A Clue to the Mystery of Colombia’s Missing Zika Cases

In December of 2015, Magdalena Sanz Cortes was seeing patients at Texas Children’s Hospital and teaching classes in the ob-gyn department at the Baylor College of Medicine, when she got a call from Barranquilla, Colombia. Miguel Parra Saavedra, a gynecologist in the coastal metropolis, was worried by all the patients coming to his office showing signs of the mysterious Zika virus that had hit Brazil less than a year before. Alarming reports of microcephaly—abnormally small heads and brain damage caused by the Zika virus—were beginning to come out of Colombia’s neighbor to the east. Sanz Cortes and Parra Saavedra decided to start monitoring Barranquilla’s pregnancies to see if a similar wave would hit Colombia.

It never did.

In Brazil, more than 2,300 Zika-infected babies have been born with microcephaly since 2015. In Colombia, the world’s second largest outbreak has produced far fewer: only 82. Taking total population into account, that’s still more than an order of magnitude less. The disparity has bewildered public health officials, and caused many to question the link between the birth defect and Zika. The US Centers for Disease Control formally declared a causal link between microcephaly and the virus in April of 2016, citing a compelling accumulation of data from Brazil, including finding Zika virus in the brain tissue of affected infants. But Colombia’s microcephaly cases never materialized.

By collecting detailed brain images of more than 200 developing fetuses from expecting mothers along the Colombian Caribbean coast, Sanz Cortes and Parra Saavedra think they have found something close to an explanation: Microcephaly wasn’t appearing in just a few cases, it was appearing in just the worst cases. Zika was still causing significant brain damage even in babies without below average-sized skulls.

“We now suspect that microcephaly is just the end of the spectrum,” says Sanz Cortez, who presented the results of her team’s study at a meeting of the Society for Maternal-Fetal Medicine on Friday. “But the brain tissue stops growing well before that.” What this means for doctors, she says, is that simple head measurements are not enough to make a diagnosis for the suite of developmental defects caused by the virus—sometimes called congenital Zika syndrome. Physicians should also be using ultrasound and fetal MRIs to identify less obvious signs of infection. While early detection won’t change outcomes—doctors still don’t have a treatment for the disease’s congenital effects—it’s important for expectant mothers to mentally and emotionally prepare for the challenges ahead. Especially if those challenges aren’t obvious in the delivery room.

Despite the fact that those results haven’t yet been peer-reviewed, they do match up with another recent study from a group of researchers in Seattle and Brazil who reported on 13 Zika-infected infants born with normal-sized heads. As they got older, these children began to develop new complications. Their heads didn’t grow as fast as the rest of their bodies; they had strange muscle weaknesses and spasms. MRIs showed that inside their skulls they had similar symptoms to the Colombian babies—decreased brain volume, too much fluid in certain brain tissues. That means there may be a lot of babies out there who have yet to show signs of congenital Zika defects. And if brain scans don’t expose them, time will.

“How these infants fare in the first year of life is an absolutely critical public health question that right now we don’t know the answer to,” says Margaret Honein, chief of the CDC’s Birth Defects Branch. She heads up a task force that monitors babies born to Zika-infected mothers in the US and its territories. They’ve learned a lot in the past year: Even moms without symptoms can pass on the virus and its congenital effects to their babies, for example. And the first trimester is probably the most dangerous time to get infected. “What we know less about is the full range of bad outcomes that can happen from these infections,” says Honein.

And scientists know even less about how Zika causes these bad outcomes. How does the virus get into a fetus? Where does it go once it’s inside? Why does it do more damage in some than others? That kind of research is nearly impossible to do in humans—so instead, scientists are relying on monkeys to fill in the gaps.

At the University of Wisconsin, virologist Dave O’Connor has been infecting macaques with Zika and carefully tracking the virus’ progress through time and tissues. During the pregnancies, his team repeatedly samples blood and amniotic fluid to determine how quickly the virus can infect a fetus. They take fetal MRIs to make measurements on how the baby macaque is growing. And once the pregnancy is complete, they analyze more than 60 different fetal tissues for little bits of Zika DNA and virus-induced damage.

They hope their studies, when combined with epidemiological data, will shed some light into the big black Zika box. Right now the CDC estimates that about 5 percent of babies born to Zika-infected moms show clinical signs of birth defects. Other studies in Rio de Janeiro put it closer to 30 or 40 percent. Getting to the bottom of that will take a real collaborative effort from the scientific community, a framework O’Connor says they’re going to need going forward.

“Zika is not the only virus that causes birth defects,” he says. “It’s one of many that seems to have found a niche in a new place due to globalization, and that’s a trend that isn’t going to reverse itself.”

The threat of more emerging diseases may be lingering on the horizon, but back in Barranquilla it’s still Zika that’s on Parra Saavedra’s  mind. While it’s not easy to get a fetal MRI in Colombia, ultrasound is widely available through most of the country. If Colombia’s doctors can screen for the disease’s congenital defects, they may turn up more of the missing Zika cases.

 

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source : https://www.wired.com/2017/01/clue-mystery-colombias-missing-zika-cases/

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