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"Our results remove any lingering doubt that the Zika virus is incredibly dangerous to the developing fetus, and provides details as to how the brain injury develops," said study author Dr. Kristina Adams Waldorf. She is a professor of obstetrics and gynecology at the University of Washington in Seattle.
"This study brings us closer to determining if a Zika vaccine or therapy will prevent fetal brain injury, but also be safe to take in pregnancy," Adams Waldorf said in a university news release.
But animal studies often don't produce similar findings in humans.
Since the Zika outbreak began in Brazil in 2015, thousands of babies in that country have been born with a devastating birth defect known as microcephaly, which results in abnormally small heads and brains. U.S. health officials have predicted that the spread of Zika in the United States and its territories this summer will likely result in future cases of microcephaly in this country.
Brain development in nonhuman primates, like the pigtail macaques used in the study, has key similarities to that of humans. These similarities include the structure of the placenta (the organ that connects the mother to the fetus during pregnancy and supplies nutrients to the growing fetus), when nerves and the brain develop, and the proportions of gray and white matter, the study authors said.
The monkey study closely mimicked a Zika infection during the third trimester of pregnancy, allowing the researchers to investigate the cause-and-effect relationships between the virus and brain injury in a developing fetus.
The pregnant monkeys did not develop a fever, rash or other major symptoms of infection. But within three weeks of infection the white matter of the fetuses' brain, which coordinates communication between various parts of the brain, stopped growing, the researchers found.
If this trend had continued for another month, the researchers said, microcephaly would have resulted.
"We were shocked when we saw the first MRI of the fetal brain 10 days after viral inoculation. We had not predicted that such a large area of the fetal brain would be damaged so quickly," said researcher Dr. Lakshmi Rajagopal, an associate professor of pediatrics at the University of Washington.
The study authors said that once a pregnant woman develops symptoms, the brain of the fetus may already be damaged.
"Our results suggest that a therapy to prevent fetal brain injury must either be a vaccine or a prophylactic medicine taken at the time of the mosquito bite to neutralize the virus," Rajagopal said.
The researchers observed other problems with brain development, including abnormally large fluid-filled brain cavities and a smaller-than-usual part of the brain that controls movement and other functions. They said they also detected vision problems and Zika virus genetic material in the eyes, liver and kidneys.
They added that their findings meet established criteria for how scientists determine if a microorganism is the specific cause of a disease or condition.
The researchers also said their findings prove without a doubt that the Zika virus crosses the placenta from a mother to the brain of the fetus. In fact, the study showed levels of the virus were higher in the brains of the fetuses than they were in the brains of their mothers.
The study was published online Sept. 12 in the journal Nature Medicine.
"Our entire team is deeply committed to developing an animal model in which we can rapidly test a vaccine or therapy to determine if we can prevent fetal brain injury caused by the Zika virus," Adams Waldorf said.
-- Mary Elizabeth Dallas
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