Monkey study suggests Zika infection in infancy could cause brain damage

A new study in primates raises the possibility that children infected with the Zika virus during infancy could be at risk of experiencing brain damage.

Zika is known to destroy developing brain tissue when it infects a fetus in the womb. Scientists know less — next to nothing, essentially — about how the virus might affect the brain of an infant infected after birth.

In the new study, scientists infected rhesus macaques with Zika virus at the age of about 1 month — which corresponds to about 3 months of age in a child. The macaques showed troubling brain and behavioral changes.

The findings, published Wednesday in the journal Science Translational Medicine, are worrisome, admitted Dr. Karin Nielsen-Saines, who was not involved in the research.

Nielsen-Saines, a pediatric infectious diseases specialist at the University of California, Los Angeles, who studies the Zika virus, said during the height of the Zika outbreak in 2016 she and colleagues were often asked if it was safe to take a baby to areas where Zika was transmitting.

“We sort of never knew what to answer, because there isn’t really much data, still, out there to determine if there are any issues or not,” Nielsen-Saines told STAT.

“I guess we will still not be able to appease those who call us to say, ‘Oh, can [an infant] travel to Zika-endemic areas?’ Because the data is not encouraging.”

Answering the question by studying children born in places where Zika was spreading could be surprisingly difficult.

Scientists would have to rule out the possibility that children had been infected before birth — no easy task given that Zika infections can be mild and women don’t always know they were infected. And testing for antibodies in the women or their children might not generate a clear answer, because tests don’t easily distinguish between Zika antibodies and those created by infection with dengue viruses, which also spread in places where Zika flourished.

In the macaque study, scientists led by researchers from Emory University and working at the university’s Yerkes National Primate Research Center, studied the question in eight animals. Six were infected with Zika virus while two others were used as controls.

Four of the animals — the controls and two infected macaques — were followed until they were 12 months old to see if the brain changes persisted and if they altered behavior.

Dr. Ann Chahroudi, the senior author of the study and an assistant professor of pediatric infectious diseases at Emory, said the brains of the infected animals developed differently than those of the controls. For instance, growth of the hippocampus — a part of the brain that is involved regulating emotions — was stunted in the infected animals. The hippocampus is also involved in long-term memory and spatial navigation.

In a bid to see if the changes were significant, the researchers put the macaques through a standardized stress test, called the human intruder test. The animals were exposed to a stranger, seen first in profile. Later the person made eye contact with the macaques. The control animals behaved the way they ought to have — they were scared. The animals that had been infected in infancy did not exhibit behavior that suggested fear; they were more inward focused, Chahroudi said.

With such small numbers of animals in the study, it’s important to be cautious about drawing too firm a conclusion about what this work can say about Zika infection in infants, she admitted.

It’s also not clear if an affected brain could rewire itself to overcome any damage the virus might have inflicted. “We don’t know the answer to that. You can hypothesize either way,” said Chahroudi, though she noted that brain damage caused by early infection with cytomegaloviruses or with HIV can be permanent.

Chahroudi said she would like to conduct an additional study, infecting macaques at different ages to see if there is a cutoff after which Zika infection no longer leads to changes in the animals’ brains. But she doesn’t currently have the funding to do this work.

In time there should be some human data that will hopefully shed some light on this question. Last year the National Institute of Allergy and Infectious Diseases announced funding for a study of 1,200 children in Guatemala who had been infected with the virus in their early years.

In the meantime, Chahroudi said, as a clinician, she would want to monitor the development of a young patient if told the child had been infected with Zika in infancy.