Zika breakthrough: how virus hits brain

Kindergarten children look at posters informing them about Zika virus symptoms, as part of a government campaign to prevent the spread of the aedes aegypti mosquitos in San Jose, Costa Rica.

Kindergarten children look at posters informing them about Zika virus symptoms, as part of a government campaign to prevent the spread of the aedes aegypti mosquitos in San Jose, Costa Rica.

Published Mar 7, 2016

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Washington - The body of evidence linking the Zika virus to devastating health effects on women and unborn babies grew significantly stronger.

New studies from two continents detailed how the pathogen could attack foetal brain development as well as trigger complications at any stage of pregnancy.

In one study, a team of US researchers identified a probable mechanism for how the Zika virus can cause microcephaly, in which children are born with abnormally small heads and underdeveloped brains. The rare condition has surfaced in hundreds of babies in Brazil, the epicentre of a Zika outbreak that has spread to three dozen countries and territories, primarily in the Americas.

The second study, in which US and Brazilian researchers tracked 88 pregnant women at a clinic in Rio de Janeiro, found evidence of “grave” complications and birth defects from Zika infections. Some of the problems had not been seen previously, including damage to foetuses' central nervous systems and a lack of amniotic fluid by late pregnancy.

Since the World Health Organisation designated the virus and its suspected complications in newborns as a public health emergency last month, scientists and officials have been racing to control Zika and halt its explosive spread. But their efforts have been hobbled by a fundamental lack of understanding of the once-obscure virus.

While Zika causes only minor illness in most people - about 80 percent of those infected never show symptoms - Friday's research findings reinforce an increasing consensus that the virus can have tragic consequences for pregnant women and their foetuses.

“This is truly the virus from hell,” said Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine.

In the US study, researchers from Johns Hopkins University, Florida State University and Emory University exposed lab-grown human stem cells to a strain of Zika. It selectively infected cells critical to development of the brain's outer layer, the cortex. Its assault made those cells more likely to die and less likely to make new brain cells. Studies of foetuses and babies with the characteristic marks of microcephaly often have found cortical abnormalities.

The findings, published in the journal Cell Stem Cell, fills in another crucial gap in what scientists know about Zika and foetal development.

“It strengthens the case that Zika is a culprit behind microcephaly,” said Joseph Gleeson, an investigator for the Howard Hughes Medical Institute, who was not involved in the study. “It's a very important piece in the puzzle.”

Researchers already have seen traces of the virus in brains of newborns who died, as well as in fluid from the placentas of infected women. But one key missing piece has been information about how it can slow or halt brain development in utero. Although the results don't definitively prove Zika causes microcephaly, it strengthens the link, said Guo-li Ming, a Johns Hopkins University neurologist and a lead author of the study.

It did not address whether the virus can reach brain cells. But the findings show how much destruction the virus could cause. “This virus can do a lot of damage,” Florida State University virologist Hengli Tang, a lead author of the study, said on a phone call with reporters.

Researchers used the original Zika strain, first discovered in Uganda in 1947. That strain is 89 percent identical to the current strain in the epidemic, he said.

The second study, published in the New England Journal of Medicine, detailed the 88 cases followed at the Rio de Janeiro clinic between September 2015 and last month. With those, 72 women tested positive for Zika in their blood, urine or both, and 42 of them chose to have ultrasounds. All 16 women who tested negative for Zika also underwent ultrasounds.

Those without infections showed normal results. But for nearly a third of those infected by Zika, the imaging detected critical issues.

“The frequency was so high,” said study co-author Karin Nielsen, a pediatric infectious disease specialist at the University of California at Los Angeles, who collaborated with scientists at Fiocruz, an institution in Brazil. “These abnormalities are very significant; they are not minor. These are serious, serious problems.”

Unlike previous efforts that suggested a link between Zika and potential birth defects based on case reports, the US and Brazilian researchers tested the women for infection in real time and followed them as their pregnancies unfolded. They said the women had no other risk factors.

What they found was illuminating and also “extremely concerning,” according to the study.

One mother had an emergency Caesarean section after doctors realised she had no amniotic fluid in her uterus; her baby now appears to be healthy. Of six live births, two babies were small for their gestational age, while a third was born at normal weight but with severe microcephaly. Two of the infants had lesions in their eyes, which could indicate blindness.

“It is a whole spectrum of conditions,” Nielsen said.

The two studies may help to dispel persistent rumours that pesticides are behind the spike in birth defects in Zika-outbreak countries. “These kinds of studies can help melt away all the other theories,” Hotez said.

At the same time, both studies have shortcomings. The first took place in a controlled environment with lab-grown stem cells. And the study in Brazil had a limited sample size because of the relatively small number of pregnant women. Nielsen said she and her colleagues are continuing to enrol women for ongoing research and will follow their babies' development.

 

Washington Post

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