delman said.

Meanwhile, researchers are attempting to map how varying levels of viremia affect transmission. Zika virus has been found in semen after 90 days in at least two studies, “and we don’t know if Zika can be transmitted through other bodily fluids,” Dr. Spong said.

Surveillance data from the CDC’s Zika Pregnancy Registry has shown viremia in symptomatic women can last up to 46 days after onset of symptoms. In at least one asymptomatic pregnant woman, viremia was detected 53 days after exposure. Another study found prolonged viremia – 10 weeks – in a patient who had Zika infection in her first trimester; imaging showed the fetus was developing normally until week 20, when signs of severe brain abnormalities were detected.

The emerging picture of Zika’s potential for prolonged viremia has prompted the CDC to recommend clinicians use reverse transcription–polymerase chain reaction (RT-PCR) testing rather than serologic testing, as it is more sensitive and helps rule out other flavivirus infections, which require different management, Dr. Meaney-Delman said.

Potential mechanisms of action

“It’s clear that the virus does directly infect human cortical neural progenitor cells with very high efficiency, and in doing so, stunts their growth, dysregulates transcription, and causes cell death,” Dr. Spong said.

Researchers have also found that Zika replicates in subgroups of trophoblasts and endothelial cells, and in primary human placental macrophages, resulting in vascular damage and growth restriction. Other research suggests the virus spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes, leading to the theory that uterine-placental suppression of the viral entry cofactor TIM1 could stop transmission to the fetus.

Prevention and management

CDC officials expect the current outbreak to mimic past flavivirus outbreaks which were contained locally in portions of the South and U.S. territories, Dr. Meaney-Delman said. Still, she emphasized that clinicians should screen patients, regardless of location. “Each pregnant women should be assessed for [vector] exposure, travel, and sexual exposure and asked about symptoms consistent with Zika virus,” Dr. Meaney-Delman said.

She also emphasized the importance of patients consistently using insect repellent and using condoms during pregnancy, as Zika has been detected in semen for as long as 6 months. “It’s been very hard to invoke this behavioral change in women, but it’s very effective.”

The CDC continues to update guidance, including how to evaluate newborns for Zika-related defects.

As for what resources might be needed in future to help affected families, in an interview Dr. Meaney-Delman said that depends on information still unknown. “Zika is a public health concern that we should be factoring in long term, but what we do about it will depend upon the outcomes,” she said. “If there are children that are born normal but who have lab evidence of Zika, then we will probably not do much. I don’t think we have a projection yet.”

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