Are you starting to think the Zika epidemic is the most confusing outbreak ever?
Join the club.
Since Zika surfaced on the global radar about a year ago, scientists have been trying to figure out if what seemed like a pretty paltry virus could cause serious birth defects if it infected a fetus in the womb and, if so, how often?
There is really no doubt now that the answer to the first question is yes. Over the course of 2016 a lot of science has been published showing that the Zika virus wreaks havoc on a developing brain if it gets into a fetus.
But the “how often?” question — well, that remains a mystery. And two new reports this week — from top-flight research teams in top-drawer medical journals — not only failed to arrive at a consensus, they may have sown more confusion.
A word of warning: Scores of studies like these are in the works and will hit the medical literature in coming months. That could mean the picture will become blurrier before it starts to come into focus.
Still, Maria Van Kerkhove, an epidemiologist with the Pasteur Institute in Paris, is delighted so many studies are underway.
“But as a scientist and as someone who has to communicate this, it’s a mess. Because all of these [studies] are at different stages, they’ve all been using different methodologies, so that’s confusing,” Van Kerkhove said.
Van Kerkhove has studied Zika, but she was not involved in the two articles that came out this week. Let’s head back to them.
One looked at a group of 125 pregnant Brazilian women from Rio de Janeiro who were known to have been infected with Zika. Scientists found the pregnancies of 46 percent were affected in some way — the pregnancy was lost or the baby had some signs of brain problems. When they looked only at the babies born, 42 percent showed some issues that might have been related to Zika.
The other study, conducted by scientists from the Centers for Disease Control and Prevention, looked at pregnancy outcomes in 442 women in the US who tested positive for Zika. The research team calculated the rate of bad outcomes — birth defects — at 6 percent.
There’s a whole lot of daylight between those figures. And yet, interestingly, neither group is challenging the other’s findings.
And they found some things that are similar. For instance, the rate of cases of microcephaly, in which an infant is born with an abnormally small head, was very similar in the two studies — 3 or 4 percent in total, 10 or 11 percent if infection occurred in the first trimester of pregnancy.
But what about the differences?
Before we answer that question, we need to provide some important context.
A fetus infected today during the first trimester won’t be born for months. And in many cases it may take weeks or months after birth to realize that a baby can’t hear or can’t see or isn’t developing cognitively at the rate other babies are.
As a result, the scientists who reported the high number of bad outcomes, the 42 percent, cast a very wide net when they were looking for problems Zika may have caused.
That team, made up of researchers from Brazil and the US, included pregnancy losses (miscarriages and stillbirths), obvious birth defects linked to Zika, and even signs of possible brain changes seen using imaging technologies. The study was published in the New England Journal of Medicine.
Some of those anomalies — for instance, cerebral palsy-like limb stiffness — will have an impact on the lives of these babies. But it won’t be known for a while if, or to what degree, some of the more subtle differences this group included will affect a child’s ability to function and develop, said Margaret Honein, the lead author of the second study, the one suggesting the rate of Zika-related birth defects might be lower.
Honein, who heads the CDC’s birth defects branch, said the Brazilian study’s findings highlight why it will be critical to follow babies infected in the womb over time.
It’s also crucial to get more data — and data that can be more easily compared.
Van Kerkhove and other experts worked with the World Health Organization earlier this year to devise standardized protocols for studying Zika in pregnancy. The hope, she said, was that if lots of different research groups used the same template for their studies, the ensuing results would be an apple-to-apple comparison.
Groups in a number of different countries appear to be using the protocols, she said. But not all are. So results that come out will look at slightly different groups of pregnant women or include more or fewer problems in the list of birth anomalies they count. And that will likely mean Zika risk estimates don’t cluster neatly around a tight range of numbers, at least not for a while.
To complicate matters even further, there isn’t one accepted definition of microcephaly. That means the same baby could be counted as microcephalic in one country, and not in another.
“This outbreak has been plagued by problems of definition and it’s hard when we’re using different surveillance definitions to compare data across locations,” Honein said.
So, about those two studies …
STAT consulted a number of experts in epidemiology about these studies and there appears to be no single answer that explains the huge gap between the CDC number (6 percent) and the Rio number (42 percent). But here are some things that may be at play.
The women being studied were different: The Rio study enrolled women who had a rash and fever, then tested them for Zika. That means they didn’t look at women without symptoms. Despite the fact the CDC study didn’t find a difference in the pregnancy outcomes between symptomatic and asymptomatic women, it’s a theory that experts haven’t given up yet and it needs further investigation.
The CDC study, on the other hand, enrolled women who had been to places where Zika was spreading and who tested positive for the virus. But Zika testing is notoriously difficult. If it’s not done during or very soon after the infection, you cannot be sure a positive test is a true positive. The test may be picking up antibodies to related viruses like dengue.
That means the CDC study may actually include some women who didn’t really have Zika, which would make the virus’s impact appear to be less than it was. Preben Aavitsland, Norway’s former chief epidemiologist, said that’s a possibility, but it can’t go all the way to explain the big gap between the findings.
Another way in which the two sets of women may have been different: geography.
Scientists have been wondering if some unidentified condition or conditions in Brazil — which has had the highest numbers of microcephalic babies due to Zika — is making Zika’s impact there worse.
An obvious thought is that dengue, a closely related virus, circulates there commonly. Some scientists have wondered if previous bouts of dengue would raise the risk for pregnant women infected with Zika, because it’s known prior infection with one type of dengue (there are four) can make a subsequent infection with another type worse. Still other scientists have theorized that dengue antibodies might actually protect pregnant women from Zika’s worst damage.
The Rio study compared women who had previously had dengue to women who had not and saw no difference.
But they did see an unusually high rate of birth defects and pregnancy losses — 11.5 percent — in the women they were following who did not contract Zika, their so-called control group.
You wouldn’t see that high a rate of abnormal outcomes in pregnancies in the US, which suggests there are differences between the Brazilian women and the US women that haven’t been accounted for, Maia Majumder, a research fellow at HealthMap, noted on Twitter.
The upshot is that, for now, even the experts cannot quantify for a pregnant woman what the chances are that her fetus will be affected if she contracts Zika. But they do know this: Pregnant women should try as hard as is humanly possible not to get infected with this virus.
“We’re finding pretty high levels of abnormalities in [pregnant] women who are infected with Zika,” said Van Kerkhove. “The exact numbers are not completely clear at the moment. But the studies are being done and we’re hoping to get a clearer picture in the coming months or years. I hope it’s not years, but certainly months.”
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