Doctors have found the Zika virus in the brain of a fetus with severe microcephaly, providing more strong evidence that the virus gets into the brains of developing babies and can damage them.
The New England Journal of Medicine has rushed publication of the report, which adds a big piece to the puzzle of whether and how the epidemic of Zika virus has caused a matching surge in birth defects in Brazil.
The case provides the elements needed to virtually catch the virus in the act: A pregnant women with a Zika-like illness who was living in Brazil, a developing fetus that suddenly stopped growing, clear brain damage in the fetus and, finally, the full genome of the virus found in the brain.
At the same time, the Centers for Disease Control and Prevention released details of its study of two newborns killed by microcephaly and two miscarriages in which evidence of Zika was found in the brains and placentas.
"To me that just confirms what I think many of us thought it was just a matter of time before we could confirm,” said Dr. Marjorie Treadwell, a specialist in high-risk pregnancies at the University of Michigan, who was not involved in the study.
“I think the actual isolation of the virus in the brains strengthens the thought that the Zika virus is causing these cases of microcephaly.”
Tatiana Avsic Zupanc of University Medical Center in Ljubljana, Slovenia, and colleagues detailed the case of a woman who showed up with a troubled pregnancy in October of last year.
"The actual isolation of the virus in the brains strengthens the thought that the Zika virus is causing these cases of microcephaly.”
The 25-year-old woman had been working as a volunteer in Natal, Brazil. “She had become pregnant at the end of February 2015. During the 13th week of gestation, she had become ill with high fever,” they wrote in their report. She also had severe muscle aches and an itchy rash.
Zika was circulating, but her first ultrasound looked normal. She came home to Europe when she was seven months pregnant and another ultrasound showed evidence of microcephaly — a severe birth defect in which the brain is underdeveloped and in which the baby’s head is also too small.
She also noticed the baby wasn’t moving as much as before. By 32 weeks, the fetus was clearly smaller than it should have been, with a very small head and evidence of extensive brain damage.
“The mother requested that the pregnancy be terminated and the procedure was subsequently approved by national and hospital ethics committees,” the researchers wrote. That is very late in pregnancy to perform an abortion, but the fetus was almost certainly not going to survive.
The team did an extensive autopsy. The fetus was very small but the only obvious abnormality was an extremely small head. The brain was very underdeveloped, and was scarred throughout.
The brain was almost completely smooth — meaning it did not have the folds that characterize a human brain. There were many areas of dead and calcified brain tissue.
“It sounds like a pretty clear case of extreme microcephaly,” said Aubree Gordon, an epidemiologist at the University of Michigan who’s studying the effects of viruses on pregnancy in central America.
And the researchers found Zika virus in the brain of the fetus — not just traces, but the entire genome of the virus.
"It looks like that Zika virus 'likes' brain tissue (e.g. neurotrophism) and likely the virus can replicate in neurons of the brain," Avsic said by email. She said Zika virus may be able to stay in the brain longer than it does in other parts of the body, because the immune system is less able to reach it there. That way it can do more damage than it does to other tissues.
The fetus had no evidence of any other infection that could have caused the damage and the mother did not have any of the known genetic causes of microcephaly, Avsic’s team said.
“This really does strengthen the evidence that Zika virus is causing microcephaly,” Gordon, who was not involved in the study, told NBC news.
Until late last year, Zika was an obscure virus that wasn’t considered much of a threat. It’s a cousin of dengue, yellow fever and chikungunya viruses and, like them, is carried by mosquitoes. But Zika causes almost no symptoms in most people it infects and only mild symptoms in about 20 percent.
“It sounds like a pretty clear case of extreme microcephaly.”
Zika swept across Brazil last year and authorities there raised the alarm when they noticed an increase in microcephaly cases.
The World Health Organization has declared the spread and its link with birth defects to be a global emergency and the U.S. Centers for Disease Control and Prevention has cautioned pregnant women to avoid areas where the virus is spreading. It’s in more than two dozen countries in the Americas now. Some governments, such as El Salvador’s, have advised women to avoid getting pregnant until the virus has time to settle down.
It’s not clear how many cases of microcephaly Zika may be responsible for. Brazil has reported a big increase in the number of cases, but some experts say that it may be that people are now reporting more cases than they did before.
Zika has been found in the amniotic fluid of affected pregnancies and in the mothers. And CDC has found strong evidence of the virus in the brains of two babies that died hours after birth with microcephaly and in tissue from two miscarried fetuses with microcephaly in Brazil.
“CDC was able to identify the genetic material of the Zika virus in the brain,” CDC Director Dr. Thomas Frieden told a hearing in Congress Wednesday. "This is the strongest evidence to date that Zika virus is the cause of microcephaly.”
Tests that would show a definitive cause cannot be done on living children, and the body’s immune system usually clears away the virus after a time, leaving the damage but making it hard to prove the virus did it.
There’s evidence Zika may cause other birth defects, as well — notably to the eyes. And doctors are also checking into reports that it may cause a paralyzing neurological condition called Guillain-Barre syndrome in adults.
Treadwell says it is likely that the early stages of pregnancy are the most dangerous. Other viruses known to cause birth defects, such as rubella and cytomegalovirus, are the most destructive if the mother is infected early in pregnancy. But that’s not certain.
“The hard part is we don’t know,” she said. “A lot of viruses cause scarring or they can cause destruction of brain tissue. There are a lot of different possibilities.”
Zika and its relatives had never before been known to cross the placenta and affect a growing fetus, which is why doctors had so many doubts about whether it was doing so in Brazil. Scientists are trying to figure out if the virus has changed or if some other factors are allowing it to do so.
"We're not aware of any other mosquito-borne cause of birth defects," Frieden said.